WorldWideScience

Sample records for non-mutation-carrying high-grade serous

  1. 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.

  2. 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.

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

    Science.gov (United States)

    2015-10-01

    that serous tubal intraepithelial carcinoma (STIC) is the precursor and not a metastasis of many, if not most, pelvic high-grade serous carcinomas...HGSCs) but we believe all the other proposed candidates should be investigated in order to determine if STIC is the precursor of all ovarian and pelvic ...regulated process to maintain genetic stability (20). Overexpression of cyclin E1 can be detected in many HGSCs as well as in some STICs (14). In fact

  4. Serous Tubal Carcinogenesis: The Recent Concept of Origin of Ovarian, Primary Peritoneal and Fallopian Tube High-Grade Serous Carcinoma.

    Science.gov (United States)

    Kar, Tushar; Kar, Asaranti; Dhal, Ipsita; Panda, Sasmita; Biswal, Priyadarshini; Nayak, Bhagyalaxmi; Rout, Niranjan; Samantray, Sagarika

    2017-12-01

    Pelvic (non-uterine) high-grade serous carcinomas (PHGSC) including ovarian, tubal and primary peritoneal serous carcinomas have increased death: incidence ratio due to presentation at advanced stage, rapid progression, poor prognosis and high morbidity. Ambiguity regarding their pathogenesis and lack of a proper screening method is the cause of their late detection and high fatality rate. This study was undertaken to assess the fallopian tube for the presence of precursor lesions in pelvic serous carcinoma. This was a prospective case-control study carried out in a tertiary care center. Consecutive specimens of 55 cases of pelvic high-grade serous carcinoma and 41 controls inclusive of 21 low-grade serous carcinoma, 10 benign adnexal masses and 10 normal adnexa were included in the study. Both side fallopian tubes in each case were subjected to histopathological examination and p53, Ki67 immunohistochemistry. There were 55 cases of PHGSC comprising of 50 cases of ovarian HGSC, two cases of primary peritoneal carcinoma (PPC) and three cases of tubal carcinoma. Serous tubal intraepithelial carcinoma (STIC) was detected in 14 cases (28%), p53 signature in 13 cases (26%) and tubal intraepithelial lesion in transition in 10 cases (20%) of ovarian HGSC. One case (50%) of PPC and one (33%) case of tubal carcinoma revealed the presence of STIC. None of the controls exhibited any precursor lesion except ovarian low-grade serous carcinoma where p53 was detected in 20% of cases. This revelation concludes that fallopian tubes are the sites of precursors of PHGSC to a large extent. In the absence of a proper screening method of HGSC, prophylactic bilateral salpingectomy at hysterectomy for benign diseases can achieve ultimate goal of reduction in incidence of PHGSC.

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

    Science.gov (United States)

    2014-10-01

    iso - form expression in luteal phase fallopian tube epithelium and high-grade serous carcinoma. Endocr Relat Cancer (2011) 18:221–34. doi:10.1530/ERC-10...0 -1 -2 -3 8 norma ] samp1es - ,-, - • • 1 CM Control Lovastatin (50 mg/kg) C on tro l S ta tin (5 0m g/ kg ) S ta

  6. Immunohistochemical overexpression of p16 and p53 in uterine serous carcinoma and ovarian high-grade serous carcinoma.

    Science.gov (United States)

    Chiesa-Vottero, Andres G; Malpica, Anais; Deavers, Michael T; Broaddus, Russell; Nuovo, Gerard J; Silva, Elvio G

    2007-07-01

    The immunohistochemical expression pattern of p16 in biopsy samples has been useful as part of a panel to distinguish adenocarcinomas arising from the endometrium from those arising from the endocervix. However, no information is available on the expression of p16 in uterine serous carcinoma (USC) or ovarian high-grade serous carcinoma that could be used for diagnostic purposes. Here, we retrospectively analyzed the immunohistochemical expression of p16 in 11 cases of USC (5 pure and 6 mixed with endometrioid adenocarcinoma) and 10 cases of ovarian high-grade serous carcinoma and compared p16 expression with that of p53 in the same samples. p16 was strongly expressed by 100% of tumor cells in all 11 uterine specimens and in 5 of the 10 ovarian specimens; of the other 5 ovarian specimens, 4 showed strong positivity in 20% to 80% of tumor cells, and 1 case showed only weak expression. Positivity for p53 was strong and diffuse (100% of tumor cells) in 5 uterine tumors and in 3 ovarian tumors. p53 expression in 6 of the uterine specimens and 7 of the ovarian specimens was present in fewer tumor cells, of weak intensity, or both. We also performed human papilloma virus (HPV) DNA in situ hybridization in 4 uterine pure serous carcinomas; all 4 were negative. The negative results were confirmed by reverse transcriptase in situ polymerase chain reaction. We conclude that p16, owing to its diffuse expression in USC, should not be interpreted as indicating cervical origin or HPV-induced carcinogenesis; however, p16 may be a better marker (albeit unspecific) than p53 for identifying USC. The overexpression of p16 in USC is unrelated to HPV. Further studies are necessary to determine whether p16 expression is useful in the differential diagnosis of ovarian high-grade serous carcinoma.

  7. 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.

  8. 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).

  9. 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.

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

    Science.gov (United States)

    2016-10-01

    pathology. Springer 2015 25 ▪ Other publications, conference papers, and presentations. Abstracts S George , A Milea, N Salman and P Shaw...11-2-0230) Title: Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Change 2011-Current 1. George SH, Greenaway J, Milea...Cancer Res 2012, 18:4334-44. PMID: 22753593 4 11. George SH, Milea A, Shaw P: Proliferation in the normal FTE is a hallmark of the follicular phase

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Anders eOhman

    2014-11-01

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

  14. Origin and molecular pathogenesis of ovarian high-grade serous carcinoma.

    Science.gov (United States)

    Kurman, R J

    2013-12-01

    A new paradigm for the pathogenesis of ovarian cancer has recently been proposed which helps to explain persistent problems in describing the development and diverse morphology of these neoplasms. The paradigm incorporates recent advances in our understanding of the molecular pathogenesis of epithelial 'ovarian' cancer with new insights into the origin of these tumors. Correlated clinicopathologic and molecular genetic studies led to the development of a dualistic model that divides all the various histologic types of epithelial ovarian carcinomas into two broad categories designated 'type I' and 'type II'. The prototypic type I tumor is low-grade serous carcinoma and the prototypic type II tumor is high-grade serous carcinomas (HGSCs). As the serous tumors comprise ∼70% of all epithelial ovarian tumors and account for the majority of deaths, the serous tumors will be the subject of this review. There are marked differences between the low-grade and high-grade serous tumors. Briefly, the former are indolent, present in stage I (tumor confined to the ovary) and develop from well-established precursors, so-called 'atypical proliferative (borderline) tumors,' which are characterized by specific mutations, including KRAS, BRAF and ERBB2; they are relatively genetically stable. In contrast, HGSCs are aggressive, present in the advanced stage, and develop from intraepithelial carcinomas in the fallopian tube. They harbor TP53 mutations in over 95% of cases, but rarely harbor the mutations detected in the low-grade serous tumors. At the time of diagnosis they demonstrate marked chromosomal aberrations but over the course of the disease these changes remain relatively stable. Along with the recent advances in understanding the molecular pathogenesis of these tumors, studies have demonstrated that the long sought for precursor of ovarian HGSC appears to develop from an occult intraepithelial carcinoma in the fimbrial region of the fallopian tube designated 'serous tubal

  15. High grade serous ovarian carcinoma with serous tubal intraepithelial carcinoma in a case presented with atypical glandular cell favor neoplasm cervical cytology and dermatomyositis.

    Science.gov (United States)

    Hong, Mun-Kun; Lee, Ming-Hsun; Ding, Dah-Ching; Chu, Sung-Chao; Chu, Tang-Yuan

    2015-04-01

    This report describes a case of serous ovarian carcinoma with occult serous tubal intraepithelial carcinoma (STIC), which presented as atypical glandular cells favor neoplasia (AGC-FN) with Pap cytology and dermatomyositis. A 48-year-old woman presented with symptoms of dermatomyositis. An AGC-FN result from a Pap smear, with an absence of a cervical or endometrial lesion was noted. After cancer surveillance, ovarian high grade serous carcinoma associated with serous tubal intraepithelial carcinoma was diagnosed. Two weeks following surgical excision of the carcinoma, dramatic remission of the dermatomyositis symptoms was evident. The patient had serous carcinoma of the ovary with tubal STIC, which presented as dermatomyositis. The AGC-FN identified from a Pap smear hinted at a diagnosis of ovarian carcinoma. These presentations point to an occult malignancy in the genital tract and demand careful diagnostic workup. Copyright © 2015. Published by Elsevier B.V.

  16. 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...... clusters differed with respect to chemotherapy resistance, and the extent of LOH correlated with PFS. LOH burden may indicate vulnerability to treatment targeting DNA repair, such as PARP1 inhibitors. Clin Cancer Res; 18(20); 5806–15. ©2012 AACR....... into two subgroups. The second group contained remarkably less LOH. BRCA1 promoter methylation was associated with the major group. LOH clusters were reproducible when validated in two independent HGSC datasets. LOH burden in the major cluster of HGSC was similar to triple-negative, and distinct from other...

  17. 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.

  18. 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

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

    NARCIS (Netherlands)

    Lawrenson, K.; Li, Q.; Kar, S.; Seo, J.H.; Tyrer, J.; Spindler, T.J.; Lee, J. van der; Chen, Y; Karst, A.; Drapkin, R.; Aben, K.K.H.; Anton-Culver, H.; Antonenkova, N.; Baker, H.; Bandera, E.V.; Bean, Y.; Beckmann, M.W.; Berchuck, A.; Bisogna, M.; Bjorge, L.; Bogdanova, N.; Brinton, L.A.; Brooks-Wilson, A.; Bruinsma, F.; Butzow, R.; Campbell, I.G.; Carty, K.; Chang-Claude, J.; Chenevix-Trench, G.; Chen, A; Chen, Z.; Cook, L.S.; Cramer, D.W; Cunningham, J.M.; Cybulski, C.; Dansonka-Mieszkowska, A.; Dennis, J.; Dicks, E.; Doherty, J.A.; Dork, T.; Bois, A. du; Durst, M.; Eccles, D.; Easton, D.T.; Edwards, R.P.; Eilber, U.; Ekici, A.B.; Fasching, P.A.; Fridley, B.L.; Gao, Y.T.; Gentry-Maharaj, A.; Giles, G.G.; Glasspool, R.; Goode, E.L.; Goodman, M.T.; Grownwald, J.; Harrington, P.; Harter, P.; Hasmad, H.N.; Hein, A.; Heitz, F.; Hildebrandt, M.A.; Hillemanns, P.; Hogdall, E.; Hogdall, C.; Hosono, S.; Iversen, E.S.; Jakubowska, A.; James, P.; Jensen, A.; Ji, B.T.; Karlan, B.Y.; Kjaer, S. Kruger; Kelemen, L.E.; Kellar, M.; Kelley, J.L.; Kiemeney, L.A.; Krakstad, C.; Kupryjanczyk, J.; Lambrechts, D.; Lambrechts, S.; Le, N.D.; Lee, A.W.; Lele, S.; Leminen, A.; Lester, J.; Levine, D.A.; Liang, D.; Lissowska, J.; Lu, K.; Lubinski, J.; Lundvall, L.; Massuger, L.F.; Matsuo, K.; McGuire, V.; McLaughlin, J.R.; Nevanlinna, H.; McNeish, I.; Menon, U.; Modugno, F.; et al.,

    2015-01-01

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions

  20. Checkpoint kinase 2 (Chk2) supports sensitivity to platinum-based treatment in high grade serous ovarian cancer

    NARCIS (Netherlands)

    Alkema, N. G.; Tomar, T.; van der Zee, A.G.J.; Everts, M.; Meersma, G. J.; Hollema, H.; de Jong, S.; van Vugt, M. A. T. M.; Wisman, G. B. A.

    Objective. Platinum-based chemotherapy is the standard treatment in advanced stage high grade serous ovarian cancer (HGSOC), but the majority of patients will relapse with drug-resistant disease. Platinum induces double-strand DNA breaks and subsequently activation of the DNA damage response (DDR).

  1. Studying platinum sensitivity and resistance in high-grade serous ovarian cancer : Different models for different questions

    NARCIS (Netherlands)

    Alkema, Nicolette G.; Wisman, G. Bea A.; van der Zee, Ate G. J.; van Vugt, Marcel A. T. M.; de Jong, Steven

    High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among all gynecological cancers. Patients are generally diagnosed in an advanced stage with the majority of cases displaying platinum resistant relapses. Recent genomic interrogation of large numbers of HGSOC patient samples

  2. Candidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma.

    Science.gov (United States)

    de Cristofaro, Tiziana; Di Palma, Tina; Soriano, Amata Amy; Monticelli, Antonella; Affinito, Ornella; Cocozza, Sergio; Zannini, Mariastella

    2016-07-05

    Understanding the biology and molecular pathogenesis of ovarian epithelial cancer (EOC) is key to developing improved diagnostic and prognostic indicators and effective therapies. Although research has traditionally focused on the hypothesis that high-grade serous carcinoma (HGSC) arises from the ovarian surface epithelium (OSE), recent studies suggest that additional sites of origin exist and a substantial proportion of cases may arise from precursor lesions located in the Fallopian tubal epithelium (FTE). In FTE cells, the transcription factor PAX8 is a marker of the secretory cell lineage and its expression is retained in 96% of EOC. We have recently reported that PAX8 is involved in the tumorigenic phenotype of ovarian cancer cells. In this study, to uncover genes and pathways downstream of PAX8 involved in ovarian carcinoma we have determined the molecular profiles of ovarian cancer cells and in parallel of Fallopian tube epithelial cells by means of a silencing approach followed by an RNA-seq analysis. Interestingly, we highlighted the involvement of pathways like WNT signaling, epithelial-mesenchymal transition, p53 and apoptosis. We believe that our analysis has led to the identification of candidate genes and pathways regulated by PAX8 that could be additional targets for the therapy of ovarian carcinoma.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Eric J. Norris

    2018-02-01

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

  6. Survival of Advanced Stage High-Grade Serous Ovarian Cancer Patients in the Republic of Macedonia.

    Science.gov (United States)

    Aluloski, Igor; Tanturovski, Mile; Jovanovic, Rubens; Kostadinova-Kunovska, Slavica; Petrusevska, Gordana; Stojkovski, Igor; Petreska, Bojana

    2017-12-15

    The primary objective of the study was to evaluate the overall survival of women with advanced stage (Stage IIIA-IV) high-grade serous ovarian cancer in Macedonia. The study was a cross-sectional medical record review of patients diagnosed with advanced stage HGSC. Patients were deemed eligible for inclusion if they were diagnosed with an advanced stage (Stage IIIA-IV) HGSC of the ovary, fallopian tube or peritoneum between 2009 and 2015. The data were analyzed in a descriptive fashion and summary statistics were provided, as appropriate. Survival was calculated using the Kaplan-Meier method. A total of 81 eligible patients were identified and included in the study. The average overall survival in the studied cohort was 46.59 months (95%CI = 39.11-54.06). Patients that were optimally debulked and patients that had a platinum-free interval larger than 12 months had significantly longer survival in the current series (p < 0.001). the average overall survival of advanced stage HGSC patients in the studied series was 46.59 months (95%CI = 39.11-54.06). Patients aged 65 years or younger tended to live approximately ten months longer than patients older than 65 years, but this difference was not statistically significant. There was no difference in HGSC survival in the groups of patients with grade 2 and grade 3 disease. However, optimal surgical debulking and platinum sensitivity were associated with significantly better overall survival.

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

    Directory of Open Access Journals (Sweden)

    Paula eCunnea

    2014-04-01

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

  8. 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.

  9. 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.

  10. Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Matsuo, Koji; Sheridan, Todd B; Mabuchi, Seiji; Yoshino, Kiyoshi; Hasegawa, Kosei; Studeman, Kimberley D; Im, Dwight D; Rosenshein, Neil B; Roman, Lynda D; Sood, Anil K

    2014-06-01

    Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma. Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I-IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes. LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression was positively correlated to PR expression (r=0.31, p=0.001). LVSI was only correlated with ER (odds ratio 6.27, 95%CI 1.93-20.4, p=0.002) but not with other biomarkers. In multivariate analysis, ER remained significantly associated with LVSI (p=0.039). LVSI remained a significant prognostic factor for decreased progression-free survival (HR 3.01, 95%CI 1.54-5.88, p=0.001) and overall survival (HR 2.69, 95%CI 1.18-6.23, p=0.021) while ER-expression did not remain as a significant variable in multivariate analysis. Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. [Clinicopathologic study and immunohistochemistry comparison of Pax2, p53 and Ki-67 in low- and high-grade ovarian serous carcinomas].

    Science.gov (United States)

    Shen, Xu-xia; Yu, Lin; Bi, Rui; Yang, Wen-tao

    2011-08-01

    To evaluate the two-tier system for the grading of ovarian serous carcinomas, and to analyze Pax2, p53, Ki-67 protein expression and their prognostic values for low- and high-grade ovarian serous carcinomas. A total of 38 cases of low-grade and 100 cases of high-grade ovarian serous carcinomas were selected based on the two-tier grading system. Immunohistochemistry was used to detect Pax2, p53 and Ki-67 protein expression in all cases. Correlation of the two-tier system with immunohistochemical results and prognostic parameters were performed. (1) The overall survival, disease-free survival and 5-year survival rates were significantly higher in the low-grade serous carcinoma cases than in the high-grade cases (P carcinomas. The high-grade serous carcinomas had a significantly higher expression level of p53 (55.0% vs 13.2%, P carcinomas had a significantly higher expression level of Pax2 (65.8% vs 13.0%, P p53 and Ki-67 were found to have little correlation with overall survival and disease-free survival (P > 0.05). The two-tier system for the grading of ovarian serous carcinomas has a good prognostic value. There are significantly differences in expressions of Pax2, p53 and Ki-67 between low- and high-grade ovarian serous carcinomas. Compared with p53 and Ki-67, Pax2 is likely a better prognostic indicator for ovarian serous carcinoma.

  12. Reconstitution of high-grade serous ovarian carcinoma from primary fallopian tube secretory epithelial cells.

    Science.gov (United States)

    Nakamura, Kohei; Nakayama, Kentaro; Ishikawa, Noriyoshi; Ishikawa, Masako; Sultana, Razia; Kiyono, Tohru; Kyo, Satoru

    2018-02-27

    Fallopian tube secretory epithelial cells (FTSECs) have been suggested to be the source of high-grade serous ovarian carcinoma (HGSOC). Although several genetic alterations are known to be involved in HGSOC development, the minimal requirements remain unclear. We aimed to identify oncogenic mutations indispensable for HGSOC development in a stepwise model, using immortalized FTSECs. FTSECs were isolated from clinical samples and immortalized by overexpression of cyclin D1, CDK4 R24C , and hTERT . Oncogenic mutations in the p53, c-Myc, and RAS/PI3K pathways were mimicked by lentiviral transduction. We found two distinct patterns of gene alteration essential for HGSOC development: p53/KRAS/AKT and p53/KRAS/c-Myc. Dominant-negative p53, alone or combined with oncogenic KRAS ( KRASV12 ), constitutively active AKT (CA-AKT), and c-Myc, did not induce tumorigenesis in immortalized cells; however, overexpression of CA-AKT or c-Myc, along with dominant-negative p53 and KRASV12 , conferred tumorigenic potential. Transformed FTSECs formed tumors in nude mice that were grossly, histologically, and immunohistochemically similar to human HGSOCs. Interestingly, mice harboring tumors with c-Myc amplifications displayed extensive metastases, consistent with the increased dissemination in their human counterparts. Thus, aberrant p53/ KRASV12 /c-Myc or p53/ KRASV12 /PI3K-AKT signaling was the minimum requirement for FTSEC carcinogenesis. The model based on this evidence could shed light on the early stages of HGSOC development.

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

    Science.gov (United States)

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

    2016-06-28

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

  14. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-01

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

  16. 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

  17. Serous tubal intraepithelial carcinoma localizes to the tubal-peritoneal junction: a pivotal clue to the site of origin of extrauterine high-grade serous carcinoma (ovarian cancer).

    Science.gov (United States)

    Seidman, Jeffrey D

    2015-03-01

    Recent data suggest that intraepithelial carcinoma of the fallopian tube [serous tubal intraepithelial carcinoma (STIC)] is the precursor of high-grade extrauterine serous carcinoma. A more specific location for the origin of this lesion is suggested by the recently described junction between the fallopian tubal epithelium and the peritoneum [tubal-peritoneal junction (TPJ)]. Fallopian tubes from 202 patients with advanced-stage high-grade extrauterine serous carcinoma or carcinosarcoma were evaluated histologically as were 124 prophylactic salpingo-oophorectomy specimens. These included 54 patients with BRCA or other high-risk mutation or a family history of BRCA mutation and 70 with a personal or family history of breast carcinoma. STIC was found in 81 of 202 patients with serous carcinoma (40.1%). STIC was present in 73 of 141 (52%) cases in which the fimbriae were present and in 62 of 100 (62%) cases in which the TPJ was present (P not significant). In comparison with these groups, when fimbriae and TPJ were absent, STIC was found in 8 of 61 (13%) cases (PSTIC. The mean size of STIC was 1.7 mm. In 32 cases (39.5%), the lesion was flat and in 49 (60.5%), papillary. The mean size of flat STICs was 0.8 mm as compared with 2.3 mm for papillary STICs (P=0.00005). STIC was identified in the same tissue fragment as the junction in 48 cases. The mean distance of STIC to the junction was 1.8 mm. In 11 cases, STIC was flanked by peritoneal mesothelium on one side and tubal epithelium on the opposite side. In 51 patients, the mean distance of invasive carcinoma from the TPJ was 1.8 mm. This distance was 1.9 mm when STIC was present (37 cases) in comparison with 1.5 mm when STIC was absent (14 cases) (P not significant). In 27 of 42 cases (64%), STIC was contiguous with invasive carcinoma. Lamina propria invasion was present in 71% of cases in which STIC was present as compared with 26% of cases in which STIC was absent (PSTIC was present as compared with 26% of cases in

  18. Cytokeratin 5/6 expression, prognosis, and association with estrogen receptor α in high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Taube, Eliane Tabea; Denkert, Carsten; Sehouli, Jalid; Unger, Ulrike; Kunze, Catarina Alisa; Budczies, Jan; Dietel, Manfred; Braicu, Elena; Darb-Esfahani, Silvia

    2017-09-01

    High-grade serous ovarian carcinoma remains one of the most lethal malignancies in women. For histopathologic differentiation from mesothelioma cytokeratin, 5/6 immunohistochemistry is widely used. Another preferred marker for differential diagnosis to mesothelioma is estrogen receptor α (ER-α). In this study, we determined the rate of cytokeratin 5/6-positive cells in primary high-grade serous carcinoma. A cohort of 215 patients with high-grade serous ovarian carcinoma was evaluated immunohistochemically for the protein expression of cytokeratin 5/6. Most tumors demonstrated at least partly positive for cytokeratin 5/6 (n=148; 68.3%), showing different staining patterns from scattered stained cells to a diffuse staining, at times with a distinctive tumor-stroma border motif. Sixty-seven (31%) were entirely negative. No correlation of cytokeratin immunoreactivity score (IRS) with conventional staging parameters could be demonstrated. From the different IRS values for cytokeratin 5/6, IRS=12 (n=6; 2.9%) seemed to indicate a worse prognosis, albeit not statistically significant. An association with ER-α expression could not be detected but the combination of cytokeratin 5/6 IRS=12 and ER-α negativity resulted in a significant negative prognostic marker (overall survival: P=.003 and progression-free survival: Povarian carcinoma with various staining patterns, an important fact for the routine differential diagnosis with mesothelioma. Furthermore, cytokeratin 5/6 in combination with ER-α proved to be a negative prognostic marker, wherefore we suggest further investigation of its biological significance and possible manifestation of a basal differentiation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma

    OpenAIRE

    Dong, Ruifen; Liu, Xiaolin; Zhang, Qing; Jiang, Zhijun; Li, Yingwei; Wei, Yuyan; Li, Yinuo; Yang, Qifeng; Liu, Jinsong; Wei, Jian-Jun; Shao, Changshun; Liu, Zhaojian; Kong, Beihua

    2014-01-01

    High-grade serous ovarian carcinoma (HGSOC), the most common and aggressive subtype of epithelial ovarian cancer, is characterized by TP53 mutations and genetic instability. Using miRNA profiling analysis, we found that miR-145, a p53 regulated miRNA, was frequently down-regulated in HGSOC. miR-145 down-regulation was further validated in a large cohort of HGSOCs by qPCR. Overexpression of miR-145 in ovarian cancer cells significantly suppressed proliferation, migration and invasion in vitro ...

  20. Nadir CA-125 level as prognosis indicator of high-grade serous ovarian cancer.

    Science.gov (United States)

    Xu, Xia; Wang, Yan; Wang, Fang; Jia, Lizhou; Zhou, Yiqin; Deng, Fei; Qu, Junwei; Zhou, Bifang; Meng, Aifeng; Fu, Bole; Chen, Xiaoxiang; Qian, Zhiying; Wang, Jinhua

    2013-01-01

    The capacity of nadir CA-125 levels to predict the prognosis of epithelial ovarian cancer remains controversial. This study aimed to explore whether the nadir CA-125 serum levels could predict the durations of overall survival (OS) and progression free survival (PFS) in patients with high-grade serous ovarian cancer (HG-SOC) from the USA and PRC. A total of 616 HG-SOC patients from the MD Anderson Cancer Center (MDACC, USA) between 1990 and 2011 were retrospectively analyzed. The results of 262 cases from the Jiangsu Institute of Cancer Research (JICR, PRC) between 1992 and 2011 were used to validate the MDACC data. The CA-125 immunohistochemistry assay was performed on 280 tissue specimens. The Cox proportional hazards model and the log-rank test were used to assess the associations between the clinicopathological characteristics and duration of survival. The nadir CA-125 level was an independent predictor of OS and PFS (p CA-125 levels (≤10 U/mL) were associated with longer OS and PFS (median: 61.2 and 16.8 months with 95% CI: 52.0-72.4 and 14.0-19.6 months, respectively) than their counterparts with shorter OS and PFS (median: 49.2 and 10.5 months with 95% CI: 41.7-56.7 and 6.9-14.1 months, respectively). The nadir CA-125 levels in JICR patients were similarly independent when predicting the OS and PFS (p CA-125 levels less than or equal to 10 U/mL were associated with longer OS and PFS (median: 59.9 and 15.5 months with 95% CI: 49.7-70.1 and 10.6-20.4 months, respectively), as compared with those more than 10 U/mL (median: 42.0 and 9.0 months with 95% CI: 34.4-49.7 and 6.6-11.2 months, respectively). Baseline serum CA-125 levels, but not the CA-125 expression in tissues, were associated with the OS and PFS of HG-SOC patients in the MDACC and JICR groups. However, these values were not independent. Nadir CA-125 levels were not associated with the tumor burden based on second-look surgery (p = 0.09). Patients who achieved a pathologic complete

  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. 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

  3. High levels of pretreatment CA125 are associated to improved survival in high grade serous ovarian carcinoma.

    Science.gov (United States)

    Morales-Vásquez, Flavia; Pedernera, Enrique; Reynaga-Obregón, Jesús; López-Basave, Horacio Noé; Gómora, María José; Carlón, Elisa; Cárdenas, Sandra; Silva-Ayala, Raúl; Almaraz, Miguel; Méndez, Carmen

    2016-07-07

    Serum levels of CA125 measured before any treatment have been evaluated in epithelial ovarian cancer (EOC) as a predictor of patient survival; however, results in survival index are controversial, as CA125 levels are influenced by several variables. Taking this into consideration, the present study evaluated the association of pretreatment levels of CA125 serum with the clinical stage, histology and differentiation grade of the tumor and the survival rate in a group of patients from an oncology referral center in Mexico, all of them diagnosed with ovarian carcinoma. This retrospective study consisted of 1009 patients with EOC, diagnosed between 2006 and 2013 at the National Cancerology Institute (Instituto Nacional de Cancerología-INCan), considering only those with CA125 measurements before any chemotherapy or surgical cytoreduction. Patients with three years of medical follow-up having pretreatment CA125 value and simultaneous diagnoses of histological subtype, clinical stage and differentiation grade of the tumor (n = 656) were studied in order to determine their survival rate. The abnormal level (>35 U/mL) of CA125 was observed in 99 % of serous carcinoma cases rated I to IV in the FIGO stages. Abnormal CA125 proportions were 89 % in endometrioid subtype and 69 % in mucinous tumors, with the highest absolute value of CA125 observed in serous carcinoma surpassing any other histological subtype. Clinical stages III and IV displayed increased CA125 values compared to stages I and II. Undifferentiated carcinomas show the highest level of this indicator compared with those of low and moderate differentiated grade. Survival evaluation by Kaplan-Meier analysis including only high grade serous carcinoma at FIGO stage III (n = 57) demonstrated 57.1 % chances of survival in patients with CA125 pretreatment levels higher than 500 U/mL. Survival was 26.7 % in patients with CA125 lower than 500 U/mL and the hazard ratio for CA125 ≤ 500 U/mL was 2.28, 95

  4. BRCA mutational status, initial disease presentation, and clinical outcome in high-grade serous advanced ovarian cancer: a multicenter study.

    Science.gov (United States)

    Petrillo, Marco; Marchetti, Claudia; De Leo, Rossella; Musella, Angela; Capoluongo, Ettore; Paris, Ida; Benedetti Panici, Pierluigi; Scambia, Giovanni; Fagotti, Anna

    2017-09-01

    In the last decades, there have been several efforts to clarify the role of BRCA mutational status in women with advanced ovarian cancer, demonstrating its role in cancer development, as well as the prognostic significance of BRCA genotype. Our aim is to evaluate the correlation between BRCA mutational status and disease presentation in a large series of advanced high-grade serous ovarian cancer patients. This is a retrospective multicenter study including a consecutive series of newly diagnosed high-grade serous ovarian cancer patients with International Federation of Gynecology and Obstetrics stage IIIC-IV disease, at least 18 months of follow-up time, and tested for BRCA 1/2 germline mutation status. Disease presentation was analyzed using the following variables: laparoscopic predictive index value, incidence of bulky lymph nodes, and ovarian masses. Progression-free survival was defined as the months elapsed from initial diagnosis (staging laparoscopy) and recurrent disease or last follow-up. In all, 324 high-grade serous ovarian cancer patients received BRCA testing, and 273 fulfilled inclusion criteria. BRCA1/2 germline mutations were observed in 107 women (39.2%). No differences were documented according to BRCA mutation status in terms of International Federation of Gynecology and Obstetrics stage, CA125 levels, or presence of ascites. In patients with BRCA1/2 mutations we observed a higher incidence of peritoneal spread without ovarian mass (25.2% vs 13.9%; P value = .018) and of bulky lymph nodes (30.8% vs 17.5%; P value = .010) compared with women showing BRCA1/2 wild type genotype. Furthermore, women with BRCA1/2 mutations showed high peritoneal tumor load (laparoscopic predictive index value ≥8; 42.1% vs 27.1%; P value = .016) more frequently. Focusing on survival, no differences in term of median progression-free survival were observed among women treated with primary debulking surgery and neoadjuvant chemotherapy in the group of patients with

  5. Cancer stem cells, epithelial-mesenchymal transition, and drug resistance in high-grade ovarian serous carcinoma.

    Science.gov (United States)

    Chen, Xiaoxiang; Zhang, Jing; Zhang, Zhihong; Li, Hongxia; Cheng, Wenjun; Liu, Jinsong

    2013-11-01

    Although epithelial ovarian cancer cells are eliminated by debulking surgery and chemotherapy during initial treatment, it is believed that only a subset of cancer cells, that is, cancer stem cells, may be an important source of tumor recurrence and drug resistance. This review highlights our current understanding of high-grade serous carcinoma, ovarian cancer stem cells, common methods for enrichment of ovarian cancer stem cells, mechanisms involved in drug resistance, and potential strategies for overcoming drug resistance, with associated potential controversies and pitfalls. We also review the potential relationship between epithelial-to-mesenchymal transition and cancer stem cells and how we can induce cancer cells to differentiate into benign stromal fibroblasts in response to certain chemotherapy drugs. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. 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.

  7. Loss of ALDH1A1 expression is an early event in the pathogenesis of ovarian high-grade serous carcinoma.

    Science.gov (United States)

    Chui, M Herman; Wang, Yihong; Wu, Ren-Chin; Seidman, Jeffrey; Kurman, Robert J; Wang, Tian-Li; Shih, Ie-Ming

    2015-03-01

    Tumor-initiating cells are thought to share features with normal somatic stem cells. In mice, stem cells at the ovarian hilum have been shown to express the stem cell marker, aldehyde dehydrogenase isoform 1A1 (ALDH1A1), and are prone to malignant transformation. The potential relevance of this finding to humans has not been established. In this study, we used immunohistochemistry to assess the distribution of ALDH1A1 staining in the epithelium of human fallopian tubes, with particular reference to the transition of tubal epithelium to mesothelium (ie, tubal-mesothelial junction), ovarian surface epithelium, as well as putative precursors of ovarian high-grade serous carcinoma, namely, serous tubal intraepithelial carcinoma and 'p53 signatures,' and overt serous carcinoma. Expression of ALDH1A1 was detected in both secretory and ciliated tubal epithelial cells, tubal-mesothelial junctions and ovarian surface epithelium, but was absent in serous tubal intraepithelial carcinoma and p53 signatures. Positive staining in high-grade serous carcinoma, when present, was typically limited to rare tumor cells. In silico analyses of the mRNA expression data set from The Cancer Genome Atlas revealed downregulation of ALDH1A1 transcripts in high-grade serous carcinoma relative to normal tubal epithelium, and no association between ALDH1A1 expression levels and overall survival. Our results do not support ALDH1A1 as a specific marker of stem cells in human fallopian tube and demonstrate that its loss of expression is an early event in the development of high-grade serous carcinoma.

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

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Li, Qiyuan; Kar, Siddhartha

    2015-01-01

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions assoc...

  9. TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma—evidence supporting the clonal relationship of the two lesions

    Science.gov (United States)

    Kuhn, Elisabetta; Kurman, Robert J; Vang, Russell; Sehdev, Ann Smith; Han, Guangming; Soslow, Robert; Wang, Tian-Li; Shih, Ie-Ming

    2016-01-01

    Serous tubal intraepithelial carcinomas (STICs) have been proposed to be the most likely precursor of ovarian, tubal and ‘primary peritoneal’ (pelvic) high-grade serous carcinoma (HGSC). As somatic mutation of TP53 is the most common molecular genetic change of ovarian HGSC, occurring in more than 95% of cases, we undertook a mutational analysis of 29 pelvic HGSCs that had concurrent STICs to demonstrate the clonal relationship of STICs and HGSCs. In addition, we correlated the mutational data with p53 immunostaining to determine the role of p53 immunoreactivity as a surrogate for TP53 mutations in histological diagnosis. Somatic TP53 mutations were detected in all 29 HGSCs analysed and the identical mutations were detected in 27 of 29 pairs of STICs and concurrent HGSCs. Missense mutations were observed in 61% of STICs and frameshift/splicing junction/nonsense mutations in 39%. Interestingly, there were two HGSCs with two distinctly different TP53 mutations each, but only one of the mutations was detected in the concurrent STICs. Missense mutations were associated with intense and diffuse (≥ 60%) p53 nuclear immunoreactivity, while most of the null mutations were associated with complete loss of p53 staining (p STIC and pelvic HGSC and demonstrate the utility of p53 immunostaining as a surrogate for TP53 mutation in the histological diagnosis of STIC. In this regard, it is important to appreciate the significance of different staining patterns. Specifically, strong diffuse staining correlates with a missense mutation, whereas complete absence of staining correlates with null mutations. PMID:21990067

  10. TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma--evidence supporting the clonal relationship of the two lesions.

    Science.gov (United States)

    Kuhn, Elisabetta; Kurman, Robert J; Vang, Russell; Sehdev, Ann Smith; Han, Guangming; Soslow, Robert; Wang, Tian-Li; Shih, Ie-Ming

    2012-02-01

    Serous tubal intraepithelial carcinomas (STICs) have been proposed to be the most likely precursor of ovarian, tubal and 'primary peritoneal' (pelvic) high-grade serous carcinoma (HGSC). As somatic mutation of TP53 is the most common molecular genetic change of ovarian HGSC, occurring in more than 95% of cases, we undertook a mutational analysis of 29 pelvic HGSCs that had concurrent STICs to demonstrate the clonal relationship of STICs and HGSCs. In addition, we correlated the mutational data with p53 immunostaining to determine the role of p53 immunoreactivity as a surrogate for TP53 mutations in histological diagnosis. Somatic TP53 mutations were detected in all 29 HGSCs analysed and the identical mutations were detected in 27 of 29 pairs of STICs and concurrent HGSCs. Missense mutations were observed in 61% of STICs and frameshift/splicing junction/nonsense mutations in 39%. Interestingly, there were two HGSCs with two distinctly different TP53 mutations each, but only one of the mutations was detected in the concurrent STICs. Missense mutations were associated with intense and diffuse (≥ 60%) p53 nuclear immunoreactivity, while most of the null mutations were associated with complete loss of p53 staining (p STIC and pelvic HGSC and demonstrate the utility of p53 immunostaining as a surrogate for TP53 mutation in the histological diagnosis of STIC. In this regard, it is important to appreciate the significance of different staining patterns. Specifically, strong diffuse staining correlates with a missense mutation, whereas complete absence of staining correlates with null mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. Outcomes of Incidental Fallopian Tube High-Grade Serous Carcinoma and Serous Tubal Intraepithelial Carcinoma in Women at Low Risk of Hereditary Breast and Ovarian Cancer.

    Science.gov (United States)

    Chay, Wen Yee; McCluggage, W Glenn; Lee, Cheng-Han; Köbel, Martin; Irving, Julie; Millar, Joanne; Gilks, C Blake; Tinker, Anna V

    2016-03-01

    The natural history and optimal management of serous tubal intraepithelial carcinoma (STIC), regardless of BRCA status, is unknown. We report the follow-up findings of a series of incidental fallopian tube high-grade serous carcinomas (HGSCs) and STICs identified in women at low risk for hereditary breast and ovarian cancer (HBOC), undergoing surgery for other indications. Cases of incidental STIC and HGSC were identified from 2008. Patients with known BRCA1 or BRCA2 mutations, or a family history of ovarian or breast cancer before the diagnosis of STIC or HGSC were excluded. A retrospective chart review was conducted to obtain clinical data. Eighteen cases were identified with a median follow-up of 25 months (range, 4-88 months). Twelve of 18 patients had a diagnosis of STIC with no associated invasive HGSC and 6 had STIC associated with other invasive malignancies. Completion staging surgery was performed on 7 of the 18 patients, including 5 of 12 in which there was STIC only identified on primary surgery; 3 cases were upstaged from STIC only to HGSC based on the staging surgery. Recurrence of HGSC occurred in 2 of the 18 patients. BRCA testing was performed on 3 patients, 1 of whom tested positive for a pathogenic BRCA1 mutation. Our study suggests that completion staging surgery for incidental STICs in non-BRCA patients may be considered. These patients should be offered hereditary testing. The Pelvic-Ovarian cancer INTerception (POINT) Project is an international registry set up to add to our understanding of STICs.

  12. Gross genomic alterations and gene expression profiles of high- grade serous carcinoma of the ovary with and without BRCA1 inactivation

    International Nuclear Information System (INIS)

    Pradhan, Manohar; Risberg, Björn Å; Tropé, Claes G; Rijn, Matt van de; Gilks, C Blake; Lee, Cheng-Han

    2010-01-01

    BRCA1 gene inactivation causes chromosomal instability, leading to rapid accumulation of chromosomal rearrangements and mutations. The loss of BRCA1 function due to either germline/somatic mutation or epigenetic silencing is observed in most high-grade serous carcinomas of the ovary. DNA ploidy and gene expression profile were used in order to compare gross genomic alteration and gene expression pattern between cases with BRCA1 loss through mutation, BRCA1 epigenetic loss, and no BRCA1 loss in cases of high-grade serous carcinoma with known BRCA1 and BRCA 2 status. Using image cytometry and oligonucleotide microarrays, we analyzed DNA ploidy, S-phase fraction and gene expression profile of 28 consecutive cases of ovarian high-grade serous adenocarcinomas, which included 8 tumor samples with BRCA1 somatic or germline mutation, 9 samples with promoter hypermethylation of BRCA1, and 11 samples with no BRCA1 loss. None had BRCA2 mutations. The prevalence of aneuploidy and tetraploidy was not statistically different in the three groups with different BRCA1 status. The gene expression profiles were also very similar between the groups, with only two genes showing significant differential expression when comparison was made between the group with BRCA1 mutation and the group with no demonstrable BRCA1 loss. There were no genes showing significant differences in expression when the group with BRCA1 loss through epigenetic silencing was compared to either of the other two groups. In this series of 28 high-grade serous carcinomas, gross genomic alteration characterized by aneuploidy did not correlate with BRCA1 status. In addition, the gene expression profiles of the tumors showed negligible differences between the three defined groups based on BRCA1 status. This suggests that all ovarian high-grade serous carcinomas arise through oncogenic mechanisms that result in chromosomal instability, irrespective of BRCA status; the molecular abnormalities underlying this in the BRCA

  13. 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.

  14. Ovarian transitional cell carcinoma represents a poorly differentiated form of high-grade serous or endometrioid adenocarcinoma.

    Science.gov (United States)

    Takeuchi, Tadahisa; Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kobayashi, Hiroaki; Kato, Kiyoko; Oda, Yoshinao

    2013-07-01

    Ovarian transitional cell tumors include Brenner tumors (BTs) and transitional cell carcinoma (TCC; non-BTs) according to the most recent World Health Organization classification. However, it remains a matter of debate whether TCC represents a distinct entity or a morphologic variant of high-grade serous adenocarcinoma (HG-SC). The purpose of this study was to resolve the above question by clarifying the morphologic, immunohistochemical, and molecular features of TCC. We reviewed 488 cases of epithelial ovarian carcinomas and reclassified them on the basis of the most recent World Health Organization classification with the modifications proposed by Köbel and colleagues, and 35 cases of TCC were identified; 25 and 6 TCCs were admixed with HG-SC and endometrioid adenocarcinoma (EC), respectively, and the remaining 4 cases were pure TCC. TCC components were not observed in any clear cell carcinomas or mucinous adenocarcinomas. Only 2 cases of malignant BT were identified. In addition to TCCs, malignant BTs, and related adenocarcinomas, benign and borderline BTs were included in the following immunohistochemical and molecular analyses. Immunohistochemically, pure TCCs, TCCs admixed with HG-SC, and pure HG-SCs were characterized by frequent aberrant p53 expression (diffuse or null pattern) and WT1+/ER+/PR+/IMP2+ immunophenotype, whereas BTs, including benign, borderline, and malignant BTs, were characterized by lack of aberrant p53 expression and WT1-/ER-/PR-/IMP2- immunophenotype. In contrast to the BTs, pure ECs and TCCs admixed with EC showed an ER+/PR+ immunophenotype. Nearly all the tumors with a TP53 gene mutation by molecular analysis showed aberrant p53 staining patterns. In conclusion, TCC is not a distinct entity but a poorly differentiated form of serous or EC, as (1) most TCCs coexist with HG-SC (mostly) or EC (occasionally), and (2) the immunophenotype and molecular features are similar to those of HG-SC or EC but different from those of BTs.

  15. Wilms tumor protein 1 (WT1)-- not only a diagnostic but also a prognostic marker in high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Taube, Eliane Tabea; Denkert, Carsten; Sehouli, Jalid; Kunze, Catarina Alisa; Dietel, Manfred; Braicu, Ioana; Letsch, Anne; Darb-Esfahani, Silvia

    2016-03-01

    Wilms tumor protein 1 (WT1) expression is used in gynecological pathology as a diagnostic marker of serous differentiation, and is frequently co-expressed with ER-α. Early phase studies on WT1 vaccine in gynecological cancers are ongoing. In this study we aimed to determine the prognostic value of WT1 in high-grade serous ovarian carcinoma. WT1 protein expression was determined by immunohistochemistry in a cohort of 207 primary high-grade serous ovarian carcinomas. WT1 mRNA expression was evaluated in a cohort of 1137 ovarian carcinomas from publically available gene expression datasets. High WT1 expression was a significant positive prognostic factor in primary high-grade serous ovarian carcinoma regarding overall survival (OS, p=0.008) and progression free survival (PFS, p=0.015), which was independent of age, stage, and residual tumor (OS: p=0.024, PFS: p=0.047). The prognostic significance of immunohistochemical WT1 expression could be reproduced in an independent cohort of 72 patients. On the mRNA level the prognostic significance was validated in silico in publically available gene expression datasets including TCGA data (OS: p=0.002, PFS: p=0.011). WT1 expression was significantly linked to ER-α expression (p=0.001), and tumors that co-expressed both markers (WT1+/ER-α+) had a longer survival time than tumors of all other marker combinations (OS: p=0.002, PFS: p=0.013). We present WT1 as a robust prognostic marker in high-grade serous ovarian carcinoma, which adds prognostic information to ER-α. This should be kept in mind when WT1 is used as a biomarker in the context of WT1-targeting therapies. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Establishment and characterization of a platinum- and paclitaxel-resistant high grade serous ovarian carcinoma cell line.

    Science.gov (United States)

    Teng, Pang-Ning; Bateman, Nicholas W; Wang, Guisong; Litzi, Tracy; Blanton, Brian E; Hood, Brian L; Conrads, Kelly A; Ao, Wei; Oliver, Kate E; Darcy, Kathleen M; McGuire, William P; Paz, Keren; Sidransky, David; Hamilton, Chad A; Maxwell, G Larry; Conrads, Thomas P

    2017-07-01

    High grade serous ovarian cancer (HGSOC) patients have a high recurrence rate after surgery and adjuvant chemotherapy due to inherent or acquired drug resistance. Cell lines derived from HGSOC tumors that are resistant to chemotherapeutic agents represent useful pre-clinical models for drug discovery. Here, we describe establishment of a human ovarian carcinoma cell line, which we term WHIRC01, from a patient-derived mouse xenograft established from a chemorefractory HGSOC patient who did not respond to carboplatin and paclitaxel therapy. This newly derived cell line is platinum- and paclitaxel-resistant with cisplatin, carboplatin, and paclitaxel half-maximal lethal doses of 15, 130, and 20 µM, respectively. Molecular characterization of this cell line was performed using targeted DNA exome sequencing, transcriptomics (RNA-seq), and mass spectrometry-based proteomic analyses. Results from exomic sequencing revealed mutations in TP53 consistent with HGSOC. Transcriptomic and proteomic analyses of WHIRC01 showed high level of alpha-enolase and vimentin, which are associated with cell migration and epithelial-mesenchymal transition. WHIRC01 represents a chemorefractory human HGSOC cell line model with a comprehensive molecular profile to aid future investigations of drug resistance mechanisms and screening of chemotherapeutic agents.

  17. Progesterone Prevents High-Grade Serous Ovarian Cancer by Inducing Necroptosis of p53-Defective Fallopian Tube Epithelial Cells.

    Science.gov (United States)

    Wu, Na-Yiyuan; Huang, Hsuan-Shun; Chao, Tung Hui; Chou, Hsien Ming; Fang, Chao; Qin, Chong-Zhen; Lin, Chueh-Yu; Chu, Tang-Yuan; Zhou, Hong Hao

    2017-03-14

    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. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. PAX8 activates a p53-p21-dependent pro-proliferative effect in high grade serous ovarian carcinoma.

    Science.gov (United States)

    Ghannam-Shahbari, Dima; Jacob, Eyal; Kakun, Reli Rachel; Wasserman, Tanya; Korsensky, Lina; Sternfeld, Ofir; Kagan, Juliana; Bublik, Debora Rosa; Aviel-Ronen, Sarit; Levanon, Keren; Sabo, Edmond; Larisch, Sarit; Oren, Moshe; Hershkovitz, Dov; Perets, Ruth

    2018-01-30

    High grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer and it is now widely accepted that this disease often originates from the fallopian tube epithelium. PAX8 is a fallopian tube lineage marker with an essential role in embryonal female genital tract development. In the adult fallopian tube, PAX8 is expressed in the fallopian tube secretory epithelial cell (FTSEC) and its expression is maintained through the process of FTSEC transformation to HGSC. We now report that PAX8 has a pro-proliferative and anti-apoptotic role in HGSC. The tumor suppressor gene TP53 is mutated in close to 100% of HGSC; in the majority of cases, these are missense mutations that endow the mutant p53 protein with potential gain of function (GOF) oncogenic activities. We show that PAX8 positively regulates the expression of TP53 in HGSC and the pro-proliferative role of PAX8 is mediated by the GOF activity of mutant p53. Surprisingly, mutant p53 transcriptionally activates the expression of p21, which localizes to the cytoplasm of HGSC cells where it plays a non-canonical, pro-proliferative role. Together, our findings illustrate how TP53 mutations in HGSC subvert a normal regulatory pathway into a driver of tumor progression.

  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. 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; Bowtell, David; Webb, Penelope M.; deFazio, Anna; 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.

    2015-01-01

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions 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. PMID:26391404

  1. CDKN2D-WDFY2 is a cancer-specific fusion gene recurrent in high-grade serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Kalpana Kannan

    2014-03-01

    Full Text Available Ovarian cancer is the fifth leading cause of cancer death in women. Almost 70% of ovarian cancer deaths are due to the high-grade serous subtype, which is typically detected only after it has metastasized. Characterization of high-grade serous cancer is further complicated by the significant heterogeneity and genome instability displayed by this cancer. Other than mutations in TP53, which is common to many cancers, highly recurrent recombinant events specific to this cancer have yet to be identified. Using high-throughput transcriptome sequencing of seven patient samples combined with experimental validation at DNA, RNA and protein levels, we identified a cancer-specific and inter-chromosomal fusion gene CDKN2D-WDFY2 that occurs at a frequency of 20% among sixty high-grade serous cancer samples but is absent in non-cancerous ovary and fallopian tube samples. This is the most frequent recombinant event identified so far in high-grade serous cancer implying a major cellular lineage in this highly heterogeneous cancer. In addition, the same fusion transcript was also detected in OV-90, an established high-grade serous type cell line. The genomic breakpoint was identified in intron 1 of CDKN2D and intron 2 of WDFY2 in patient tumor, providing direct evidence that this is a fusion gene. The parental gene, CDKN2D, is a cell-cycle modulator that is also involved in DNA repair, while WDFY2 is known to modulate AKT interactions with its substrates. Transfection of cloned fusion construct led to loss of wildtype CDKN2D and wildtype WDFY2 protein expression, and a gain of a short WDFY2 protein isoform that is presumably under the control of the CDKN2D promoter. The expression of short WDFY2 protein in transfected cells appears to alter the PI3K/AKT pathway that is known to play a role in oncogenesis. CDKN2D-WDFY2 fusion could be an important molecular signature for understanding and classifying sub-lineages among heterogeneous high-grade serous ovarian

  2. 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

  3. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors.

    Directory of Open Access Journals (Sweden)

    Katy Milne

    Full Text Available BACKGROUND: Tumor-infiltrating T cells are associated with survival in epithelial ovarian cancer (EOC, but their functional status is poorly understood, especially relative to the different risk categories and histological subtypes of EOC. METHODOLOGY/PRINCIPAL FINDINGS: Tissue microarrays containing high-grade serous, endometrioid, mucinous and clear cell tumors were analyzed immunohistochemically for the presence of lymphocytes, dendritic cells, neutrophils, macrophages, MHC class I and II, and various markers of activation and inflammation. In high-grade serous tumors from optimally debulked patients, positive associations were seen between intraepithelial cells expressing CD3, CD4, CD8, CD45RO, CD25, TIA-1, Granzyme B, FoxP3, CD20, and CD68, as well as expression of MHC class I and II by tumor cells. Disease-specific survival was positively associated with the markers CD8, CD3, FoxP3, TIA-1, CD20, MHC class I and class II. In other histological subtypes, immune infiltrates were less prevalent, and the only markers associated with survival were MHC class II (positive association in endometrioid cases and myeloperoxidase (negative association in clear cell cases. CONCLUSIONS/SIGNIFICANCE: Host immune responses to EOC vary widely according to histological subtype and the extent of residual disease. TIA-1, FoxP3 and CD20 emerge as new positive prognostic factors in high-grade serous EOC from optimally debulked patients.

  4. Clinical relevance of gain-of-function mutations of p53 in high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Kang, Hyo Jeong; Chun, Sung-Min; Kim, Kyu-Rae; Sohn, Insuk; Sung, Chang Ohk

    2013-01-01

    Inactivation of TP53, which occurs predominantly by missense mutations in exons 4-9, is a major genetic alteration in a subset of human cancer. In spite of growing evidence that gain-of-function (GOF) mutations of p53 also have oncogenic activity, little is known about the clinical relevance of these mutations. The clinicopathological features of high-grade serous ovarian carcinoma (HGS-OvCa) patients with GOF p53 mutations were evaluated according to a comprehensive somatic mutation profile comprised of whole exome sequencing, mRNA expression, and protein expression profiles obtained from the Cancer Genome Atlas (TCGA). Patients with a mutant p53 protein (mutp53) with a GOF mutation showed higher p53 mRNA and protein expression levels than patients with p53 mutation with no evidence of GOF (NE-GOF). GOF mutations were more likely to occur within mutational hotspots, and at CpG sites, and resulted in mutp53 with higher functional severity (FS) scores. Clinically, patients with GOF mutations showed a higher frequency of platinum resistance (22/58, 37.9%) than patients with NE-GOF mutations (12/56, 21.4%) (p=0.054). Furthermore, patients with GOF mutations were more likely to develop distant metastasis (36/55, 65.5%) than local recurrence (19/55, 34.5%), whereas patients with NE-GOF mutations showed a higher frequency of locoregional recurrence (26/47, 55.3%) than distant metastasis (21/47, 44.7%) (p=0.035). There were no differences in overall or progression-free survival between patients with GOF or NE-GOF mutp53. This study demonstrates that patient with GOF mutp53 is characterized by a greater likelihood of platinum treatment resistance and distant metastatic properties in HGS-OvCa.

  5. Clinical relevance of gain-of-function mutations of p53 in high-grade serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Hyo Jeong Kang

    Full Text Available PURPOSE: Inactivation of TP53, which occurs predominantly by missense mutations in exons 4-9, is a major genetic alteration in a subset of human cancer. In spite of growing evidence that gain-of-function (GOF mutations of p53 also have oncogenic activity, little is known about the clinical relevance of these mutations. METHODS: The clinicopathological features of high-grade serous ovarian carcinoma (HGS-OvCa patients with GOF p53 mutations were evaluated according to a comprehensive somatic mutation profile comprised of whole exome sequencing, mRNA expression, and protein expression profiles obtained from the Cancer Genome Atlas (TCGA. RESULTS: Patients with a mutant p53 protein (mutp53 with a GOF mutation showed higher p53 mRNA and protein expression levels than patients with p53 mutation with no evidence of GOF (NE-GOF. GOF mutations were more likely to occur within mutational hotspots, and at CpG sites, and resulted in mutp53 with higher functional severity (FS scores. Clinically, patients with GOF mutations showed a higher frequency of platinum resistance (22/58, 37.9% than patients with NE-GOF mutations (12/56, 21.4% (p=0.054. Furthermore, patients with GOF mutations were more likely to develop distant metastasis (36/55, 65.5% than local recurrence (19/55, 34.5%, whereas patients with NE-GOF mutations showed a higher frequency of locoregional recurrence (26/47, 55.3% than distant metastasis (21/47, 44.7% (p=0.035. There were no differences in overall or progression-free survival between patients with GOF or NE-GOF mutp53. CONCLUSION: This study demonstrates that patient with GOF mutp53 is characterized by a greater likelihood of platinum treatment resistance and distant metastatic properties in HGS-OvCa.

  6. High-Grade Serous Ovarian Cancer: Associations between BRCA Mutation Status, CT Imaging Phenotypes, and Clinical Outcomes.

    Science.gov (United States)

    Nougaret, Stephanie; Lakhman, Yulia; Gönen, Mithat; Goldman, Debra A; Miccò, Maura; D'Anastasi, Melvin; Johnson, Sarah A; Juluru, Krishna; Arnold, Angela G; Sosa, Ramon E; Soslow, Robert A; Vargas, Hebert Alberto; Hricak, Hedvig; Kauff, Noah D; Sala, Evis

    2017-11-01

    Purpose To investigate the associations between BRCA mutation status and computed tomography (CT) phenotypes of high-grade serous ovarian cancer (HGSOC) and to evaluate CT indicators of cytoreductive outcome and survival in patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. Materials and Methods This HIPAA-compliant, institutional review board-approved retrospective study included 108 patients (33 with BRCA mutant and 75 with BRCA wild-type HGSOC) who underwent CT before primary debulking. Two radiologists independently reviewed the CT findings for various qualitative CT features. Associations between CT features, BRCA mutation status, cytoreductive outcome, and progression-free survival (PFS) were evaluated by using logistic regression and Cox proportional hazards regression, respectively. Results Peritoneal disease (PD) pattern, presence of PD in gastrohepatic ligament, mesenteric involvement, and supradiaphragmatic lymphadenopathy at CT were associated with BRCA mutation status (multiple regression: P BRCA-mutant HGSOC, presence of PD in lesser sac (odds ratio [OR] = 2.40) and left upper quadrant (OR = 1.19), mesenteric involvement (OR = 7.10), and lymphadenopathy in supradiaphragmatic (OR = 2.83) and suprarenal para-aortic (OR = 4.79) regions were associated with higher odds of incomplete cytoreduction in BRCA wild-type HGSOC (multiple regression: P BRCA-mutant HGSOC (multiple regression: hazard ratio [HR] = 26.7 P BRCA wild-type HGSOC (univariate analysis: reader 1, HR = 2.42, P BRCA-mutant HGSOC and patients with BRCA wild-type HGSOC. CT indicators of cytoreductive outcome varied according to BRCA mutation status. Mesenteric involvement at CT was an indicator of significantly shorter PFS for both patients with BRCA-mutant HGSOC and those with BRCA wild-type HGSOC. © RSNA, 2017 Online supplemental material is available for this article.

  7. Genetics Consultation Rates Following a Diagnosis of High-Grade Serous Ovarian Carcinoma in the Canadian Province of Ontario.

    Science.gov (United States)

    McGee, Jacob; Panabaker, Karen; Leonard, Sean; Ainsworth, Peter; Elit, Laurie; Shariff, Salimah Z

    2017-03-01

    In 2001, the province of Ontario expanded cancer genetic testing eligibility to include all women with high-grade serous ovarian carcinoma (HGSC) of the ovary, fallopian tube, and peritoneum. The aim of this study was to determine the proportion of women who attended genetics counseling for consideration of BRCA1/2 gene analysis. We also sought to examine if regional differences in consultation rate exist across administrative health regions in the province of Ontario. We identified all women with a pathological diagnosis of HGSC in the province of Ontario between 1997 until 2011. Our primary outcome was the 2-year rate of genetics consultation following a diagnosis of HGSC. We compared consultation rates over time and geographical regions and applied multiple logistic regression to identify predictors of genetics consultation. Of the 5412 women with a diagnosis of HGSC over the study period, 6.6% were seen for genetics consultation within 2 years of diagnosis. Factors predictive of genetics consultation included history of breast cancer (odds ratio [OR], 3.56; 95% confidence interval [CI], 1.87-6.78), era of diagnosis (2009-2011 vs 1997-2000; OR, 10.59; 95% CI, 5.02-22.33), and younger age at diagnosis (OR, 0.95; 95% CI, 0.94-0.97 for each additional year). No regional differences in consultation rate were seen. Despite an increasing rate across eras, a small proportion of women with HGSC undergo genetics consultation. Efforts are required to increase cancer genetics consultation in patients with HGSC in the province of Ontario.

  8. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Katelin N Townsend

    Full Text Available When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer.In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3 and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1 correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049-5.106; p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097-5.799; p = 0.0294].Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.

  9. Low RAP80 mRNA expression correlates with shorter survival in sporadic high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Romeo, Margarita; Karachaliou, Niki; Chaid, Imane; Queralt, Cristina; De Aguirre, Itziar; Del Carmen Gómez, María; Sanchez-Ronco, María; Radua, Joaquim; Ramírez, José Luís; Rosell, Rafael

    2017-03-02

    Homologous recombination (HR) is frequently impaired in sporadic high-grade serous ovarian carcinoma (sHGSOC) due to deficiencies in BRCA1/2 genes, a situation associated with hypersensitivity to platinum compounds. Alterations in other genes can also cause HR deficiency. Preclinical data show that RAP80 is an HR-pathway-related gene that influences BRCA1 activity. RAP80 has been reported to affect outcome in some solid neoplasms. This study investigates the role of RAP80 in sHGSOC survival. mRNA expression of RAP80 was analyzed in tumor samples from 35 patients who postoperatively received standard platinum-based chemotherapy. The effects of RAP80 expression on progression-free survival (PFS) and overall survival (OS) were examined by means of Cox regressions. The clinical variables known to have prognostic value (FIGO stage, residual disease at surgery, and debulking surgery) were included as covariates in the analysis. BRCA1 was analyzed given the moderate correlations with RAP80. Median follow-up, PFS and OS were 61.3, 20.2 and 62.8 months, respectively. Low RAP80 expression levels were associated with shorter PFS (HR = 1.449, p = 0.007) and OS (HR = 1.331, p = 0.047). This is the first study to show a potential prognostic role of RAP80 expression in patients with HGSOC. The results suggest that HR deficiency due to low RAP80 expression is not associated with hypersensitivity to platinum compounds in sHGSOC.

  10. Profound elevation of CD8+ T cells expressing the intraepithelial lymphocyte marker CD103 (alphaE/beta7 Integrin) in high-grade serous ovarian cancer.

    Science.gov (United States)

    Webb, John R; Wick, Darin A; Nielsen, Julie S; Tran, Eric; Milne, Katy; McMurtrie, Elissa; Nelson, Brad H

    2010-09-01

    Tumor-infiltrating CD8(+) T cells are strongly associated with survival in high-grade serous ovarian cancer, but their functional phenotype remains poorly defined. The mucosal integrin CD103 (alpha(E)/beta(7)) facilitates the infiltration of T cells into epithelial tissues, including gut and lung mucosa, solid organ allografts, and various epithelial cancers. We reasoned that CD103 might also be expressed by tumor-reactive T cells in ovarian cancer. Flow cytometry was used to assess the frequency and phenotype of CD103-expressing T cells in primary ascites fluid from 13 patients with high-grade serous ovarian cancer and 2 patients with recurrent disease. We report that a subset of patients with advanced serous ovarian cancer have profoundly elevated frequencies of CD103-expressing CD8(+) cells in ascites (between 20% and 70% of CD8(+) cells in ascites were CD103(+)) and that CD103 expression correlated with levels of TGF-beta in ascitic fluid. Conversely, CD103 was not expressed on CD4(+) cells, even in those patients with very high frequencies of CD8(+)CD103(+) cells. CD8(+)CD103(+) cells were antigen-experienced (CD45RA(-)CD45RO(+)CD62L(lo)CCR7(-)) and of an intermediate (EM2) effector memory phenotype (CD27(+)CD28(-)). TCR repertoire analysis indicated significant skewing between CD8(+)CD103(-) and CD8(+)CD103(+) T cell subsets, suggesting the two populations contain distinct antigenic specificities. Lastly, HLA pentamer analysis revealed that one patient in the cohort harbored a high frequency of CD8(+) T cells in ascites that were specific for the tumor antigen NY-ESO-1, and that approximately 75% of these NY-ESO-1 specific CD8(+) T cells were CD103(+). CD103(+) may be a marker of activated and tumor-reactive CD8(+) T cells in high-grade serous ovarian cancer. Copyright 2010 Elsevier Inc. All rights reserved.

  11. Bilateral synchronous high-grade serous carcinoma and clear cell carcinoma in right and left ovaries with immunohistochemical confirmation: An exceptional finding

    Directory of Open Access Journals (Sweden)

    Agarwal Preeti

    2014-01-01

    Full Text Available Synchronous epithelial or mixed epithelial and germ cells tumors in the same ovary is a recognized event, however, having two different surface epithelial tumors in contra lateral ovaries is a rare occurrence; prognosis and pathogenesis of which is still not clear. We came across similar finding in a 60-year-old female with different types of surface epithelial neoplasm in right and left ovaries at the same time; both of which were malignant. Clinicoradiologically only the left ovary revealed tumor, right ovary was atrophic. To our surprise, left ovary revealed high grade serous carcinoma and the right ovary displayed clear cell carcinoma. We performed immunohistochemistry to rule out the possibility of clear cell variant of serous papillary carcinoma. On literature search, we found; only single case with synchronous presentation of two different surface epithelial ovarian tumors in the same patient, both of which were benign.

  12. [Significance and expression of PAX8, PAX2, p53 and RAS in ovary and fallopian tubes to origin of ovarian high grade serous carcinoma].

    Science.gov (United States)

    Mao, Y N; Zeng, L X; Li, Y H; Liu, Y Z; Wu, J Y; Li, L; Wang, Q

    2017-10-25

    Objective: To explore the origin of ovarian high grade serous carcinoma (HGSC) through analysing the expression and significance of PAX8, PAX2, p53 and RAS in the ovary and fallopian tube of different types and grades of serous carcinoma. Methods: A total of 44 cases tissue samples of ovarian tumor including 34 malignant ovarian tumor and 10 normal normal tissue (as control group) were collected from the admitted patients in Affiliated Tumor Hospital of Guangxi Medical University from January 2015 to January 2016. Fallopian tube tissues were segmented in accordance with the fimbria, ampulla, isthmus and the corresponding ovarian tissues were by the side. There were 34 cases of patients with ovarian cancer including 29 cases of epithelial ovarian cancer (27 serous carcinoma, 1 mucinous carcinoma,1 endometrioid adenocarcinoma) and 5 non-epithelial ovarian cancer (sex cord-interstitial tumor). Among 27 cases of patients with ovarian serous cancer, there were 23 HGSC and 4 low-grade ovarian serous cancer (LGSC). One hundred fifty-three cases of samples were diagnosed as ovarian serous cancer by Shandong University Affiliated Qilu Hospital from 2005 to 2013 and these samples were made tissue microarray. (1) To analyze the expression and differences of PAX8, PAX2, p53 and RAS in the above tissues and tissue microarray from ovarian and tubal of HGSC and control women by immunohistochemistry methods. (2) To compare the expression levels of PAX8, PAX2, p53 and RAS in ovarian and fallopian tubes of ovarian cancer patients with different pathological types. (3) To analyze the correlations of tubal and ovarian tissue in PAX8, PAX2, p53 and RAS expression of HGSC. (4) To analyze the factors of the prognosis of ovarian serous cancer in tissue microarray by single factor analysis method. Results: (1) PAX8, PAX2, p53 and RAS expression was negative in normal ovarian epithelium of control group, but the expression of PAX8, PAX2, p53 and RAS were strongly positive brown in secrete

  13. Frequency of "incidental" serous tubal intraepithelial carcinoma (STIC) in women without a history of or genetic risk factor for high-grade serous carcinoma: A six-year study.

    Science.gov (United States)

    Meserve, Emily E K; Mirkovic, Jelena; Conner, James R; Yang, Eric; Muto, Michael G; Horowitz, Neil; Strickland, Kyle C; Howitt, Brooke E; Crum, Christopher P

    2017-07-01

    Objective The purpose of this study was to determine the prevalence of incidentally discovered serous tubal intraepithelial carcinoma in women without a genetic risk for or history of high grade serous carcinoma (HGSC) in the gynecologic tract. All pathology reports at our institution that included bilateral salpingectomies from January 2006-December 2011 were examined in women >50years old in which the entire tube or the distal one-third was examined histologically with the complete (proximal and distal fallopian tube) or modified (distal one third of the tube) SEE-FIM protocol. Cases were divided into: Group 1, a history of or known risk factors (BRCA1 or BRCA2 mutations) for HGSC and Group 2, those without these attributes for whom a STIC would be unexpected (incidental). Women undergoing unspecified "risk-reducing" procedures were included in Group 1. Of 4051 identified total, 2268 had complete examination of the distal fallopian tube and were age 50 or above. Of these, 1747 were in group 2. Two STICs were identified (0.1%), one associated with a grade 2 endometrial endometrioid adenocarcinoma and one with a low-grade ovarian serous carcinoma in the setting of a serous borderline tumor. Incidental STICs in women over age 50 are uncommon. However, the significance of lesser tubal atypias (0.3% in this study), risk of STIC in women with no epithelial pathology and the risk imposed by coexisting endometrioid neoplasia are unclear and require further study. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. High grade serous ovarian carcinoma with serous tubal intraepithelial carcinoma in a case presented with atypical glandular cell favor neoplasm cervical cytology and dermatomyositis

    Directory of Open Access Journals (Sweden)

    Mun-Kun Hong

    2015-04-01

    Conclusion: The patient had serous carcinoma of the ovary with tubal STIC, which presented as dermatomyositis. The AGC-FN identified from a Pap smear hinted at a diagnosis of ovarian carcinoma. These presentations point to an occult malignancy in the genital tract and demand careful diagnostic workup.

  15. Comparative transcriptome analysis links distinct peritoneal tumor spread types, miliary and non-miliary, with putative origin, tubes and ovaries, in high grade serous ovarian cancer.

    Science.gov (United States)

    Auer, Katharina; Bachmayr-Heyda, Anna; Aust, Stefanie; Grunt, Thomas W; Pils, Dietmar

    2017-03-01

    High grade serous ovarian cancer (HGSOC) is characterized by extensive local, i.e. peritoneal, tumor spread, manifested in two different clinical presentations, miliary (many millet sized peritoneal implants) and non-miliary (few large exophytically growing peritoneal nodes), and an overall unfavorable outcome. HGSOC is thought to arise from fallopian tube secretory epithelial cells, via so called serous tubal intraepithelial carcinomas (STICs) but an ovarian origin was never ruled out for at least some cases. Comparative transcriptome analyses of isolated tumor cells from fresh HGSOC tissues and (immortalized) ovarian surface epithelial and fallopian tube secretory epithelial cell lines revealed a close relation between putative origin and tumor spread characteristic, i.e. miliary from tubes and non-miliary from ovaries. The latter were characterized by more mesenchymal cell characteristics, more adaptive tumor immune infiltration, and a favorable overall survival. Several molecular sub-classification systems (Crijns' overall survival signature, Yoshihara's subclasses, and a collagen-remodeling signature) seem to already indicate origin. Putative origin alone is a significant independent predictor for HGSOC outcome, validated in independent patient cohorts. Characteristics of both spread types could guide development of new targeted therapeutics, which are urgently needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. CRISPR/Cas9-Mediated Trp53 and Brca2 Knockout to Generate Improved Murine Models of Ovarian High-Grade Serous Carcinoma.

    Science.gov (United States)

    Walton, Josephine; Blagih, Julianna; Ennis, Darren; Leung, Elaine; Dowson, Suzanne; Farquharson, Malcolm; Tookman, Laura A; Orange, Clare; Athineos, Dimitris; Mason, Susan; Stevenson, David; Blyth, Karen; Strathdee, Douglas; Balkwill, Frances R; Vousden, Karen; Lockley, Michelle; McNeish, Iain A

    2016-10-15

    There is a need for transplantable murine models of ovarian high-grade serous carcinoma (HGSC) with regard to mutations in the human disease to assist investigations of the relationships between tumor genotype, chemotherapy response, and immune microenvironment. In addressing this need, we performed whole-exome sequencing of ID8, the most widely used transplantable model of ovarian cancer, covering 194,000 exomes at a mean depth of 400× with 90% exons sequenced >50×. We found no functional mutations in genes characteristic of HGSC (Trp53, Brca1, Brca2, Nf1, and Rb1), and p53 remained transcriptionally active. Homologous recombination in ID8 remained intact in functional assays. Further, we found no mutations typical of clear cell carcinoma (Arid1a, Pik3ca), low-grade serous carcinoma (Braf), endometrioid (Ctnnb1), or mucinous (Kras) carcinomas. Using CRISPR/Cas9 gene editing, we modeled HGSC by generating novel ID8 derivatives that harbored single (Trp53 -/- ) or double (Trp53 -/- ;Brca2 -/- ) suppressor gene deletions. In these mutants, loss of p53 alone was sufficient to increase the growth rate of orthotopic tumors with significant effects observed on the immune microenvironment. Specifically, p53 loss increased expression of the myeloid attractant CCL2 and promoted the infiltration of immunosuppressive myeloid cell populations into primary tumors and their ascites. In Trp53 -/- ;Brca2 -/- mutant cells, we documented a relative increase in sensitivity to the PARP inhibitor rucaparib and slower orthotopic tumor growth compared with Trp53 -/- cells, with an appearance of intratumoral tertiary lymphoid structures rich in CD3 + T cells. This work validates new CRISPR-generated models of HGSC to investigate its biology and promote mechanism-based therapeutics discovery. Cancer Res; 76(20); 6118-29. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.

    LENUS (Irish Health Repository)

    Furlong, Fiona

    2012-04-01

    Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3\\' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3\\'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3\\' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict

  18. Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer.

    Science.gov (United States)

    Harrington, Brittney S; He, Yaowu; Davies, Claire M; Wallace, Sarah J; Adams, Mark N; Beaven, Elizabeth A; Roche, Deborah K; Kennedy, Catherine; Chetty, Naven P; Crandon, Alexander J; Flatley, Christopher; Oliveira, Niara B; Shannon, Catherine M; deFazio, Anna; Tinker, Anna V; Gilks, C Blake; Gabrielli, Brian; Brennan, Donal J; Coward, Jermaine I; Armes, Jane E; Perrin, Lewis C; Hooper, John D

    2016-02-16

    Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer. CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis. Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1-mediated activation of Src was observed in cultured cells and mouse xenografts. CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer.

  19. Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer

    Science.gov (United States)

    Harrington, Brittney S; He, Yaowu; Davies, Claire M; Wallace, Sarah J; Adams, Mark N; Beaven, Elizabeth A; Roche, Deborah K; Kennedy, Catherine; Chetty, Naven P; Crandon, Alexander J; Flatley, Christopher; Oliveira, Niara B; Shannon, Catherine M; deFazio, Anna; Tinker, Anna V; Gilks, C Blake; Gabrielli, Brian; Brennan, Donal J; Coward, Jermaine I; Armes, Jane E; Perrin, Lewis C; Hooper, John D

    2016-01-01

    Background: Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer. Methods: CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis. Results: Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1-mediated activation of Src was observed in cultured cells and mouse xenografts. Conclusions: CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer. PMID:26882065

  20. TP53 Mutation Status of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma with a Wild-type p53 Immunostaining Pattern.

    Science.gov (United States)

    Na, Kiyong; Sung, Ji-Youn; Kim, Hyun-Soo

    2017-12-01

    Diffuse and strong nuclear p53 immunoreactivity and a complete lack of p53 expression are regarded as indicative of missense and nonsense mutations, respectively, of the TP53 gene. Tubo-ovarian and peritoneal high-grade serous carcinoma (HGSC) is characterized by aberrant p53 expression induced by a TP53 mutation. However, our experience with some HGSC cases with a wild-type p53 immunostaining pattern led us to comprehensively review previous cases and investigate the TP53 mutational status of the exceptional cases. We analyzed the immunophenotype of 153 cases of HGSC and performed TP53 gene sequencing analysis in those with a wild-type p53 immunostaining pattern. Immunostaining revealed that 109 (71.3%) cases displayed diffuse and strong p53 expression (missense mutation pattern), while 39 (25.5%) had no p53 expression (nonsense mutation pattern). The remaining five cases of HGSC showed a wild-type p53 immunostaining pattern. Direct sequencing analysis revealed that three of these cases harbored nonsense TP53 mutations and two had novel splice site deletions. TP53 mutation is almost invariably present in HGSC, and p53 immunostaining can be used as a surrogate marker of TP53 mutation. In cases with a wild-type p53 immunostaining pattern, direct sequencing for TP53 mutational status can be helpful to confirm the presence of a TP53 mutation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.

    Science.gov (United States)

    Goranova, T; Ennis, D; Piskorz, A M; Macintyre, G; Lewsley, L A; Stobo, J; Wilson, C; Kay, D; Glasspool, R M; Lockley, M; Brockbank, E; Montes, A; Walther, A; Sundar, S; Edmondson, R; Hall, G D; Clamp, A; Gourley, C; Hall, M; Fotopoulou, C; Gabra, H; Freeman, S; Moore, L; Jimenez-Linan, M; Paul, J; Brenton, J D; McNeish, I A

    2017-05-09

    Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC). Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA. We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 μg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients. Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs.

  2. MAP3K8/TPL-2/COT is a potential predictive marker for MEK inhibitor treatment in high-grade serous ovarian carcinomas

    Science.gov (United States)

    Gruosso, Tina; Garnier, Camille; Abelanet, Sophie; Kieffer, Yann; Lemesre, Vincent; Bellanger, Dorine; Bieche, Ivan; Marangoni, Elisabetta; Sastre-Garau, Xavier; Mieulet, Virginie; Mechta-Grigoriou, Fatima

    2015-01-01

    Ovarian cancer is a silent disease with a poor prognosis that urgently requires new therapeutic strategies. In low-grade ovarian tumours, mutations in the MAP3K BRAF gene constitutively activate the downstream kinase MEK. Here we demonstrate that an additional MAP3K, MAP3K8 (TPL-2/COT), accumulates in high-grade serous ovarian carcinomas (HGSCs) and is a potential prognostic marker for these tumours. By combining analyses on HGSC patient cohorts, ovarian cancer cells and patient-derived xenografts, we demonstrate that MAP3K8 controls cancer cell proliferation and migration by regulating key players in G1/S transition and adhesion dynamics. In addition, we show that the MEK pathway is the main pathway involved in mediating MAP3K8 function, and that MAP3K8 exhibits a reliable predictive value for the effectiveness of MEK inhibitor treatment. Our data highlight key roles for MAP3K8 in HGSC and indicate that MEK inhibitors could be a useful treatment strategy, in combination with conventional chemotherapy, for this disease. PMID:26456302

  3. External validation of chemotherapy response score system for histopathological assessment of tumor regression after neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma.

    Science.gov (United States)

    Lee, Jung Yun; Chung, Young Shin; Na, Kiyong; Kim, Hye Min; Park, Cheol Keun; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae; Kim, Hyun Soo

    2017-11-01

    The chemotherapy response score (CRS) system based on histopathological examination has been recently proposed for tubo-ovarian high-grade serous carcinoma (HGSC) to assess response to neoadjuvant chemotherapy (NAC). This study was aimed at validating the CRS system in an external cohort of tubo-ovarian HGSC patients. This study included 110 tubo-ovarian HGSC patients who underwent NAC followed by interval debulking surgery. The 3-tiered CRS of the omental and adnexal tissue sections was determined by 3 independent pathologists. Differences in patient outcomes according to CRS were analyzed. The CRS system was highly reproducible among the 3 pathologists. Fleiss' kappa value and Kendall's coefficient of concordance for the omental CRS were 0.656 and 0.669, respectively. The omental CRS significantly predicted progression-free survival (PFS). The median PFS of patients whose tumors exhibited the omental CRS 1-2 (15 months) was significantly shorter than that of patients with an omental CRS of 3 (19 months; p=0.016). In addition, after adjusting for age, stage, and debulking status, the omental CRS was an independent prognostic factor for PFS of tubo-ovarian HGSC patients who were treated with NAC (adjusted hazard ratio [HR]=1.74; 95% confidence interval [CI]=1.05-2.87). The CRS system for assessing NAC response was a reproducible prognostic tool in our cohort. The application of the CRS system after NAC can improve survival estimation in HGSC patients. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

  4. A comparison of p53 and WT1 immunohistochemical expression patterns in tubo-ovarian high-grade serous carcinoma before and after neoadjuvant chemotherapy.

    Science.gov (United States)

    Casey, Laura; Köbel, Martin; Ganesan, Raji; Tam, Simone; Prasad, Rajeev; Böhm, Steffen; Lockley, Michelle; Jeyarajah, Arjun J; Brockbank, Eleanor; Faruqi, Asma; Gilks, C Blake; Singh, Naveena

    2017-11-01

    The treatment of patients with tubo-ovarian high-grade serous carcinoma (HGSC) is increasingly based on diagnosis on small biopsy samples, and the first surgical sample is often taken post-chemotherapy. p53 and WT1 are important diagnostic markers for HGSC. The effect of neoadjuvant chemotherapy on p53 and WT1 expression has not been widely studied. We aimed to compare p53 and WT1 expression in paired pre-chemotherapy and post-chemotherapy samples of HGSC. Immunohistochemistry (IHC) was carried out for p53 and WT1 on paired omental HGSC samples pre-chemotherapy and post-chemotherapy. p53 IHC was recorded as normal (wild-type) or abnormal (mutation-type), and was further classified as overexpression, complete absence, or cytoplasmic. WT1 IHC was classified as positive or negative. A subset of cases were further assessed for the extent of nuclear immunoreactivity of WT1 by use of the H-score. Fifty-seven paired samples were stained with p53. Fifty-six of 57 (98%) cases showed mutation-type p53 staining. Pre-chemotherapy and post-chemotherapy IHC results were concordant in 55 of 57 (96%) cases. For WT1, pre-chemotherapy and post-chemotherapy IHC results were concordant in 56 of 58 (97%) cases. In 23 paired WT1 cases, the mean post-treatment H-score decreased from 227 [range 20-298, standard deviation (SD) 64] to 151 (range 0-288, SD 78) (P = 0.0008). Immunohistochemical expression of p53 (abnormal/mutation-type pattern) and WT1 in HGSC is almost universal and is largely concordant before and after chemotherapy. This finding underscores the reliability of these diagnostic markers in small samples and in surgical samples following neoadjuvant chemotherapy, with very few exceptions. A novel finding was the significant diminution in intensity of WT1 staining following chemotherapy. © 2017 John Wiley & Sons Ltd.

  5. Radiogenomics of High-Grade Serous Ovarian Cancer: Multireader Multi-Institutional Study from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group.

    Science.gov (United States)

    Vargas, Hebert Alberto; Huang, Erich P; Lakhman, Yulia; Ippolito, Joseph E; Bhosale, Priya; Mellnick, Vincent; Shinagare, Atul B; Anello, Maria; Kirby, Justin; Fevrier-Sullivan, Brenda; Freymann, John; Jaffe, C Carl; Sala, Evis

    2017-11-01

    Purpose To evaluate interradiologist agreement on assessments of computed tomography (CT) imaging features of high-grade serous ovarian cancer (HGSOC), to assess their associations with time-to-disease progression (TTP) and HGSOC transcriptomic profiles (Classification of Ovarian Cancer [CLOVAR]), and to develop an imaging-based risk score system to predict TTP and CLOVAR profiles. Materials and Methods This study was a multireader, multi-institutional, institutional review board-approved, HIPAA-compliant retrospective analysis of 92 patients with HGSOC (median age, 61 years) with abdominopelvic CT before primary cytoreductive surgery available through the Cancer Imaging Archive. Eight radiologists from the Cancer Genome Atlas Ovarian Cancer Imaging Research Group developed and independently recorded the following CT features: characteristics of primary ovarian mass(es), presence of definable mesenteric implants and infiltration, presence of other implants, presence and distribution of peritoneal spread, presence and size of pleural effusions and ascites, lymphadenopathy, and distant metastases. Interobserver agreement for CT features was assessed, as were univariate and multivariate associations with TTP and CLOVAR mesenchymal profile (worst prognosis). Results Interobserver agreement for some features was strong (eg, α = .78 for pleural effusion and ascites) but was lower for others (eg, α = .08 for intraparenchymal splenic metastases). Presence of peritoneal disease in the right upper quadrant (P = .0003), supradiaphragmatic lymphadenopathy (P = .0004), more peritoneal disease sites (P = .0006), and nonvisualization of a discrete ovarian mass (P = .0037) were associated with shorter TTP. More peritoneal disease sites (P = .0025) and presence of pouch of Douglas implants (P = .0045) were associated with CLOVAR mesenchymal profile. Combinations of imaging features contained predictive signal for TTP (concordance index = 0.658; P = .0006) and CLOVAR profile (mean

  6. Epigenetic Reprogramming Strategies to Reverse Global Loss of 5-Hydroxymethylcytosine, a Prognostic Factor for Poor Survival in High-grade Serous Ovarian Cancer.

    Science.gov (United States)

    Tucker, Douglass W; Getchell, Christopher R; McCarthy, Eric T; Ohman, Anders W; Sasamoto, Naoko; Xu, Shuyun; Ko, Joo Yeon; Gupta, Mamta; Shafrir, Amy; Medina, Jamie E; Lee, Jonathan J; MacDonald, Lauren A; Malik, Ammara; Hasselblatt, Kathleen T; Li, Wenjing; Zhang, Hong; Kaplan, Samuel J; Murphy, George F; Hirsch, Michelle S; Liu, Joyce F; Matulonis, Ursula A; Terry, Kathryn L; Lian, Christine G; Dinulescu, Daniela M

    2018-03-15

    Purpose: A major challenge in platinum-based cancer therapy is the clinical management of chemoresistant tumors, which have a largely unknown pathogenesis at the level of epigenetic regulation. Experimental Design: We evaluated the potential of using global loss of 5-hydroxymethylcytosine (5-hmC) levels as a novel diagnostic and prognostic epigenetic marker to better assess platinum-based chemotherapy response and clinical outcome in high-grade serous tumors (HGSOC), the most common and deadliest subtype of ovarian cancer. Furthermore, we identified a targetable pathway to reverse these epigenetic changes, both genetically and pharmacologically. Results: This study shows that decreased 5-hmC levels are an epigenetic hallmark for malignancy and tumor progression in HGSOC. In addition, global 5-hmC loss is associated with a decreased response to platinum-based chemotherapy, shorter time to relapse, and poor overall survival in patients newly diagnosed with HGSOC. Interestingly, the rescue of 5-hmC loss restores sensitivity to platinum chemotherapy in vitro and in vivo , decreases the percentage of tumor cells with cancer stem cell markers, and increases overall survival in an aggressive animal model of platinum-resistant disease. Conclusions: Consequently, a global analysis of patient 5-hmC levels should be included in future clinical trials, which use pretreatment with epigenetic adjuvants to elevate 5-hmC levels and improve the efficacy of current chemotherapies. Identifying prognostic epigenetic markers and altering chemotherapeutic regimens to incorporate DNMTi pretreatment in tumors with low 5-hmC levels could have important clinical implications for newly diagnosed HGSOC disease. Clin Cancer Res; 24(6); 1389-401. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Combining serum microRNA and CA-125 as prognostic indicators of preoperative surgical outcome in women with high-grade serous ovarian cancer.

    Science.gov (United States)

    Shah, Jaynish S; Gard, Gregory B; Yang, Jean; Maidens, Jayne; Valmadre, Susan; Soon, Patsy S; Marsh, Deborah J

    2018-01-01

    The most widely used approach for the clinical management of women with high-grade serous ovarian cancer (HGSOC) is surgery, followed by platinum and taxane based chemotherapy. The degree of macroscopic disease remaining at the conclusion of surgery is a key prognostic factor determining progression free and overall survival. We sought to develop a non-invasive test to assist surgeons to determine the likelihood of achieving complete surgical resection. This knowledge could be used to plan surgical approaches for optimal clinical management. We profiled 170 serum microRNAs (miRNAs) using the Serum/Plasma Focus miRNA PCR panel containing locked nucleic acid (LNA) primers (Exiqon) in women with HGSOC (N=56) and age-matched healthy volunteers (N=30). Additionally, we measured serum CA-125 levels in the same samples. The HGSOC cohort was further classified based on the degree of macroscopic disease at the conclusion of surgery. Stepwise logistic regression was used to identify predictive markers. We identified a combination of miR-375 and CA-125 as the strongest discriminator of healthy versus HGSOC serum, with an area under the curve (AUC) of 0.956. The inclusion of miR-210 increased the AUC to 0.984; however, miR-210 was affected by hemolysis. The combination of miR-34a-5p and CA-125 was the strongest predictor of completeness of surgical resection with an AUC of 0.818. A molecular test incorporating circulating miRNA to predict completeness of surgical resection for women with HGSOC has the potential to contribute to planning for optimal patient management, ultimately improving patient outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study.

    Directory of Open Access Journals (Sweden)

    Christine A Parkinson

    2016-12-01

    Full Text Available Circulating tumour DNA (ctDNA carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC. We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP.We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22% compared to 0.7% (IQR 0.3%-2.0% for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28-54 compared with a median time to nadir of 84 d (IQR 42-116 for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in

  9. Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma: A Rereview of Cases Lacking TP53 Mutations in The Cancer Genome Atlas Ovarian Study.

    Science.gov (United States)

    Vang, Russell; Levine, Douglas A; Soslow, Robert A; Zaloudek, Charles; Shih, Ie-Ming; Kurman, Robert J

    2016-01-01

    The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the

  10. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma.

    Science.gov (United States)

    Darb-Esfahani, Silvia; Kunze, Catarina Alisa; Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna

    2016-01-12

    Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity.

  11. Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women: A Study of PD-L1 and IDO in 112 Cases From the African American Cancer Epidemiology Study (AACES).

    Science.gov (United States)

    Mills, Anne M; Peres, Lauren C; Meiss, Alice; Ring, Kari L; Modesitt, Susan C; Abbott, Sarah E; Alberg, Anthony J; Bandera, Elisa V; Barnholtz-Sloan, Jill; Bondy, Melissa L; Cote, Michele L; Funkhouser, Ellen; Moorman, Patricia G; Peters, Edward S; Schwartz, Ann G; Terry, Paul D; Wallace, Kristin; Schildkraut, Joellen M

    2018-02-26

    African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29% and 58% of cases, respectively. The majority showed dual immunotherapy, diffuse expression of PD-L1 and IDO is rare, invoking caution regarding the potential for immunotherapeutic response.

  12. γ-Glutamyl cyclotransferase contributes to tumor progression in high grade serous ovarian cancer by regulating epithelial-mesenchymal transition via activating PI3K/AKT/mTOR pathway.

    Science.gov (United States)

    Li, Yanli; Wu, Tingting; Wang, Yanan; Yang, Liu; Hu, Chengcheng; Chen, Limo; Wu, Sufang

    2018-02-08

    High grade serous ovarian cancer (HGSC) remains one of the most lethal malignancies in females. We previously reported that γ-glutamyl cyclotransferase (GGCT) was significantly upregulated in serous ovarian cancer. The current study was aimed to explore the function and underlying mechanism of GGCT in HGSC. GGCT expression was assessed by immunohistochemistry in 128 HGSC patients. Stable cell lines with GGCT gene overexpression or knockdown were established to investigate the function of GGCT in HGSC in vitro and in vivo. GGCT is highly upregulated in HGSC tissues and associated with FIGO stage, lymph node metastasis and ascitic fluid volume. High expression of GGCT is associated with poor survival in HGSC patients. The Harrell's c-indexes of the prognostic models for overall survival and progression-free survival prediction were 0.758 and 0.726, respectively. GGCT knockdown suppresses proliferation, clone formation, migration, and invasion of tumor cells in vitro while forced GGCT overexpression presents opposite results. Furthermore, GGCT silencing inhibits tumor growth and spread in vivo. Epithelial-mesenchymal transition (EMT) and PI3K/AKT/mTOR signaling pathway are suppressed in GGCT silenced cells and enhanced in GGCT overexpressed cells. Inactivation of PI3K/AKT/mTOR signaling pathway in GGCT overexpressed cells induces EMT inhibition. Our data reveals an important role of GGCT in regulating EMT and progression of HGSC, providing a valuable prognostic marker and potential target for treatment of HGSC patients. Published by Elsevier Inc.

  13. Beside P53 and PTEN: Identification of molecular alterations of the RAS/MAPK and PI3K/AKT signaling pathways in high-grade serous ovarian carcinomas to determine potential novel therapeutic targets.

    Science.gov (United States)

    Chen, Shuhui; Cavazza, Elisa; Barlier, Catherine; Salleron, Julia; Filhine-Tresarrieu, Pierre; Gavoilles, Céline; Merlin, Jean-Louis; Harlé, Alexandre

    2016-11-01

    Despite great histological and molecular heterogeneity, the clinical management of high-grade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify 'druggable' targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59.1 years; range, 25-87 years) with histologically proven HGSOC. Breast cancer 1/2 ( BRCA1 /2) germline mutations were screened in 17 patients with a familial or personal history of cancer, which was justified by oncogenetic investigations. Tumor protein 53 (P53) and phosphatase and tensin homolog (PTEN) expression were assessed in formalin-fixed paraffin-embedded tissues using immunohistochemistry. Somatic mutations of Kirsten rat sarcoma viral oncogene homolog, neuroblastoma RAS viral oncogene homolog ( NRAS ), B-Raf proto-oncogene, serine/threonine kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α ( PIK3CA ) and MET proto-oncogene, receptor tyrosine kinase ( MET ) were screened using NGS on DNA extracts from frozen tumor specimens obtained at diagnosis. With a median follow-up of 38 months (range, 6-93 months), 20 patients are alive, 10 patients are disease-free and 14 patients progressed within 6 months following platinum-based therapy. P53 overexpression was detected in 67% of patients and PTEN loss was detected in 38% of the patients. The overexpression of mutant P53 was found to be associated with a longer progression-free and overall survival. In total, 2 NRAS (exon 3), 3 PIK3CA (exon 5 and 10) and 5 MET mutations (exons 14 and 18) were detected. In HGSOCs, in addition to P53 and PTEN alterations, somatic genetic abnormalities can be detected using NGS and provide molecular

  14. Biological and clinical evidence for somatic mutations in BRCA1 and BRCA2 as predictive markers for olaparib response in high-grade serous ovarian cancers in the maintenance setting.

    Science.gov (United States)

    Dougherty, Brian A; Lai, Zhongwu; Hodgson, Darren R; Orr, Maria C M; Hawryluk, Matthew; Sun, James; Yelensky, Roman; Spencer, Stuart K; Robertson, Jane D; Ho, Tony W; Fielding, Anitra; Ledermann, Jonathan A; Barrett, J Carl

    2017-07-04

    To gain a better understanding of the role of somatic mutations in olaparib response, next-generation sequencing (NGS) of BRCA1 and BRCA2 was performed as part of a planned retrospective analysis of tumors from a randomized, double-blind, Phase II trial (Study 19; D0810C00019; NCT00753545) in 265 patients with platinum-sensitive high-grade serous ovarian cancer. BRCA1/2 loss-of-function mutations were found in 55% (114/209) of tumors, were mutually exclusive, and demonstrated high concordance with Sanger-sequenced germline mutations in matched blood samples, confirming the accuracy (97%) of tumor BRCA1/2 NGS testing. Additionally, NGS identified somatic mutations absent from germline testing in 10% (20/209) of the patients. Somatic mutations had >80% biallelic inactivation frequency and were predominantly clonal, suggesting that BRCA1/2 loss occurs early in the development of these cancers. Clinical outcomes between placebo- and olaparib-treated patients with somatic BRCA1/2 mutations were similar to those with germline BRCA1/2 mutations, indicating that patients with somatic BRCA1/2 mutations benefit from treatment with olaparib.

  15. Serous tubal intraepithelial neoplasia : The concept and its application

    NARCIS (Netherlands)

    Meserve, Emily E. K.; Brouwer, Jan; Crum, Christopher P.

    In recent years it has become clear that many extra-uterine (pelvic) high-grade serous carcinomas (serous carcinomas) are preceded by a precursor lesion in the distal fallopian tube. Precursors range from small self-limited 'p53 signatures' to expansile serous tubal intraepithelial neoplasms that

  16. Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment. Project 1 - Molecular Characterization of Ovarian Serous Tumors Developing Along Different Pathways

    National Research Council Canada - National Science Library

    Kurman, Robert

    2003-01-01

    .... We hypothesize that the development of serous carcinoma proceeds along two main pathways: one is rapid progression from ovarian surface epithelium to high-grade serous carcinoma without well-established morphological precursors ("de novo" pathway...

  17. Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment

    National Research Council Canada - National Science Library

    Kurman, Robert J; Shih, Ie-Ming; Roden, Richard

    2005-01-01

    .... We hypothesize that the development of serous carcinoma proceeds along two main pathways: one is rapid progression from ovarian surface epithelium to high-grade serous carcinoma without well-established morphological precursors ( de novo pathway...

  18. Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment

    National Research Council Canada - National Science Library

    Kurman, Robert J

    2006-01-01

    .... We hypothesize that the development of serous carcinoma proceeds along two main pathways: one is rapid progression from ovarian surface epithelium to high-grade serous carcinoma without well-established morphological precursors ("de novo" pathway...

  19. Profile of differentially expressed miRNAs in high-grade serous carcinoma and clear cell ovarian carcinoma, and the expression of miR-510 in ovarian carcinoma.

    Science.gov (United States)

    Zhang, Xinchen; Guo, Gordon; Wang, Guang; Zhao, Jinyao; Wang, Bo; Yu, Xiaotang; Ding, Yanfang

    2015-12-01

    Improved insight into the molecular and genetic profile of different types of epithelial ovarian cancer (EOC) is required for understanding the carcinogenesis of EOC and may potentially be exploited by future targeted therapies. The aim of the present study was to identify a unique microRNA (miRNA) patterns and key miRNAs, which may assist in predicting progression and prognosis in high‑grade serous carcinoma (HGSC) and clear cell carcinoma (CCC). To identify unique miRNA patterns associated with HGSC and CCC, a miRNA microarray was performed using Chinese tumor bank specimens of patients with HGSC or CCC in a retrospective analysis. The expression levels of four deregulated miRNAs were further validated using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in an external cohort of 42 cases of HGSC and 36 cases of CCC. Kaplan‑Meier analysis was performed to analyze the correlation between the expression levels of the four miRNAs and patient prognosis. Among these validated miRNAs, miR‑510 was further examined in another cohort of normal ovarian tissues, as well as the HGSC, low‑grade serous carcinoma (LGSC) and CCC specimens using RT‑qPCR and in situ hybridization. The results revealed that, of the 768 miRNAs analyzed in the microarray, 33 and 50 miRNAs were significantly upregulated and downregulated, respectively, with at least a 2‑fold difference in HGSC, compared with CCC. The quantitative analysis demonstrated that miR‑510 and miR‑129‑3p were significantly downregulated, and that miR‑483‑5p and miR‑miR‑449a were significantly upregulated in CCC, compared with HGSC (Povarian tissues. The results of the present study suggested that different subtypes of EOC have specific miRNA signatures, and that miR‑510 may be involved differently in HGSC and CCC. Thus, miR‑510 and miR‑129‑3p may be considered as potential novel candidate clinical biomarkers for predicting the outcome of EOC.

  20. Prognostic indicators in ovarian serous borderline tumours.

    Science.gov (United States)

    Malpica, Anais; Longacre, Teri A

    2018-02-01

    There have been great strides in our understanding of the serous group of borderline and malignant pelvic epithelial neoplasms in the past decade. While most serous borderline tumours have a favourable prognosis, recurrences and progression to carcinoma occur, often following a protracted clinical course. Clinical and pathological risk factors tend to co-vary, but the presence and type of extraovarian disease is the most important predictor for progression. Progression usually takes the form of low-grade serous carcinoma, although transformation to high-grade carcinoma is occasionally seen. A serous borderline - low-grade serous carcinoma pathway analogous to neoplastic transformation pathways seen in other organ systems has been proposed, based on global gene expression profiling, shared mutations in KRAS or BRAF, and in most cases, the presence of serous borderline tumour in de novo low-grade serous carcinoma. This discussion focuses on the key prognostic factors that predispose to disease progression and/or transformation to carcinoma in serous borderline tumours. Published by Elsevier B.V.

  1. Exploring the clonal evolution of CD133/aldehyde-dehydrogenase-1 (ALDH1)-positive cancer stem-like cells from primary to recurrent high-grade serous ovarian cancer (HGSOC). A study of the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.

    Science.gov (United States)

    Ruscito, Ilary; Cacsire Castillo-Tong, Dan; Vergote, Ignace; Ignat, Iulia; Stanske, Mandy; Vanderstichele, Adriaan; Ganapathi, Ram N; Glajzer, Jacek; Kulbe, Hagen; Trillsch, Fabian; Mustea, Alexander; Kreuzinger, Caroline; Benedetti Panici, Pierluigi; Gourley, Charlie; Gabra, Hani; Kessler, Mirjana; Sehouli, Jalid; Darb-Esfahani, Silvia; Braicu, Elena Ioana

    2017-07-01

    High-grade serous ovarian cancer (HGSOC) causes 80% of all ovarian cancer (OC) deaths. In this setting, the role of cancer stem-like cells (CSCs) is still unclear. In particular, the evolution of CSC biomarkers from primary (pOC) to recurrent (rOC) HGSOCs is unknown. Aim of this study was to investigate changes in CD133 and aldehyde dehydrogenase-1 (ALDH1) CSC biomarker expression in pOC and rOC HGSOCs. Two-hundred and twenty-four pOC and rOC intrapatient paired tissue samples derived from 112 HGSOC patients were evaluated for CD133 and ALDH1 expression using immunohistochemistry (IHC); pOCs and rOCs were compared for CD133 and/or ALDH1 levels. Expression profiles were also correlated with patients' clinicopathological and survival data. Some 49.1% of the patient population (55/112) and 37.5% (42/112) pOCs were CD133+ and ALDH1+ respectively. CD133+ and ALDH1+ samples were detected in 33.9% (38/112) and 36.6% (41/112) rOCs. CD133/ALDH1 coexpression was observed in 23.2% (26/112) and 15.2% (17/112) of pOCs and rOCs respectively. Pairwise analysis showed a significant shift of CD133 staining from higher (pOCs) to lower expression levels (rOCs) (p cancer cells, providing also a first evidence that there is no correlation between CSCs and BRCA status. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Incidental serous tubal intraepithelial carcinoma and early invasive serous carcinoma in the nonprophylactic setting: analysis of a case series.

    Science.gov (United States)

    Morrison, Jane C; Blanco, Luis Z; Vang, Russell; Ronnett, Brigitte M

    2015-04-01

    A precursor for invasive ovarian/pelvic high-grade serous carcinoma, termed serous tubal intraepithelial carcinoma (STIC), has been identified and characterized through careful analysis of the fallopian tubes in both prophylactic salpingo-oophorectomy specimens obtained from women with either a family history of breast and/or ovarian cancer or germline mutations of BRCA1 and BRCA2 and in cases of pelvic high-grade serous carcinoma. Data on incidental STICs and clinically occult microscopic invasive high-grade serous carcinomas are limited. We analyzed the clinicopathologic features of 22 cases, including 15 pure STICs and 7 STICs associated with microscopic invasive high-grade serous carcinomas, identified incidentally in fallopian tubes removed for nonprophylactic indications. Patient age ranged from 39 to 79 years (mean: 62.7; median: 61), with only 1 patient under the age of 50. No patients were known to carry BRCA1 or BRCA2 mutations. Of the 12 pure STICs for which the location in the fallopian tube could be established, 9 were in the fimbriated portion, 1 was at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. Of the 7 STICs with associated invasive high-grade serous carcinoma, 3 were located in the fimbriated portion, 2 were at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. The invasive components were in the fallopian tube in 6 cases, 4 in subepithelial stroma of tubal mucosa, and 2 as an intramucosal (exophytic) luminal lesion without invasion of underlying subepithelial stroma (size range: 1 to 4 mm). The remaining case had a microscopic focus of high-grade serous carcinoma within the ipsilateral ovary (1.3 mm cortical focus) identified only on deeper sections, without an associated invasive component in the fallopian tube. The preferential finding of atypical epithelium with the cytologic features of high-grade serous carcinoma, namely STIC, in the fallopian tubes rather than the

  3. Molecular characterization of 103 ovarian serous and mucinous tumors.

    Science.gov (United States)

    Vereczkey, Ildikó; Serester, Orsolya; Dobos, Judit; Gallai, Mónika; Szakács, Orsolya; Szentirmay, Zoltán; Tóth, Erika

    2011-09-01

    The pathogenesis of ovarian carcinomas is heterogeneous, with even the same entities showing great variance. In our study we investigated the mutations of the BRAF, KRAS, and p53 genes in serous and mucinous borderline tumors and in low grade and high grade serous and mucinous tumors. The mutations of BRAF and KRAS genes have been shown in 60% of borderline and low grade (well differentiated) serous and mucinous tumors, but very rarely in high grade (moderately and poorly differentiated) carcinomas. However mutations of p53 are very common in high grade tumors and this indicates a "dualistic" model of ovarian tumorigenesis. A total of 80 serous tumors, including serous borderline, low grade and high grade tumors, and 23 mucinous tumors, including borderline and invasive tumors were analysed for BRAF and KRAS mutations using real time PCR method followed by melting point analysis. P53 mutation was investigated by immunohistochemistry. We assumed mutation of the p53 gene when 100% of tumor cells showed strong nuclear positivity. We observed differences in genetic alterations in the development of the low grade tumors and between low and high grade tumors too. In some bilateral or stage II-III cases we observed differences between the mutation status of the left and right ovarian tumors and between the primary tumor and its implants. In one case in a tumor with micropapillary pattern showing high grade nuclear atypia we could detect mutations in both KRAS and p53 genes. The majority of our mucinous ovarian tumor cases showed a KRAS mutation. We have not found mutations of the BRAF and p53 genes in these cases. We have found as have others, that there is a dualistic pathway of ovarian carcinogenesis. In the majority of cases, low grade epithelial tumors develop in a stepwise manner due to genetic alterations of the members of MAP-kinase pathway; however mutation of the p53 gene is the key event in the development of high grade tumors.

  4. A new grading system “two-tier” in clasification of ovarian serous carcinoma and evaluation of P53 gene expression by immunohistochemical staining

    Directory of Open Access Journals (Sweden)

    Narges Izadi-Mood

    2014-01-01

    Conclusion: Since the presence of P53 negative expression in all of low-grade serous carcinoma by immunostaining and low-grade serous carcinoma accounts for small pupulation of all ovarian serous carcinoma and also few cases in our study, we did not find significant differences between P53 expression and survival in two low-grade vs high-grade serous carcinoma groups.

  5. B7-H4 expression in ovarian serous carcinoma: a study of 306 cases.

    Science.gov (United States)

    Liang, Li; Jiang, Yi; Chen, Jun-Song; Niu, Na; Piao, Jin; Ning, Jing; Zu, Youli; Zhang, Jing; Liu, Jinsong

    2016-11-01

    The B7 family of immune costimulatory ligands is a group of cell surface proteins that bind to the surface receptors of lymphocytes to fine-tune immune responses. The aberrant expression of these proteins plays a key role in tumor immune evasion. Immunotherapy targeting certain B7 family members, including programmed death ligand 1, has proven quite effective in suppressing tumor growth. However, why such therapy works in only a subgroup of tumors is unclear. We hypothesized that other B7 family members, either alone or in concert with programmed death ligand 1, play a crucial role in tumor pathogenesis and progression. We therefore examined the expression of a newly discovered B7 family member, B7-H4, in 306 cases of ovarian serous carcinoma by immunohistochemistry. We found that 91% (267/293) of the high-grade ovarian serous carcinomas and 69% (9/13) of the low-grade ovarian serous carcinomas expressed B7-H4. The difference between B7-H4 expression in high-grade and low-grade ovarian serous carcinoma was statistically significant (P=.002). Moreover, B7-H4 protein expression in high-grade serous carcinoma was associated with tumor stage (Povarian serous carcinomas, especially high-grade serous carcinomas, and may represent a novel immunotherapeutic target in this cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Serous tubal intraepithelial carcinoma, chronic fallopian tube injury, and serous carcinoma development.

    Science.gov (United States)

    Malmberg, Karin; Klynning, Charlotta; Flöter-Rådestad, Angelique; Carlson, Joseph W

    2016-06-01

    Ovarian carcinoma is the deadliest gynecological malignancy. Previous studies have suggested that the fallopian tube may be the primary site for high-grade serous carcinoma. In prophylactic salpingo-oophorectomies from women with hereditary high risk for ovarian cancer, precursors can be assessed prior to onset and studied as a model for serous cancer precursor lesions. Epidemiologic studies indicate that carcinogenesis may be a result of chronic fallopian tube injury. The aims of this study were to (1) to examine the incidence of serous tubal intraepithelial carcinoma (STIC) in relation to other clinical parameters and (2) to evaluate whether chronic fallopian tube injury was related to cancer development. This study enrolled 101 women, comprising the following three groups: hereditary (n = 60), sporadic serous cancer (n = 18; endometrial cancers were excluded), and control (n = 23). The cases were histologically examined and clinical risk factors were collected. The histological changes were compared between different patients and correlated to clinical risk factors. STICs were identified primarily on the fallopian tube fimbria. The incidence of STIC was 3 % in the hereditary patients. In sporadic serous cancer cases, 61 % were associated with STIC and tubal carcinoma (p STIC and invasive cancer were seen more often in the older patients than in the younger patients (p = 0.528). This small study, no correlation with chronic tubal injury or inflammation was identified.

  7. ARID1A loss correlates with mismatch repair deficiency and intact p53 expression in high-grade endometrial carcinomas.

    Science.gov (United States)

    Allo, Ghassan; Bernardini, Marcus Q; Wu, Ren-Chin; Shih, Ie-Ming; Kalloger, Steve; Pollett, Aaron; Gilks, C Blake; Clarke, Blaise A

    2014-02-01

    BAF250a (ARID1A) loss is a frequent event in high-grade endometrial cancers. It has been proposed that ARID1A is a driver gene, with ARID1A mutations occurring secondary to deregulated mismatch repair mechanism in gastric cancers, representing an alternative oncogenic pathway to p53 alteration. The prognostic significance of ARID1A loss is controversial. In this study, we investigated the frequency of BAF250a immunohistochemical loss in a cohort of high-grade endometrial cancers (n=190) and correlated it with mismatch repair (hMLH1, hMSH2, hMSH6, and hPMS2) and p53 protein expression. The 190 cases consisted of 82 high-grade endometrioid, 88 serous, 10 clear cell, and 10 mixed (carcinosarcomas and mixed histology). There was BAF250a loss in 55/190 (29%) cancers, most commonly in high-grade endometrioid carcinomas (46 vs 9% in serous carcinomas, Pmismatch repair proteins was observed in 63/190 (33%) cancers, most commonly in high-grade endometrioid carcinomas (57 vs 10% in serous carcinomas, Pmismatch repair loss (Pgenes; we found that ARID1A mutations were negatively associated with TP53 mutations but were unrelated to mismatch repair gene mutations. In conclusion, BAF250a loss is more common in high-grade endometrioid carcinomas than in other high-grade endometrial cancers and is associated with mismatch repair deficiency and normal p53 expression.

  8. Are all pelvic (nonuterine) serous carcinomas of tubal origin?

    Science.gov (United States)

    Przybycin, Christopher G; Kurman, Robert J; Ronnett, Brigitte M; Shih, Ie-Ming; Vang, Russell

    2010-10-01

    It has been proposed that the presence of tubal intraepithelial carcinoma (TIC), in association with one-third to nearly half of pelvic serous carcinomas, is evidence of fallopian tube origin for high-grade serous carcinomas that would have been otherwise classified as primary ovarian or peritoneal. To address this hypothesis, we evaluated a series of 114 consecutive pelvic (nonuterine) gynecologic carcinomas at our institution (2006 to 2008) to determine the frequency of TIC in 52 cases in which all the resected fallopian tube tissue was examined microscopically. These 52 cases were classified as ovarian (n=37), peritoneal (n=8), or fallopian tube (n=7) in origin as per conventional criteria based on disease distribution. The presence of TIC and its location and relationship to invasive carcinoma in the fallopian tubes and ovaries were assessed. Among the 45 cases of ovarian/peritoneal origin, carcinoma subtypes included 41 high-grade serous, 1 endometrioid, 1 mucinous, 1 high-grade, not otherwise specified, and 1 malignant mesodermal mixed tumor. TIC was identified in 24 cases (59%) of high-grade serous carcinoma but not among any of the other subtypes; therefore, the term serous TIC (STIC) is a more specific appellation. STICs were located in the fimbriated end of the tube in 22 cases (92%) and in the ampulla in 2 (8%); they were unilateral in 21 (88%) and bilateral in 3 (13%). STICs in the absence of an associated invasive carcinoma in the same tube were detected in 7 cases (30%) and with invasive carcinoma in the same tube in 17 (71%). Unilateral STICs were associated with bilateral ovarian involvement in 15 cases and unilateral (ipsilateral) ovarian involvement in 5 (the remaining case with a unilateral STIC had a primary peritoneal tumor with no ovarian involvement); the bilateral STICs were all associated with bilateral ovarian involvement. Six of the 7 primary tubal tumors were high-grade serous carcinomas, and 4 of these 6 (67%) had STICs. Based on

  9. STICS, SCOUTs and p53 signatures; a new language for pelvic serous carcinogenesis.

    Science.gov (United States)

    Mehra, Karishma; Mehrad, Mitra; Ning, Geng; Drapkin, Ronny; McKeon, Frank D; Xian, Wa; Crum, Christopher P

    2011-01-01

    The events leading to the most common and most lethal ovarian carcinoma - high grade serous carcinoma - have been poorly understood. However, the detailed pathologic study of asymptomatic women with germ-line BRCA 1 or BRCA2 (BCRA+) mutations has unearthed an early malignancy, serous tubal intraepithelial carcinomas (STIC), which has linked many peritoneal and ovarian serous carcinomas to the fimbria. The distinction between high-grade serous and endometrioid carcinomas continues to narrow, with shared alterations in expression of pTEN, PAX2 and p53. Moreover, the discovery of clonal alterations in p53 in benign tubal epithelium, - p53 signatures - has established a foundation for a serous cancer precursor in the fimbria. We have expanded this concept to include a generic secretory cell outgrowth (SCOUT) in the fallopian tube that is associated with altered PAX2 expression. As the repertoire of gene alterations is expanded and its link to serous carcinogenesis clarified, a cogent pathway to high-grade Mullerian carcinomas will emerge. This will challenge conventional thinking about ovarian carcinogenesis but will provide a new template for studies of ovarian cancer prevention.

  10. Ovarian serous carcinoma: recent concepts on its origin and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Li Jie

    2012-03-01

    Full Text Available Abstract Recent morphologic and molecular genetic studies have led to a paradigm shift in our conceptualization of the carcinogenesis and histogenesis of pelvic (non-uterine serous carcinomas. It appears that both low-grade and high-grade pelvic serous carcinomas that have traditionally been classified as ovarian in origin, actually originate, at least in a significant subset, from the distal fallopian tube. Clonal expansions of the tubal secretory cell probably give rise to serous carcinomas, and the degree of ciliated conversion is a function of the degree to which the genetic hits deregulate normal differentiation. In this article, the authors review the evidentiary basis for aforementioned paradigm shift, as well as its potential clinical implications.

  11. Secretory cell outgrowths, p53 signatures, and serous tubal intraepithelial carcinoma in the fallopian tubes of patients with sporadic pelvic serous carcinoma

    Directory of Open Access Journals (Sweden)

    Neha Mittal

    2016-01-01

    Full Text Available Context: High-grade serous carcinomas of ovarian, tubal, and peritoneal origin are together referred as pelvic serous carcinoma. The fallopian tubes, ovarian surface epithelium, and the tuboperitoneal junctional epithelium are all implicated in pelvic serous carcinogenesis. Aims: The aim of this study is to identify putative precursor lesions of serous carcinoma including secretory cell outgrowths (SCOUTs, serous tubal intraepithelial carcinoma (STIC, and p53 signatures and assign its probable site of origin. Settings and Design: Prospective case-control study of consecutive specimen comprising 32 serous carcinomas and 31 controls (10 normal adnexa, 10 benign and 6 atypically proliferative surface epithelial tumors, and 5 other carcinomas. Subjects and Methods: Sectioning and extensive examination of the fimbrial end (SEE-FIM protocol along with immunohistochemistry for Bcl-2, p53, and Ki-67 was employed for evaluating invasive carcinoma and precursor lesions in cases versus controls. Results: SCOUT, p53 signatures, and STIC were most frequent in the serous carcinomas. p53 signatures and STIC were always seen in the fimbrial end. STICs were exclusively present in serous carcinomas, more common in ipsilateral tubes of cases with dominant ovarian mass. Multifocal p53 signatures with STIC were seen in 7 (21.9% cases. STIC was present with or without an invasive carcinoma in 25% and in 6.25% of cases of pelvic serous carcinomas, respectively. The junctional epithelia did not show any lesion in any group. Conclusions: SEE-FIM protocol is recommended for evaluation of sporadicpelvic (ovarian/tubal/peritoneal serous carcinoma. Based on the presence of STIC or invasive carcinoma, nearly 60% of all pelvic serous carcinomas are of fallopian tubal origin.

  12. Secretory cell outgrowths, p53 signatures, and serous tubal intraepithelial carcinoma in the fallopian tubes of patients with sporadic pelvic serous carcinoma.

    Science.gov (United States)

    Mittal, Neha; Srinivasan, Radhika; Gupta, Nalini; Rajwanshi, Arvind; Nijhawan, Raje; Gautam, Upasana; Sood, Swati; Dhaliwal, Lakhbir

    2016-01-01

    High-grade serous carcinomas of ovarian, tubal, and peritoneal origin are together referred as pelvic serous carcinoma. The fallopian tubes, ovarian surface epithelium, and the tuboperitoneal junctional epithelium are all implicated in pelvic serous carcinogenesis. The aim of this study is to identify putative precursor lesions of serous carcinoma including secretory cell outgrowths (SCOUTs), serous tubal intraepithelial carcinoma (STIC), and p53 signatures and assign its probable site of origin. Prospective case-control study of consecutive specimen comprising 32 serous carcinomas and 31 controls (10 normal adnexa, 10 benign and 6 atypically proliferative surface epithelial tumors, and 5 other carcinomas). Sectioning and extensive examination of the fimbrial end (SEE-FIM) protocol along with immunohistochemistry for Bcl-2, p53, and Ki-67 was employed for evaluating invasive carcinoma and precursor lesions in cases versus controls. SCOUT, p53 signatures, and STIC were most frequent in the serous carcinomas. p53 signatures and STIC were always seen in the fimbrial end. STICs were exclusively present in serous carcinomas, more common in ipsilateral tubes of cases with dominant ovarian mass. Multifocal p53 signatures with STIC were seen in 7 (21.9%) cases. STIC was present with or without an invasive carcinoma in 25% and in 6.25% of cases of pelvic serous carcinomas, respectively. The junctional epithelia did not show any lesion in any group. SEE-FIM protocol is recommended for evaluation of sporadicpelvic (ovarian/tubal/peritoneal) serous carcinoma. Based on the presence of STIC or invasive carcinoma, nearly 60% of all pelvic serous carcinomas are of fallopian tubal origin.

  13. Serous tubal intraepithelial neoplasia: the concept and its application.

    Science.gov (United States)

    Meserve, Emily E K; Brouwer, Jan; Crum, Christopher P

    2017-05-01

    In recent years it has become clear that many extra-uterine (pelvic) high-grade serous carcinomas (serous carcinomas) are preceded by a precursor lesion in the distal fallopian tube. Precursors range from small self-limited 'p53 signatures' to expansile serous tubal intraepithelial neoplasms that include both serous tubal epithelial proliferations (or lesions) of uncertain significance and serous tubal intraepithelial carcinomas. These precursors can be considered from three perspectives. The first is biologic underpinnings, which are multifactorial, and include the intersection of DNA damage with Tp53 mutations and disturbances in transcriptional regulation that increase with age. The second perspective is the morphologic discovery and classification of intraepithelial neoplasms that are intercepted early in their natural history, either incidentally or in risk-reduction surgeries for germline mutations. For the practicing pathologist, as well as the investigators, a distinction between a primary intraepithelial neoplasm and an intramucosal carcinoma must be made to avoid misinterpreting (or underestimating) the significance of these proliferations. The third perspective is the application of this information to intervention, devising strategies that will actually lower the ovarian cancer death rate by opportunistic salpingectomy, widespread comprehensive genetic screening and early detection. Central to this issue are the questions of (1) whether some STICs are metastatic, (2) whether lower-grade epithelial proliferations can invade prior to evolving into intraepithelial carcinoma, or (3) metastasize and become malignant elsewhere ('precursor escape'). An important caveat is the persistent and unsettling reality that many high-grade serous carcinomas are not associated with an obvious point of initiation in the fallopian tube. The pathologist sits squarely in the midst of all of these issues, and has a pivotal role in managing expectations for stemming the death

  14. Central serous chorioretinopathy

    DEFF Research Database (Denmark)

    Wang, M.; Munch, I.C.; Hasler, P.W.

    2008-01-01

    Central serous chorioretinopathy (CSC) is a disease of the retina characterize by serous detachment of the neurosensory retina secondary to one or more focal lesions of the retinal pigment epithelium (RPE). CSC occurs most frequently in mid-life and more often in men than in women. Major symptoms...... and hypercortisolism. Ophthalmoscopic signs of CSC range from mono- or paucifocal RPE lesions with prominent elevation of the neurosensory retina by clear fluid - typical of cases of recent onset - to shallow detachments overlying large patches of irregularly depigmented RPE. The spectrum of lesions includes RPE...... detachments. Granular or fibrinous material may accumulate in the subretinal cavity. Serous detachment often resolves spontaneously. From first contact, counselling about the potential relation to stress and glucocorticoid medication is warranted. After 3 months without resolution of acute CSC or in chronic...

  15. Serous cystadenocarcinoma of pancreas

    International Nuclear Information System (INIS)

    Rathore, M. U.; Arif, A.; Umair, B.

    2013-01-01

    Serous cystic neoplasms of pancreas are relatively rare tumours. Malignancy in these tumours is even more rare which is confirmed by metastasis to other organs or by perineural, vascular or surrounding soft tissue invasion. A 60 years old lady presented with vague upper abdominal pain. Computed tomography scan showed multiloculated cystic mass in the body of pancreas measuring 9 x 6 x 5 cm and not involving spleen. Pancreatectomy specimen showed a multicystic tumour having sponge-like appearance which showed vascular and soft tissue invasion of surrounding stroma on microscopic examination and was diagnosed as serous cystadenocarcinoma of pancreas. (author)

  16. Central Serous Retinopathy Treatment

    Science.gov (United States)

    ... under the RPE. As a result, a small detachment forms under the retina, causing vision to become distorted. This image from ... a blister-like swelling in layers of the retina. Central serous chorioretinopathy usually affects just one ... is retinal detachment for people with high myopia? Mar 29, 2017 ...

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

    Science.gov (United States)

    2013-10-01

    risk assessment, development of new therapies and personalized treatment regimens for this deadly disease. 4 BODY D.1 Background Single mass...2010.1.2-1 and a DoD CDMRP Teal Innovator Award. Conflict of interest statement: G.P.N. has personal financial interest in the company DVS Sciences, the...cells in polychromatic flow cytometry. J Immunol Methods 2006, 313:199-208. 46. Cossarizza A, Baccarani- Contri M, Kalashnikova G, Franceschi C: A new

  18. Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Change

    Science.gov (United States)

    2013-10-01

    for ovarian cancer . In addition, Project 5 will determine if these biomarkers and associated precursor lesions are modifiable by oral contraceptives ...conference. Oral Presentations: Sophia HL George Origins of ovarian cancer , the biology of premalignancy, and cancer health disparities. AACR The...3. Determine whether oral contraceptives (OCPs) and NSAIDs reduce the morphologic and molecular changes that are associated with early “ovarian

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

    Science.gov (United States)

    2015-10-01

    systematic approach to successful treatment the disease. Furthermore, given the genetic plasticity of HG-SOC each patient can manifest one disease at...Davis MM. Single-cell systems-level analysis of human Toll-like receptor activation defines a chemokine signature in patients with systemic lupus

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

    Science.gov (United States)

    2014-10-01

    we will focus this report on the 1c, g and i. Task 3 Although the presence of infiltrating cytotoxic T cells correlates with good prognosis...Cytometry: Next generation flow cytometry, Tokyo, Japan Nolan: Nature – Genomic Technologies and Biomaterials for Understanding Disease, June 23, 2014

  1. Precursors of ovarian cancer in the fallopian tube: serous tubal intraepithelial carcinoma--an update.

    Science.gov (United States)

    Zeppernick, Felix; Meinhold-Heerlein, Ivo; Shih, Ie-Ming

    2015-01-01

    Ovarian tumors comprise a wide variety of entities. The largest group, epithelial ovarian carcinoma, can be classified into two main groups, type I and type II tumors. Recent advances in the understanding of ovarian cancer development have resulted in the finding of 'serous tubal intraepithelial carcinoma', which is believed to represent the precursor lesion in high-grade serous ovarian carcinoma. In this review, lines of evidence for this are discussed and possible future implications for clinical and research settings are outlined. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  2. 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

  3. Metal recovery from high-grade WEEE

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  4. Spina bifida occulta in high grade spondylolisthesis.

    Science.gov (United States)

    Babbi, L; Terzi, S; Bandiera, S; Barbanti Brodano, G

    2014-01-01

    A 14-year-old boy presented with symptomatic high-grade dysplastic type spondylolisthesis, with a presence of spina bifida occulta, not diagnosed by plain radiographs, but confirmed on preoperative CT and MR. Circumferential fusion with partial reduction of L5/S1 was performed. Awareness of the coexistence of spondylolisthesis and spina bifida by an accurate preoperative planning is paramount to avoid iatrogenic damage to neural elements during surgery.

  5. Synchronous Bilateral Clear Cell Carcinoma and Papillary Serous Cystadenocarcinoma of the Ovaries

    Directory of Open Access Journals (Sweden)

    Bhavna Nayal

    2014-02-01

    Full Text Available The presence of synchronous bilateral ovarian malignancy with similar histology is well recognized. The presence of two tumours with different pathology in both the ovaries is extremely uncommon and pose a diagnostic and therapeutic challenge. Only one such case has been reported in a postmenopausal lady. We present second such case with synchronous presence of high grade serous and clear cell carcinoma in a premenopausal woman. [J Interdiscipl Histopathol 2014; 2(1.000: 52-55

  6. High-grade fimbrial-ovarian carcinomas are unified by altered p53, PTEN and PAX2 expression.

    Science.gov (United States)

    Roh, Michael H; Yassin, Yosuf; Miron, Alexander; Mehra, Karishma K; Mehrad, Mitra; Monte, Nicolas M; Mutter, George L; Nucci, Marisa R; Ning, Geng; Mckeon, Frank D; Hirsch, Michelle S; Wa, Xian; Crum, Christopher P

    2010-10-01

    High-grade endometrioid and serous carcinomas of the ovary and fallopian tube are responsible for the majority of cancer deaths and comprise a spectrum that includes early or localized (tubal intraepithelial carcinoma) and advanced (invasive or metastatic) disease. We subdivided a series of these tumors into three groups, (1) classic serous, (2) mixed serous and endometrioid and (3) endometrioid carcinomas and determined: (1) the frequencies of coexisting tubal intraepithelial carcinoma, (2) frequency of a dominant ovarian mass suggesting an ovarian origin and (3) immuno-localization of WT-1, p53, PTEN, PAX2 and p16(ink4). All tumors were analyzed for p53 mutations. Thirty six, 25 and 8% of groups 1-3 were associated with tubal intraepithelial carcinoma (P=0.09) and 34, 45 and 62% predominated in one ovary (P=0.028), respectively. Differences in frequencies of diffuse p53 immunostaining (85-93%), WT-1 (70-98%) and p16(ink4) positivity (69-75%) were not significant for all groups. Greater than 95% reduction in PAX2 and PTEN occurred in 67-75 and 5-12%, respectively; however, PAX2 and PTEN staining intensity, when present, was often heterogeneous, highlighting different tumor populations. PAX2 and PTEN expression were markedly reduced or absent in 12 of 12 and 4 of 12 tubal intraepithelial carcinomas. In summary, high-grade müllerian carcinomas share identical frequencies of altered or reduced expression of p53, PTEN and PAX2, all of which can be appreciated in tubal intraepithelial carcinomas. Because only a subset of these tumors appears to arise in the fallopian tube, attention to expression of these biomarkers in the ovary and other müllerian sites might facilitate the identification of other carcinogenic pathways. PAX2 and PTEN, in addition to p53 and p16(ink4), comprise a potentially important gene combination in high-grade pelvic carcinogenesis.

  7. Gene expression profiles of ovarian low-grade serous carcinoma resemble those of fallopian tube epithelium.

    Science.gov (United States)

    Qiu, Chunping; Lu, Nan; Wang, Xiao; Zhang, Qing; Yuan, Cunzhong; Yan, Shi; Dongol, Samina; Li, Yingwei; Sun, Xiaomei; Sun, Chenggong; Zhang, Zhiwei; Zheng, Wenxin; Kong, Beihua

    2017-12-01

    The cell of origin of ovarian low-grade serous carcinoma (LGSC) remains unclarified. Our recent morphologic and immunophenotypic study suggests that most LGSCs may be derived from the fallopian tube. The purpose of the current study was to gain further insight into the origin of LGSC at the molecular level. RNA-seq analysis was performed on a total of 31 tissue samples including LGSC (n=6), serous borderline tumors (SBT, n=6), fallopian tube epithelia (FTE, n=5), ovarian surface epithelia (OSE, n=4), and human peritoneal mesothelia (HPM, n=4). HGSC cases (n=6) served as a positive control. Gene expression profiles were compared and analyzed. To validate the findings from the gene expression array study, we selected the highly differentially expressed genes (PAX8, CDH1, FOXA2, and ARX) as well as those corresponding proteins and examined their expression levels in tissue samples of ovarian serous tumors, fallopian tube, ovarian surface epithelia, and peritoneal mesothelia. Dendrograms revealed that OSE samples clustered with HPM, while ovarian serous tumors, including LGSC, SBT and high-grade serous carcinoma (HGSC), clustered with FTE. Furthermore, LGSC showed a significantly closer relationship with FTE than with OSE and HPM samples. PAX8, CDH1, and FOXA2 were highly and specifically expressed in serous tumors and FTE samples but not in OSE samples. In contrast, ARX was mainly expressed in OSE samples but not in FTE and serous tumors. The findings of the current study provide further evidence at a molecular level that the fallopian tube is likely the cellular source of LGSC. This finding may enable new prevention strategies, improve early detection, and allow novel therapies to be tested. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    Science.gov (United States)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev; Kimbung, Siker; Jönsson, Mats; Bonde, Jesper Hansen; Kannisto, Päivi; Måsbäck, Anna; Malander, Susanne; Nilbert, Mef; Hedenfalk, Ingrid

    2014-01-01

    Objective Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer. Methods Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset. Results 5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged. Conclusions These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast

  9. 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.

  10. 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.

  11. Posterior surgery in high-grade spondylolisthesis.

    Science.gov (United States)

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

    2014-09-01

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

  12. Serous tubal intraepithelial carcinoma: its potential role in primary peritoneal serous carcinoma and serous cancer prevention.

    Science.gov (United States)

    Carlson, Joseph W; Miron, Alexander; Jarboe, Elke A; Parast, Mana M; Hirsch, Michelle S; Lee, Yonghee; Muto, Michael G; Kindelberger, David; Crum, Christopher P

    2008-09-01

    A diagnosis of primary peritoneal serous carcinoma (PPSC) requires exclusion of a source in other reproductive organs. Serous tubal intraepithelial carcinoma (STIC; stage 0) has been described in asymptomatic women with BRCA mutations and linked to a serous cancer precursor in the fimbria. This study examined the frequency of STIC in PPSC and its clinical outcome in BRCA-positive women. Presence or absence of STIC was recorded in consecutive cases meeting the 2001 WHO criteria for PPSC, including 26 patients with nonuniform sampling of the fallopian tubes (group 1) and 19 patients with complete tubal examination (group 2; sectioning and extensively examining the fimbriated end, or SEE-FIM protocol). In selected cases, STIC or its putative precursor and the peritoneal tumor were analyzed for p53 mutations (exons 1 to 11). Outcome of STIC was ascertained by literature review. Thirteen (50%) of 26 PPSCs in group 1 involved the endosalpinx, with nine STICs (35%). Fifteen (79%) of 19 cases in group 2 contained endosalpingeal involvement, with nine STICs (47%). STIC was typically fimbrial and unifocal, with variable invasion of the tubal wall. In five of five cases, the peritoneal and tubal lesion shared an identical p53 mutation. Of 10 reported STICs in BRCA-positive women, all patients were without disease on follow-up. The fimbria is the source of nearly one half of PPSCs, suggesting serous malignancy originates in the tubal mucosa but grows preferentially at a remote peritoneal site. The generally low risk of recurrence in stage 0 (STIC) disease further underscores STIC as a possible target for early serous cancer detection and prevention.

  13. FGF18 as a potential biomarker in serous and mucinous ovarian tumors.

    Science.gov (United States)

    El-Gendi, Saba; Abdelzaher, Eman; Mostafa, Mohamed Farouk; Sheasha, Ghada Abu

    2016-03-01

    Fibroblast growth factor 18 (FGF18) has been suggested to play important roles in promoting progression of ovarian high-grade serous carcinoma. Our aim was to investigate FGF18 expression in the whole spectrum of serous and mucinous ovarian tumors, highlighting differences in expression within the adenoma-carcinoma sequence and differences between type I and type II tumors. We also aimed to test the prognostic significance of this expression and its relation to microvessel density (MVD). We evaluated the immunohistochemical expression of FGF18 and CD31 in 103 ovarian tumors and statistically analyzed their association with clinicopathological variables and patients' outcome. FGF18 score increased significantly within the adenoma-carcinoma sequence for serous and mucinous tumors. MVD increased significantly only among serous tumors. FGF18 and MVD correlated significantly (overall and among serous tumors only) and were significantly higher in type II than type I tumors. Cox regression models were built. Independent predictors could not be determined due to multicollinearity between the predictors. However, the combination of International Federation of Gynecology and Obstetrics (FIGO) stage, ovarian carcinoma type, and/or FGF18 score achieved the highest predictability of poor prognosis. FGF18 could play a role within the adenoma-carcinoma sequence in type I tumors and might modulate angiogenesis among serous tumors. Our findings further augment the differences between type I and type II tumors. The combination of FIGO stage, ovarian carcinoma type, and/or FGF18 score could predict poor prognosis among ovarian carcinoma patients. Our work identifies FGF18 in ovarian neoplasia as a promising field of research, although evaluation of the performance of the developed models is still needed.

  14. Giant serous microcystic pancreas adenoma.

    Science.gov (United States)

    Dikmen, Kursat; Bostanci, Hasan; Yildirim, Ali Cihat; Sakrak, Omer; Kerem, Mustafa

    2012-10-10

    Serous cystadenomas are rare tumors comprising 1-2% of exocrine pancreas tumors. They are mostly known as benign conditions but malign transformation as serous cystadenocarcinoma is also reported. It is usually seen in females. Non-specific symptoms, such as abdominal pain or symptoms due to mass affect, are usually seen. A 64-year old female patient was investigated for abdominal pain. Physical and laboratory findings were normal. Abdomen ultrasonography confirmed an 11×9.5 cm solid cystic lesion and abdomen computed tomography scan confirmed a 12×11 cm lobulated cystic solid lesion which had central cystic necrotic areas extending from liver hilus inferiorly. Fine needle biopsy confirmed benign cytology and trucut biopsy of the pancreatic mass reported chronic inflamation. Nevertheless, this mass could have malignant contents and transformation potential. A laparatomy was decided due to patient's symptoms and mass effect. Due to vascular invasion of the tumor, Whipple procedure was performed. The pathology report confirmed serous microcystic adenoma. These rare tumors are usually benign but pre-operative malignity criterias are not identified. There are few differential diagnostic tools for excluding malignity. We suggest surgical resection as best treatment approach for selected cases.

  15. Giant serous microcystic pancreas adenoma

    Directory of Open Access Journals (Sweden)

    Mustafa Kerem

    2012-10-01

    Full Text Available Serous cystadenomas are rare tumors comprising 1-2% of exocrine pancreas tumors. They are mostly known as benign conditions but malign transformation as serous cystadenocarcinoma is also reported. It is usually seen in females. Non-specific symptoms, such as abdominal pain or symptoms due to mass affect, are usually seen. A 64-year old female patient was investigated for abdominal pain. Physical and laboratory findings were normal. Abdomen ultrasonography confirmed an 11x9.5 cm solid cystic lesion and abdomen computed tomography scan confirmed a 12x11 cm lobulated cystic solid lesion which had central cystic necrotic areas extending from liver hilus inferiorly. Fine needle biopsy confirmed benign cytology and trucut biopsy of the pan creatic mass reported chronic inflamation. Nevertheless, this mass could have malignant contents and transformation potential. A laparatomy was decided due to patient’s symptoms and mass effect. Due to vascular invasion of the tumor, Whipple procedure was performed. The pathology report confirmed serous microcystic adenoma. These rare tumors are usually benign but pre-operative malignity criterias are not identified. There are few differential diagnostic tools for excluding malignity. We suggest surgical resection as best treatment approach for selected cases.

  16. Clinicopathologic study of serous tubal intraepithelial carcinoma with invasive carcinoma: is serous tubal intraepithelial carcinoma a reliable feature for determining the organ of origin?

    Science.gov (United States)

    Gao, Faye F; Bhargava, Rohit; Yang, Huaitao; Li, Zaibo; Zhao, Chengquan

    2013-08-01

    In the past several decades, the concept of serous ovarian carcinoma has been revised repeatedly. However, the exact pathogenesis remains controversial. The most popular current concept is origin from the epithelium of the fimbriated ends of the fallopian tubes. The objective of our study was to evaluate the characteristic clinical and morphologic features of serous tubal intraepithelial carcinoma (STIC) and associated invasive carcinomas. One hundred sixteen consecutive cases of STIC seen from 2007 to 2011 were included in this study. High-grade serous carcinoma (HGSC) with or without a mixed component was identified in 107 cases (92.2%), non-HGSC in 5 cases, and STICs without invasive carcinoma in 4 cases. Using conventional criteria, HGSCs were classified as fallopian tube in origin in 65 cases (60.7%), as ovarian in 30 (28.0%), as peritoneal in 9 (8.4%), and as endometrial in 3 (2.8%). Among the 107 cases with HGSCs, most STICs (86; 80%) were present unilaterally, whereas invasive tumors more commonly involved the ovaries bilaterally (79%; 84 cases). These findings support the hypothesis that STIC acts as a precursor lesion for most fallopian tube, ovarian, and peritoneal HGSCs, but not for endometrial HGSC. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. 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

  18. Cyclin E1 as a Therapeutic Target in Women with High Grade Serous Ovarian Cancer and Primary Treatment Failure

    Science.gov (United States)

    2016-09-01

    mutant Tp53, and Pten deletion • Monitor animals by ultrasound, body weight, and 18-24 x 0% 3 physical examination on a weekly basis...INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) (Animal Welfare Assurance # A3079-01) RONNY DRAPKIN 4333 - OB-Obstetrics and Gynecology 421 Curie...amplified cancers and potential strategies to over- 14 come resistance to targeted agents. 15 Experimental Design: To examine dependency on CDK2 in 16 CCNE1

  19. 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.

  20. 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. ...

  1. [How to biopsy only men with high grade prostate cancer].

    Science.gov (United States)

    Benecchi, Luigi; Bocchi, Francesca; Martinotti, Mario; Perucchini, Laura; Quarta, Matteo; Russo, Fabrizio; Tonghini, Mario; Del Boca, Carlo

    2013-04-24

    Fuzzy logic and Artificial Neural Networks (ANN) are complementary technologies that together generate neuro-fuzzy system. The aim of our study is to compare 2 models for predicting the presence of high-grade prostate cancer (Gleason score 7 or more). We evaluated data from 1000 men with PSA less than 50 ng/mL, who underwent prostate biopsy. A prostate cancer was found in 313 (31%), and in 172 (17.2%) we detected high-grade prostate cancer. With those data, we developed 2 Co-Active Neuro-Fuzzy Inference Systems to predict the presence of high-grade prostate cancer. The first model had four input neurons (PSA, free PSA percentage [%freePSA], PSA density, and age) and the second model had three input neurons (PSA, %freePSA, and age). The model with four input neurons (PSA, %freePSA, PSA density, and age) showed better performances than the one with three input neurons (PSA, %freePSA, and age). In fact the average testing error was 0.42 for the model with four input neurons and 0.44 for the other model. The addition of PSA density to the model has allowed to obtain better results for the diagnosis of high grade prostate cancer.

  2. 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

  3. Demographic Clinical and Prognostic Factors of Primary Ovarian Adenocarcinomas of Serous and Clear Cell Histology—A Comparative Study

    DEFF Research Database (Denmark)

    Schnack, Tine H; Høgdall, Estrid; Nedergaard, Lotte

    2016-01-01

    OBJECTIVE: To compare clinical demographic and prognostic factors as well as overall survival in a nationwide cohort of patients diagnosed with ovarian clear cell carcinoma (oCCC) and high grade ovarian serous adenocarcinoma (oSAC) during 2005 to 2013. MATERIALS AND METHODS: Population......SAC cases. Furthermore, our findings confirm that advanced stages of oCCC have a poorer prognosis compared with oSAC probably because of the resistance toward adjuvant chemotherapy. The observed differences highlight the need for subtype-specific research and individualized treatment within ovarian cancer....

  4. Central serous chorioretinopathy secondary to trauma

    Directory of Open Access Journals (Sweden)

    Thomas E Jackson

    2012-01-01

    Full Text Available The first case of central serous chorioretinopathy secondary to blunt trauma is presented. Optical coherence tomography performed on presentation, 3 days after trauma, demonstrated a neurosensory detachment of the macular, thus confirming clinical findings. At 3 months after injury, the retina had spontaneously flattened at the macular and vision had returned to normal.

  5. 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.

  6. 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.

  7. Eosinophilic endomyocardial disease due to high grade chest wall sarcoma.

    Science.gov (United States)

    Hussain, A.; Brown, P. J.; Thwaites, B. C.; Hastings, A. G.

    1994-01-01

    Eosinophilic endomyocardial disease is characterised by persisting blood eosinophilia and acute endocardial lesions which progress to endomyocardial fibrosis. In most cases the cause is unknown but it has been described in association with malignant tumours. A fatal case is presented of a 64 year old woman with this disease due to a high grade sarcoma of the chest wall, an association not previously reported. Images PMID:7974303

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma.

    Science.gov (United States)

    Lassus, Heini; Staff, Synnöve; Leminen, Arto; Isola, Jorma; Butzow, Ralf

    2011-01-01

    Aurora-A is a potential oncogene and therapeutic target in ovarian carcinoma. It is involved in mitotic events and overexpression leads to centrosome amplification and chromosomal instability. The objective of this study was to evaluate the clinical significance of Aurora-A and DNA ploidy in serous ovarian carcinoma. Serous ovarian carcinomas were analysed for Aurora-A protein by immunohistochemistry (n=592), Aurora-A copy number by CISH (n=169), Aurora-A mRNA by real-time PCR (n=158) and DNA ploidy by flowcytometry (n=440). Overexpression of Aurora-A was found in 27% of the tumors, cytoplasmic overexpression in 11% and nuclear in 17%. The cytoplasmic and nuclear overexpression were nearly mutually exclusive. Both cytoplasmic and nuclear overexpression were associated with shorter survival, high grade, high proliferation index and aberrant p53. Interestingly, only cytoplasmic expression was associated with aneuploidy and expression of phosphorylated Aurora-A. DNA ploidy was associated with poor patient outcome as well as aggressive clinicopathological parameters. In multivariate analysis, Aurora-A overexpression appeared as an independent prognostic factor for disease-free survival, together with grade, stage and ploidy. Aurora-A protein expression is strongly linked with poor patient outcome and aggressive disease characteristics, which makes Aurora-A a promising biomarker and a potential therapeutic target in ovarian carcinoma. Cytoplasmic and nuclear Aurora-A protein may have different functions. DNA aneuploidy is a strong predictor of poor prognosis in serous ovarian carcinoma. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. The diagnostic and biological implications of laminin expression in serous tubal intraepithelial carcinoma.

    Science.gov (United States)

    Kuhn, Elisabetta; Kurman, Robert J; Soslow, Robert A; Han, Guangming; Sehdev, Ann Smith; Morin, Patrick J; Wang, Tian-Li; Shih, Ie-Ming

    2012-12-01

    There is compelling evidence to suggest that serous tubal intraepithelial carcinoma (STIC) is the likely primary site for the development of many pelvic high-grade serous carcinomas (HGSCs). Identifying molecules that are upregulated in STIC is important not only to provide biomarkers to assist in the diagnosis of STIC but also to elucidate our understanding of the pathogenesis of HGSC. In this study, we performed RNA sequencing to compare transcriptomes between HGSC and normal fallopian tube epithelium (FTE), and we identified LAMC1 encoding laminin γ1 as one of the preferentially upregulated genes associated with HGSC. Reverse transcription polymerase chain reaction further validated LAMC1 upregulation in HGSC as compared with normal FTE. Immunohistochemical analysis was performed on 32 cases of concurrent HGSC and STIC. The latter was diagnosed on the basis of morphology, TP53 mutations, and p53 and Ki-67 immunohistochemical patterns. Laminin γ1 immunostaining intensity was found to be significantly higher in STIC and HGSC compared with adjacent FTE in all cases (PSTIC and HGSC cells, laminin γ1 staining was diffuse and intense throughout the cytoplasm. More importantly, strong laminin γ1 staining was detected in all 13 STICs, which lacked p53 immunoreactivity because of null mutations. These findings suggest that the overexpression of laminin γ1 immunoreactivity and alteration of its staining pattern in STICs can serve as a useful tissue biomarker, especially for those STICs that are negative for p53 and have a low Ki-67 labeling index.

  11. Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

    Science.gov (United States)

    Lim, Diana; Murali, Rajmohan; Murray, Melissa P; Veras, Emanuela; Park, Kay J; Soslow, Robert A

    2016-03-01

    Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology

  12. 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

  13. Differential expression of argininosuccinate synthetase in serous and non‐serous ovarian carcinomas

    Science.gov (United States)

    Cheon, Dong‐Joo; Walts, Ann E; Beach, Jessica A; Lester, Jenny; Bomalaski, John S; Walsh, Christine S; Ruprecht Wiedemeyer, W; Karlan, Beth Y

    2014-01-01

    Abstract The current standard of care for epithelial ovarian cancer does not discriminate between different histologic subtypes (serous, clear cell, endometrioid and mucinous) despite the knowledge that ovarian carcinoma subtypes do not respond uniformly to conventional platinum/taxane‐based chemotherapy. Exploiting addictions and vulnerabilities in cancers with distinguishable molecular features presents an opportunity to develop individualized therapies that may be more effective than the current ‘one size fits all' approach. One such opportunity is arginine depletion therapy with pegylated arginine deiminase, which has shown promise in several cancer types that exhibit low levels of argininosuccinate synthetase including hepatocellular and prostate carcinoma and melanoma. Based on the high levels of argininosuccinate synthetase previously observed in ovarian cancers, these tumours have been considered unlikely candidates for arginine depletion therapy. However, argininosuccinate synthetase levels have not been evaluated in the individual histologic subtypes of ovarian carcinoma. The current study is the first to examine the expression of argininosuccinate synthetase at the mRNA and protein levels in large cohorts of primary and recurrent ovarian carcinomas and ovarian cancer cell lines. We show that the normal fallopian tube fimbria and the majority of primary high‐grade and low‐grade serous ovarian carcinomas express high levels of argininosuccinate synthetase, which tend to further increase in recurrent tumours. In contrast to the serous subtype, non‐serous ovarian carcinoma subtypes (clear cell, endometrioid and mucinous) frequently lack detectable argininosuccinate synthetase expression. The in vitro sensitivity of ovarian cancer cell lines to arginine depletion with pegylated arginine deiminase was inversely correlated with argininosuccinate synthetase expression. Our data suggest that the majority of serous ovarian carcinomas are not susceptible

  14. 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.

  15. Transpupillary thermotherapy for atypical central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Kawamura R

    2012-01-01

    Full Text Available Ryosuke Kawamura1,2, Hidenao Ideta1, Hideyuki Hori1, Kenya Yuki2, Tsuyoshi Uno1, Tatsurou Tanabe1, Kazuo Tsubota2, Tsutomu Kawasaki11Ideta Eye Hospital, Kumamoto, Japan; 2Keio University, School of Medicine, Department of Ophthalmology, Tokyo, JapanBackground: Central serous chorioretinopathy (CSC has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC.Methods: We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50–250 mW, spot size of 500–1200 µm, and exposure time of 13–60 seconds to minimize retinal damage.Results: In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30. Final BCVA

  16. Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship.

    Science.gov (United States)

    Ardighieri, Laura; Mori, Luigi; Conzadori, Sara; Bugatti, Mattia; Falchetti, Marcella; Donzelli, Carla Maria; Ravaggi, Antonella; Odicino, Franco E; Facchetti, Fabio

    2016-07-01

    Pelvic carcinosarcomas (PCSs) are rare aggressive biphasic tumors that localize in the ovary, fallopian tube, or peritoneum and present frequently as bilateral disease. We undertook a morphological, p53 immunohistochemical and TP53 gene mutational analysis study in a single institution cohort of 16 PCSs in order to investigate the nature of bilateral tumors and to shed light on their origin and pathogenesis. Of the 16 patients, 10 presented with bilateral disease, 6 with a carcinosarcoma in both adnexa, and the remaining cases with a carcinosarcoma in one adnexum and a carcinoma in the opposite. The carcinoma component showed high-grade serous features in 13/16 of cases (81 %). In 10 patients (63 %), a serous tubal intraepithelial carcinoma (STIC) was found, in one case bilateral, making a total of 11 STICs. STIC was found only in cases with a carcinoma component with high-grade serous features. All 10 bilateral tumors and all 11 PCS-associated STICs showed a similar p53 immunostaining pattern. At mutation analysis of the TP53 gene, all five bilateral PCS contained an identical mutation in both localizations. Furthermore, a TP53 mutation was found in 8 of 10 STICs, with an identical mutation in the associated PCS. The finding of similar p53 immunostaining in all bilateral cases and identical TP53 mutations in most PCS-associated STIC provides evidence for a clonal relation between these neoplastic lesions, supporting a metastatic nature of bilateral PCS and suggesting that they have an extraovarian origin in a STIC.

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

    Science.gov (United States)

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

    2016-04-01

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

  18. Serous ovarian, fallopian tube and primary peritoneal cancers

    DEFF Research Database (Denmark)

    Sørensen, Rie D; Schnack, Tine H; Karlsen, Mona A

    2015-01-01

    of whether or not these disorders should be considered as separate entities. METHODS: A systematic literature search was conducted in PubMed and MEDLINE. Case-control studies comparing primary serous peritoneal or fallopian tube carcinomas with primary serous ovarian carcinomas or a control group were...

  19. Management of Patients with High-Grade Glioma

    Directory of Open Access Journals (Sweden)

    Simge Yukse

    2014-11-01

    Full Text Available The scientific basis for the surgical management of patients with glioma is rapidly evolving. The infiltrative nature of these cancers precludes a surgical cure, but despite this, cytoreductive surgery remains central to high-quality patient’s care. In addition to tissue sampling for accurate histopathological diagnosis and molecular genetic characterisation, clinical benefit from decompression of space-occupying lesions and microsurgical cytoreduction has been reported in patients with different grades of glioma. By integrating advanced surgical techniques with molecular genetic characterisation of the disease and targeted radiotherapy and chemotherapy, it is possible to construct a programme of personalised surgical therapy throughout the patient’s journey. The goal of therapeutic packages tailored to each patient is to optimise patient safety and clinical outcome, and must be delivered in a multidisciplinary setting. Here we review the current concepts that underlie surgical management of patients with high-grade glioma.

  20. 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

  1. Heap leaching process of high-grade uranium ore

    International Nuclear Information System (INIS)

    Lin Sirong; Gao Xizheng; Guo Erhua; Lu Shijie

    1994-08-01

    A heap leaching process for high-grade primary uranium ore has been studied. The minerals mainly are uraninite. In the process the manganese dioxide is used as oxidant and ferric sulphate solution as leaching agent. The two-stage counter current heap leach method is used in the process. The leached liquor which contains dissolved uranium and iron returns to the neutralizing stage and the iron in the leached liquor is precipitated in the stage. The acid is added to the main stage and the precipitated iron is dissolved as Fe 2 (SO 4 ) 3 in the stage. Comparing with conventional agitation acid leaching method, this process decreases the consumption of acid by 21% and manganese dioxide by 29%. The extraction rate of uranium reduces 1.86%. (3 figs., 12 tabs.)

  2. Transition of endometrial stromal sarcoma into high-grade sarcoma.

    Science.gov (United States)

    Amant, Frederic; Woestenborghs, Heidi; Vandenbroucke, Vanessa; Berteloot, Patrick; Neven, Patrick; Moerman, Philippe; Vergote, Ignace

    2006-12-01

    Endometrial stromal sarcoma typically is of low grade and hormone-sensitive. Although these characteristics result in an indolent behavior, little data are available on the evolution over time. We report on two cases where microscopic and immunohistochemic assessment of the tumor on several occasions during 8 and 25 years of follow up enabled us to document a transition of a low-grade into a high-grade malignancy. These were mainly characterized by increased cellular atypia, absence of spiral arterioles and an increased mitotic index and proliferation index (MIB1). Since this transition was related to clinical loss of hormone sensitivity, the therapeutic approach consisting of hormonal treatment in combination with repetitive surgery was switched to chemotherapy only. These long-term follow up data provide insight in endometrial stromal sarcoma tumor biology and highlight the importance of sampling recurrent tumors to estimate biologic behavior in order to tailor subsequent treatment.

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

    Science.gov (United States)

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

    2015-12-01

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

  4. 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

  5. EGF-induced EMT and invasiveness in serous borderline ovarian tumor cells: a possible step in the transition to low-grade serous carcinoma cells?

    Science.gov (United States)

    Cheng, Jung-Chien; Auersperg, Nelly; Leung, Peter C K

    2012-01-01

    In high-grade ovarian cancer cultures, it has been shown that epidermal growth factor (EGF) induces cell invasion by activating an epithelial-mesenchymal transition (EMT). However, the effect of EGF on serous borderline ovarian tumors (SBOT) and low-grade serous carcinomas (LGC) cell invasion remains unknown. Here, we show that EGF receptor (EGFR) was expressed, that EGF treatment increased cell migration and invasion in two cultured SBOT cell lines, SBOT3.1 and SV40 large T antigen-infected SBOT cells (SBOT4-LT), and in two cultured LGC cell lines, MPSC1 and SV40 LT/ST-immortalized LGC cells (ILGC). However, EGF induced down-regulation of E-cadherin and concurrent up-regulation of N-cadherin in SBOT cells but not in LGC cells. In SBOT cells, the expression of the transcriptional repressors of E-cadherin, Snail, Slug and ZEB1 were increased by EGF treatment. Treatment with EGF led to the activation of the downstream ERK1/2 and PI3K/Akt. The MEK1 inhibitor PD98059 diminished the EGF-induced cadherin switch and the up-regulation of Snail, Slug and ZEB1 and the EGF-mediated increase in SBOT cell migration and invasion. The PI3K inhibitor LY294002 had similar effects, but it could not block the EGF-induced up-regulation of N-cadherin and ZEB1. This study demonstrates that EGF induces SBOT cell migration and invasion by activating EMT, which involves the activation of the ERK1/2 and PI3K/Akt pathways and, subsequently, Snail, Slug and ZEB1 expression. Moreover, our results suggest that there are EMT-independent mechanisms that mediate the EGF-induced LGC cell migration and invasion.

  6. EGF-induced EMT and invasiveness in serous borderline ovarian tumor cells: a possible step in the transition to low-grade serous carcinoma cells?

    Directory of Open Access Journals (Sweden)

    Jung-Chien Cheng

    Full Text Available In high-grade ovarian cancer cultures, it has been shown that epidermal growth factor (EGF induces cell invasion by activating an epithelial-mesenchymal transition (EMT. However, the effect of EGF on serous borderline ovarian tumors (SBOT and low-grade serous carcinomas (LGC cell invasion remains unknown. Here, we show that EGF receptor (EGFR was expressed, that EGF treatment increased cell migration and invasion in two cultured SBOT cell lines, SBOT3.1 and SV40 large T antigen-infected SBOT cells (SBOT4-LT, and in two cultured LGC cell lines, MPSC1 and SV40 LT/ST-immortalized LGC cells (ILGC. However, EGF induced down-regulation of E-cadherin and concurrent up-regulation of N-cadherin in SBOT cells but not in LGC cells. In SBOT cells, the expression of the transcriptional repressors of E-cadherin, Snail, Slug and ZEB1 were increased by EGF treatment. Treatment with EGF led to the activation of the downstream ERK1/2 and PI3K/Akt. The MEK1 inhibitor PD98059 diminished the EGF-induced cadherin switch and the up-regulation of Snail, Slug and ZEB1 and the EGF-mediated increase in SBOT cell migration and invasion. The PI3K inhibitor LY294002 had similar effects, but it could not block the EGF-induced up-regulation of N-cadherin and ZEB1. This study demonstrates that EGF induces SBOT cell migration and invasion by activating EMT, which involves the activation of the ERK1/2 and PI3K/Akt pathways and, subsequently, Snail, Slug and ZEB1 expression. Moreover, our results suggest that there are EMT-independent mechanisms that mediate the EGF-induced LGC cell migration and invasion.

  7. 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.

  8. Irradiation and Bevacizumab in High-Grade Glioma Retreatment Settings

    Energy Technology Data Exchange (ETDEWEB)

    Niyazi, Maximilian; Ganswindt, Ute; Schwarz, Silke Birgit [Department of Radiation Oncology, Ludwig-Maximilians-University Munich, Munich (Germany); Kreth, Friedrich-Wilhelm; Tonn, Joerg-Christian [Department of Neurosurgery, Ludwig-Maximilians-University Munich, Munich (Germany); Geisler, Julia; Fougere, Christian la [Department of Nuclear Medicine, Ludwig-Maximilians-University Munich, Munich (Germany); Ertl, Lorenz; Linn, Jennifer [Department of Neuroradiology, Ludwig-Maximilians-University Munich, Munich (Germany); Siefert, Axel [Department of Radiation Oncology, Ludwig-Maximilians-University Munich, Munich (Germany); Belka, Claus, E-mail: claus.belka@med.uni-muenchen.de [Department of Radiation Oncology, Ludwig-Maximilians-University Munich, Munich (Germany)

    2012-01-01

    Purpose: Reirradiation is a treatment option for recurrent high-grade glioma with proven but limited effectiveness. Therapies directed against vascular endothelial growth factor have been shown to exert certain efficacy in combination with chemotherapy and have been safely tested in combination with radiotherapy in a small cohort of patients. To study the feasibility of reirradiation combined with bevacizumab treatment, the toxicity and treatment outcomes of this approach were analyzed retrospectively. Patients and Methods: After previous treatment with standard radiotherapy (with or without temozolomide) patients with recurrent malignant glioma received bevacizumab (10 mg/kg intravenous) on Day 1 and Day 15 during radiotherapy. Maintenance therapy was selected based on individual considerations, and mainly bevacizumab-containing regimens were chosen. Patients received 36 Gy in 18 fractions. Results: The data of the medical charts of the 30 patients were analyzed retrospectively. All were irradiated in a single institution and received either bevacizumab (n = 20), no additional substance (n = 7), or temozolomide (n = 3). Reirradiation was tolerated well, regardless of the added drug. In 1 patient treated with bevacizumab, a wound dehiscence occurred. Overall survival was significantly better in patients receiving bevacizumab (p = 0.03, log-rank test). In a multivariate proportional hazards Cox model, bevacizumab, Karnovsky performance status, and World Health Organization grade at relapse turned out to be the most important predictors for overall survival. Conclusion: Reirradiation with bevacizumab is a feasible and effective treatment for patients with recurrent high-grade gliomas. A randomized trial is warranted to finally answer the question whether bevacizumab adds substantial benefit to a radiotherapeutic retreatment setting.

  9. TGF-beta induces serous borderline ovarian tumor cell invasion by activating EMT but triggers apoptosis in low-grade serous ovarian carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jung-Chien Cheng

    Full Text Available Apoptosis in ovarian surface epithelial (OSE cells is induced by transforming growth factor-beta (TGF-β. However, high-grade serous ovarian carcinomas (HGC are refractory to the inhibitory functions of TGF-β; their invasiveness is up-regulated by TGF-β through epithelial-mesenchymal transition (EMT activation. Serous borderline ovarian tumors (SBOT have been recognized as distinct entities that give rise to invasive low-grade serous carcinomas (LGC, which have a relatively poor prognosis and are unrelated to HGC. While it is not fully understood how TGF-β plays disparate roles in OSE cells and its malignant derivative HGC, its role in SBOT and LGC remains unknown. Here we demonstrate the effects of TGF-β on cultured SBOT3.1 and LGC-derived MPSC1 cells, which express TGF-β type I and type II receptors. TGF-β treatment induced the invasiveness of SBOT3.1 cells but reduced the invasiveness of MPSC1 cells. The analysis of apoptosis, which was assessed by cleaved caspase-3 and trypan blue exclusion assay, revealed TGF-β-induced apoptosis in MPSC1, but not SBOT3.1 cells. The pro-apoptotic effect of TGF-β on LGC cells was confirmed in another immortalized LGC cell line ILGC. TGF-β treatment led to the activation of Smad3 but not Smad2. The specific TβRI inhibitor SB431542 and TβRI siRNA abolished the SBOT3.1 invasion induced by TGF-β, and it prevented TGF-β-induced apoptosis in MPSC1 cells. In SBOT3.1 cells, TGF-β down-regulated E-cadherin and concurrently up-regulated N-cadherin. TGF-β up-regulated the expression of the transcriptional repressors of E-cadherin, Snail, Slug, Twist and ZEB1. In contrast, co-treatment with SB431542 and TβRI depletion by siRNA abolished the effects of TGF-β on the relative cadherin expression levels and that of Snail, Slug, Twist and ZEB1 as well. This study demonstrates dual TGF-β functions: the induction of SBOT cell invasion by EMT activation and apoptosis promotion in LGC cells.

  10. Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kan Casina WS

    2012-12-01

    Full Text Available Abstract Background There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC. MicroRNAs are stable in the circulation and may have utility as biomarkers of malignancy. We investigated whether levels of serum microRNA could discriminate women with high-grade SEOC from age matched healthy volunteers. Methods To identify microRNA of interest, microRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells. Total RNA was extracted from 500 μL aliquots of serum collected from patients with SEOC (n = 28 and age-matched healthy donors (n = 28. Serum microRNA levels were assessed by quantitative RT-PCR following preamplification. Results microRNA (miR-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers. miR-103, miR-92a and miR -638 had relatively invariant expression across all ovarian cell lines, and with small-nucleolar C/D box 48 (RNU48 were assessed in RNA extracted from serum as candidate endogenous normalizers. No correlation between serum levels and age were observed (age range 30-79 years for any of these microRNA or RNU48. Individually, miR-200a, miR-200b and miR-200c normalized to serum volume and miR-103 were significantly higher in serum of the SEOC cohort (P  Conclusions We identified serum microRNAs able to discriminate patients with high grade SEOC from age-matched healthy controls. The addition of these microRNAs to current testing regimes may improve diagnosis for women with SEOC.

  11. 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.

  12. 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.

  13. Concurrent thermochemoradiotherapy for brain high-grade glioma

    Science.gov (United States)

    Ryabova, A. I.; Novikov, V. A.; Choinzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G.; Baranova, A. V.

    2016-08-01

    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.

  14. Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment. Project 2 - Identification of Autologous Antigens in Early Stage Serous Carcinoma

    National Research Council Canada - National Science Library

    Kurman, Robert

    2003-01-01

    Our goal is to develop an early detection screening test for serous carcinoma. Specific aim 1: Obtain cDNAs of autologous tumor antigens recognized by sera of patients with early stage serous carcinoma, but not controls...

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

    Science.gov (United States)

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

    2012-01-01

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

  16. 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.

  17. Cervical cytology in serous and endometrioid endometrial cancer

    NARCIS (Netherlands)

    Roelofsen, T.; Geels, Y.P.; Pijnenborg, J.M.A.; Ham, M.A.P.C. van; Zomer, S.F.; Tilburg, J.M. van; Snijders, M.P.; Siebers, A.G.; Bulten, J.; Massuger, L.F.A.G.

    2013-01-01

    The aim of this study was to determine the frequency of abnormal cervical cytology in preoperative cervical cytology of patients diagnosed with uterine papillary serous carcinoma (UPSC) and endometrioid endometrial carcinoma (EEC). In addition, associations between abnormal cervical cytology and

  18. Mevalonate Pathway Antagonist Suppresses Formation of Serous Tubal Intraepithelial Carcinoma and Ovarian Carcinoma in Mouse Models.

    Science.gov (United States)

    Kobayashi, Yusuke; Kashima, Hiroyasu; Wu, Ren-Chin; Jung, Jin-Gyoung; Kuan, Jen-Chun; Gu, Jinghua; Xuan, Jianhua; Sokoll, Lori; Visvanathan, Kala; Shih, Ie-Ming; Wang, Tian-Li

    2015-10-15

    Statins are among the most frequently prescribed drugs because of their efficacy and low toxicity in treating hypercholesterolemia. Recently, statins have been reported to inhibit the proliferative activity of cancer cells, especially those with TP53 mutations. Because TP53 mutations occur in almost all ovarian high-grade serous carcinoma (HGSC), we determined whether statins suppressed tumor growth in animal models of ovarian cancer. Two ovarian cancer mouse models were used. The first one was a genetically engineered model, mogp-TAg, in which the promoter of oviduct glycoprotein-1 was used to drive the expression of SV40 T-antigen in gynecologic tissues. These mice spontaneously developed serous tubal intraepithelial carcinomas (STICs), which are known as ovarian cancer precursor lesions. The second model was a xenograft tumor model in which human ovarian cancer cells were inoculated into immunocompromised mice. Mice in both models were treated with lovastatin, and effects on tumor growth were monitored. The molecular mechanisms underlying the antitumor effects of lovastatin were also investigated. Lovastatin significantly reduced the development of STICs in mogp-TAg mice and inhibited ovarian tumor growth in the mouse xenograft model. Knockdown of prenylation enzymes in the mevalonate pathway recapitulated the lovastatin-induced antiproliferative phenotype. Transcriptome analysis indicated that lovastatin affected the expression of genes associated with DNA replication, Rho/PLC signaling, glycolysis, and cholesterol biosynthesis pathways, suggesting that statins have pleiotropic effects on tumor cells. The above results suggest that repurposing statin drugs for ovarian cancer may provide a promising strategy to prevent and manage this devastating disease. ©2015 American Association for Cancer Research.

  19. Mevalonate Pathway Antagonist Inhibits Proliferation of Serous Tubal Intraepithelial Carcinoma and Ovarian Carcinoma in Mouse Models

    Science.gov (United States)

    Kobayashi, Yusuke; Kashima, Hiroyasu; Wu, Ren-Chin; Jung, Jin- Gyoung; Kuan, Jen-Chun; Gu, Jinghua; Xuan, Jianhua; Sokoll, Lori; Visvanathan, Kala; Shih, Ie-Ming; Wang, Tian-Li

    2015-01-01

    Purpose Statins are among the most frequently prescribed drugs because of their efficacy and low toxicity in treating hypercholesterolemia. Recently, statins have been reported to inhibit the proliferative activity of cancer cells, especially those with TP53 mutations. Since TP53 mutations occur in almost all of the ovarian high-grade serous carcinoma, we determined if statins suppressed tumor growth in animal models of ovarian cancer. Experimental Design Two ovarian cancer mouse models were employed. The first one was a genetically engineered model, mogp-TAg, in which the promoter of oviduct glycoprotein-1 was used to drive the expression of SV40 T-antigen in gynecologic tissues. These mice spontaneously develop serous tubal intraepithelial carcinomas (STICs), which are known as ovarian cancer precursor lesions. The second model was a xenograft tumor model in which human ovarian cancer cells were inoculated into immunocompromised mice. Mice in both models were treated with lovastatin, and effects on tumor growth were monitored. The molecular mechanisms underlying the anti-tumor effects of lovastatin were also investigated. Results Lovastatin significantly reduced the development of STICs in mogp-TAg mice and inhibited ovarian tumor growth in the mouse xenograft model. Knockdown of prenylation enzymes in the mevalonate pathway recapitulated the lovastatin-induced anti-proliferative phenotype. Transcriptome analysis indicated that lovastatin affected the expression of genes associated with DNA replication, Rho/PLC signaling, glycolysis, and cholesterol biosynthesis pathways, suggesting that statins have pleiotropic effects on tumor cells. Conclusion The above results suggest that repurposing statin drugs for ovarian cancer may provide a promising strategy to prevent and manage this devastating disease. PMID:26109099

  20. Prognostic significance of normal-sized ovary in advanced serous epithelial ovarian cancer.

    Science.gov (United States)

    Paik, E Sun; Kim, Ji Hye; Kim, Tae Joong; Lee, Jeong Won; Kim, Byoung Gie; Bae, Duk Soo; Choi, Chel Hun

    2018-01-01

    We compared survival outcomes of advanced serous type epithelial ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian tumors by propensity score matching analysis. The medical records of EOC patients treated at Samsung Medical Center between 2002 and 2015 were reviewed retrospectively. We investigated EOC patients with high grade serous type histology and International Federation of Gynecology and Obstetrics (FIGO) stage IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant chemotherapy to identify patients with normal-sized ovaries. Propensity score matching was performed to compare patients with normal-sized ovaries to patients with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial cancer antigen (CA)-125 level, and residual disease status after PDS. Of the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged-ovarian tumor were younger (54.0±10.3 vs. 58.4±9.2 years, p=0.005) than those with normal-sized ovary, and there was a statistically significant difference in residual disease status between the 2 groups. In total cohort with a median follow-up period of 43 months (range, 3-164 months), inferior overall survival (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months; p=0.003). After propensity score matching, the group with normal-sized ovary showed inferior OS compared to the group with enlarged-ovarian tumor (median OS, 72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized ovary remained a significant factor. Normal-sized ovary was associated with poor OS compared with the common presentation of enlarged ovaries in EOC, independent of CA-125 level or residual disease. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

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

    Science.gov (United States)

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

    2017-08-01

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

  2. Serous degeneration of bone marrow mimics spinal tumor.

    Science.gov (United States)

    Sung, Chih-Wei; Hsieh, Kevin Li-Chun; Lin, Yun-Ho; Lin, Chun-Yi; Lee, Chian-Her; Tsuang, Yang-Hwei; Kuo, Yi-Jie

    2017-05-01

    To present a rare case of serous degeneration of bone marrow which resembles primary spinal tumor or bony metastasis to spine. Serous degeneration of bone marrow or gelatinous marrow transformation is a rare disease characterized by focal marrow hypoplasia, fat atrophy, and accumulation of extracellular mucopolysaccharides abundant in hyaluronic acid. Few literature was reviewed and few clinical case was presented. Two cases of serous marrow transformation were reported. In the first case, a 29-year-old man suffered from severe left buttock pain. Bone metastasis was impressed in radiology examinations. Percutaneous endoscopic lumbar discectomy was performed along with bone biopsy. In the second case, a 49-year-old man presented lower back pain with radiation to bilateral lower legs. Magnetic resonance imaging revealed a water-like signal lesion in sacrum. Serous marrow transformation was confirmed pathologically in both cases. To the best of our knowledge, a case of serous degeneration of bone marrow resembling malignancy has not been reported in the literature. In this report, two cases demonstrate serous transformation of bone marrow mimics spinal tumor.

  3. Preoperative CA-125 Values as a Predictive Factor for the Postoperative Outcome in Primary Serous Ovarian Cancer.

    Science.gov (United States)

    Muallem, Mustafa Zelal; Parashkevova, Asya; Almuheimid, Jumana; Richter, Rolf; Diab, Yasser; Braicu, Elena Ioana; Sehouli, Jalid

    2017-06-01

    The purpose of the study was to examine the preoperative CA-125 values as a predictive factor for postoperative outcome in primary serous ovarian cancer (POC) for complete tumor resection (CTR) and evaluate the preoperative CA-125 levels with other vital clinical dynamics such as ascites, lymph node involvement, diffuse peritoneal carcinomatosis, grading and staging. A cohort of 277 POC-patients aged 18-75 years, who had undergone primary cytoreductive surgery at the Department of Gynecology & Oncological Surgery, Charité, Campus Virchow Klinikum (CVK) between 2000 und 2009 was analyzed in correlation with the preoperative CA-125 values. The median preoperative CA-125 value in high-grade serous POC patients was 636 U/ml (204- 2312 U/ml) compared to 284 U/ml (148.5-1,378 U/ml) in low-grade serous POC patients (p=0.016). For the survival analyses both the cut-off values 252 and 475 U/ml, with highest sum from sensitivity (79.1% and 65.9%, respectively) and specificity (41.9% and 55.1%, respectively), were used to compare the relationship between preoperative CA-125 levels and (CTR), progression-free (PFS) and overall survival (OS). There was no significant difference between PFS and OS in three different groups of patients (preoperative CA-125 levels CA 125 levels between 252-475 U/ml and >475 U/ml). Preoperative CA-125 is a poor, but statistically significant predictive factor for CTR after PCS. Preoperative CA-125 can predict neither the progression-free nor overall survival for POC patients. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Serous Tubal Intraepithelial Carcinoma or Not? Metastases to Fallopian Tube Mucosa Can Masquerade as In Situ Lesions.

    Science.gov (United States)

    Singh, Reena; Cho, Kathleen R

    2017-10-01

    - Nonuterine high-grade serous carcinomas (HGSCs) are believed to arise most often from precursors in the fallopian tube referred to as serous tubal intraepithelial carcinomas (STICs). A designation of tubal origin has been suggested for all cases of nonuterine HGSC if a STIC is identified. - To highlight that many different types of nongynecologic and gynecologic carcinomas, including HGSC, can metastasize to the tubal mucosa and mimic de novo STIC. - A mini-review of several recently published studies that collectively examine STIC-like lesions of the fallopian tube. - The fallopian tube mucosa can be a site of metastasis from carcinomas arising elsewhere, and pathologists should exercise caution in diagnosing STIC without first considering the possibility of metastasis. Routinely used immunohistochemical stains can often be used to determine if a STIC-like lesion is tubal or nongynecologic in origin. In the context of uterine and nonuterine HGSC, STIC may represent a metastasis rather than the site of origin, particularly when widespread disease is present.

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

    NARCIS (Netherlands)

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

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

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

    African Journals Online (AJOL)

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

  7. Spontaneous Large Serous Retinal Pigment Epithelial Tear

    Directory of Open Access Journals (Sweden)

    Voraporn Chaikitmongkol

    2012-10-01

    Full Text Available Purpose: To report cases of spontaneous retinal pigment epithelial (RPE tear complicating serous pigment epithelial detachment (PED. Methods: The records of 3 Asian patients with spontaneous giant RPE tear were reviewed retrospectively by including clinical presentation, angiography, optical coherence tomography, fundus autofluorescence imaging, and visual outcome. Results: Three patients (4 eyes were included in this study, with a mean age of 48.3 (42–56 years, and a mean follow-up period of 7.75 (4–18 months. Fundus examination in all patients showed giant RPE tear associated with bullous PED. Two cases had a history of prior corticosteroid use, and 1 had no history of medication use. All 3 patients developed spontaneous resolution of subretinal fluid with no treatment. However, in patients who used corticosteroids, initial progression of the tear and subretinal fluid were observed despite ceasing medication. On subsequent follow-up, an incomplete RPE regeneration was demonstrated by fundus autofluorescence imaging, and choroidal neovascularization developed in 1 patient. Conclusion: Large PED with RPE tear is a rare manifestation. When the fovea is spared, visual prognosis is favorable. No specific treatment is required, but careful choroidal neovascularization monitoring should be performed.

  8. Foveal function and thickness after verteporfin photodynamic therapy in central serous chorioretinopathy with hyperautofluorescent subretinal deposits

    DEFF Research Database (Denmark)

    Pryds, Anders; Larsen, Michael

    2013-01-01

    : To assess the prognostic effect of subretinal deposits in eyes with central serous chorioretinopathy (CSC).......: To assess the prognostic effect of subretinal deposits in eyes with central serous chorioretinopathy (CSC)....

  9. Characterization of MicroRNA-200 pathway in ovarian cancer and serous intraepithelial carcinoma of fallopian tube.

    Science.gov (United States)

    Yang, Junzheng; Zhou, Yilan; Ng, Shu-Kay; Huang, Kuan-Chun; Ni, Xiaoyan; Choi, Pui-Wah; Hasselblatt, Kathleen; Muto, Michael G; Welch, William R; Berkowitz, Ross S; Ng, Shu-Wing

    2017-06-17

    Ovarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors. RNA prepared from ovarian and fallopian tube epithelial and stromal fibroblasts was subjected to quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to determine the expression of miR-200 families, target and effector genes and analyzed for clinical association. The effects of exogenous miR-200 on marker expression in normal cells were determined by qRT-PCR and fluorescence imaging after transfection of miR-200 precursors. Ovarian epithelial tumor cells showed concurrent up-regulation of miR-200, down-regulation of the four target genes (ZEB1, ZEB2, TGFβ1 and TGFβ2), and up-regulation of effector genes that were negatively regulated by the target genes. STIC tumor cells showed a similar trend of expression patterns, although the effects did not reach significance because of small sample sizes. Transfection of synthetic miR-200 precursors into normal ovarian surface epithelial (OSE) and fallopian tube epithelial (FTE) cells confirmed reduced expression of the target genes and elevated levels of the effector genes CDH1, CRB3 and EpCAM in both normal OSE and FTE cells. However, only FTE cells had a specific induction of CA125 after miR-200 precursor transfection. The activation of the miR-200 pathway may be an early event that renders the OSE and FTE cells more susceptible to oncogenic mutations and histologic differentiation. As high-grade

  10. Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors.

    Science.gov (United States)

    Ortiz, B H; Ailawadi, M; Colitti, C; Muto, M G; Deavers, M; Silva, E G; Berkowitz, R S; Mok, S C; Gershenson, D M

    2001-10-01

    The role of serous borderline ovarian tumors (BOTs) in the pathogenesis of serous ovarian carcinomas is unclear. Some authors have compared mutations in serous BOTs to those in serous ovarian carcinomas, but the data on two common oncogenes, p53 and K-ras, remain inconclusive. To further clarify the relationship between the two tumors, we performed mutational analysis on tumors from a set of eight patients who first presented with advanced-stage serous BOTs and later developed grade 1 serous carcinomas. Epithelium from eight advanced-stage serous BOTs and subsequent grade 1 papillary serous carcinomas was microdissected and retrieved using a PixCell laser-capture microscope. Stroma was dissected as an internal control. The DNA was extracted with proteinase K and analyzed by single-strand conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered motility were analyzed by direct cycle sequencing. Seven of eight patients demonstrated different mutations in the secondary tumor compared with the primary tumor. For three patients, p53 mutations were identified in the BOTs that were absent from the carcinomas, suggesting a nonclonal origin for the carcinomas. These findings are consistent with the hypothesis that advanced-stage serous BOTs represent a distinct pathological entity compared with grade 1 serous epithelial ovarian carcinoma.

  11. Serous retinal detachment after trabeculectomy in angle recession glaucoma

    Directory of Open Access Journals (Sweden)

    Roy, Avik Kumar

    2015-12-01

    Full Text Available An 18-year-old male with 360 degree angle recession after blunt trauma in his right eye developed uncontrolled intraocular pressure (IOP despite four antiglaucoma medications (AGM with advancing disc damage. He underwent trabeculectomy with intraoperative mitomycin-c (MMC application. There was an intraoperative vitreous prolapse which was managed accordingly. On post-surgery day 1, he had shallow choroidal detachment superiorly with non-recordable IOP. This was deteriorated 1 week postoperatively as choroidal detachment proceeded to serous retinal detachment. He was started with systemic steroid in addition to topical route. The serous effusions subsided within 2 weeks time. At the last follow up at 3 months, he was enjoying good visual acuity, deep anterior chamber, diffuse bleb, an IOP in low teens off any AGM and attached retina. This case highlights the rare occurrence of serous retinal detachment after surgical management of angle recession glaucoma.

  12. Argon laser treatment of central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Ting- Bing Fang

    2013-04-01

    Full Text Available AIM: To observe the efficacy of the argon laser photocoagulation treatment of central serous chorioretinopathy(CSC. METHODS: The treatment groups: 18 patients(18 eyes, argon laser photocoagulation and oral jolethin, vitamin B1, inosine and venoruton tablets. Control group: 18 patients(18 eyes, oral lecithin complex iodine, vitamin B1, inosine, venoruton tablets. Foveal thickness and neuroepithelial layer detachment range were measured by optical coherence tomography(OCTbefore treatment, after 1 month and 3 months post-operation to compare the decline in value of foveal thickness and neuroepithelial layer detachment range of the two groups. RESULTS: After 1 month of treatment, the decline in value of the center foveal thickness: the value of treatment group was 256±72μm; the value of the control group was 82±57μm, and the difference of the two groups, P <0.05; the decline in value of neuroepithelial layer detachment range: the value of the treatment group was 3 548±168μm, the value of the control group was 1 520±143μm, And the difference of the two groups, P<0.05. After three months of treatment, the decline in value of the center foveal thickness: the value of treatment group was 383±75μm, the value of the control group was 312±67 μm, and the difference of the two groups, P<0.05; decline in value of neuroepithelial layer detachment range: the value of the treatment group was 4 908±172μm, the value of the control group was 4 211±153μm, and the difference of the two groups, P <0.05. The differences were statistically significant between the treatment and the control groups(two independent samples t-test. CONCLUSION:Argon laser photocoagulation treatment of CSC is an effective treatment method and can significantly shorten the course.

  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. P53, MAPK, topoisomerase II alpha and Ki67 immunohistochemical expression and KRAS/BRAF mutation in ovarian serous carcinomas.

    Science.gov (United States)

    Sundov, Dinka; Caric, Ana; Mrklic, Ivana; Gugic, Dijana; Capkun, Vesna; Hofman, Irena Drmic; Mise, Branka Petric; Tomic, Snjezana

    2013-02-06

    We investigated the immunohistochemical expression of p53, MAPK, topoisomerase II alpha (topoII alpha) and Ki67 in ovarian serous carcinomas (OSCs) along with mutational analysis for KRAS and BRAF. Eighty one cases of OSCs were reviewed and examined immunohistochemically using antibodies against p53, MAPK, topoII alpha and Ki67. Staining was evaluated as a percentage of immunopositive cells with cut-off levels at 10% for p53 and topoII alpha, and 5% for MAPK. The Ki67 immunoexpression was assessed by means of Olympus Image Analysis System as a percentage of immunopositive cells in 1000 tumor cells. KRAS and BRAF mutational analysis was performed on 73 available microdissected samples. Of 81 cases of OSCs 13.6% were of low-grade and 86.4% were of high-grade morphology. In the high-grade group there was a significantly higher immunoexpression of p53 (P p53 immunopositivity. Although this study is limited by its humble number of low-grade samples, our data fit the proposed dualistic pathway of ovarian carcinogenesis. Mutational analysis for KRAS and BRAF discloses some possible interactions between different tumorigenic pathways of low- and high-grade carcinomas. Immunohistochemical staining for MAPK was not sufficiently sensitive, nor specific, to precisely predict the KRAS mutation. However, it appears to be quite reliable in ruling out a KRAS mutation if the staining is negative. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9283563368804632.

  15. 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

    . 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......BACKGROUND: Distinguishing between low- and high-grade prostate cancers (PCa) is important, but biopsy may underestimate the actual grade of cancer. We have previously shown that urine/plasma-based prostate-specific biomarkers can predict high grade PCa. Our objective was to determine the accuracy......, 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...

  16. International Differences in Treatment and Clinical Outcomes for High Grade Glioma

    OpenAIRE

    Chien, Li-Nien; Ostrom, Quinn T.; Gittleman, Haley; Lin, Jia-Wei; Sloan, Andrew E.; Barnett, Gene H.; Elder, J. Bradley; McPherson, Christopher; Warnick, Ronald; Chiang, Yung-Hsiao; Lin, Chieh-Min; Rogers, Lisa R.; Chiou, Hung-Yi; Barnholtz-Sloan, Jill S.

    2015-01-01

    Background High grade gliomas are the most common type of malignant brain tumor, and despite their rarity, cause significant morbidity and mortality. This study aimed to compare the treatment patterns of high grade glioma to examine survival patterns in patients who receive specific treatments between cohorts in Ohio and Taiwan. Method Patients aged 18 years and older at age of diagnosis with World Health Organization (WHO) grade III or IV astrocytoma from 2007-2012 were selected from the Ohi...

  17. 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...

  18. Central serous chorioretinopathy: a pathogenetic model

    Directory of Open Access Journals (Sweden)

    et al

    2011-02-01

    Full Text Available Antonio Caccavale1, Filippo Romanazzi1, Manuela Imparato1, Angelo Negri2, Anna Morano3, Fabio Ferentini21Department of Ophthalmology, Neuropthalmology and Ocular Immunology Service, 2Department of Ophthalmology, Hospital “C. Cantù”, Abbiategrasso, Milan, Italy; 3University Eye Clinic, Foundation IRCCS San Matteo Hospital, Pavia, ItalyAbstract: Despite numerous studies describing predominantly its demography and clinical course, many aspects of central serous chorioretinopathy (CSCR remain unclear. Perhaps the major impediment to finding an effective therapy is the difficulty of performing studies with large enough cohorts, which has meant that clinicians have focused more on therapy than on a deeper understanding of the pathogenesis of the disease. Hypotheses on the pathogenesis of CSCR have ranged from a basic alteration in the choroid to an involvement of the retinal pigment epithelium (RPE. Starting from evidence that affected subjects often present a personality prone to stress with altered pituitary–hypothalamic axis response (HPA and that they have higher levels of serum and urinary cortisol and catecholamines than healthy subjects, we hypothesize a cascade of events that may lead to CSCR through hypercoagulability and augmented platelet aggregation. In particular we investigated the role of tissue plasminogen activator, increasing plasminogen activator inhibitor 1 (PAI-1, and plasmin-α2- plasmin inhibitor complexes. We reviewed the different therapeutic approaches, including adrenergic antagonists, carbonic anhydrase inhibitors, mifepristone, ketoconazole, laser photocoagulation, intravitreal injection of bevacizumab, and photodynamic therapy with verteporfin (PDT and our model of pathogenesis seems to be in agreement with the clinical effects obtained from these treatments. In accord with our thesis, we began to treat a group of patients affected by CSCR with low-dose aspirin (75–100 mg, because of its effectiveness in other

  19. A nationwide study of ovarian serous borderline tumors in Denmark 1978-2002

    DEFF Research Database (Denmark)

    Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette

    2017-01-01

    OBJECTIVE: Absolute risk and risk factors for recurrence and ovarian serous carcinoma following ovarian serous borderline tumors (SBTs) is not well-established. METHODS: We included all women with SBTs in Denmark, 1978-2002. Diagnoses were confirmed by centralized pathology review and classified...... as atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Implants were classified as noninvasive or invasive. Medical records were collected and reviewed, and follow-up was obtained. Subsequent diagnoses were also confirmed by centralized pathology review. We examined...... absolute risk and risk factors for recurrent APST and serous carcinoma using Cox regression. RESULTS: The absolute serous carcinoma risk after, respectively, 5 and 20years was 5.0% and 13.9% for noninvasive LGSC, and 0.9% and 3.7% for APST. Serous carcinoma risk was significantly higher following...

  20. Bilateral ovarian serous cystadenocarcinoma in a teenager: a case ...

    African Journals Online (AJOL)

    Epithelial ovarian cancers are uncommon among young girls and teenagers compared to germ cell tumors. We report a case of bilateral ovarian serous cystadenocarcinoma in a teenage girl with the attendant challenges of diagnosis, management and follow up. HT, 19 year old had presented at a secondary care level with ...

  1. Molecular pathogenesis of serous Fallopian tube and ovarian carcinoma

    NARCIS (Netherlands)

    Nowee, M.E.

    2009-01-01

    Serous type Fallopian tube carcinoma (FTC) and ovarian carcinoma (OVCA) are gynaecological malignancies with a poor prognosis. Although most of the encountered tumours are sporadic, a positive family history is an important risk factor. Both tumour types have been linked to mutations in the BRCA1

  2. CHOROIDAL NEOVASCULARIZATION IN CAUCASIAN PATIENTS WITH LONGSTANDING CENTRAL SEROUS CHORIORETINOPATHY

    NARCIS (Netherlands)

    Peiretti, Enrico; Ferrara, Daniela C.; Caminiti, Giulia; Mura, Marco; Hughes, John

    2015-01-01

    To report the frequency of choroidal neovascularization (CNV) in Caucasian patients with chronic central serous chorioretinopathy (CSC). Retrospective consecutive series of 272 eyes (136 patients) who were diagnosed as having chronic CSC based on clinical and multimodal fundus imaging findings and

  3. Cervicovaginal Smear Findings of Endometrial Serous Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Figen Barut

    2008-08-01

    Although cervicovaginal smear generally is not a sensitive screening test for endometrial carcinomas, it played an important role in determining serous carcinoma. This may be related with advanced stage and/or aggressive features of the neoplastic process.

  4. Rare Papillary Serous Carcinoma In A Nigerian: Case Report And ...

    African Journals Online (AJOL)

    Objective: To present a rare case of papillary serous carcinoma of the cervix and review the literature. Materials and Methods: An illustrative case seen by the authors in a fifty-two year old Nigerian woman with stage III carcinoma of the cervix. Results: The clinical and pathological features of this rare tumour are discussed ...

  5. Bilateral ovarian serous cystadenocarcinoma in a teenager: A case ...

    African Journals Online (AJOL)

    abp

    2017-09-12

    Sep 12, 2017 ... Key words: Adolescent, ovarian epithelial cancer, ovariectomy, serous cystadenocarcinoma. Received: ... Epithelial ovarian cancers are uncommon among young girls and teenagers compared to germ cell tumors. We report a case of .... molecular biologic features, and diagnostic problems. Adv Anat.

  6. Ki-67 labeling index as an adjunct in the diagnosis of serous tubal intraepithelial carcinoma.

    Science.gov (United States)

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

    2012-09-01

    There is mounting evidence that serous tubal intraepithelial carcinoma (STIC) may be the immediate precursor of ovarian high-grade serous carcinoma (HGSC) but the criteria for its diagnosis are not well established as highlighted in a recent study showing that interobserver reproducibility, even among expert gynecologic pathologists, was moderate at best. Given the clinical significance of a diagnosis of STIC in a patient who has no other evidence of ovarian carcinoma, this is a serious issue that we felt needed to be addressed. Although it is not clear, at this time, whether such a patient should or should not be treated, the importance of an accurate and reproducible diagnosis of precursors of ovarian carcinoma cannot be underestimated. We hypothesized that an elevated Ki-67 labeling index may aid the diagnosis of STIC. Accordingly, we compared the Ki-67 index of STIC and HGSC to normal fallopian tube epithelium (FTE) in the same patients and to a control group of patients without carcinoma, matched for age. A total of 41 STICs were analyzed, of which 35 were associated with a concurrent HGSC. In FTE, immunoreactivity for Ki-67 was restricted to a few scattered cells (mean 2.0%). No statistically significant difference was found between patients with and without HGSC (P>0.05). However, both STICs and HGSC had significantly higher Ki-67 indices than normal FTE (PSTICs uniformly had an elevated Ki-67 labeling index that ranged from 11.7% to 71.1% (average 35.6%). There was no correlation of the Ki-67 labeling index in the STICs and the associated HGSC, as the labeling index was lower in STIC in 18/35 (51.4%) whereas it was higher in 17/35 (48.6%) (P=0.86). In conclusion, the findings in this study indicate that compared with FTE, STICs have a significantly higher Ki-67 index similar to HGSC. Accordingly, the Ki-67 index can aid the diagnosis of intraepithelial tubal proliferations suspicious for STIC. Therefore, we propose that a Ki-67 index of 10% is a useful

  7. 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

  8. Detection of High Grade Prostate Cancer among PLCO Participants Using a Prespecified 4-Kallikrein Marker Panel.

    Science.gov (United States)

    Kim, Eric H; Andriole, Gerald L; Crawford, E David; Sjoberg, Daniel D; Assel, Melissa; Vickers, Andrew J; Lilja, Hans

    2017-04-01

    We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial). Levels of free, intact, total prostate specific antigen, human kallikrein-2 and microseminoprotein-β were measured while blinded to outcomes in cryopreserved serum from men in the intervention arm of PLCO. Marker levels of 946 men, of whom 100 were African American, were incorporated into a prespecified statistical model to predict high grade prostate cancer on biopsy. The detection of high grade prostate cancer in 94 men (10%) was enhanced by the 4-kallikrein panel with an AUC of 0.79 compared to 0.73 for PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), representing a 0.060 increase (95% CI 0.032-0.088, p panel. In African American men, the 4-kallikrein panel model also enhanced high grade prostate cancer detection over that of prostate specific antigen (AUC 0.80 vs 0.67). As an illustration of clinical implications, using 1 cutoff point for biopsy (6% risk of high grade prostate cancer) with the 4-kallikrein panel model would have eliminated unnecessary biopsies in 420 per 1,000 men (42%) while detecting high grade prostate cancer in 83 of 93 (88%). In a multiethnic United States population, the 4-kallikrein panel demonstrated improved risk discrimination for high grade prostate cancer over conventional clinical variables (age, prostate specific antigen and digital rectal examination) as well as PCPTRC. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. [Expression and significance of microRNAs in the p53 pathway in ovarian cancer cells and serous ovarian cancer tissues].

    Science.gov (United States)

    Zhang, Qi; He, Xiang-jun; Ma, Li-ping; Li, Na; Yang, Jing; Cheng, Ye-xia; Cui, Heng

    2011-12-01

    The aim of this study was to investigate whether miR-449a, miR-449b and miR-192 family microRNAs play the same roles in p53 pathway as miR-34 family in ovarian cancer. Wild-type p53 ovarian carcinoma cell line A2780 cells were treated with genotoxic agent adriamycin. The reactivation of p53 was detected by Western blot. The expression of miR-449a/b, miR-34a, miR-34b, miR-34c, miR-192 and miR-194 were detected by real-time quantitative PCR. Mutant p53 ovarian cancer cell line SKOV3.ipl cells were transfected with pre-microRNAs and the cell-cycle changes were detected. The expression level of miR-449a/b, miR-34a, miR-34b, miR-34c, miR-192 and miR-194 in serous ovarian carcinomas of varying grade and stage were compared with real-time PCR. The expressions of miR-449a/b, miR-34b and miR-34c were 19-fold to 21-fold elevated after p53 activation by genotoxic agent. Ectopic expression of miR-449b, as well as miR-34c, resulted in cell-cycle arrest in SKOV3.ipl cells. The expression of miR-449a/b was parallel with that of miR-34b, miR-34c, and were significantly lower in late stage and high-grade serous carcinomas than in the normal fallopian tube, early stage and low-grade serous carcinomas. The expression of miR-192, miR-194 and miR-34a did not show evident features in serous ovarian carcinomas and were much lower than miR-449a/b, miR-34b and miR-34c in normal fallopian tube. As tumor-suppressor microRNAs, miR-449a/b, miR-34b and miR-34c cooperate and play important roles in p53 pathway. Their inactivation may contribute to the carcinogenesis and progression of serous ovarian carcinomas.

  10. [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.

  11. High-grade internal rectal prolapse: Does it explain so-called "idiopathic" faecal incontinence?

    Science.gov (United States)

    Bloemendaal, A L A; Buchs, N C; Prapasrivorakul, S; Cunningham, C; Jones, O M; Hompes, R; Lindsey, I

    2016-01-01

    Faecal incontinence is a multifactorial disorder, with multiple treatment options. The role of internal rectal prolapse in the aetiology of faecal incontinence is debated. Recent data has shown the importance of high-grade internal rectal prolapse in case of faecal incontinence. We aimed to determine the incidence and relevance of internal rectal prolapse in patients with faecal incontinence without an anal sphincter defect. Patient data, collected in a prospective pelvic floor database, were assessed. All females with moderate to severe pure faecal incontinence, without obstructed defecation and sphincter muscle defects, were included. Data on defecation proctography, anorectal physiology and incontinence scores were analysed. Of 2082 females in the database, 174 fitted the inclusion criteria. High-grade internal rectal prolapse was found in 49% of patients and was associated predominantly with urge faecal incontinence. Passive faecal incontinence was more common in low-grade compared to high-grade internal rectal prolapse patients. Maximum resting pressure was lower in older patients and in patients with high-grade compared to low-grade internal rectal prolapse. Internal rectal prolapse grade was not significantly correlated with faecal incontinence severity score. High-grade internal rectal prolapse is common in female patients suffering particularly urge faecal incontinence, without anal sphincter lesions. Defecation proctography should be routine in the work up of faecal incontinence. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  12. Incidence of serous tubal intraepithelial carcinoma (STIC) by algorithm classification in serous ovarian tumor associated with PAX8 expression in tubal epithelia: a study of single institution in Japan.

    Science.gov (United States)

    Munakata, Satoru; Yamamoto, Toshiya

    2015-01-01

    Serous ovarian carcinoma is now hypothesized to originate from fallopian tube epithelium (FTE). We investigated the FTE abnormalities in the patients with epithelial ovarian tumors. Our study included 55 cases of serous tumors (24 carcinomas, 8 borderline tumors, and 23 adenomas), 14 mucinous carcinomas, 22 endometrioid carcinomas, 5 clear cell carcinomas, and 2 malignant Brenner tumors. FTE was diagnosed by the diagnostic algorithm, which combines the data of morphology, and p53, Ki-67 immunostaining, as serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive. Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive were observed in 5, 3, 0, and 16 cases in serous carcinoma; 0, 3, 0, and 5 cases in serous borderline tumor; 0, 1, 1, and 21 cases in serous adenoma; 0, 0, 1, and 13 cases in mucinous carcinoma; 0, 0, 3, and 19 cases in endometrioid carcinoma; 0, 0, 0, and 5 cases in clear cell carcinoma; and 0, 1, 0, and 1 case in malignant Brenner tumor. Among tumors of serous histology and between carcinomas, FTE abnormalities differed significantly (Pcarcinomas were only found in serous carcinoma. The incidence of secretory cell proliferation (SCP) was examined by PAX8 expression. The rate of SCP was extremely high in serous carcinoma (96%). Among tumors of serous histology and between carcinomas, an incidence of SCP differed significantly (Povarian carcinogenesis. The SCP has a meaningful association with serous ovarian cancer.

  13. Stathmin 1 and p16(INK4A) are sensitive adjunct biomarkers for serous tubal intraepithelial carcinoma.

    Science.gov (United States)

    Novak, Marián; Lester, Jenny; Karst, Alison M; Parkash, Vinita; Hirsch, Michelle S; Crum, Christopher P; Karlan, Beth Y; Drapkin, Ronny

    2015-10-01

    To credential Stathmin 1 (STMN1) and p16(INK4A) (p16) as adjunct markers for the diagnosis of serous tubal intraepithelial carcinoma (STIC), and to compare STMN1 and p16 expression in p53-positive and p53-negative STIC and invasive high-grade serous carcinoma (HGSC). Immunohistochemistry (IHC) was used to examine STMN1 and p16 expression in fallopian tube specimens (n=31) containing p53-positive and p53-negative STICs, invasive HGSCs, and morphologically normal FTE (fallopian tube epithelium). STMN1 and p16 expression was scored semiquantitatively by four individuals. The semiquantitative scores were dichotomized, and reported as positive or negative. Pooled siRNA was used to knockdown p53 in a panel of cell lines derived from immortalized FTE and HGSC. STMN1 and p16 were expressed in the majority of p53-positive and p53-negative STICs and concomitant invasive HGSCs, but only scattered positive cells were present in morphologically normal FTE. Both proteins were expressed consistently across multiple STICs from the same patient and in concomitant invasive HGSC. Knockdown of p53 in immortalized FTE cells and in four HGSC-derived cell lines expressing different missense p53 mutations did not affect STMN1 protein levels. This study demonstrates that STMN1 and p16 are sensitive and specific adjunct biomarkers that, when used with p53 and Ki-67, improve the diagnostic accuracy of STIC. The addition of STMN1 and p16 helps to compensate for practical limitations of p53 and Ki-67 that complicate the diagnosis in up to one third of STICs. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Stathmin 1 and p16INK4A are sensitive adjunct biomarkers for serous tubal intraepithelial carcinoma

    Science.gov (United States)

    Novak, Marián; Lester, Jenny; Karst, Alison M.; Parkash, Vinita; Hirsch, Michelle S.; Crum, Christopher P.; Karlan, Beth Y.

    2015-01-01

    Objective To credential Stathmin 1 (STMN1) and p16INK4A (p16) as adjunct markers for the diagnosis of serous tubal intraepithelial carcinoma (STIC), and to compare STMN1 and p16 expression in p53-positive and p53-negative STIC and invasive high-grade serous carcinoma (HGSC). Methods Immunohistochemistry (IHC) was used to examine STMN1 and p16 expression in fallopian tube specimens (n=31) containing p53-positive and p53-negative STICs, invasive HGSCs, and morphologically normal FTE (fallopian tube epithelium). STMN1 and p16 expression was scored semiquantitatively by four individuals. The semiquantitative scores were dichotomized, and reported as positive or negative. Pooled siRNA was used to knockdown p53 in a panel of cell lines derived from immortalized FTE and HGSC. Results STMN1 and p16 were expressed in the majority of p53-positive and p53-negative STICs and concomitant invasive HGSCs, but only scattered positive cells were positive in morphologically normal FTE. Both proteins were expressed consistently across multiple STICs from the same patient and in concomitant invasive HGSC. Knockdown of p53 in immortalized FTE cells and in four HGSC-derived cell lines expressing different missense p53 mutations did not affect STMN1 protein levels. Conclusions This study demonstrates that STMN1 and p16 are sensitive and specific adjunct biomarkers that, when used with p53 and Ki-67, improve the diagnostic accuracy of STIC. The addition of STMN1 and p16 helps to compensate for practical limitations of p53 and Ki-67 that complicate the diagnosis in up to one third of STICs. PMID:26206555

  15. 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.

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

    Science.gov (United States)

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

    2012-11-01

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

  17. A nationwide study of ovarian serous borderline tumors in Denmark 1978-2002. Risk of recurrence, and development of ovarian serous carcinoma.

    Science.gov (United States)

    Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette; Frederiksen, Kirsten; Kurman, Robert J; Kjaer, Susanne K

    2017-01-01

    Absolute risk and risk factors for recurrence and ovarian serous carcinoma following ovarian serous borderline tumors (SBTs) is not well-established. We included all women with SBTs in Denmark, 1978-2002. Diagnoses were confirmed by centralized pathology review and classified as atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Implants were classified as noninvasive or invasive. Medical records were collected and reviewed, and follow-up was obtained. Subsequent diagnoses were also confirmed by centralized pathology review. We examined absolute risk and risk factors for recurrent APST and serous carcinoma using Cox regression. The absolute serous carcinoma risk after, respectively, 5 and 20years was 5.0% and 13.9% for noninvasive LGSC, and 0.9% and 3.7% for APST. Serous carcinoma risk was significantly higher following noninvasive LGSC compared with APST among stage I patients/patients without implants (HR=5.3; 95% CI: 1.7-16.3), whereas no significant association with tumor type was found in advanced stage patients/patients with implants. Advanced stage - notably invasive implants - bilaterality, surface involvement, and residual disease increased serous carcinoma risk. However, women with stage I APST also had a higher risk than the general population. This largest population-based cohort of verified SBTs revealed that women with noninvasive LGSC are significantly more likely to develop serous carcinoma than women with APST, which could not entirely be explained by invasive implants. Although invasive implants was a strong risk factor for serous carcinoma, even women with stage I APST were at increased risk compared with the general population. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Canine ovarian serous papillary adenocarcinoma with neoplastic hypercalcemia.

    Science.gov (United States)

    Hori, Yasutomo; Uechi, Masami; Kanakubo, Kayo; Sano, Tadashi; Oyamada, Toshifumi

    2006-09-01

    A female golden retriever was referred to assess a history of a palpable abdominal mass. A serum chemistry analysis revealed elevated concentrations of blood urea nitrogen, creatinine, calcium, and parathyroid hormone-related protein (PTH-rP). Exploratory laparotomy revealed an ovoid mass within the right ovary. This mass was removed surgically by performing an ovariohysterectomy. The right ovarian mass was diagnosed as a serous papillary adenocarcinoma. Following surgery, the dog recovered, and the serum calcium and PTH-rP concentrations decreased. Therefore, concentrations of PTH-rP and calcium might be associated with serous papillary adenocarcinomas. Serial evaluation of the serum PTH-rP and calcium was useful for evaluating the prognosis.

  19. Treatment of central serous chorioretinopathy with beta-blocker metipranolol.

    Science.gov (United States)

    Chrapek, Oldrich; Jirkova, Barbora; Kandrnal, Vit; Rehak, Jiri; Sin, Martin

    2015-03-01

    The purpose of this study was to evaluate the effect of the systemically administered betablocker metipranolol on the course of central serous chorioretinopathy (CSC). A prospective double-blind study involving 48 patients with a first attack of CSC not exceeding two weeks and who agreed to the follow-up ophthalmology examinations every week. The group was divided into a metipranolol group (n=23), receiving 10 mg of drug twice per day and a placebo group (n=25). The outcome measure was time in weeks from drug intervention (metipranolol vs. placebo) to reattachment of macula neuroepithelium. There was no statistically significant difference in duration of CSC in patients who used metipranolol and those who used placebo (P=0.341). In a prospective double-blind study, we found no effect of the betablocker metipranolol on the duration of central serous chorioretinopathy.

  20. Incidental Serous Tubal Intraepithelial Carcinoma and Non-Neoplastic Conditions of the Fallopian Tubes in Grossly Normal Adnexa: A Clinicopathologic Study of 388 Completely Embedded Cases.

    Science.gov (United States)

    Seidman, Jeffrey D; Krishnan, Jayashree; Yemelyanova, Anna; Vang, Russell

    2016-09-01

    Serous tubal intraepithelial carcinoma (STIC), the putative precursor of the majority of extrauterine high-grade serous carcinomas, has been reported in both high-risk women (those with a germline BRCA mutation, a personal history of breast carcinoma, and/or family history of breast or ovarian carcinoma) and average risk women from the general population. We reviewed grossly normal adnexal specimens from 388 consecutive, unselected women undergoing surgery, including those with germline BRCA mutation (37 patients), personal history of breast cancer or family history of breast/ovarian cancer (74 patients), endometrial cancer (175 patients), and a variety of other conditions (102 patients). Among 111 high-risk cases and 277 non-high-risk cases, 3 STICs were identified (0.8%), all in non-high-risk women (high risk vs. non-high risk: P=not significant). STIC was found in 2 women with nonserous endometrial carcinoma and 1 with complex atypical endometrial hyperplasia. Salpingoliths (mucosal calcifications), found in 9% of high-risk cases, and fimbrial adenofibromas in 9.9% of high-risk cases, were significantly more common in high-risk as compared with non-high-risk women (1.8% and 2.5%, respectively; PSTIC and endometrial hyperplasia and carcinoma, and clarify the frequency of non-neoplastic tubal findings in grossly normal fallopian tubes.

  1. Detection of serous precursor lesions in resected fallopian tubes from patients with benign diseases and a relatively low risk for ovarian cancer.

    Science.gov (United States)

    Nishida, Naoyo; Murakami, Fumihiro; Higaki, Koichi

    2016-06-01

    The frequency of ovarian cancers in Japan has increased; however, doubts have been raised concerning the mechanism by which high-grade serous adenocarcinomas (HGSCs) arise. Conventionally, HGSC is thought to originate from the ovarian surface epithelium or epithelial inclusion cyst. However, recent data indicate that HGSCs may in fact develop from precursor lesions in the fallopian tube, including epithelia with a p53 signature, serous tubal intraepithelial carcinomas (STICs), secretory cell outgrowths (SCOUTs), and tubal intraepithelial lesions in transition (TILT). Here, we determined the frequency of these fallopian tube precursors in surgically excised samples from 123 patients with benign pelvic diseases. We identified 12 cases with a p53 signature (9.7%), 26 with observable SCOUTs (21.1%), and 4 with TILT (3.2%), but no STIC cases. Although the lifetime risk for developing ovarian cancer is only around 1.4% for women without germ-line mutations, it is important to evaluate the presence of precursor lesions to understand HGSC pathogenesis better. Taken together, salpingectomy appears to be an option for women who are past their childbearing age and plan to undergo elective pelvic surgery. To our knowledge, this is the first study to investigate the presence of these specific precursors post-salpingectomy in low-risk patients. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  2. Immunophenotypic Analysis in Early Müllerian Serous Carcinogenesis.

    Science.gov (United States)

    Nafisi, Houman; Ghorab, Zeina; Ismill, Nadia; Dubé, Valerie; Plotkin, Anna; Han, Guangming; Cesari, Matthew; Lu, Fang-I; Saad, Reda; Khalifa, Mahmoud; Nofech-Mozes, Sharon

    2015-09-01

    Studies on the immunophenotypes of early forms of serous carcinoma arising from female genital tract are limited. We aimed to examine p53, p16(Ink4a), estrogen receptor (ER), progesterone receptor (PR), ERBB2, WT1, and Ki-67 protein expression in endometrial intraepithelial carcinoma (n=29), serous tubal intraepithelial lesion (n=4) and carcinoma (STIC, n=10), and the putative precursor p53 signature (n=11). Among endometrial intraepithelial carcinoma, 80% demonstrated p53 overexpression and 10% were consistent with a null phenotype. p16(Ink4a) immunostaining were observed in all endometrial intraepithelial carcinoma cases. ER, PR, ERBB2, and WT1 were positive in 54%, 25%, 11%, and 18% of cases, respectively. STIC cases demonstrated p53 overexpression and null phenotype in 90% and 10%, respectively. All STIC cases were p16(Ink4a) and WT1 positive, whereas ER and PR were positive in 70% and 20%, respectively. All STICs were negative for ERBB2. Among serous tubal intraepithelial lesion cases, 75% demonstrated p53 overexpression and 25% a null phenotype. p53 was positive in all 11 p53 signature cases, whereas p16(Ink4a) was universally negative. Finally, ER and PR were positive in 100% and 73% of p53 signature cases, respectively. These results suggest that p16(Ink4a) has a role in early Müllerian serous carcinogenesis but is absent in the earliest noncommitted lesion. p16(Ink4a) immunohistochemistry can be used as an adjunct confirmatory tool in p53-null cases with limited surface area.

  3. Frequency of Serous Otitis Media in Children without Otolaryngological Symptoms.

    Science.gov (United States)

    Kocyigit, Murat; Ortekin, Safiye Giran; Cakabay, Taliye; Ozkaya, Guven; Bezgin, Selin Ustun; Adali, Mustafa Kemal

    2017-04-01

    Introduction  Otitis media with effusion is the fluid in the middle ear with no signs or symptoms of acute ear infection. Objective  This study aims to research the frequency of serous otitis media in patients referred to the pediatric clinic between 3-16 years of age without any active ear, nose, and throat complaints. Methods  This study included 589 children patients (280 boys, 309 girls; mean age: 9.42; range 3-16) who were administered to the pediatric clinic without otolaryngologic complaints. Patients underwent examination with flexible nasopharyngoscopy for adenoid hypertrophy. An otorhinolaryngologist examined all children on both ears using an otoscope and tested with tympanometry. We used tympanometry results to diagnose SOM. Results  The study included 589 patients that underwent fiber optic examination of the nasopharynx with an endoscope. Adenoid vegetation was present in 58 patients (9.8%) and was not detected in 531 patients (90.2%). We found serous otitis media in 94 (15.9%) patients. We obtained Type A tympanogram in 47 (81%) of 58 patients with adenoid vegetation, 6 (10.3%) Type B, and 5 (8.6%) Type C. When comparing 58 patients with adenoid vegetation with 538 patients without adenoid vegetation for serous otitis media, the frequency was not statistically significant (p > 0.05). Conclusion  We believe that in children without any ear, nose, and throat complaints, it is possible to detect serous otitis media with adenoid vegetation. Thus, pediatric patients should undergo screening at regular intervals.

  4. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Sharifeh Mehrabi

    2014-01-01

    Full Text Available Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of 61±10 years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% (P<0.05 higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans.

  5. Mutation of NRAS is a Rare Genetic Event in Ovarian Low-Grade Serous Carcinoma

    DEFF Research Database (Denmark)

    Xing, Deyin; Rahmanto, Yohan Suryo; Zeppernick, Felix

    2017-01-01

    Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate...... during the progression of serous borderline tumor (SBT) to invasive low grade serous carcinoma (LGSC) remains largely unknown. While mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been...

  6. Obstructive Jaundice as a Complication of Macrocystic Serous Cystadenoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Hendra Koncoro

    2016-09-01

    Full Text Available Macrocystic serous cystadenoma is an unusual and essentially benign pancreatic tumor. Herein, we report on a 40-year-old woman diagnosed with macrocystic serous cystadenoma who presented with obstructive jaundice. A cystic lesion in the head and body of the pancreas was revealed by abdominal computed tomography. Intraoperative pancreatic cyst aspiration ruled out mucinous cystic neoplasm which has a malignant potential. The pancreatic cyst fluid cytology was basophilic amorph materials concluded as benign cystic lesion. Internal drainage was performed instead of pancreatic resection which showed good outcome. Biliary obstruction is a rare complication of serous cystadenoma. This case describes an unusual clinical presentation of macrocystic serous cystadenoma.

  7. 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

  8. 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

  9. 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...

  10. 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...

  11. 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

  12. 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.

  13. Low- to high-grade metamorphic transition in the Southern part of Karnataka Nucleus, India

    Science.gov (United States)

    Naqvi, S. M.

    1988-01-01

    The southern part of Karnataka Nucleus has a strong imprint of 2.6 Ga metamorphism. This has affected the schist belts of Karnataka Nucleus from greenschist to upper amphibolite facies. The higher grades of metamorphism are in the Holenarasipur, Nuggihalli, Krishnarajpet, Hadnur and Melkote schist belts. In the high grade transition zone, around Sargur only keels of schist belts are preserved and occur as highly dismembered, disconnected belts with the top and bottom of the stratigraphic column obliterated due to high grade metamorphism and accompanying migmatization. Absence of high-grade metamorphic minerals in the sediments of the Dharwar schist belts supports the contention that high grade metamorphism post-dated the Dharwar sedimentation and occurred around 2.6 Ga ago. Sargur type metamorphism occurred at upper crustal levels and charnockite type metamorphism occurred in lower crustal levels. The P-T conditions for the mineral assemblage in metapelites of Sargur Group indicate burial depths up to at least 15 km suggesting that they were subducted and later obducted during the development of Early Proterozoic Mobile Belt along the southern border of the Karnataka Nucleus.

  14. Transition from low-grade endometrial stromal sarcoma to high-grade endometrial stromal sarcoma.

    Science.gov (United States)

    Ohta, Yoshiki; Suzuki, Takao; Omatsu, Mutsuko; Hamatani, Shigeharu; Shiokawa, Akira; Kushima, Miki; Ota, Hidekazu

    2010-07-01

    We report on a case of a primary low-grade endometrial stromal sarcoma (ESS) that progressed to a secondary high-grade ESS. In the secondary tumor, the immunohistochemical profile and focal tumor cell proliferation pattern suggested that this tumor was not truly undifferentiated, but possessed features of endometrial stroma. Low-grade ESS of our patient's primary tumor showed p53 protein overexpression, which is unusual in low-grade ESS, and her secondary high-grade ESS showed more prominent p53 immunoreactivity. This indicates that low-grade ESS that shows p53 immunoreactivity might progress to high-grade ESS, and it is considered that such cases of low-grade ESS should pay attention to the prognosis. Immunoreactivity for epidermal growth factor receptor was observed in both tumors, suggesting a relationship between the primary and secondary tumors in our case. Further study requires more immunohistochemical data for cases in which low-grade ESS transitions to high-grade ESS; in particular, data on epidermal growth factor receptor expression are necessary to define new therapeutic strategies for ESS.

  15. Transition of low-grade to high-grade endometrial stromal sarcoma: a case report.

    Science.gov (United States)

    Kanda, M; Sonoyama, A; Hirano, H; Kizaki, T; Ohara, N

    2013-01-01

    The transition of low-grade endometrial stromal sarcoma (ESS) to high-grade ESS remains a rare clinical event. A patient presented with abdominal pain and abnormal genital bleeding. She underwent a supracervical hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and resection of peritoneal disseminated lesions. Pathological examination revealed low-grade ESS in the uterus and omentum. Immunohistochemical examination showed immunoreactivity for CD10 and Ki-67 (MIB1) in the uterus and omentum. However, estrogen receptor, progesterone receptor, alpha-SMA, desmin, h-caldesmon, and CAM5-2 were negative. P53 immunoreactivity was noted only in the omental lesion. Despite performing six courses of adjuvant chemotherapy, she recurred in the abdomen. She underwent ileostomy and resection of peritoneal disseminated lesions. Pathology showed high-grade ESS in the recurrent lesion of the ileum, which was characterized by severe cytologic atypia, high mitotic index, multifocal necrosis, increased Ki-67 index, and immunoreactivity for p53. Although rare, the transition of low-grade ESS to high-grade ESS may occur and suggests the worsening of the prognosis. Pathological examination and immunohistochemistry are useful for the diagnosis of the transition of low-grade ESS to high-grade ESS.

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

    Science.gov (United States)

    Radcliff, Kristen E; Jakoi, Andre M

    2015-04-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

  18. Transforaminal percutaneous endoscopic lumbar discectomy for very high-grade migrated disc herniation.

    Science.gov (United States)

    Ahn, Yong; Jang, Il-Tae; Kim, Woo-Kyung

    2016-08-01

    Transforaminal percutaneous endoscopic lumbar discectomy (PELD) for high-grade migrated disc herniation has been regarded as a challenging task, but because of the remarkable improvement in navigable instruments and advanced epiduroscopic technique, it can be used for the treatment of high- or very high-grade migrated disc herniation. The purpose of this study was to describe in detail the standardized technique of transforaminal PELD for very high-grade migrated disc herniation and demonstrate the clinical results. Very high-grade lumbar migrated disc herniation was defined as a disc migration beyond the inferior margin of the pedicle. Thirteen consecutive patients with very high-grade lumbar migrated disc herniation were treated with transforaminal PELD, which has three stages: (1) direction-oriented transforaminal approach, (2) release of periannular anchorage, and (3) epiduroscopic fragmentectomy with navigable instruments. The surgical outcomes were assessed using the visual analogue pain score (VAS), Oswestry disability index (ODI), and modified Macnab criteria. The operated levels were L3-4 in 2 (15.4%) patients, L4-5 in 10 (76.9%), and L5-S1 in 1 (7.7%). The directions of migration were cranial in 8 patients and caudal in 5. The mean VAS for leg pain improved from 7.86±1.28 preoperatively to 2.54±1.51 at 6 weeks postoperatively and 1.85±1.07 at 1year postoperatively (Pdisc herniation, and a standardized technique may provide a reliable and reproducible result. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Science.gov (United States)

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

    2012-07-01

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

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

    Science.gov (United States)

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

    2013-09-01

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

  2. Blood magnesium, and the interaction with calcium, on the risk of high-grade prostate cancer.

    Directory of Open Access Journals (Sweden)

    Qi Dai

    2011-04-01

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

  3. The role of hormonal therapy in patients with relapsed high-grade ovarian carcinoma: a retrospective series of tamoxifen and letrozole.

    Science.gov (United States)

    George, Angela; McLachlan, Jennifer; Tunariu, Nina; Della Pepa, Chiara; Migali, Cristina; Gore, Martin; Kaye, Stan; Banerjee, Susana

    2017-06-30

    Hormonal therapy is used as a treatment option in high-grade ovarian carcinoma (HGOC), but the role and choice of treatment remains unclear. Agents used include tamoxifen and aromatase inhibitors. Our aim was to evaluate the efficacy of tamoxifen (T) and letrozole (L) in HGOC in clinical practice and investigate factors influencing clinical outcome. A retrospective review of patients with relapsed HGOC treated with either tamoxifen or letrozole at the Royal Marsden Hospital between 2007 and 2012 was performed. The primary endpoint of the study was objective response rate (ORR). Secondary endpoints included CA125 response, clinical benefit rate (CBR) and duration of response. Platinum-sensitivity and ER-status were evaluated as predictors of treatment response. 97 patients were included (43 T, 54 L); median age 63 years (20-92); 91% high-grade serous; median number of lines of prior chemotherapy 3 (1-8); 60% platinum-resistant, 40% platinum-sensitive; 52% ER + ve, 1% ER-ve, 47% unknown. 14 patients (6 T, 8 L) achieved a partial response, with ORR (RECIST) of 14% (T) and 15% (L). The CBR for ≥3 months was 65% (22/43) for tamoxifen and 56% (22/54) for letrozole. There was no significant difference in ORR (p = 0.99) or CBR (p = 0.14) between tamoxifen and letrozole. 22 patients (23%) had a CA-125 response with hormonal therapy (10 T - 23% and 12 L - 22%). ORR did not differ by platinum sensitivity (p = 0.42); or ER-status (positive vs unknown, p = 0.12). Responders to letrozole had longer durations of response than responders to tamoxifen (26 vs 11.5 months, p = 0.03), but equivalent disease stability duration (9.6 vs 7.2 months respectively, p = 0.11). Within the constraints of a retrospective study, we identified that patients treated with letrozole had a significantly longer duration of response than those treated with tamoxifen. Treatment with either tamoxifen or letrozole is a rational treatment option for patients with ER + ve HGOC

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

    Science.gov (United States)

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

    2016-01-01

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

  5. ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Takafumi Kuroda

    Full Text Available Cancer stem-like cells (CSCs/cancer-initiating cells (CICs are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1(high population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas by the ALDEFLUOR assay. ALDH1(high cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1(high cells. ALDH1(high cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis.

  6. Perturbation of Rb, p53, and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer.

    Science.gov (United States)

    Szabova, Ludmila; Yin, Chaoying; Bupp, Sujata; Guerin, Theresa M; Schlomer, Jerome J; Householder, Deborah B; Baran, Maureen L; Yi, Ming; Song, Yurong; Sun, Wenping; McDunn, Jonathan E; Martin, Philip L; Van Dyke, Terry; Difilippantonio, Simone

    2012-08-15

    The majority of human high-grade serous epithelial ovarian cancer (SEOC) is characterized by frequent mutations in p53 and alterations in the RB and FOXM1 pathways. A subset of human SEOC harbors a combination of germline and somatic mutations as well as epigenetic dysfunction for BRCA1/2. Using Cre-conditional alleles and intrabursal induction by Cre-expressing adenovirus in genetically engineered mice, we analyzed the roles of pathway perturbations in epithelial ovarian cancer initiation and progression. Inactivation of RB-mediated tumor suppression induced surface epithelial proliferation with progression to stage I carcinoma. Additional biallelic inactivation and/or missense p53 mutation in the presence or absence of Brca1/2 caused progression to stage IV disease. As in human SEOC, mice developed peritoneal carcinomatosis, ascites, and distant metastases. Unbiased gene expression and metabolomic profiling confirmed that Rb, p53, and Brca1/2-triple mutant tumors aligned with human SEOC, and not with other intraperitoneal cancers. Together, our findings provide a novel resource for evaluating disease etiology and biomarkers, therapeutic evaluation, and improved imaging strategies in epithelial ovarian cancer. ©2012 AACR.

  7. Multifocal central serous chorioretinopathy with photoreceptor-retinal pigment epithelium diastasis in heritable pulmonary arterial hypertension

    DEFF Research Database (Denmark)

    Li, Xiao Qiang; Pryds, Anders; Carlsen, Jørn

    2015-01-01

    choroidal vessels were seen in the patient's symptomatic left eye. After treatment for pulmonary hypertension, the serous detachments disappeared and choroidal thickness gradually decreased over a period of 4 weeks and remained unchanged at 13 months of follow-up. CONCLUSION: Central serous...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    1986-01-01

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

  10. 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.

  11. Malignant Transformation of High-Grade Osteoblastoma of the Petrous Apex with Subcutaneous Metastasis

    Science.gov (United States)

    Kraft, Casey T.; Morrison, Robert J.; Arts, H. Alexander

    2015-01-01

    Objectives To present the clinical presentation, management, and pathological findings of a patient with osteosarcoma of the petrous apex with atypical metastasis to the lower abdominal wall. Methods Retrospective review of the records of a case of osteosarcoma of the petrous apex. Results A 49-year old man with facial pain is diagnosed with a right petrous apex lesion with biopsy demonstrating high-grade osteoblastoma. Multiple attempts at en bloc resection were not curative, therefore radiation and chemotherapy was recommended after two surgical attempts. The patient subsequently developed a cutaneous, lower abdominal wall mass which demonstrated osteosarcoma. Petrous apex tumor growth progressed despite treatment until the patient expired from burden of disease. Conclusions Temporal bone osteoblastoma and osteosarcoma are both extremely rare, and can be difficult to differentiate histologically. The present case illustrates these difficulties and demonstrates the possibility of malignant conversion from high-grade osteobastoma to osteosarcoma. PMID:27304442

  12. Malignant transformation of a high-grade osteoblastoma of the petrous apex with subcutaneous metastasis.

    Science.gov (United States)

    Kraft, Casey T; Morrison, Robert J; Arts, H Alexander

    2016-06-01

    We describe the clinical presentation, management, and pathologic findings in a case of osteosarcoma of the petrous apex with an atypical metastasis to the lower abdominal wall. We retrospectively reviewed the record of a 49-year-old man who was diagnosed with a right petrous apex lesion, which biopsy identified as a high-grade osteoblastoma. After two attempts at en bloc resection were not curative, radiation and chemotherapy were recommended. The patient subsequently developed a cutaneous lower abdominal mass that was diagnosed as an osteosarcoma. Meanwhile, the petrous apex tumor continued to grow despite treatment until the patient died from the burden of disease. Temporal bone osteoblastomas and osteosarcomas are both extremely rare, and they can be difficult to differentiate histologically. Our case illustrates this difficulty and demonstrates the possibility of a high-grade osteoblastoma's malignant conversion to an osteosarcoma.

  13. 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.

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

    Science.gov (United States)

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

    1986-10-01

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

  15. 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 (...

  16. Radiologic and clinical outcomes of surgery in high grade spondylolisthesis treated with temporary distraction rod.

    Science.gov (United States)

    Omidi-Kashani, Farzad; Hootkani, Alireza; Jarahi, Lida; Rezvan, Manizheh; Moayedpour, Amir

    2015-03-01

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

  17. Predictors of Progression to High-Grade Dysplasia or Adenocarcinoma in Barrett’s Esophagus

    Science.gov (United States)

    Whitson, Matthew J.; Falk, Gary W.

    2015-01-01

    Article Synopsis The prevalence of esophageal adenocarcinoma is increasing dramatically. Barrett’s esophagus remains the most well established risk factor for the development of esophageal adenocarcinoma. There are multiple clinical, endoscopic, and pathologic factors that increase the risk of neoplastic progression to high-grade dysplasia or esophageal adenocarcinoma in Barrett’s esophagus. This article will review both risk and protective factors for neoplastic progression in patients with Barrett’s esophagus. PMID:26021196

  18. Venous thromboembolism and survival in patients with high-grade glioma

    OpenAIRE

    Simanek, Ralph; Vormittag, Rainer; Hassler, Marco; Roessler, Karl; Schwarz, Martin; Zielinski, Christoph; Pabinger, Ingrid; Marosi, Christine

    2007-01-01

    Patients with malignancy, particularly patients with high-grade glioma (HGG; WHO grade III/IV), have an increased risk of venous thromboembolism (VTE). It has been suggested that VTE predicts survival in cancer patients. The aim of our study was to investigate the occurrence of symptomatic VTE and its impact on survival in patients with HGG. Consecutive patients (n = 63; 36 female, 27 male; median age, 58 years) who had neurosurgical intervention between October 2003 and December 2004 were fo...

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

    Science.gov (United States)

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

    2015-01-01

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

  20. O9.04HIGH GRADE GLIOMAS AND CAREGIVERS' PSYCHOLOGICAL BURDEN

    OpenAIRE

    Petruzzi, A.; Finocchiaro, C.Y.; Vistalli, G.; Botturi, A.; Milanesi, I.; Silvani, A.; Lamperti, E.

    2014-01-01

    The diagnosis of a brain tumor is particularly stressful both for patients and their caregivers because the prognosis is poor and life expectancy is short. This is especially true when caregivers deal with high-grade gliomas (HGG). Despite treatment advances, median survival remains low, ranging from 1 to 5 years. Focal neurological deficits, epilepsy, cognitive dysfunction and symptoms of increased intracranial pressure are prominent symptoms in HHG and they may arise in any stage of the dis...

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

    Directory of Open Access Journals (Sweden)

    Miller Robert W

    2009-10-01

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

  2. A Levering Technique Using Small Parallel Rods for Open Reduction of High-Grade Thoracolumbar Dislocation

    OpenAIRE

    Hadgaonkar, Shailesh; Shah, Kunal; Khurjekar, Ketan; Krishnan, Vibhu; Shyam, Ashok; Sancheti, Parag

    2017-01-01

    Study Design: Technical report. Objective: Dorsolumbar vertebral dislocations, with or without associated fractures, occur secondary to very high velocity trauma. The reduction procedures and techniques, which may be adopted in these situations, have been multifariously discussed in the literature. Our objective was to assess the outcome of a novel reduction maneuver, using parallel rods which we have employed in reduction of high-grade thoracolumbar fractures to achieve precise sagittal bala...

  3. Molecular and Morphologic Correlates of the Alternative Lengthening of Telomeres Phenotype in High Grade Astrocytomas

    Science.gov (United States)

    Nguyen, Doreen N.; Heaphy, Christopher M.; de Wilde, Roeland F.; Orr, Brent A.; Odia, Yazmin; Eberhart, Charles G.; Meeker, Alan K.; Rodriguez, Fausto J.

    2013-01-01

    Recent studies suggest that the telomere maintenance mechanism known as Alternative Lengthening of Telomeres (ALT) is relatively more common in specific glioma subsets and strongly associated with ATRX mutations. We retrospectively examined 116 high grade astrocytomas (32 pediatric glioblastomas, 65 adult glioblastomas,19 anaplastic astrocytomas) with known ALT status using tissue microarrays to identify associations with molecular and phenotypic features. Immunohistochemistry was performed using antibodies against ATRX, DAXX, p53 and IDH1R132H mutant protein. EGFR amplification was evaluated by FISH. When focusing on histologic subtypes, almost half of fibrillary and gemistocytic astrocytomas (44%) demonstrated ALT. Conversely all gliosarcomas (n=4), epithelioid (n=2), giant cell (n=2) and adult small cell astrocytomas (n=7) were ALT negative. The ALT phenotype was positively correlated with the presence of round cells (p=0.002), microcysts (p<0.0002), IDH1 mutant protein (p<0.0001), ATRX protein loss (p<0.0001), strong P53 expression (p<0.0001), and absence of EGFR amplification (p=0.004). There was no significant correlation with DAXX expression. We conclude that ALT represents a specific phenotype in high grade astrocytomas with distinctive pathologic and molecular features. Future studies are required to clarify the clinical and biological significance of ALT in high grade astrocytomas, and its possible utility as a diagnostic and/or therapeutic target. PMID:22928601

  4. Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas.

    Science.gov (United States)

    Nguyen, Doreen N; Heaphy, Christopher M; de Wilde, Roeland F; Orr, Brent A; Odia, Yazmin; Eberhart, Charles G; Meeker, Alan K; Rodriguez, Fausto J

    2013-05-01

    Recent studies suggest that the telomere maintenance mechanism known as alternative lengthening of telomeres (ALT) is relatively more common in specific glioma subsets and strongly associated with ATRX mutations. We retrospectively examined 116 high-grade astrocytomas (32 pediatric glioblastomas, 65 adult glioblastomas, 19 anaplastic astrocytomas) with known ALT status using tissue microarrays to identify associations with molecular and phenotypic features. Immunohistochemistry was performed using antibodies against ATRX, DAXX, p53 and IDH1(R132H) mutant protein. EGFR amplification was evaluated by fluorescence in situ hybridization (FISH). Almost half of fibrillary and gemistocytic astrocytomas (44%) demonstrated ALT. Conversely all gliosarcomas (n = 4), epithelioid (n = 2), giant cell (n = 2) and adult small cell astrocytomas (n = 7) were ALT negative. The ALT phenotype was positively correlated with the presence of round cells (P = 0.002), microcysts (P < 0.0002), IDH1 mutant protein (P < 0.0001), ATRX protein loss (P < 0.0001), strong P53 immunostaining (P < 0.0001) and absence of EGFR amplification (P = 0.004). There was no significant correlation with DAXX expression. We conclude that ALT represents a specific phenotype in high-grade astrocytomas with distinctive pathologic and molecular features. Future studies are required to clarify the clinical and biological significance of ALT in high-grade astrocytomas. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

  5. The management of high-grade spondylolisthesis and co-existent late-onset idiopathic scoliosis.

    Science.gov (United States)

    Srivastava, Abhishek; Bayley, Edward; Boszczyk, Bronek M

    2016-10-01

    It is relatively common for a scoliosis deformity to be associated with a lumbar spondylolisthesis in adolescents (up to 48 % of spondylolistheses). In the literature two types of curve have been described: 'sciatic' or 'olisthetic'. However, there is no consensus in the literature on how best to treat these deformities. Some authors advocate a single surgical intervention, where both deformities are corrected; whereas, others advocate treating them as separate entities. In this situation, it has been shown that the scoliosis will correct with treatment of the spondylolisthesis. We present a 12-year-old girl who had a concomitant high-grade spondylolisthesis and scoliosis. Her main complaints were those of low back pain and an L5 radiculopathy. We took the decision to treat the spondylolisthesis surgically, but observe the scoliosis, rather than correcting them both surgically at the same sitting. Although the immediately post-operative radiographs showed persistence of the scoliosis, 1-year follow-up demonstrated full resolution of the deformity. This young lady also had relief of her low back pain and leg pain following the surgery. There are no standard guidelines and therefore, we discuss the management of this difficult problem, exemplifying a case of a young girl who had high-grade spondylolisthesis along with a clinically non-flexible scoliosis treated at our institution. We demonstrate that it is safe to observe the scoliosis, even in high-grade spondylolistheses.

  6. 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

  7. 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.

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

    CERN Document Server

    2001-01-01

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

  9. Gynecologic Cancer InterGroup (GCIG) consensus review for high-grade undifferentiated sarcomas of the uterus

    NARCIS (Netherlands)

    Pautier, Patricia; Nam, Eun Ji; Provencher, Diane M.; Hamilton, Anne L.; Mangili, Giorgia; Siddiqui, Nadeem Ahmad; Westermann, Anneke M.; Reed, Nicholas Simon; Harter, Philipp; Ray-Coquard, Isabelle

    2014-01-01

    High-grade undifferentiated sarcomas (HGUSs) are rare uterine malignancies arising from the endometrial stroma. They are poorly differentiated sarcomas composed of cells that do not resemble proliferative-phase endometrial stroma. High-grade undifferentiated sarcomas are characterized by aggressive

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  11. Gene expression identifies heterogeneity of metastatic propensity in high-grade soft tissue sarcomas

    DEFF Research Database (Denmark)

    Skubitz, Keith M; Francis, Princy; Skubitz, Amy P N

    2012-01-01

    Metastatic propensity of soft tissue sarcoma (STS) is heterogeneous and may be determined by gene expression patterns that do not correlate well with morphology. The authors have reported gene expression patterns that distinguish 2 broad classes of clear cell renal carcinoma (ccRCC-gene set), and......), and other patterns that can distinguish heterogeneity of serous ovarian carcinoma (OVCA-gene set) and aggressive fibromatosis (AF-gene set); however, clinical follow-up data were not available for these samples.......Metastatic propensity of soft tissue sarcoma (STS) is heterogeneous and may be determined by gene expression patterns that do not correlate well with morphology. The authors have reported gene expression patterns that distinguish 2 broad classes of clear cell renal carcinoma (ccRCC-gene set...

  12. [Morphological features of the fimbria of the fallopian tube in pelvic serous adenocarcinoma].

    Science.gov (United States)

    Guo, Dong-hui; Pang, Shu-jie; Shen, Yan; Li, Yan

    2011-04-01

    To study the serous lesions of the fimbria of the fallopian tube in patients with pelvic serous adenocarcinoma and investigate its significance in the serous carcinogenesis. To observe the morphological features of the fimbria of the fallopian tube in 43 cases of pelvic serous adenocarcinoma (31 cases of ovarian carcinoma and 12 cases of peritoneal carcinoma). Immunohistochemical examination of p53 expression was performed on samples of 69 fallopian tubes of 40 cases. Fimbria carcinoma was identified in 44 tubes in 31 of 43 cases. Fourteen of the carcinoma foci were ≤ 5 mm. In 68.3% of the fimbria carcinomas demonstrated involvement of the mucosa. Twenty eight tubes of 20 cases exhibited intraepithelial carcinoma. Twenty three of 44 tubes of the fibria carcinomas showed fimbria adherence and unclear appearance. The early histological changes of the fimbria epithelium included proliferation of local secretory cells, homogeneity, and straightening of the mucous folds. Clusters of tumor epithelial cells or single gland with atypical features floated between mucosal folds were found in 71.4% of the fimbria with intraepithelial carcinoma. The positive expression rate of p53 in the fimbria carcinomas and the fimbria intraepithelial carcinomas were 86.4% and 60.7%, respectively. Fimbria carcinomas is an important component in pelvic serous adenocarcinomas. The fimbria intraepithelial carcinoma is also very common among the cases of pelvic serous adenocarcinoma. The fimbria may be an important primary site of pelvic serous adenocarcinomas.

  13. 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.

  14. International Differences in Treatment and Clinical Outcomes for High Grade Glioma.

    Directory of Open Access Journals (Sweden)

    Li-Nien Chien

    Full Text Available High grade gliomas are the most common type of malignant brain tumor, and despite their rarity, cause significant morbidity and mortality. This study aimed to compare the treatment patterns of high grade glioma to examine survival patterns in patients who receive specific treatments between cohorts in Ohio and Taiwan.Patients aged 18 years and older at age of diagnosis with World Health Organization (WHO grade III or IV astrocytoma from 2007-2012 were selected from the Ohio Brain Tumor Study and the Taiwan Cancer Registry. The treatment information was derived from medical chart reviews in Ohio and National Health Insurance Research Data in Taiwan. Treatment examined included surgical procedure (brain biopsy and/or resection, radiotherapy (radiation and/or radiosurgery, and alkylating chemotherapy. Kaplan-Meier and parametric survival models were used to examine the effect of treatment on survival, adjusted for age, sex, and comorbidities.294 patients in Ohio and 1,097 patients in Taiwan met the inclusion criteria. 70.3% patients in Ohio and 51.4% in Taiwan received surgical resection, followed by concurrent chemoradiation. Patients who received this treatment had the highest survival rate, with a 1-year survival rate of 72.8% in Ohio and 73.4% in Taiwan. Patients who did not receive surgical resection, followed by concurrent chemoradiation had an increased risk of death (hazard ratio of 5.03 [95% confidence interval (CI: 3.61-7.02] in Ohio and 1.49 [95% CI: 1.31-1.71] in Taiwan after adjustment for age, sex, and comorbidities.Surgical resection followed by concurrent chemoradiation was associated with higher survival rate of patients with high grade glioma in both Ohio and Taiwan; however, one-third of patients in Ohio and half in Taiwan did not receive this treatment.

  15. Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer.

    Science.gov (United States)

    Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Glossop, John R; Luscombe, Christopher; Cheng, K K; Zeegers, Maurice P; James, Nicholas D; Devall, Adam J; Mein, Charles A; Gommersall, Lyndon; Fryer, Anthony A; Farrell, William E

    2016-03-03

    High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a clinically unpredictable disease with greater risks of recurrence and progression relative to their low-intermediate-grade counterparts. The molecular events, including those affecting the epigenome, that characterize this disease entity in the context of tumor development, recurrence, and progression, are incompletely understood. We therefore interrogated genome-wide DNA methylation using HumanMethylation450 BeadChip arrays in 21 primary HG-NMIBC tumors relative to normal bladder controls. Using strict inclusion-exclusion criteria we identified 1,057 hypermethylated CpGs within gene promoter-associated CpG islands, representing 256 genes. We validated the array data by bisulphite pyrosequencing and examined 25 array-identified candidate genes in an independent cohort of 30 HG-NMIBC and 18 low-intermediate-grade NMIBC. These analyses revealed significantly higher methylation frequencies in high-grade tumors relative to low-intermediate-grade tumors for the ATP5G2, IRX1 and VAX2 genes (P<0.05), and similarly significant increases in mean levels of methylation in high-grade tumors for the ATP5G2, VAX2, INSRR, PRDM14, VSX1, TFAP2b, PRRX1, and HIST1H4F genes (P<0.05). Although inappropriate promoter methylation was not invariantly associated with reduced transcript expression, a significant association was apparent for the ARHGEF4, PON3, STAT5a, and VAX2 gene transcripts (P<0.05). Herein, we present the first genome-wide DNA methylation analysis in a unique HG-NMIBC cohort, showing extensive and discrete methylation changes relative to normal bladder and low-intermediate-grade tumors. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination, with more conventional therapeutic options in the treatment of this clinically unpredictable disease.

  16. Recurrent high-grade meningioma: a phase II trial with somatostatin analogue therapy.

    Science.gov (United States)

    Simó, Marta; Argyriou, Andreas A; Macià, Miquel; Plans, Gerard; Majós, Carles; Vidal, Noemi; Gil, Miguel; Bruna, Jordi

    2014-05-01

    A prospective, two-stage phase II trial with octreotide in patients with recurrent high-grade meningioma was conducted. The radiographic partial response (RPR) was set as the primary study endpoint, whereas progression-free survival at 6 months (PFS6) was defined as the secondary endpoint. Nine patients (eight men; median age 65) with histological high-grade meningioma (five with grade II and four with grade III) and progression after prior surgery and radiotherapy were included. All had positive brain octreotide SPECT scanning. Octreotide was administered intramuscularly once every 28 days at a dose of 30 mg for the first two cycles and 40 mg for subsequent cycles until progression. Magnetic resonance imaging was performed every 3 months. Progression and RPR were defined as an increase of ≥25 % and as a decrease of ≥50 % in two-dimensional maximum diameters, respectively. Patients received a median of three octreotide cycles (range 1-8) without grade ≥2 toxicities. No RPRs were observed. Stable disease was the best response in 33.3 % (n = 3). All patients had progressive disease at 10 months of follow-up. Median time to progression was 4.23 months (range 1-9.4), and the PFS6 was 44.4 % (n = 4). Our study failed to provide evidence to support the use of monthly long-acting somatostatin analogue schedule in recurrent high-grade meningiomas, as none of our patients demonstrated RPR. The modest median PFS of 4-5 months along with the unknown natural history of recurrent meningiomas render the use of this therapy against these aggressive brain tumors uncertain.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Arindam Sarkar

    2014-01-01

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

  19. 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

    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...... variability of WSAs than healthy controls. Perfusion on the side of the stenosis was delayed within individual watershed masks as compared to a watershed template derived from controls, being independent from the grade of the stenosis and collateralization status of the circle of Willis. Conclusion: Results...

  20. Application of the CAB process for the manufacture of high-grade forgings

    International Nuclear Information System (INIS)

    Grimm, W.; Feller, J.; Plaul, H.U.

    1981-01-01

    The suitability of the ladle metallurgy CAB process (deoxidation and desulphurization with calcium and degassing with argon) is investigated for the manufacture of high-grade forgings for the construction of power-generating machines. The primary function of the CAB metallurgy, the improvement of the sulphide and oxide cleanness, was combined with established casting parameters so that the macrosegregates too in large forging ingots could be minimized. A comparison of various methods for the manufacture of large forging ingots revealed that the CAB metallurgy can meet demands, which so far could be satisfied by remelting technologies only. (orig.) [de

  1. 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

  2. A nationwide study of serous “borderline” ovarian tumors in Denmark 1978–2002

    DEFF Research Database (Denmark)

    Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette

    2014-01-01

    OBJECTIVE: To describe the study population and estimate overall survival of women with a serous "borderline" ovarian tumor (SBT) in Denmark over 25 years relative to the general population. METHODS: The Danish Pathology Data Bank and the Danish Cancer Registry were used to identify 1487 women...... diagnosed with SBTs from 1978 to 2002. The histologic slides were collected from Danish pathology departments and reviewed by expert pathologists and classified as SBT/atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Associated implants were classified...

  3. Indirect exploration techniques in search for concealed and high grade uranium ore in India

    International Nuclear Information System (INIS)

    Chaki, Anjan

    2009-01-01

    Atomic Minerals Directorate for Exploration and Research is engaged in uranium exploration for nearly six decades. Initial approach was 'from known to the unknown' i.e., to extend exploration to the subsurface, essentially by drilling from the known surface indication. Repeated reconnaissance has more or less identified major deposits in the country from initial surface indication. Now the exploration strategy has been largely oriented more on 'concept based'. The deposits of unconformity type, well known in Canada and Australia, are of high grade and such deposits have little or no surface manifestation, have become the ideal hunt targets. These deposits are known as 'concealed deposits', which warrant exploration largely by indirect techniques. In India, unconformity related type uranium deposits have been targeted in some of the Proterozoic basins like Cuddapah, Bhima, Kaladgi, Chhattisgarh and Vindhyan, to locate high grade large tonnage deposits. Beside extensive surface and borehole core based detailed geochemical studies, remote sensing techniques like airborne gamma ray spectrometric survey, aerial photo interpretation and very recently airborne FEM and TDEM surveys are being conducted to a depth of 5000m. Satpura Gondwana basins in central India as well as Mahadek Basin in Meghalaya are in different stages of integrated exploration programme for uranium and it includes ground geophysical, as well as airborne radiometric magnetic and EM survey

  4. 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.

  5. 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.

  6. DAPK1, MGMT and RARB promoter methylation as biomarkers for high-grade cervical lesions.

    Science.gov (United States)

    Sun, Yin; Li, Shu; Shen, Keng; Ye, Shuang; Cao, Dongyan; Yang, Jiaxin

    2015-01-01

    Gene promoter methylation may be used a potential biomarker for detecting solid tumor including cervical cancer. Here, we used methylation sensitive-high resolution melting (MS-HRM) analysis to detecting promoter methylation ratios of DAPK1, MGMT and RARB gene in patients with different cervical disease grade. The detection of gene promoter methylation was conducted in two hundred fifty patients' samples including normal cytology (n=48), cervical intraepithelial neoplasia grade 1 (CIN1, n=54), cervical intraepithelial neoplasia grade 2 (CIN2, n=47), cervical intraepithelial neoplasia grade 3 (CIN3, n=56) and cervical squamous cell carcinomas (SCS, n=45). We found there were a significant positive correlation between the promoter methylation status of DAPK1 and cervical disease grade (P=0.022). In addition, the methylated promoters of DAPK1 combined with MGMT, MGMT combined with RARB, DAPK1 combined with RARB were positive correlated with cervical disease grade (P methylated were positive correlated with cervical disease grade (P methylation could be used to be a potential marker for diagnosing high grade cervical disease (HSIL and SCC). The cutoff values for the methylation rates of all these genes were 0-5%. Regrettably, only the methylation of MGMT combined with DAPK1 gave 43.4% sensitivity and 68.6% specificity. The current results indicated that MS-HRM-based testing for DNA methylations of MGMT plus DAPK1 genes holds some promise for high grade cervical disease screening.

  7. A Levering Technique Using Small Parallel Rods for Open Reduction of High-Grade Thoracolumbar Dislocation.

    Science.gov (United States)

    Hadgaonkar, Shailesh; Shah, Kunal; Khurjekar, Ketan; Krishnan, Vibhu; Shyam, Ashok; Sancheti, Parag

    2017-06-01

    Technical report. Dorsolumbar vertebral dislocations, with or without associated fractures, occur secondary to very high velocity trauma. The reduction procedures and techniques, which may be adopted in these situations, have been multifariously discussed in the literature. Our objective was to assess the outcome of a novel reduction maneuver, using parallel rods which we have employed in reduction of high-grade thoracolumbar fractures to achieve precise sagittal balance as well as accurate vertebral alignment with minimal soft tissue damage. The study included a total of 11 cases of thoracolumbar dislocations, who had presented to our emergency spine services following high-velocity trauma. After appropriate systemic stabilization and necessary investigations, all patients were surgically treated using the described technique. There were no surgical complications at 2-year follow-up. Radiographs showed good reduction and maintained sagittal balance. We believe that this technique is an excellent means of achieving safer, easier, and accurate reduction for restoration of sagittal/coronal balance and alignment in high-grade thoracolumbar dislocations. It is easily reproducible and predictable.

  8. Wilms tumor gene 1 (WT1) is a prognostic marker in high-grade uterine sarcoma.

    Science.gov (United States)

    Coosemans, An; Van Calster, Ben; Verbist, Godelieve; Moerman, Philippe; Vergote, Ignace; Van Gool, Stefaan W; Amant, Frédéric

    2011-02-01

    Wilms tumor gene 1 (WT1) contributes to uterine sarcoma tumor biology. In this study, we aimed to clarify the prognostic value of WT1. A retrospective clinical and histopathological review of 71 women with high-grade uterine sarcoma (leiomyosarcoma [n = 24], undifferentiated sarcoma [n = 9]), and carcinosarcoma (n = 38) was performed. Patients were followed up for at least 12 months. Wilms tumor gene 1 expression was determined by immunohistochemistry. Data on recurrence (progression-free survival) and overall survival (OS) were available for all patients. Univariate and multivariate analyses of WT1 expression were carried out using Kaplan-Meier curves and Cox regression, respectively. Forty-nine (69%) tumors were WT1 positive. Forty-seven (66%) patients died of the disease, with a median OS time of 22 months. Wilms tumor gene 1 was a predictor of survival in the univariate analysis: the hazard ratio of WT1 positivity was 2.44 (95% confidence interval, 1.34-4.71) for progression-free survival and 2.48 (95% confidence interval, 1.26-4.90) for OS. Multivariate analysis including stage, age, tumor size, and sarcoma subtype identified only stage and WT1 positivity as independent prognostic markers for survival. The identification of WT1 as a prognostic marker confirms its role in high-grade uterine sarcoma and carcinosarcoma tumor biology.

  9. 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.

  10. Serous tubal intraepithelial carcinoma: diagnostic reproducibility and its implications.

    Science.gov (United States)

    Carlson, Joseph W; Jarboe, Elke A; Kindelberger, David; Nucci, Marisa R; Hirsch, Michelle S; Crum, Christopher P

    2010-07-01

    Serous tubal intraepithelial carcinoma (STIC) is detected in between 5% and 7% of women undergoing risk-reduction salpingooophorectomy for mutations in the BRCA1 or 2 genes (BRCA+), and seems to play a role in the pathogenesis of many ovarian and "primary peritoneal" serous carcinomas. The recognition of STIC is germane to the management of BRCA+ women; however, the diagnostic reproducibility of STIC is unknown. Twenty-one cases were selected and classified as STIC or benign, using both hematoxylin and eosin and immunohistochemical stains for p53 and MIB-1. Digital images of 30 hematoxylin and eosin-stained STICs (n=14) or benign tubal epithelium (n=16) were photographed and randomized for blind digital review in a Powerpoint format by 6 experienced gynecologic pathologists and 6 pathology trainees. A generalized kappa statistic for multiple raters was calculated for all groups. For all reviewers, the kappa was 0.333, indicating poor reproducibility; kappa was 0.453 for the experienced gynecologic pathologists (fair-to-good reproducibility), and kappa=0.253 for the pathology residents (poor reproducibility). In the experienced group, 3 of 14 STICs were diagnosed by all 6 reviewers, and 9 of 14 by a majority of the reviewers. These results show that interobserver concordance in the recognition of STIC in high-quality digital images is at best fair-to-good for even experienced gynecologic pathologists, and a proportion cannot be consistently identified even among experienced observers. In view of these findings, a diagnosis of STIC should be corroborated by a second pathologist, if feasible.

  11. Transpupillary thermotherapy for central serous chorioretinopathy with parafoveal leaks

    Directory of Open Access Journals (Sweden)

    Qing Xiao

    2014-04-01

    Full Text Available AIM:To explore the clinical effect of transpupillary thermotherapy(TTTfor the treatment of central serous chorioretinopathy(CSCwith parafoveal leaks.METHODS: Twenty-three eyes from nineteen patients with long-standing CSC and parafoveal leaks(50-200μm around the foveawho opted for TTT and observation were enrolled in this study. Eighteen of nineteen patients(23 eyeswere male, fourteen of twenty-three eyes were right eyes. The patients' mean age was 44.00±4.973 years(range from 32-52 years. TTT was performed using 810nm infrared diode laser. All patients underwent Snellen visual acuity measurement(converted to LogMAR for analysisfundus examination, fluorescein angiography(FFAand optical coherence tomography(OCT. Follow-up was scheduled at 1, 2, 6mo. RESULTS:Following treatment of TTT, complete resolution of neurosensory detachment on OCT and disappearance of leakage on FFA was seen in fourteen eyes(61%, twenty-one eyes(91%at the 2mo and twenty-three eyes(100%at the 6mo respectively. A total of 74% had ≥3 lines of improvement after 6mo. Success was defined as resolution of neurosensory on OCT and disappearance of leakage on FFA at the 2mo. Failure was defined as no change at the 6mo and no improvement of visual acuity.CONCLUSION:TTT is safe and effective therapeutic option in patients with CSC and parafoveal leaks. It may improve the visual acuity by shortening the persistent serous elevation of the macula.

  12. Serous Cystadenoma of the Pancreas Presenting as a Third Primary Neoplasm

    Directory of Open Access Journals (Sweden)

    Aydın Şeref Köksal

    2003-01-01

    Full Text Available Serous cystadenomas are the most common cystic neoplasms of the pancreas. They may occur solely or coexist with other neoplasms. A 10 cm mass involving the body of the pancreas was observed in the computed tomography of a 61-year-old man with a previous history of bladder and prostate carcinoma. Ultrasonography and computed tomography of the mass demonstrated multiple small cysts associated with a central calcified scar. A distal pancreatectomy was performed. Pathological examination confirmed the diagnosis of serous microcystic adenoma. This is the first report of a serous cystadenoma of the pancreas with two metachronous neoplasms. This feature should be kept in mind during the diagnosis and evaluation of patients with serous cystadenoma.

  13. Pancreatic Serous Cystadenoma with Compression of the Main Pancreatic Duct: An Unusual Entity

    Directory of Open Access Journals (Sweden)

    Stéphanie Truant

    2011-01-01

    Full Text Available Serous cystadenoma is a common benign neoplasm that can be managed without surgery in asymptomatic patients provided that the diagnosis is certain. We describe a patient, whose pancreatic cyst exhibited a radiological appearance distinct from that of typical serous cystadenoma, resulting in diagnostic difficulties. CT and MRI showed a 10 cm-polycystic tumor with upstream dilatation of the main pancreatic duct (MPD, suggestive of intraductal papillary mucinous tumor (IPMT. Ultrasonographic aspect and EUS-guided fine-needle aspiration gave arguments for serous cystadenoma. ERCP showed a communication between cysts and the dilated MPD, compatible with IPMT. The patient underwent left pancreatectomy with splenectomy. Pathological examination concluded in a serous cystadenoma, with only a ductal obstruction causing proximal dilatation.

  14. Central serous chorioretinopathy and glucocorticoids: an update on evidence for association.

    Science.gov (United States)

    Nicholson, Benjamin P; Atchison, Elizabeth; Idris, Amrou Ali; Bakri, Sophie J

    Central serous chorioretinopathy is a common idiopathic retinal disease characterized by central vision loss from serous detachment of the neurosensory retina, serous pigment epithelial detachments, and leakage of fluid through the retinal pigment epithelium into the subretinal space. The concept of an association between exogenous glucocorticoid use and central serous chorioretinopathy is widely accepted among ophthalmologists. Here, we review the evidence for and against such an association. This evidence includes 2 large, case-control studies that found strong associations, and a smaller, population-based study that found no association. We conclude that the preponderance of the literature on this topic supports the existence of an association. Both exogenous and endogenous glucocorticoids have been implicated. Although a mechanism and a causal relationship remain to be established, the association deserves broader recognition among physicians who prescribe glucocorticoids. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Pancreatic Serous Cystadenoma with Compression of the Main Pancreatic Duct: An Unusual Entity

    Science.gov (United States)

    Truant, Stéphanie; Izgarevic, D.; Maunoury, Vincent; Buob, David; Bulois, Philippe; Ernst, Olivier; Huet, Guillemette; Zerbib, Philippe; Pruvot, François-René

    2011-01-01

    Serous cystadenoma is a common benign neoplasm that can be managed without surgery in asymptomatic patients provided that the diagnosis is certain. We describe a patient, whose pancreatic cyst exhibited a radiological appearance distinct from that of typical serous cystadenoma, resulting in diagnostic difficulties. CT and MRI showed a 10 cm-polycystic tumor with upstream dilatation of the main pancreatic duct (MPD), suggestive of intraductal papillary mucinous tumor (IPMT). Ultrasonographic aspect and EUS-guided fine-needle aspiration gave arguments for serous cystadenoma. ERCP showed a communication between cysts and the dilated MPD, compatible with IPMT. The patient underwent left pancreatectomy with splenectomy. Pathological examination concluded in a serous cystadenoma, with only a ductal obstruction causing proximal dilatation. PMID:21436987

  16. Demographic clinical and prognostic characteristics of primary ovarian, peritoneal and tubal adenocarcinomas of serous histology-

    DEFF Research Database (Denmark)

    Schnack, Tine H; Sørensen, Rie D; Nedergaard, Lotte

    2014-01-01

    OBJECTIVES: Invasive serous adenocarcinomas may present as primary ovarian (POC), primary fallopian tube (PFC) or primary peritoneal (PPC) carcinomas. Whether they are variants of the same malignancy or develop through different pathways is debated. METHODS: Population-based prospectively collect...

  17. Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

    DEFF Research Database (Denmark)

    Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev

    2014-01-01

    OBJECTIVE: Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities...... with the well-established intrinsic molecular subtypes of breast cancer. METHODS: Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published...... expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal...

  18. The prognostic significance of pre- and post-treatment CA-125 in grade 1 serous ovarian carcinoma: a gynecologic Oncology Group study.

    Science.gov (United States)

    Fader, Amanda Nickles; Java, James; Krivak, Thomas C; Bristow, Robert E; Tergas, Ana I; Bookman, Michael A; Armstrong, Deborah K; Tanner, Edward J; Gershenson, David M

    2014-03-01

    The study objective was to determine the prognostic significance of serum CA-125 levels in patients with grade 1 serous ovarian carcinoma (SOC) enrolled in a Phase III study. An ancillary analysis of a phase III study of women with advanced epithelial ovarian cancer treated with carboplatin/paclitaxel versus triplet or sequential doublet regimens. Grade 1 SOC was used as a surrogate for low-grade serous carcinoma. Among 3686 enrolled patients, 184 (5%) had grade 1 disease and CA-125 levels available. For those with grade 1 SOC, the median patient age was 56.5; 87.3% had Stage III disease. Median follow-up was 102 months and there was no difference in pre-chemotherapy CA-125 by treatment arm (P=0.91). Median pretreatment CA-125 for those with grade 1 SOC was lower (119.1) than for patients with grade 2-3 SOC (246.7; PCA-125 was not prognostic of outcome. However, patients with CA-125 levels that normalized after cycle 1, 2 or 3 were 60-64% less likely to experience disease progression as compared to those who never normalized or normalized after 4 cycles (P ≤ 0.024). Normalization of CA-125 levels before the second cycle was negatively associated with death, with a HR of 0.45 (P=0.025). Pretreatment CA-125 level was significantly lower in women with grade 1 SOC compared to those with high-grade SOC. While pretreatment CA-125 was not associated with survival, serial CA-125 measurements during chemotherapy treatment were prognostic, with normalization before the second chemotherapy cycle associated with a decreased risk of death. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. The prognostic significance of pre- and post-treatment CA-125 in grade 1 serous ovarian carcinoma: A Gynecologic Oncology Group study☆, ☆☆

    Science.gov (United States)

    Fader, Amanda Nickles; Java, James; Krivak, Thomas C.; Bristow, Robert E.; Tergas, Ana I.; Bookman, Michael A.; Armstrong, Deborah K.; Tanner, Edward J.; Gershenson, David M.

    2014-01-01

    Objectives The study objective was to determine the prognostic significance of serum CA-125 levels in patients with grade 1 serous ovarian carcinoma (SOC) enrolled in a Phase III study. Methods An ancillary analysis of a phase III study of women with advanced epithelial ovarian cancer treated with carboplatin/paclitaxel versus triplet or sequential doublet regimens. Grade 1 SOC was used as a surrogate for low-grade serous carcinoma. Results Among 3686 enrolled patients, 184 (5%) had grade 1 disease and CA-125 levels available. For those with grade 1 SOC, the median patient age was 56.5; 87.3% had Stage III disease. Median follow-up was 102 months and there was no difference in pre-chemotherapy CA-125 by treatment arm (P = 0.91). Median pretreatment CA-125 for those with grade 1 SOC was lower (119.1) than for patients with grade 2–3 SOC (246.7; P CA-125 was not prognostic of outcome. However, patients with CA-125 levels that normalized after cycle 1, 2 or 3 were 60–64% less likely to experience disease progression as compared to those who never normalized or normalized after 4 cycles (P ≤ 0.024). Normalization of CA-125 levels before the second cycle was negatively associated with death, with a HR of 0.45 (P = 0.025). Conclusions Pretreatment CA-125 level was significantly lower in women with grade 1 SOC compared to those with high-grade SOC. While pretreatment CA-125 was not associated with survival, serial CA-125 measurements during chemotherapy treatment were prognostic, with normalization before the second chemotherapy cycle asso ciated with a decreased risk of death. PMID:24333362

  20. Helicobacter pylori as a potential target for the treatment of central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Antonio Marcelo Barbante Casella

    2012-09-01

    Full Text Available OBJECTIVES: The objective of this study was to evaluate the relationship between the treatment of Helicobacter pylori gastric infection and changes in best-corrected visual acuity and macular detachment in patients with chronic central serous chorioretinopathy. METHODS: Seventeen patients diagnosed with central serous chorioretinopathy were examined for gastric infection with Helicobacter pylori using the urease test and gastric biopsy. Helicobacter pylory-positive patients were treated with the appropriate medication. The response to therapy was monitored by evaluating the best-corrected visual acuity and optical coherence tomography. The data were analyzed using Student's t-test before and after treatment. RESULTS: Fourteen patients (15 eyes aged 30-56 years (mean 43.4 ± 8.3 years were positive for Helicobacter pylori. Most of the positive patients had gastric symptoms (78.5%; one had bilateral central serous chorioretinopathy. The mean baseline best-corrected visual acuity was 20/98 (logMAR = 0.53 ± 0.28. Three months after starting treatment with antibiotics, the serous detachment had resolved in 14 of 15 eyes, but two cases required laser treatment. The follow-up period ranged from 6 to 27 months. The mean final best-corrected visual acuity differed significantly from baseline. CONCLUSION: Our findings suggest that Helicobacter pylori infection may be present in many chronic central serous chorioretinopathy patients and that treatment for the infection may have a favorable effect on the outcome of chronic central serous chorioretinopathy. Due to the possibility of the spontaneous regression of chronic central serous chorioretinopathy and the high prevalence of the infection in the general population, prospective and masked clinical trials are necessary to confirm that treatment for Helicobacter pylori infection may benefit patients with chronic central serous chorioretinopathy.

  1. Serous cystadenoma of the pancreas: clinical and pathological features in 33 patients.

    Science.gov (United States)

    Colonna, Jorge; Plaza, Jose Antonio; Frankel, Wendy L; Yearsley, Martha; Bloomston, Mark; Marsh, William L

    2008-01-01

    To report the clinicopathological features of patients with serous cystadenomas of the pancreas. Thirty-three cases of serous cystadenoma diagnosed between 1977 and 2006 were retrieved from the files of the Ohio State University Medical Center. Clinical data and microscopic slides were reviewed. The patients included 27 women and 6 men with an age range of 38-83 (mean 64.3) years. The clinical presentation included 13 patients with abdominal pain and 8 patients with abdominal mass; 9 tumors were found incidentally. Abdominal CT scans in 25 patients were interpreted as suspicious for carcinoma in 8 (32%), suspicious for serous cystadenoma in 8, neoplasm not otherwise specified in 8, and suspicious for a pseudocyst in 1. Only 7 patients underwent a preoperative biopsy, and 5 of these were diagnosed as having a serous cystadenoma. All but 2 of the patients underwent surgical resection of the tumor. The serous cystadenomas varied in size from 1.0 to up to 13 cm in maximum dimension, and all but one had a multicystic appearance. Of the 33 serous cystadenomas, 20 (61%) were located in the pancreatic tail, 4 (12%) in the pancreatic body, 4 in the pancreatic body and tail, and 5 (15%) in the head of the pancreas. Follow-up in 17 patients (median 3 years, range from 1 month to 11 years) showed no recurrence of serous cystadenomas. One patient had von Hippel-Lindau syndrome, 4 patients had diabetes mellitus, 3 patients had metastatic cancer, and 2 patients had ovarian tumors. Serous cystadenoma is an uncommon neoplasm that can be confused with malignancy both clinically and radiologically; a correct diagnosis is important in order to provide an accurate prognosis. Copyright 2008 S. Karger AG, Basel.

  2. Ovarian Low-grade Serous Carcinoma: A Clinicopathologic Study of 33 Cases With Primary Surgery Performed at a Single Institution.

    Science.gov (United States)

    Okoye, Ekene; Euscher, Elizabeth D; Malpica, Anais

    2016-05-01

    Ovarian low-grade serous carcinoma (LGSC) is an entity with distinct pathologic and clinical features. The number of studies on this type of tumor is limited. In this article, we present our experience with 33 cases of ovarian LGSC with primary surgical treatment at our institution. For comparison, a cohort of ovarian high-grade serous carcinoma (HGSC) was also studied. Clinical information was obtained from the patients' charts or from the treating physicians. Hematoxylin and eosin slides were reviewed of 28 available LGSCs, and the following parameters were recorded: presence/absence of a serous borderline tumor (SBT), presence/absence of micropapillary/cribriform pattern (MP/CP), architectural pattern in the invasive component, and presence/absence of desmoplasia or fibrosis. The incidence of ovarian LGSC was 4.7%. LGSC patients ranged in age from 19 to 79 years (mean, 52 y), with 21.2% younger than 40 years. HGSC patients ranged in age from 38 to 90 years (mean, 62 y), with 1.6% younger than 40 years. LGSCs were staged as follows: stage I (2), stage III (23), and stage IV (8). Twenty-eight of 33 LGSC cases had concurrent SBT, with this component accounting for >50% of the neoplasm in 15 cases. In addition, MP/CP was noted in 19 cases. Invasion patterns included micropapillae (93%), cribriform nests (74%), elongated papillae (26%), glandular (44.4%), medium-sized papillae (33.3%), solid nests (22.2%), macropapillae (19%), and single cells (19%). In addition, desmoplasia (44.4%) and fibrosis (37%) were noted. Follow-up data ranging from 13 to 195 months (median 61.2 mo) were available on 30/33 LGSC patients: 18 (60%) were dead of disease; 1 (3.3%) was dead of other cause; 5 (16.7%) were alive with disease; and 6 (20%) had no evidence of disease. Follow-up data from 1 to 169 months (median 48 mo) were available on 185 HGSC patients: 132 (71.4%) were dead of disease; 3 (1.6%) were dead of other cause; 21 (11.4%) were alive with disease; and 29 (15.7%) had no

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

    Directory of Open Access Journals (Sweden)

    Sanjay Konakondla

    2017-02-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery...... for patients undergoing resection of the primary tumor and resection/radiofrequency ablation of synchronous metastatic liver disease (n = 12), and 13 months for patients with synchronous metastatic disease given systemic chemotherapy alone (n = 78). The 3-year survival rate after surgery of the primary tumor....... Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment....

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-09-15

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

  7. Study on trickle leaching of a high-grade uranium ore

    International Nuclear Information System (INIS)

    Lin Sirong; Gao Xizhen; Guo Erhua; Lu Shijie

    1996-01-01

    The trickle leaching process for a high-grade silicate uranium ore existing mainly as uraninite form has been studied. Two-stage counter-current trickle leaching with manganese dioxide as oxidant and ferric sulphate solution as leaching agent is used in the process. The leached solution which contains dissolved uranium and iron is carried back to the neutralizing stage and the iron is precipitated in this stage. The acid is added to the main stage and the precipitated iron is dissolved into Fe 2 (SO 4 ) 3 serving as lixiviant in the stage. Compared with conventional agitation acid leaching method, this process decreases the acid consumption by 21% and manganese dioxide by 29%, the extraction rate of uranium reduces by 1.86%

  8. Synchronous Penile Metastasis from a High-Grade Adenocarcinoma of the Prostate

    Directory of Open Access Journals (Sweden)

    S. Dijkstra

    2012-01-01

    Full Text Available Metastasis to the glans penis is a rare phenomenon and usually occurs in a late stage of disease. A 68-year-old man was referred to our clinic because of two indurated lesions of the glans penis and minor lower urinary tract symptoms. Digital rectal examination revealed a hard nodular prostate, and serum prostate-specific antigen (sPSA level was 13.3 ng/mL. Biopsies of the penile lesions and transrectal ultrasound-guided prostate biopsies were taken. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue exposed a synchronous penile metastasis from a high-grade adenocarcinoma of the prostate. Except a pathologically enlarged lymph node detected with MRI there was no suspicion on other metastases. Currently this patient is being treated with a Gonadoreline (GnRH antagonist. Nevertheless, the prognosis will be poor.

  9. 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)

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

    DEFF Research Database (Denmark)

    Piil, Karin; Juhler, Marianne; Jakobsen, Johannes

    2015-01-01

    BACKGROUND: There is a lack of knowledge regarding the breadth of needs for rehabilitation and supportive care across the disease and treatment trajectory for patients with a high-grade glioma (HGG) and their caregivers. OBJECTIVE: The aim of this study was to elucidate the experiences and needs...... for rehabilitation and supportive care in patients with HGG and their caregivers. METHODS: Patients with malignant glioma (N = 30) and their caregivers (N = 33) were interviewed five times during the first year of the HGG trajectory. A thematic analysis of interviews at five time points revealed five main themes......, the need for information and guidance regarding symptoms and supportive care interventions became evident. Caregivers play a significant supporting role for the patients and need special support themselves and practical assistance especially when symptoms progress. Finally, there is a need...

  11. 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

  12. Fusion-segment of high-grade Lumbar Spondylolisthesis: 2-year follow-up.

    Science.gov (United States)

    Li, X; Xu, L; Kong, Q

    2016-12-01

    The clinical efficacy of reduction and fusion surgery and the suitable range of fusion-segment were evaluated in 12 pediatric patients treated for high-grade spondylolisthesis. Pre/post-operative clinical and radiological assessments were analyzed. A transient L5 nerve root paralysis was observed in one patient with L5 spondylolisthesis. No degenerative spondylolisthesis or adjacent segmental instability occurred above the fusion segments. In conclusion, we suggest that, in case of spondylolisthesis without severe structural scoliosis deformity or only associated with lumbosacral deformity, the posterior ligament complex should be protected in case of adjacent segmental instability and spondylolisthesis. If the spondylolisthesis is complicated with severe structural scoliosis deformity (Cobb ≥ 70°), in principle, the treatment should be performed according to the characteristics of the two diseases respectively.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity......-being increased significant, indicating a better HRQOL attend of followup. The diagnosis of a HGG leads to an ongoing functional decline measured as a decline of the KPS and a reduced physical activity during leisure time. Supportive care combined with rehabilitative and palliative approaches might well...... 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...

  14. High grade CIN diagnosis by combined visual inspection with Lugol's iodine and cytology in symptomatic women.

    Science.gov (United States)

    Russo, Evandro; Kupek, Emil; Zanine, Rita Maria

    2011-05-01

    To investigate the diagnostic performance of combining the visual inspection with Lugol's iodine (VILI) and cytology screening to detect high-grade cervical intraepithelial neoplasia (CIN-2 or CIN-3) in symptomatic women, using histological examination as the standard reference test. Cross-sectional referral study utilizing secondary data from 538 medical records from a clinic specialized in cervical pathology in Brazil. Although the sensitivity reached 96.8%, the specificity was only 8.1%, with positive predictive value of 18.3% and negative predictive value of 92.3%. The combination of both tests proved to be highly sensitive, leading to a large decrease in the false negative results. This was achieved, however, at the cost of an excess in the rate of false positive results, thus making the combination unviable for screening in symptomatic women. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Fractionated stereotactic radiotherapy boost after post-operative radiotherapy in patients with high-grade gliomas

    International Nuclear Information System (INIS)

    Baumert, Brigitta G.; Lutterbach, Johannes; Bernays, Rene; Davis, J. Bernard; Heppner, Frank L.

    2003-01-01

    Purpose: To determine the value and the toxicity of an additional fractionated stereotactic boost as used in the joint randomized EORTC-22972/MRC-BR10 study in patients with malignant gliomas. Materials and methods: Seventeen patients (11 male, six female) with a high-grade glioma (two WHO III, 15 WHO IV) ≤4 cm in maximum diameter, with a good performance status (WHO ≥2), were treated with a fractionated stereotactic radiotherapy (SRT) boost to 20 Gy in four fractions following partial brain irradiation to a dose of 60 Gy in 30 fractions. This patient group was compared with historical data in a matched-pair analysis. Results: All patients were treated by conventional radiotherapy and a SRT boost (15 patients received 20 Gy and two patients 10 Gy). Acute side effects included fatigue (two), impairment of short-term memory (one) and worsening of pre-existing symptoms (one). No patient developed steroid dependence after SRT. One patient was re-operated for radiation necrosis. At a median follow-up of 25 months (9-50 months) 14 patients recurred locally. Survival was 77% at 1 year and 42% at 2 years; progression-free survival was 70% at 1 year and 35% at 2 years for all patients, respectively. Median survival for the whole patient group is 20 months. Comparison with a matched historical group showed a significantly better survival for the group treated with a stereotactic boost (P<0.0001). Conclusion: A fractionated stereotactic boost after standard external beam radiotherapy in selected patients with high-grade glioma is feasible and well tolerated with low toxicity. Compared to historical data survival is significantly better with an additional SRT boost. However, its effectiveness has to be proven in a randomized trial

  16. 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.

  17. Intensity-modulated radiotherapy in high-grade gliomas: Clinical and dosimetric results

    International Nuclear Information System (INIS)

    Narayana, Ashwatha; Yamada, Josh; Berry, Sean; Shah, Priti B.S.; Hunt, Margie; Gutin, Philip H.; Leibel, Steven A.

    2006-01-01

    Purpose: To report preliminary clinical and dosimetric data from intensity-modulated radiotherapy (IMRT) for malignant gliomas. Methods and Materials: Fifty-eight consecutive high-grade gliomas were treated between January 2001 and December 2003 with dynamic multileaf collimator IMRT, planned with the inverse approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per fraction was delivered. A total of three to five noncoplanar beams were used to cover at least 95% of the target volume with the prescription isodose line. Glioblastoma accounted for 70% of the cases, and anaplastic oligodendroglioma histology (pure or mixed) was seen in 15% of the cases. Surgery consisted of biopsy only in 26% of the patients, and 80% received adjuvant chemotherapy. Results: With a median follow-up of 24 months, 85% of the patients have relapsed. The median progression-free survival time for anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months, respectively. The overall survival time for anaplastic glioma and glioblastoma was 36 and 9 months, respectively. Ninety-six percent of the recurrences were local. No Grade IV/V late neurologic toxicities were noted. A comparative dosimetric analysis revealed that regardless of tumor location, IMRT did not significantly improve target coverage compared with three-dimensional planning. However, IMRT resulted in a decreased maximum dose to the spinal cord, optic nerves, and eye by 16%, 7%, and 15%, respectively, owing to its improved dose conformality. The mean brainstem dose also decreased by 7%. Intensity-modulated radiotherapy delivered with a limited number of beams did not result in an increased dose to the normal brain. Conclusions: It is unlikely that IMRT will improve local control in high-grade gliomas without further dose escalation compared with conventional radiotherapy. However, it might result in decreased late toxicities associated with radiotherapy

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

    Science.gov (United States)

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

    2017-07-01

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

  19. Genomic predictors of survival in patients with high-grade urothelial carcinoma of the bladder.

    Science.gov (United States)

    Kim, Philip H; Cha, Eugene K; Sfakianos, John P; Iyer, Gopa; Zabor, Emily C; Scott, Sasinya N; Ostrovnaya, Irina; Ramirez, Ricardo; Sun, Arony; Shah, Ronak; Yee, Alyssa M; Reuter, Victor E; Bajorin, Dean F; Rosenberg, Jonathan E; Schultz, Nikolaus; Berger, Michael F; Al-Ahmadie, Hikmat A; Solit, David B; Bochner, Bernard H

    2015-02-01

    Urothelial carcinoma of the bladder (UCB) is genomically heterogeneous, with frequent alterations in genes regulating chromatin state, cell cycle control, and receptor kinase signaling. To identify prognostic genomic markers in high-grade UCB, we used capture-based massively parallel sequencing to analyze 109 tumors. Mutations were detected in 240 genes, with 23 genes mutated in ≥5% of cases. The presence of a recurrent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation was associated with improved recurrence-free survival (RFS) (hazard ratio [HR]: 0.35; p=0.014) and improved cancer-specific survival (CSS) (HR: 0.35; p=0.040) in patients treated with radical cystectomy (RC). In multivariable analyses controlling for pT and pN stages, PIK3CA mutation remained associated with RFS (HR: 0.39; p=0.032). The most frequent alteration, TP53 mutation (57%), was more common in extravesical disease (69% vs 32%, p=0.005) and lymph node-positive disease (77% vs 56%, p=0.025). Patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-altered tumors experienced worse RFS (HR: 5.76; pHR: 2.94; p=0.029) in multivariable analyses. Mutations in chromatin-modifying genes were highly prevalent but not associated with outcomes. In UCB patients treated with RC, PIK3CA mutations are associated with favorable outcomes, whereas TP53 and CDKN2A alterations are associated with poor outcomes. Genomic profiling may aid in the identification of UCB patients at highest risk following RC. Using next-generation sequencing, we identified genomic subsets of high-grade urothelial bladder cancer associated with favorable and unfavorable outcomes. These findings may aid in the selection of patients most likely to benefit from novel combined modality approaches. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-11-01

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

  1. 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.)

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

    Science.gov (United States)

    Xue, Xuhong; Wei, Xiaochun; Li, Li

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-09-01

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

  5. 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

  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. 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

  8. Reirradiation with concurrent bevacizumab for recurrent high-grade gliomas in adult patients.

    Science.gov (United States)

    Schernberg, A; Dhermain, F; Ammari, S; Dumont, S N; Domont, J; Patrikidou, A; Pallud, J; Dezamis, É; Deutsch, É; Louvel, G

    2018-02-01

    To analyse feasibility, prognostic factors and patterns of recurrence after concurrent reirradiation and bevacizumab for recurrent high-grade gliomas. Between 2009 and 2015, 35 patients (median 57-year-old; 21 men, 14 women) with WHO grade III (n=11) or grade IV (n=24) gliomas were included in this retrospective and consecutive single-centre study. All patients received bevacizumab (median number of treatments: 12) concomitant with reirradiation (median dose: 45Gy, median number of fractions: 18) for recurrence with median 22 months (range: 5.6-123.7 months) from first irradiation (median dose: 60Gy). The median follow-up was 9.2 months from reirradiation. The median overall survival from reirradiation was 10.5 months (95% confidence interval [95% CI]: 4.9-16.1) and the progression-free survival from reirradiation was 6.7 months (95% CI: 2.9-10.5). The median overall survival from initial diagnosis was 44.6 months (95% CI: 32-57.1). No grade 3 toxicity or above was reported. Prognostic factors significantly correlated with better overall survival in univariate analysis were: age at least 55 (P=0.024), initial surgery (P=0.003), and 2Gy equivalent dose (EQD2) at least 50Gy at reirradiation (P=0.046). Twenty-two patients bevacizumab-naïve at time of reirradiation had a significantly increased overall survival from reirradiation compared to patients treated with reirradiation after bevacizumab failure (17.7 vs. 5.4 months, P0.05). Concomitant reirradiation with bevacizumab in high-grade recurrent gliomas shows encouraging results in terms of survival and toxicities. Our data suggest that reirradiation should be favoured at initiation of bevacizumab, with EQD2 at least 50Gy. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  9. [Serous cystadenoma in supernumerary ovary. Case report and literature review].

    Science.gov (United States)

    Fregoso-García, María del Carmen; Campomanes-Azamar, Rubén Darío; Rodríguez-Chávez, José Luis; Madrigal-Rodríguez, Victor Manuel; Bañuelos-Franco, Alberto

    2015-11-01

    The ovaries accessories, ectopic and supernumerary represent a rare gynecological disorder; incidence ranges from 129,000 to 1:700,000 cases. Patient 55 years of age who arrived at by diffuse abdominal pain 2 weeks of evolution, nausea and vomiting, with no history of chronic degenerative diseases or surgical. Palpation abdomen soft depressible globoso palpable mass at the expense of 30x20 cm, painless to superficial and deep pressure. Bimanual: anteversoflexion uterus 9 cm, 20 cm tumor, soft, fixed, mild pain in the cervical mobilization funds free bag. Laboratory tests and tumor markers for ovarian unchanged. The abdominopelvic ultrasound ecomixta reported prodomain cystic mass of 28x13x26 cm, volume 5,470 mL, with papillary projections, septa and caps 6 mm thick. Contrasted abdominal tomography: nodular image of 20 cm, heterogeneous, predominantly cystic, with septa, uptake of contrast medium in the pelvic cavity of probable ovarian origin. laparotomy was performed and found: 8 cm uterus, normal, both atrophic ovaries; 30x20 cm tumor, smooth edges, with neovascularization and areas of calcification with serous content of 5,000 cc, attached to the handles of the jejunum and ileum; transverse colon, back and tail of the pancreas; It was dissected into the retroperitoneum and great vessels, apparent root of the prevertebral fascia. The supernumerary ovary is an extremely rare disorder, but should be considered in patients with abdominal tumors.

  10. Shift Work: A Risk Factor for Central Serous Chorioretinopathy.

    Science.gov (United States)

    Bousquet, Elodie; Dhundass, Myriam; Lehmann, Mathieu; Rothschild, Pierre-Raphaël; Bayon, Virginie; Leger, Damien; Bergin, Ciara; Dirani, Ali; Beydoun, Talal; Behar-Cohen, Francine

    2016-05-01

    To investigate if shift work or sleep disturbances are risk factors for central serous chorioretinopathy (CSCR). Prospective case-control study. Forty patients with active CSCR and 40 controls (age- and sex-matched) were prospectively recruited from the Ophthalmology Department of Hôtel Dieu Hospital, Paris, between November 2013 and December 2014. All patients were asked to complete a questionnaire addressing previously described risk factors and working hours, as well as the Insomnia Severity Index (ISI), a validated instrument for assessing sleep disturbances. The mean age of the CSCR group was 44 ± 9 years, whereas the mean age of the control group was 43 ± 10 years. By use of multivariate analysis, shift work (odds ratio [OR] [95% confidence interval]: 5 [1.2-20.4]; P = .02), steroid use (OR: 5.5 [1.1-26.2]; P = .03), and recent psychological stress (OR: 15.3 [4.1-54.5]; P work is an independent risk factor of CSCR. Further studies are required to confirm these results and to examine if work reconversion would be beneficial in the treatment of patients with chronic/recurrent CSCR. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. CHOROIDAL NEOVASCULARIZATION IN CAUCASIAN PATIENTS WITH LONGSTANDING CENTRAL SEROUS CHORIORETINOPATHY.

    Science.gov (United States)

    Peiretti, Enrico; Ferrara, Daniela C; Caminiti, Giulia; Mura, Marco; Hughes, John

    2015-07-01

    To report the frequency of choroidal neovascularization (CNV) in Caucasian patients with chronic central serous chorioretinopathy (CSC). Retrospective consecutive series of 272 eyes (136 patients) who were diagnosed as having chronic CSC based on clinical and multimodal fundus imaging findings and documented disease activity for at least 6 months. The CNVs were mainly determined by indocyanine-green angiography. Patients were evaluated and followed for a maximum of 6 years, with an average follow-up of 14 ± 12 months. Distinct CNV was identified in 41 eyes (34 patients). Based on fluorescein angiography, 37 eyes showed occult with no classic CNV, 3 eyes showed predominantly classic and 1 eye had a disciform CNV. Furthermore, indocyanine-green angiography revealed polypoidal choroidal vasculopathy lesions, in 27 of the 37 eyes, classified as occult CNV on fluorescein angiography. In total, 17.6% of our patients with chronic CSC were found to have CNV that upon indocyanine-green angiography were recognized as being polypoidal choroidal vasculopathy. In our series of Caucasian patients, we found a significant correlation between chronic CSC and CNV, in which the majority of patients with CNV were found to have polypoidal choroidal vasculopathy. Our findings suggest that indocyanine-green angiography is an indispensable tool in the investigation of chronic CSC.

  12. QT interval dispersion in the patients with central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Necati Dagli

    2015-02-01

    Full Text Available AIM: To evaluate QT dispersion (QTD in patients with central serous chorioretinopathy (CSC. METHODS: This clinical, comperative, case-control study included 30 patients with CSC at acute phase (Group 1 and 30 age- and sex-matched healthy subjects (Group 2, the control group. From all subjects, a 12-lead surface electrocardiography was obtained. The heart rate (HR, QT maximum (QTmax, QT minimum (QTmin, QT corrected (QTc, QTD and Tmean were manually measured and analyzed. Student’s t-test and Pearson’s method of correlation were used for statistical analysis. RESULTS: The patient and control groups were matched for age, smoking status (rate and duration and gender. There were no significant differences with regard to these among the groups (P>0.05. The participants included 19 men (63.3% and 11 women (36.7% in Group 1, 20 men (66.7% and 10 women (33.3% in Group 2. QTmax, QTD and QTc were significantly higher than those of healthy controls (P0.05 for HR. No significant correlation was found between duration of the disorder and QTD values (r=0.13, P>0.05. CONCLUSION: These findings suggest that CSC may be associated with an increase in QTD and that the patients might be at risk for ventricular arrhythmia.

  13. Frequency of Systemic Risk Factors in Central Serous Chorioretinopathy.

    Science.gov (United States)

    Islam, Qamar Ul; Hanif, Muhammad Kashif; Tareen, Sheraz

    2016-08-01

    To determine the frequency of various systemic risk factors associated with acute central serous chorioretinopathy (CSCR) in our setup. Descriptive case series. Armed Forces Institute of Ophthalmology (AFIO), Rawalpindi, from July 2011 to June 2014. All consecutive patients with acute CSCR who presented in the outpatient department during the study period were recruited. Clinical findings were endorsed on a pre-devised proforma with special emphasis on inquiring about known systemic risk factors for CSCR in detail from each patient. Patients were managed conservatively with control of modifiable risk factors and topical 0.1% Nepafenac eye drops. Analysis of data was done using SPSS version 13.0. Forty-four eyes of 42 patients were eligible for final analysis. The mean age of study population was 37.38 ±6.31 years with 38 (90.47%) male patients. Elevated serum cortisol and serum testosterone levels were found in 3 and 2 patients, respectively. Known systemic risk factors for CSCR were present in 36 (85.71%) patients with emotional stress/psychiatric disorder 15 (35.71%), Type Apersonality 11 (26.19%), smoking 10 (19.04%), hypertension 5 (11.90%), and acid peptic disease 4 (9.52%) were the most frequently found risk factors. Emotional stress/psychiatric illness, hypertension, acid peptic disease and use of exogenous steroids and other medicines are the established risk factors for CSCR that can be modified/withdrawn to reduce the morbidity related to CSCR.

  14. p53 signature and serous tubal in-situ carcinoma in cases of primary tubal and peritoneal carcinomas and serous borderline tumors of the ovary.

    Science.gov (United States)

    Leonhardt, Karoline; Einenkel, Jens; Sohr, Sindy; Engeland, Kurt; Horn, Lars-Christian

    2011-09-01

    The objective of this study was to evaluate the role of the fimbriated end and nonfimbriated epithelium of fallopian tubes with regard to p53 signature, tubal intraepithelial lesions in transition (TILT), and serous tubal in-situ carcinoma (STIC) in cases of different kinds of serous pelvic cancer. This study immunohistochemically evaluated (by Ki-67 and p53 staining) the presence of p53 signature, TILT lesions, and STIC in 14 consecutive cases of prophylactic salpingo-oophorectomy in women with BRCA-1/2 mutation (bilateral salpingo-oophorectomy), 11 cases of macroscopically inconspicuous adnexae of patients with primary contralateral tubal cancer (TC), 9 cases of primary peritoneal cancer (PPC), and 10 cases of serous ovarian borderline tumors, evaluating the fallopian tubes (using the Sectioning and Extensively Examining the FIMbria protocol), ovarian surface epithelium, and ovarian cortical inclusion cysts. The frequencies of p53 signature, TILT, and STIC were 35.7%, 7.1%, and 0% in cases of prophylactic surgery, 18.2%, 9.1%, and 18.2% in TC, and 11.1%, 0%, and 33.3% in PPC. These precursor lesions were missed during the initial routine screening and were found in the fimbriated end of the fallopian tubes in 94%. In 1 case of PPC, staining for p53 was negative in STIC. The studied adnexal tissue of serous ovarian borderline tumor and ovarian cortical inclusion cysts of all cases showed no alterations according to p53 signature, TILT, or STIC. STIC and p53 signature as precursor lesions of pelvic serous cancer were seen in macroscopically inconspicuous contralateral fallopian tubes in unilateral TC, in patients with elective bilateral salpingo-oophorectomy, and in patients affected by PPC. Therefore, we propose the complete processing of adnexal tissue and the use of step sectioning to establish the correct diagnosis. Immunohistochemistry for p53 and ki-67 may aid in the diagnosis, but is not necessary for routine investigation.

  15. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres; Schellhorn, Till; Haakonsen, Monika; Nakstad, Per H. (Section of Neuroradiology, Dept. of Medical Imaging and Intervention, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway)), e-mail: a.s.alonso@medisin.uio.no; Josefsen, Roger (Dept. of Neurosurgery, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway)); Kulle, Bettina (Epi-Gen Faculty Division, Akershus Univ. Hospital, and Dept. of Biostatistics, Univ. of Oslo, Oslo (Norway)); Maehlen, Jan; Kumar, Theresa (Dept. of Pathology, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway)); Gadmar, Oeystein (Dept. of Diagnostic Physics, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway)); Langberg, Carl W. (Cancer Center, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway))

    2010-04-15

    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

  17. 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.

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

    Science.gov (United States)

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

    2017-05-01

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

  19. Response of recurrent high-grade glioma to treatment with (90)Y-DOTATOC.

    Science.gov (United States)

    Heute, Dirk; Kostron, Herwig; von Guggenberg, Elisabeth; Ingorokva, Shota; Gabriel, Michael; Dobrozemsky, Georg; Stockhammer, Günther; Virgolini, Irene J

    2010-03-01

    The treatment of patients with high-grade malignant glioma still represents an unsolved clinical problem. We report the treatment of 3 patients who had World Health Organization grade IV recurrent glioblastoma: a 23-y-old woman and 2 men aged 61 and 62 y. All 3 patients were treated with the somatostatin receptor radiopharmaceutical (90)Y-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid(0)-d-Phe(1),Tyr(3)]octreotide (DOTATOC). A cumulated dose of 1.7-2.2 GBq given in 3 or 4 cycles was locally injected into a previously implanted catheter system. Treatment was successful in all 3 patients, with only minor side effects reported. After treatment, MRI and PET showed complete remission in one patient and partial remission in the other patients. These findings correlated well with clinical improvement and improved quality of life. Receptor-mediated radionuclide therapy by locally injected (90)Y-DOTATOC is feasible and well tolerated. This approach represents an attractive strategy for the treatment of locally recurring or progressing glioblastoma.

  20. 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.

  1. 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.

  2. 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.

  3. Return of motor evoked potentials after knee flexion in the setting of high-grade spondylolisthesis.

    Science.gov (United States)

    Tilan, Justin; Andras, Lindsay M; Krieger, Mark D; Skaggs, David L

    2017-03-01

    To present a case of loss of motor-evoked potentials (MEPs) to the left foot in the supine position after a partial reduction and instrumented fusion from L4 to pelvis which was managed successfully without revision or removal of implants. We report a patient with high-grade spondylolisthesis who demonstrated loss of motor-evoked potentials after posterior spinal fusion and transfer to supine position. The patient's knees were flexed to 90° and signals were immediately restored. Systemic steroids were administered and circumferential fusion was delayed 21 days. Anterior-interbody cage was placed without complication. She was discharged on post-operative day 2. At 7 months, she is pain free and doing well with plans to return to gymnastics completely. Knee flexion can be instituted when encountering a neuromonitoring signal change following posterior spinal fusion for spondylolisthesis as a means to alleviate acute nerve stretch injury and may in some cases prevent the need to lessen the correction. IV.

  4. 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.

  5. Recent Application of Advanced MR Imaging to Predict Pseudoprogression in High-grade Glioma Patients.

    Science.gov (United States)

    Yoo, Roh-Eul; Choi, Seung Hong

    2016-01-01

    Pseudoprogression is regarded as a subacute form of treatment-related change with a reported incidence of 20-30%, occurring predominantly within the first three months after the completion of concurrent chemoradiotherapy (CCRT) in glioblastoma multiforme (GBM) patients. Occurrence of progressive lesions on conventional contrast-enhanced MR imaging may also accompany clinical deterioration, posing considerable diagnostic challenges to clinicians and radiologists. False interpretation of treatment-related change as true progression may lead to the cessation of effective first-line therapy (i.e., adjuvant temozolomide) and unnecessary surgery. Increasing awareness of the diagnostic challenge of the phenomenon has underscored the need for better imaging techniques that may aid in differentiating the treatment-related change from true progression. In this review, we discuss the recent applications of advanced MR imaging such as diffusion-weighted and perfusion-weighted imaging in the evaluation of treatment response in high-grade glioma patients and highlight their potential role in differentiating pseudoprogression from true progression.

  6. 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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Alessandro Della Puppa

    2014-01-01

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

  9. Mutation of NRAS is a rare genetic event in ovarian low-grade serous carcinoma.

    Science.gov (United States)

    Xing, Deyin; Suryo Rahmanto, Yohan; Zeppernick, Felix; Hannibal, Charlotte G; Kjaer, Susanne K; Vang, Russell; Shih, Ie-Ming; Wang, Tian-Li

    2017-10-01

    Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate during the progression of SBT to invasive low-grade serous carcinoma (LGSC) remains largely unknown. Although mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been postulated to facilitate progression. In this study, we analyzed NRAS exon 3 mutational status in 98 cases that were diagnosed with SBT/atypical proliferative serous tumor, noninvasive LGSC, or invasive LGSC. Of the latter, NRAS Q61R (CAA to CGA) mutations were detected in only 2 of 56 (3.6%) cases. The same mutation was not detected in any of the SBTs (atypical proliferative serous tumors) or noninvasive LGSCs. Mutational analysis for hotspots in KRAS and BRAF demonstrated a wild-type pattern of KRAS and BRAF in one of the NRAS-mutated cases. Interestingly, another LGSC case with NRAS mutation harbored a concurrent BRAF V600L mutation. These findings indicate that, although recurrent NRAS mutations are present, their low prevalence indicates that NRAS plays a limited role in the development of LGSC. Further studies to identify other oncogenic events that drive LGSC progression are warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Early stage primary ovarian mucinous carcinoma: Outcome-based clinicopathological study in comparison with serous carcinoma.

    Science.gov (United States)

    Tian, Qifang; Lu, Bingjian; Ye, Jing; Lu, Weiguo; Xie, Xing; Wang, Xinyu

    2016-04-01

    To compare clinicopathological characteristics and survival rates between patients with primary ovarian mucinous carcinoma and those with primary ovarian serous carcinoma. This retrospective study reviewed archival tumour specimens, originally diagnosed as primary ovarian mucinous carcinoma, using refined histological criteria. All patients were contacted to establish survival status. Clinicopathological characteristics and patient survival data were compared with a group of control patients with primary ovarian serous carcinoma. Of the 33 patients originally diagnosed with primary ovarian mucinous carcinoma, this diagnosis was only confirmed in 18. Primary ovarian mucinous carcinoma was more commonly associated with early International Federation of Gynecology and Obstetrics tumour stages and low-grade histology than primary ovarian serous carcinoma. Patients with primary ovarian mucinous carcinoma had a significantly higher overall 5-year survival rate than those with primary ovarian serous carcinoma (12/12 [100%] versus 14/24 [58%]). Kaplan-Meier survival plots demonstrated that patients with primary ovarian mucinous carcinoma had a survival advantage over patients with primary ovarian serous carcinoma. Primary ovarian mucinous carcinomas are frequently low-grade, stage I tumours and have an excellent prognosis. © The Author(s) 2016.

  11. Immunophenotype and human papillomavirus status of serous adenocarcinoma of the uterine cervix.

    Science.gov (United States)

    Togami, Shinichi; Sasajima, Yuko; Kasamatsu, Takahiro; Oda-Otomo, Rie; Okada, Satoshi; Ishikawa, Mitsuya; Ikeda, Shun-ichi; Kato, Tomoyasu; Tsuda, Hitoshi

    2015-04-01

    Serous adenocarcinoma of the cervix (SACC) is a very rare tumor. Our study aimed to characterize the immune profile and human papillomavirus (HPV) status of SACC, in comparison with other serous adenocarcinomas arising in the female genital tract. The pathological specimens obtained from 81 patients with serous carcinoma of the uterine cervix (n = 12), 29 endometrium, 20 ovary and 20 patients with mucinous carcinoma of the uterine cervix were reviewed. We assessed the expression of WT-1, p53, p16, HER2, CEA, and CA125 by immunohistochemistry and HPV DNA by PCR in 12 SACC samples. Their immune profile was compared with that of uterine papillary serous carcinoma (UPSC), ovarian serous adenocarcinoma (OSA), and mucinous endocervical adenocarcinoma (MEA). WT-1 and HER2 were expressed in very few SACC samples (0 and 0%, respectively), but p16, CA125, CEA and p53 were present in 100, 92, 58 and 50%, respectively. The difference in WT-1 expression between SACC and UPSC, MEA is not significant, but SACC differ significantly from OSA (p p53 expression was associated with worse clinical outcome in patients with SACC, and that HPV infection was related to its occurrence.

  12. Serous carcinomatous component championed by heparin-binding EGF-like growth factor (HB-EGF) predisposing to metastasis and recurrence in stage I uterine malignant mixed mullerian tumor.

    Science.gov (United States)

    Zhang, Lei; Shimizu, David; Killeen, Jeffrey L; Honda, Stacey A; Lu, Di; Stanoyevitch, Alexander; Lin, Fritz; Wang, Beverly; Monuki, Edwin S; Carbone, Michele

    2016-07-01

    The stage I uterine malignant mixed mullerian tumor (MMMT) shows different potential for progression. We reason that MMMTs with high-grade carcinomatous component and positivity for HB-EGF are prone to recurrence/metastasis in the early stage. A retrospective clinical and histopathologic review with immunohistochemical staining for HB-EGF, EGFR, and integrin-α5 was performed for 62 surgically staged MMMT cases. Recurrence/metastasis (RM) is 6/18 (33%) in stage I disease. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component (83% [5/6] versus 17% [1/12], P = .0015) and HB-EGF expression (100% [6/6] versus 50% [6/12], P=.0339) were significantly different between groups with RM and without RM. The presence of serous carcinoma in all stages was 83% (5/6) in stage I with RM, 8% (1/12) in stage I without RM, 20% (1/5) in stage II, 36.4% (8/22) in stage III and 64.7% (11/17) in stage IV; this was paralleled by HB-EGF expression of 100% (6/6), 50% (6/12), 40% (2/5), 50% (11/22) and 71% (12/17) with a correlation coefficient r=0.9131 (P=.027). HB-EGF and integrin-α5 were highly expressed in MMMTs bearing serous carcinoma component, compared to endometrioid and unclassifiable/miscellaneous subtypes (84.6%/47.6%/33.3%, P=.025 for HB-EGF; and 61.5%/42.9%/20.0%, P=.021 for integrin-α5). The EGFR positivity was comparable among the three subtypes (48.1%, 47.6% and 26.7%, P=.326). This study indicates that serous carcinomatous component championed by expression of HB-EGF predisposes to recurrence/metastasis in stage I MMMT. This process might involve integrin-α5 and does not seem to require overexpression of EGFR. Further study is required. Published by Elsevier Inc.

  13. EphA5 protein, a potential marker for distinguishing histological grade and prognosis in ovarian serous carcinoma.

    Science.gov (United States)

    Chen, Xiao; Wang, Xuan; Wei, Xue; Wang, Jiandong

    2016-11-25

    Ovarian serous carcinoma (OSC) is the most common ovarian epithelial malignancy. Disregulation of Eph/ephrin signaling has been implicated in oncogenesis and tumor progression. EphA5 receptor is one of large families of Eph tyrosine kinase receptor and is documented in the development of nervous system. Till now, there is no published data about the role of EphA5 in ovarian epithelial neoplasmas. This study aims to investigate the expression of EphA5 protein in ovarian serous carcinoma, and its relationship to clinical pathological characteristics. Sixty-one cases of ovarian serous carcinoma, 24 cases of benign ovarian serous tumors, 42 cases of serous borderline tumors and 20 cases of normal fallopian tubes were examined using immunohistochemical staining. The relationship between EphA5 expression and pathological parameters was analyzed. Kaplan-Meier survival function was used to analyze prognosis of patients. Immunostaining analysis demonstrated that the EphA5 protein was highly expressed in 100% (20/20) of normal fallopian tube samples, 100% (24/24) of benign epithelial ovarian tumors, 76% (32/42) of ovarian serous borderline tumors, and 31% (19/61) of ovarian serous carcinomas. Loss of EphA5expression was associated with tumor grade (P ovarian serous carcinoma and a potential prognostic marker.

  14. P53, MAPK, topoisomerase II alpha and Ki67 immunohistochemical expression and KRAS/BRAF mutation in ovarian serous carcinomas

    Directory of Open Access Journals (Sweden)

    Sundov Dinka

    2013-02-01

    Full Text Available Abstract Background We investigated the immunohistochemical expression of p53, MAPK, topoisomerase II alpha (topoII alpha and Ki67 in ovarian serous carcinomas (OSCs along with mutational analysis for KRAS and BRAF. Methods Eighty one cases of OSCs were reviewed and examined immunohistochemically using antibodies against p53, MAPK, topoII alpha and Ki67. Staining was evaluated as a percentage of immunopositive cells with cut-off levels at 10% for p53 and topoII alpha, and 5% for MAPK. The Ki67 immunoexpression was assessed by means of Olympus Image Analysis System as a percentage of immunopositive cells in 1000 tumor cells. KRAS and BRAF mutational analysis was performed on 73 available microdissected samples. Results Of 81 cases of OSCs 13.6% were of low-grade and 86.4% were of high-grade morphology. In the high-grade group there was a significantly higher immunoexpression of p53 (P P = 0.001, with Ki67 median 56.5 vs. 19 in low-grade group (P P = 0.003. MAPK positive immunostaining was detected in 63.6% of low-grade vs. 17.1% of high-grade OSCs. The frequency of KRAS mutation was significantly higher in low-grade as compared to high-grade group (P = 0.006. None of the samples had BRAF mutation. In addition, we detected positive MAPK immunoexpression in 13/59 samples with wild-type KRAS, suggesting that activation of MAPK pathway is not ultimately related either to KRAS or BRAF mutation. Seven morphologically high-grade samples (11.7% showed both KRAS mutation and p53 immunopositivity. Conclusions Although this study is limited by its humble number of low-grade samples, our data fit the proposed dualistic pathway of ovarian carcinogenesis. Mutational analysis for KRAS and BRAF discloses some possible interactions between different tumorigenic pathways of low- and high-grade carcinomas. Immunohistochemical staining for MAPK was not sufficiently sensitive, nor specific, to precisely predict the KRAS mutation. However, it appears

  15. Immunohistochemical identification of primary peritoneal serous cystadenocarcinoma mimicking advanced colorectal carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    von Riedenauer Wesley B

    2007-11-01

    Full Text Available Abstract Primary peritoneal cystadenocarcinoma is a rare tumor of similar histogenic origin as primary ovarian carcinoma. We present a case of primary peritoneal serous cystadenocarcinoma mimicking advanced colorectal cancer in a 68 yr-old African American female. Radiology, endoscopy and cytology yielded only inconclusive findings. Immunohistochemical analysis of percutaneously obtained ascitic fluid provided a correct diagnosis of primary peritoneal cystadenocarcinoma. The discovery of serous ascites at the time of laparotomy confirmed a diagnosis of primary peritoneal serous cystadenocarcinoma. Final surgical pathology reconfirmed the diagnosis of primary peritoneal cystadenocarcinoma. This case demonstrates the utility of immunohistochemistry for accurately diagnosing patients with inconclusive findings in the setting of peritoneal carcinomatosis and primary peritoneal cystadenocarcinoma.

  16. Recurrent central serous chorioretinopathy after peripheral retinal laser photocoagulation: a case report.

    Science.gov (United States)

    Semeraro, Francesco; Russo, Andrea; Delcassi, Luisa; Costagliola, Ciro

    2013-01-01

    To report a case of recurrent central serous chorioretinopathy (CSC) after performing peripheral laser photocoagulation for retinal degenerations. A 44-year-old woman with ocular history of CSC presented to the emergency room of our department complaining of heavy photopsia due to retinal tuft and lattice degenerations, and underwent laser photocoagulation to prevent retinal detachment. Two days after laser treatment, the visual acuity dropped, and optical coherence tomography scan showed the onset of CSC. The serous detachment completely resolved in 20 days with no therapy. A new CSC episode occurred in the same eye after another analogous laser treatment and, similarly, quickly resolved spontaneously. We reviewed the literature and discuss the possibility that laser-induced inflammation could rouse an inflammatory cascade mediated by proinflammatory cytokines and PAI-1, leading to the exacerbation of retinal serous detachment in susceptible patients.

  17. Simultaneous Serous Cyst Adenoma and Ovarian Pregnancy in An Infertile Woman

    Directory of Open Access Journals (Sweden)

    Mahbod Ebrahimi

    2014-03-01

    Full Text Available Ovarian pregnancy is a rare form of extra uterine pregnancy. Serous cyst adenoma is a benign variant of epithelial cell tumors of ovary. The coexistence of a cyst adenoma with an ovarian pregnancy in the same ovary is extremely rare. Some studies suggested that infertility or ovulation-inducing drugs can be involved in increased risk of ovarian tumors and ovarian pregnancies. A 28-year-old infertile woman presented with a ruptured ovarian pregnancy following ovulation induction with metformin. She had a concurrent benign serous cyst adenoma in the same ovary. Resection of both ovarian pregnancy and tumoral mass were performed. The ovary was preserved. Removal of gestational tissue and preservation of the involved ovary are the best options for management of ovarian pregnancy in young patient. Although there is an association between infertility/ovulation inducting medications and ovarian gestation, their connections with serous cyst adenoma are undetermined.

  18. A Rare Case of Deep Pelvic Endometriosis Presenting with Serous Ascites and Infertility

    Directory of Open Access Journals (Sweden)

    Türkan Gürsu

    2016-02-01

    Full Text Available In this study it is aimed to define a rare case of deep pelvic endometriosis with massive serous ascites and infertility. Literature search revealed sporadic cases of endometriosis presenting with bloody or brownish ascites, some had also pleural effusion and CA-125 levels were elevated in all cases. Our case had normal CA-125 level and normal looking ovaries. Besides classic endometriosis symptoms, our case was asymptomatic. Endometriosis is diagnosed postoperatively on the basis of histopathology. Management of infertility was IVF-ET, which resulted with a succesful pregnancy. This is the first case of deep pelvic endometriosis presenting with serous ascites and infertility. More reports are required to determine whether endometriosis with serous ascites has good prognosis in infertility or not.

  19. Suprapedicular Circumferential Opening Technique of Percutaneous Endoscopic Transforaminal Lumbar Discectomy for High Grade Inferiorly Migrated Lumbar Disc Herniation

    Directory of Open Access Journals (Sweden)

    Hyeun Sung Kim

    2018-01-01

    Full Text Available Purpose. To evaluate the efficacy of suprapedicular circumferential opening technique (SCOT of percutaneous endoscopic transforaminal lumbar discectomy (PETLD for high grade inferiorly migrated lumbar disc herniation. Material and Methods. Eighteen consecutive patients who presented with back and leg pain with a single-level high grade inferiorly migrated lumbar disc herniation were included. High grade inferiorly migrated disc was removed by the SCOT through PETLD approach. Outcome evaluation was done with visual analog scale (VAS and Mac Nab’s criteria. Result. There were 14 males and 4 females. The mean age of patients was 53.3±14.12 years. One, 4, and 13 patients had disc herniation at L1-2, L3-4, and L4-5 levels, respectively, on MRI, which correlated with clinical findings. The mean follow-up duration was 8.4±4.31 months. According to Mac Nab’s criteria, 9 patients (50% reported excellent and the remaining 9 patients (50% reported good outcomes. The mean preoperative and postoperative VAS for leg pain were 7.36±0.73 and 1.45±0.60, respectively (p<0.001. Improvement in outcomes was maintained even at final follow-up. There was no complication. Conclusion. In this preliminary study we achieved good to excellent clinical results using the SCOT of PETLD for high grade inferiorly migrated lumbar disc herniation.

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  1. Frequency of fibromyalgia syndrome in patients with central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Ayse Balkarli

    Full Text Available ABSTRACT Purpose: To ınvestigate frequency of fibromyalgia syndrome (FMS among patients with central serous chorioretinopathy (CSCR. Methods: The study included 83 patients with CSCR and 201 age- and sex-matched healthy controls; the mean age was 47.5 ± 11.3 years in the CSCR group (18 women; 21.7% and 47.2 ± 11.2 years in the control group (44 women; 21.9%. All participants were assessed for FMS based on 2010 American College of Rheumatology diagnostic criteria and for depression and anxiety with the Beck Anxiety Inventory (BAI and Beck Depression Inventory (BDI. Results: FMS was diagnosed in 35 patients (42.2% from the CSCR group and in 21 individuals (10.4% from the control group (p<0.001. It was found in 77.77% of the women (14/18 and 32.3% of the men (21/65 in the CSCR group and in 22.7% of the women (10/44 and 7.0% of the men (11/157 in the control group. Familial stress, BDI and BAI scores were higher in the patients with FMS than in those without. When independent risk factors were evaluated by logistic regression analysis, it was found that only the presence of familial stress was a significant risk factor for FMS. Conclusions: Patients with CSCR should be assessed for the presence of FMS, and this should be taken into consideration when developing a treatment plan. Further studies with a larger sample size are needed to clarify the relationship between FMS and CSCR.

  2. Expression of Nestin and CD133 in serous ovarian carcinoma.

    Science.gov (United States)

    Onisim, Andrea; Iancu, Mihaela; Vlad, Catalin; Kubelac, Paul; Fetica, Bogdan; Fulop, Annamaria; Achimas-Cadariu, Andrei; Achimas-Cadariu, Patriciu

    2016-01-01

    Pupose: Nestin and CD133 are regarded as putative markers of cancer stem cells (CSCs) and related to poor prognosis in various cancer sites. Since few studies have focused on their role in ovarian cancer, we aimed to investigate their predictive value and association with neoangiogenesis. Immunohistochemical analysis for nestin and CD133 was performed on 85 serous ovarian carcinoma tumor samples using tissue microarray technique. Nestin immunoreactivity was detected in both tumor and endothelial cells, whilst CD133 was only identified in tumor cells. CD34 endothelial expression was used to assess intratumor microvessel density (MVD). Of the tissue samples 49.4% were nestin-positive and 24.7% were positive for CD133. In both univariate and multivariate analysis nestin or CD133 expressions in tumor cells were not significantly associated with clinicopathological parameters (age, serum CA125, peritoneal carcinomatosis, malignant ascites, tumor grade). However, in multivariate analysis nestin expression in tumor cells proved to be an independent prognostic factor, associated with poorer survival and time to progression (p=0.025 and p=0.05, respectively). This has not been achieved for CD133. Furthermore, a significant concordance between nestin endothelial expression (nestin-determined MVD) and CD34-determined MVD was achieved. In addition to the well-known clinicopathological characteristics, tumor expression of nestin might be a valuable prognostic factor for survival in patients with advanced ovarian cancer. With regard to its endothelial expression, nestin might be as reliable as CD34 for quantifying tumor angiogenesis. Further investigation is justified in order to better clarify the role of these biomarkers.

  3. P53 and bcl-2 assessment in serous ovarian carcinoma.

    Science.gov (United States)

    Palmer, J E; Sant Cassia, L J; Irwin, C J; Morris, A G; Rollason, T P

    2008-01-01

    The study objective was to determine the prognostic value of assessment of staining of p53 and bcl-2 in a well-selected group of serous ovarian carcinomas. Immunohistochemical detection was used to identify both p53 and bcl-2 positive tumors. One hundred thirty-two tumors were analyzed for positivity of staining, grade of staining intensity, and for p53 alone, percent expression rates. These were analyzed alongside traditional clinicopathologic parameters for their ability to predict overall survival (OS), disease-free survival (DFS), and response to chemotherapy (CR). Univariate COX analysis revealed percent p53 expression (P = 0.012) and p53 grade (P = 0.01) to be significant predictors of DFS. Neither the p53 nor bcl-2 measurement parameters were found significant for OS or prediction of CR. On multivariate analysis, incorporating clinicopathologic parameters, p53 parameters did not retain independent significance for any outcome measure. As in primary reported studies, bcl-2 was not found to be of clear independent prognostic value in this group of ovarian tumors. If mutation of p53 and its consequent overexpression is an early event in ovarian tumorigenesis, then p53 assessment may prove useful prognostically in the assessment of either low-grade ovarian carcinomas, as a possible indicator for progression, or in early-stage ovarian tumors, as a marker of tumor aggression or likelihood of recurrence. p53 analysis of a larger group of stage I ovarian tumors would be desirable to further explain the potential association with DFS.

  4. Omental Biopsy for Surgical Staging of Uterine Serous Carcinoma.

    Science.gov (United States)

    Luz, Rita; MacDonald, Nicola; Mould, Tim

    2016-10-01

    The aims of this study were to determine the role of omental sampling in staging of uterine serous carcinoma (USC) and to evaluate its impact on patient outcomes. A retrospective study of 106 women with USC who underwent primary surgery between 2005 and 2014 was done. Overall survival, disease-free survival, and progression and recurrence patterns were studied in 84 patients with follow-up over 1 year. Diagnostic characteristics were evaluated for preoperative imaging and operative findings. Univariate and multivariate analyses were performed to evaluate risk factors for omental metastasis. Survival curves were used to compare omental sampling status and the presence of omental metastasis. Of the 106 patients, 66 underwent surgical staging with omental biopsy (54; 82%) or omentectomy (12, 18%). Eight (12%) patients had metastatic disease in the omental samplings. All 6 patients with macrometastasis had visible lesions or palpable nodules and preoperative computed tomography (CT) was suspicious in 3. In 2 (3%) patients, omentum was not suspicious on CT or intraoperatively but had micrometastases. The negative predictive value regarding the staging CT scan was 92% and of the operative findings was 97%. On multivariate analysis, no variable was associated with omental involvement. Disease progressed or recurred in 40 (48%) patients. The most frequent sites of recurrence or progression were the omentum (23; 27%), peritoneum (26; 31%), pelvis (15, 18%), lung (15, 18%), and liver (12, 14%). Comparing the groups with or without omental assessment, no significant difference was found regarding progression and recurrence patterns, overall survival, and disease-free survival. Omental involvement in USC upstages patients to stage IV disease and traditional risk factors fail to predict extrauterine disease. Although omental sampling does not influence disease progression or survival, a comprehensive intraoperative evaluation of the omentum is advised as most cases have grossly

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

    Science.gov (United States)

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

    2012-12-01

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

  6. A Molecular Portrait of High-Grade Ductal Carcinoma In Situ.

    Science.gov (United States)

    Abba, Martin C; Gong, Ting; Lu, Yue; Lee, Jaeho; Zhong, Yi; Lacunza, Ezequiel; Butti, Matias; Takata, Yoko; Gaddis, Sally; Shen, Jianjun; Estecio, Marcos R; Sahin, Aysegul A; Aldaz, C Marcelo

    2015-09-15

    Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer whereas others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome, and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty-two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM, and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor-intrinsic subtypes, proliferative, immune scores, and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like, or ERBB2(+)) displayed signatures characteristic of activated Treg cells (CD4(+)/CD25(+)/FOXP3(+)) and CTLA4(+)/CD86(+) complexes indicative of a tumor-associated immunosuppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly, ncRNA and methylation profiles reproduce changes observed postinvasion. Among the most significant findings, we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a preinvasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer. ©2015 American Association for Cancer Research.

  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. 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.

  9. 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.

  10. Stathmin is a highly sensitive and specific biomarker for vulvar high-grade squamous intraepithelial lesions.

    Science.gov (United States)

    Nooij, Linda S; Dreef, Enno J; Smit, Vincent T H B M; van Poelgeest, Mariëtte I E; Bosse, Tjalling

    2016-12-01

    Differentiating between human papilloma virus-dependent vulvar low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) remains difficult in selected cases. Stathmin, a protein involved in cell cycle progression, might be a useful additional marker for this differentiation. The aim of this study was to investigate the additional diagnostic value of stathmin expression in vulvar intraepithelial neoplastic (VIN) lesions. Immunohistochemical analysis was used to evaluate stathmin, P16 and Ki67 expression in 91 samples, including LSILs (n=16), HSILs (n=50), differentiated VIN (dVIN; n=10), lichen sclerosis (LS; n=10) and normal vulvar tissue (n=5). Stathmin was expressed in more than one-third of the epithelium in all HSILs and in 20% of LSILs. P16 and Ki67 were expressed in more than one-third of the epithelium in 94% of HSILs and in 13% and 40% of LSILs, respectively. Stathmin was expressed in more than one-third of the epithelium in 10% of the dVIN and in none of the LS or normal lesions. P16 and Ki67 expression was not present in more than one-third of the epithelium in any of these lesions. The sensitivity of stathmin for differentiating between LSILs and HSILs was 100% compared with a sensitivity of 94% for both p16 and Ki67. The specificity of stathmin, p16 and Ki67 was 80%, 87% and 60%, respectively. Stathmin is a highly sensitive and specific biomarker for the diagnosis of vulvar HSIL. In addition to the more commonly used immunohistochemical markers p16 and Ki67, stathmin can be a useful diagnostic tool for identifying HSILs, especially in cases in which differentiating between LSIL and HSIL is difficult. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. EGFR is involved in dermatofibrosarcoma protuberans progression to high grade sarcoma.

    Science.gov (United States)

    Osio, Amélie; Xu, Shuo; El Bouchtaoui, Morad; Leboeuf, Christophe; Gapihan, Guillaume; Lemaignan, Christine; Bousquet, Guilhem; Lebbé, Céleste; Janin, Anne; Battistella, Maxime

    2018-02-02

    Dermatofibrosarcoma protuberans (DFSP), amounting to 6% of all soft tissue sarcomas, has a slow growth rate, contrasting with a likelihood for local recurrence and a 10-20% evolution to higher-grade sarcoma, or "transformed DFSP" (DFSP-T). At molecular level, the characteristic COL1A1-PDGFB rearrangement, leading to sustained PDGFR signaling, is not linked to the evolutive potential. Here, we studied EGFR, another tyrosine kinase receptor, using laser-microdissection to select the different histologic components of DFSP (DFSP center, DFSP infiltrative periphery, DFSP-T higher-grade sarcoma), in 22 patients followed over 3 to 156 months. EGFR protein and mRNA were expressed in 13/22 patients with DFSP or DFSP-T, and increased with tumor progression, both in microdissected areas of higher-grade sarcomas and in microdissected areas of local extension. No cancer-associated EGFR gene mutation or copy-number variation, nor any KRAS, BRAF, NRAS hotspot mutations were found in any microdissected area. Among epithelial-mesenchymal transition factors tested, SNAIL 1/2 had the same expression pattern as EGFR while ZEB1/2 or TWIST1/2 did not. Using a proteome profiler phospho-kinase array on 3 DFSP and 3 DFSP-T cryopreserved tissue samples, EGFR phosphorylation was detected in each case. Among EGFR downstream pathways, we found positive correlations between phosphorylation levels of EGFR and STAT5a/b (r = 0.87, p 0.70). We thus demonstrated that in DFSP evolution to high grade sarcoma, EGFR and SNAIL were involved, with EGFR activation and signaling through TOR and STAT5a/b downstream effectors, which could lead on to new therapies for advanced DFSP.

  12. Signaling pathways and mesenchymal transition in pediatric high-grade glioma.

    Science.gov (United States)

    Meel, Michaël H; Schaper, Sophie A; Kaspers, Gertjan J L; Hulleman, Esther

    2018-03-01

    Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal types of cancer in children. In recent years, it has become evident that these tumors are driven by epigenetic events, mainly mutations involving genes encoding Histone 3, setting them apart from their adult counterparts. These tumors are exceptionally resistant to chemotherapy and respond only temporarily to radiotherapy. Moreover, their delicate location and diffuse growth pattern make complete surgical resection impossible. In many other forms of cancer, chemo- and radioresistance, in combination with a diffuse, invasive phenotype, are associated with a transcriptional program termed the epithelial-to-mesenchymal transition (EMT). Activation of this program allows cancer cells to survive individually, invade surrounding tissues and metastasize. It also enables them to survive exposure to cytotoxic therapy, including chemotherapeutic drugs and radiation. We here suggest that EMT plays an important, yet poorly understood role in the biology and therapy resistance of pHGG and DIPG. This review summarizes the current knowledge on the major signal transduction pathways and transcription factors involved in the epithelial-to-mesenchymal transition in cancer in general and in pediatric HGG and DIPG in particular. Despite the fact that the mesenchymal transition has not yet been specifically studied in pHGG and DIPG, activation of pathways and high levels of transcription factors involved in EMT have been described. We conclude that the mesenchymal transition is likely to be an important element of the biology of pHGG and DIPG and warrants further investigation for the development of novel therapeutics.

  13. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    C. Abrudan

    2011-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Chika Anele Ndubuisi

    2017-01-01

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

  17. Histologic variation in high grade oral epithelial dysplasia when associated with high-risk human papillomavirus.

    Science.gov (United States)

    Khanal, Sujita; Trainor, Patrick J; Zahin, Maryam; Ghim, Shin-Je; Joh, Joongho; Rai, Shesh N; Jenson, Alfred Bennett; Shumway, Brian S

    2017-05-01

    Reported cytologic alterations associated with high-risk human papillomavirus (HR-HPV) in oral epithelial dysplasia (HPV-OED) need further characterization. Archival cases of high-grade oral epithelial dysplasia (hgOED) (N = 38) were assigned a cytologic score (CS) based on the average number of mitotic, karyorrhectic, and apoptotic cells per high-power field. Three groups were then generated on the basis of increasing CS: Focal (group 1, N = 14), Intermediate (group 2, N = 12), and Diffuse (group 3, N = 12). Polymerase chain reaction-based HPV genotyping and p16 immunohistochemistry were performed. HR-HPV was found significantly more in group 3 (83.3%) compared with groups 1 and 2 (group 1&2; 42.9% and 41.7%, respectively; P = .047). HPV16 predominated in HR-HPV-positive cases (90.5%). By location, the tongue or the floor of mouth was associated with all groups (P = .04). Increasing CS was associated with a slightly younger age (P = .04) and increased expression of p16 (P = .005). CS and p16 expression were not sensitive but were highly specific predictors for HR-HPV presence. Based on limited follow-up information, HPV-OED does not differ in clinical aggressiveness compared with conventional OED. Increased CS in hgOED is strongly associated with HR-HPV (mostly HPV16) and p16 expression. CS and p16 expression are specific predictors of HR-HPV presence. Further molecular study and long-term follow-up of HPV-OED are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Taphoorn, Martin J.B.; Uitdehaag, Bernard; Heimans, Jan J.; Deliens, Luc; Reijneveld, Jaap C.; Pasman, H. Roeline 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 dignity as perceived by their relatives and (b) identify disease and care factors correlated with dying with dignity in HGG patients. Methods. 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. Results. 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. Conclusions. 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. PMID:23335620

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-02-01

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

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

    International Nuclear Information System (INIS)

    Karunamuni, Roshan; Bartsch, Hauke; White, Nathan S.; Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah C.; Seibert, Tyler M.; McDonald, Carrie R.; Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua; Mell, Loren; Brewer, James B.; Dale, Anders M.; Hattangadi-Gluth, Jona A.

    2016-01-01

    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.

  1. Molecular Requirements for Transformation of Fallopian Tube Epithelial Cells into Serous Carcinoma

    Directory of Open Access Journals (Sweden)

    Amir A. Jazaeri

    2011-10-01

    Full Text Available Although controversial, recent studies suggest that serous ovarian carcinomas may arise from fallopian tube fimbria rather than ovarian surface epithelium. We developed an in vitro model for serous carcinogenesis in which primary human fallopian tube epithelial cells (FTECs were exposed to potentially oncogenic molecular alterations delivered by retroviral vectors. To more closely mirror in vivo conditions, transformation of FTECs was driven by the positive selection of growth-promoting alterations rather antibiotic selection. Injection of the transformed FTEC lines in SCID mice resulted in xenografts with histologic and immunohistochemical features indistinguishable from poorly differentiated serous carcinomas. Transcriptional profiling revealed high similarity among the transformed and control FTEC lines and patient-derived serous ovarian carcinoma cells and was used to define a malignancy-related transcriptional signature. Oncogene-treated FTEC lines were serially analyzed using quantitative reverse transcription-polymerase chain reaction and immunoblot analysis to identify oncogenes whose expression was subject to positive selection. The combination of p53 and Rb inactivation (mediated by SV40 T antigen, hTERT expression, and oncogenic C-MYC and HRAS accumulation showed positive selection during transformation. Knockdown of each of these selected components resulted in significant growth inhibition of the transformed cell lines that correlated with p27 accumulation. The combination of SV40 T antigen and hTERT expression resulted in immortalized cells that were nontumorigenic in mice, whereas forced expression of a dominant-negative p53 isoform (p53DD and hTERT resulted in senescence. Thus, our investigation supports the tubal origin of serous carcinoma and provides a dynamic model for studying early molecular alterations in serous carcinogenesis.

  2. Effect of Tubal Sterilization Technique on Risk of Serous Ovarian and Primary Peritoneal Carcinoma

    Science.gov (United States)

    LESSARD-ANDERSON, Collette R.; HANDLOGTEN, Kathryn S.; MOLITOR, Rochelle J.; DOWDY, Sean C.; CLIBY, William A.; WEAVER, Amy L.; SAUVER, Jennifer ST.; BAKKUM-GAMEZ, Jamie N.

    2014-01-01

    Objective To determine the effect of excisional tubal sterilization on subsequent development of serous epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC). Methods We performed a population-based, nested case-control study using the Rochester Epidemiology Project. We identified all patients with a diagnosis of serous EOC or PPC from 1966 through 2009. Each case was age-matched to 2 controls without either diagnosis. Odds ratios (ORs) and corresponding 95% CIs were estimated from conditional logistic regression models. Models were adjusted for prior hysterectomy, prior salpingo-oophorectomy, oral contraceptive use, endometriosis, infertility, gravidity, and parity. Results In total, we identified 194 cases of serous EOC and PPC during the study period and matched them with 388 controls (mean [SD] age, 61.4 [15.2] years). Fourteen cases (7.2%) and 46 controls (11.9%) had undergone tubal sterilization. Adjusted risk of serous EOC or PPC was slightly lower after any tubal sterilization (OR, 0.59 [95% CI, 0.29–1.17]; P=.13). The rate of excisional tubal sterilization was lower in cases than controls (2.6% vs 6.4%). Adjusted risk of serous EOC and PPC was decreased by 64% after excisional tubal sterilization (OR, 0.36 [95% CI, 0.13–1.02]; P=.054) compared with those without sterilization or with nonexcisional tubal sterilization. Conclusions We present a population-based investigation of the effects of excisional tubal sterilization on the risk of serous EOC and PPC. Excisional methods may confer greater risk reduction than other sterilization methods. PMID:25316178

  3. Mucosal carcinoma of the fallopian tube coexists with ovarian cancer of serous subtype only: a study of Japanese cases.

    Science.gov (United States)

    Maeda, Daichi; Ota, Satoshi; Takazawa, Yutaka; Ohashi, Kenichi; Mori, Masaya; Imamura, Tetsuo; Nakagawa, Shunsuke; Yano, Tetsu; Taketani, Yuji; Fukayama, Masashi

    2010-11-01

    Previous studies in Western countries have revealed that mucosal carcinoma of the fallopian tube frequently coexists with pelvic (ovarian, tubal, and peritoneal) serous carcinomas, and early tubal carcinoma is now regarded as a possible origin of these tumors. However, the relationship between early tubal carcinoma and non-serous ovarian cancer, such as clear cell adenocarcinoma, has not been studied in detail. In this study, we sought to examine the coexistence of mucosal carcinoma of the fallopian tube in Japanese ovarian cancer cases. We submitted the fallopian tubes in toto for histological examination in 52 ovarian carcinoma cases and three peritoneal serous carcinoma cases. The ovarian tumors included 12 serous adenocarcinomas, 23 clear cell adenocarcinomas, nine endometrioid adenocarcinomas, three mucinous adenocarcinomas, and four mixed epithelial carcinomas. Mucosal carcinoma of the fallopian tube did not coexist with non-serous adenocarcinoma (n = 40). In contrast, mucosal carcinoma of the fallopian tube was observed in six cases of ovarian serous adenocarcinoma and one case of peritoneal serous adenocarcinoma. In these cases, the p53 immunophenotypes were similar in tubal lesions and invasive ovarian or peritoneal carcinomas. Tumors were negative for p53 in four of seven cases, and one of the p53-negative serous adenocarcinomas showed low-grade morphology. We believe that some ovarian and peritoneal serous adenocarcinomas develop from early tubal carcinomas. However, it should be noted that early tubal carcinomas are not always p53-positive immunohistochemically. Finally, it is unlikely that early tubal lesions are involved in the carcinogenesis of clear cell adenocarcinoma and other non-serous adenocarcinomas.

  4. Impact of adhesive capsulitis and economic evaluation of high-grade and low-grade mobilisation techniques.

    Science.gov (United States)

    van den Hout, Wilbert B; Vermeulen, Henricus M; Rozing, Piet M; Vliet Vlieland, Thea P M

    2005-01-01

    The purpose of this study was to estimate the impact of adhesive capsulitis on costs and health and to compare the cost-utility of high-grade and low-grade mobilisation techniques. In a randomised controlled trial, 92 patients with adhesive capsulitis received either high-grade mobilisation techniques or low-grade mobilisation techniques and were followed for one year. Outcome measures were quality adjusted life years (QALYs) according to the Short Form 6D (SF-6D) and societal costs estimated from cost questionnaires. Estimated costs and QALYs in both randomisation groups were similar, except for the number of treatment sessions (18.6 for high-grade mobilisation techniques versus 21.5 for low-grade mobilisation techniques), with an estimated cost difference of 105 euros in favour of high-grade mobilisation techniques (p = 0.001, 95% CI 43 euros to 158 euros). In the entire sample, the average valuation of health improved from 0.597 at baseline to 0.745 after a year. The burden due to adhesive capsulitis was estimated at 0.048 QALY and 4,521 euros per patient. About half these costs were due to absenteeism which, during the first quarter, amounted to 38% of the total working hours. In conclusion, the cost-utility analysis does not allow for an evidence-based recommendation on the preferred treatment. Based on the clinical outcome measures, high-grade mobilisation techniques are still preferred to low-grade mobilisation techniques. The estimated substantial burden, both to the patient and to society, suggests that effective early treatment of adhesive capsulitis is warranted to attempt to accelerate recovery.

  5. 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.

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

    Science.gov (United States)

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

    2014-04-01

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

  7. Solitary metastases and high-grade gliomas: radiological differentiation by morphometric analysis and perfusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hakyemez, B., E-mail: bahattinh@hotmail.co [Uludag University School of Medicine, Department of Radiology, Division of Neuroradiology, Bursa (Turkey); Erdogan, C.; Gokalp, G.; Dusak, A.; Parlak, M. [Uludag University School of Medicine, Department of Radiology, Division of Neuroradiology, Bursa (Turkey)

    2010-01-15

    Aim: To evaluate the value of morphometric analysis and perfusion-weighted magnetic resonance imaging (MRI) in differentiating solitary metastases from high-grade gliomas. Materials and methods: Forty-eight tumours (22 high-grade gliomas and 26 solitary hemispheric metastases) were evaluated using conventional and perfusion-weighted MRI. T2-weighted, gradient-echo, echo-planar sequences were used for perfusion-weighted MRI. Relative cerebral blood volume (rCBV) ratios were calculated by dividing the rCBV of the intratumoural and peritumoural areas with the average CBV value of the normal white matter areas. Morphometric analysis was carried out by proportioning the area of peritumoural oedema to the mass area. Mann-Whitney U test and ROC curve analysis were applied for statistical analysis. P < 0.05 was accepted as statistically significant. Results: Mean rCBV ratios of intratumoural areas of high-grade gliomas and metastases were 5.02 +- 2.47 and 4.62 +- 2.46, respectively. No statistically significant difference was found (p = 0.515). rCBV ratios of peritumoural oedema were 0.89 +- 0.51 in high-grade gliomas and 0.31 +- 0.12 in metastases. The difference was statistically significant (p < 0.001). According to the results of morphometric analysis, a statistically significant difference was present between the two tumour types (p < 0.001). Conclusion: Measuring the oedema: mass and rCBV ratios of the oedema surrounding the tumour prior to operation in solitary masses proved to be useful for differentiating metastases from high-grade gliomas.

  8. Secretory cell outgrowth, PAX2 and serous carcinogenesis in the fallopian tube

    OpenAIRE

    Chen, Eleanor Y.; Mehra, Karishma; Mehrad, Mitra; Ning, Gang; Miron, Alexander; Mutter, George L.; Monte, Nicholas; Quade, Bradley J.; McKeon, Frank D.; Yassin, Yosuf; Xian, Wa; Crum, Christopher P.

    2010-01-01

    The “p53 signature” is a benign secretory cell outgrowth in the distal fallopian tube that shares properties with ovarian serous cancer – including p53 mutations - and is a putative serous cancer precursor. We expanded the precursor definition to all secretory cell outgrowths (SCOUTs) of 30 or more cells and scored normal (N) and altered (A) expression of both p53 and PAX2, a gene down-regulated in ovarian and endometrial cancer. SCOUTs were identified by BCL2/p73 staining in tubes from women...

  9. Retinal pigment epithelial atrophy following indocyanine green dye-assisted surgery for serous macular detachment

    Directory of Open Access Journals (Sweden)

    Hussain Nazimul

    2008-01-01

    Full Text Available To report subretinal migration of indocyanine green dye (ICG and subsequent retinal pigment epithelial (RPE atrophy during macular surgery for serous macular detachment. A 65-year-old woman presented with residual epiretinal membrane and serous detachment of the macula following vitreoretinal surgery for epiretinal membrane. She underwent resurgery with ICG-assisted internal limiting membrane peeling and intraocular tamponade. Intraoperatively a large area of subretinal ICG was seen with subsequent RPE mottling and atrophy of the macula in the area involved during follow-up. This case demonstrates that subretinal migration of ICG is possible and can be toxic to RPE.

  10. Bilateral exudative retinal detachment associated with central serous chorioretinopathy in a patient treated with corticosteroids.

    Science.gov (United States)

    Rueda-Rueda, T; Sánchez-Vicente, J L; Llerena-Manzorro, L; Medina-Tapia, A; González-García, L; Alfaro-Juárez, A; Vital-Berral, C; López-Herrero, F; Muñoz-Morales, A; Ortega, L S; Herrador-Montiel, Á

    2017-10-01

    The case is presented on a 54-year-old woman with a central serous chorioretinopathy, misdiagnosed as Vogt-Koyanagi-Harada disease, and treated with systemic corticosteroids. The patient presented with a bilateral bullous exudative retinal detachment. Discontinuation of corticosteroid therapy, surgical drainage of subretinal fluid, and photodynamic therapy, led to anatomical and functional improvement. The recognition of an atypical presentation of central serous chorioretinopathy may avoid complications of the inappropriate treatment with corticosteroids. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Testicular papillary serous cystadenocarcinoma: a rare case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Sharhriar Zeighami

    2011-10-01

    Full Text Available Papillary serous cystadenocarcinoma of the ovary is a common tumor but occurrence of ovarian type papillary serous cystadenocarcinoma in the testis is very rare. Herein we report such a case in a 49-year-old man presenting with testicular swelling. In this tumor, mesothelioma of tunica vaginalis should be excluded by immunohistochemistry. The best treatment is radial orchiectomy and it is very resistant to chemoradiation. Our case was well after orchiectomy and now after a year he is doing well and completely symptom free.

  12. Expression of π-class glutathione S-transferase: two populations of high grade prostatic intraepithelial neoplasia with different relations to carcinoma

    OpenAIRE

    Montironi, R; Mazzucchelli, R; Stramazzotti, D; Pomante, R; Thompson, D; Bartels, P H

    2000-01-01

    Background/Aims—Patients with high grade prostatic intraepithelial neoplasia of the transition zone appear to be at increased risk of developing prostatic carcinoma, although not to the same degree as patients with high grade prostatic intraepithelial neoplasia of the peripheral/central zone. Previous investigations have shown loss of expression of π-class glutathione S-transferase (GST-π; an enzyme that protects against electrophilic carcinogens) in prostatic carcinoma and in high grade pros...

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, G.; Grana, C.; Chinol, M.; Cremonesi, M.; De Cicco, C.; Zoboli, S. [Div. of Nuclear Medicine, European Inst. of Oncology, Milan (Italy); De Braud, F. [Div. of Medical Oncology, European Inst. of Oncology, Milan (Italy); Robertson, C. [Div. of Epidemiology and Biostatistics, European Inst. of Oncology, Milan (Italy); Zurrida, S.; Veronesi, U. [Scientific Director Office, European Institute of Oncology, Milan (Italy); Casadio, C. [Div. of Pathology and Lab. Medicine, European Inst. of Oncology, Milan (Italy); Siccardi, A.G. [San Raffaele Scientific Institute and University of Milan (Italy)

    1999-04-29

    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{sup 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). {sup 90}Y doses of 2.22-2.96 GBq/m{sup 2} were administered; maximum tolerated dose (MTD) was determined at 2.96 GBq/m{sup 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 {sup 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{sup 2}, allowing the injection of {sup 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.) With 5 figs., 4 tabs., 34 refs.

  15. Human papillomavirus 16 non-European variants are preferentially associated with high-grade cervical lesions.

    Directory of Open Access Journals (Sweden)

    Luciana Bueno Freitas

    Full Text Available HPV16 accounts for 50-70% of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281 obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Espírito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in high-grade disease with an OR = 4.6 (1.07-20.2, p = 0.05. The association of HPV16 NE variants with an increased risk of CIN3+ is consistent with an HPV16 genetically determined enhanced oncogenicity. The prevalence of genetic variants of HPV16 is distributed across different geographical areas and with recent population admixture, only empiric data will provide information on the highest risk HPV16 variants within a given population.

  16. 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

  17. O9.04HIGH GRADE GLIOMAS AND CAREGIVERS' PSYCHOLOGICAL BURDEN

    Science.gov (United States)

    Petruzzi, A.; Finocchiaro, C.Y.; Vistalli, G.; Botturi, A.; Milanesi, I.; Silvani, A.; Lamperti, E.

    2014-01-01

    The diagnosis of a brain tumor is particularly stressful both for patients and their caregivers because the prognosis is poor and life expectancy is short. This is especially true when caregivers deal with high-grade gliomas (HGG). Despite treatment advances, median survival remains low, ranging from 1 to 5 years. Focal neurological deficits, epilepsy, cognitive dysfunction and symptoms of increased intracranial pressure are prominent symptoms in HHG and they may arise in any stage of the disease. Moreover, fatigue, mood disturbance, and anxiety are often reported. All these factors negatively affect patients' and caregivers' overall quality of life. Few studies have investigated, to date, the quality of life of the caregivers who take care of HGG patients. Thus, we sought to evaluate their quality of life and their specific reactions to caregiving. We recruited 91 caregivers of HGG patients. We used the following questionnaires in order to detect quality of life, anxiety, depression and specific reactions to patients' disease: 36-Item Short-Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS), Caregiver Reaction Assessment Scale (CRA). These psychological questionnaires were administered in the form of an interview by a psychologist. The present study shows that caregivers experience higher levels of anxiety (t (90) = 11.3, p < .01) and depression (t (90) = 9.26, p < .01) than the normative sample. Also caregivers' mental health (“Vitality”, “Social Functioning”, “Role-Emotional”, “Mental Health”) appeared to be compromised as compared to the normative sample. As specific reactions to caregiving our caregivers presented “loss of physical strength” and “financial problems”. Caregiving experience did not negatively influence “caregivers' self-esteem”, “lack of family support” and “disrupted schedule”. Although a highly positive perception of the caregivers' self-esteem is reported, the impact of HGG diagnosis

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

    Directory of Open Access Journals (Sweden)

    Bjerkehagen Bodil

    2008-06-01

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

  19. 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

  20. Methylation of HOXA9 and ISL1 Predicts Patient Outcome in High-Grade Non-Invasive Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Mark O Kitchen

    Full Text Available Inappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in low/intermediate grade non-muscle invasive bladder cancer (NMIBC have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin, novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis.Promoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correlated with tumour behaviour, including tumour recurrence and progression to muscle invasive bladder cancer or metastases.The ISL1 genes' promoter-associated island was more frequently methylated in recurrent and progressive high-grade tumours than their non-recurrent counterparts (60.0% vs. 18.2%, p = 0.008. ISL1 and HOXA9 showed significantly higher mean methylation in recurrent and progressive tumours compared to non-recurrent tumours (43.3% vs. 20.9%, p = 0.016 and 34.5% vs 17.6%, p = 0.017, respectively. Concurrent ISL1/HOXA9 methylation in HG-NMIBC reliably predicted tumour recurrence and progression within one year (Positive Predictive Value 91.7%, and was associated with disease-specific mortality (DSM.In this study we

  1. The Frequency of Serous Macular Detachment in Diabetic Macular Edema

    Directory of Open Access Journals (Sweden)

    Onur Yaya

    2015-05-01

    Full Text Available Objectives: To investigate the epidemiology and frequency of serous macular detachment (SMD in patients diagnosed with diabetic macular edema (DME. Materials and Methods: Hundred and forty-three eyes of 104 patients with DME were examined retrospectively. According to the results of OCT, the patients were separated into two groups; patients diagnosed with SMD and DME (group 1 and patients diagnosed with DME (group 2. They were assessed based on demographic characteristics, average age, duration of diabetes mellitus (DM, hypertension (HT history, best-corrected visual acuity, and diabetic retinopathy stages. Results: The average age of the patients was 61±8.7 years. Forty-three patients (41.3% were female and 61 patients (58.7% were male. Fifty-four of 104 patients (51.9% had DME with SMD. 21 (38.8% patients had bilateral SMD. In group 1, 31 patients were male (57.4% and 23 patients were female (42.6%. In group 2, 30 (60% patients were male and 20 (40% patients were female. In group 1, average age was 60.2±9.6 and the average duration of DM was 12.2±7.0 years, whereas the average age was 61.9±7.6 and the average duration of DM was 14.06±6.8 years in group 2. Forty-two patients in group 1 (77.8% and 30 patients (60% in group 2 had history of HT. Before the treatment, the average best-corrected visual acuity was found to be 0.30±0.24 in group 1 and 0.32±0.25 in group 2. Conclusion: Today, it is thought that diabetic maculopathy is the leading cause of SMD and it is a determining factor of treatment applications. In our study, we aimed at investigating the frequency of SMD in DME and the risk factors for the development of SMD. Although there were some differences between the factors, only the history of HT was found statistically higher in patients with SMD (p=0.04. (Turk J Ophthalmol 2015; 45: 92-96

  2. Histological and molecular analysis of Fallopian tube precursors in pelvic serous carcinogenesis

    NARCIS (Netherlands)

    Bijron, J.G.

    2012-01-01

    Epithelial ovarian cancer is the second most common gynaecological cancer, but has the highest fatality-to-case rate, which can be primarily attributed to diagnosis delay due to rapid disease progression and location. This is especially true for the serous subtype, which shows some form of pelvic

  3. Serous papillary adenocarcinoma of the rete testis: Unusual ultrasonography and pathological findings

    Directory of Open Access Journals (Sweden)

    Mermershtain Wilmosh

    2007-01-01

    Full Text Available We report a case of serous papillary adenocarcinoma of the rete testis in a 22-year-old man. Adenocarcinoma of the rete testis is highly resistant to radiotherapy and any known chemotherapeutic regimen. We recommend radical orchiectomy At last follow up, the patient was well, without any evidence of recurrence, ten years after surgery.

  4. Early stage primary ovarian mucinous carcinoma: Outcome-based clinicopathological study in comparison with serous carcinoma

    OpenAIRE

    Tian, Qifang; Lu, Bingjian; Ye, Jing; Lu, Weiguo; Xie, Xing; Wang, Xinyu

    2016-01-01

    Objective To compare clinicopathological characteristics and survival rates between patients with primary ovarian mucinous carcinoma and those with primary ovarian serous carcinoma. Methods This retrospective study reviewed archival tumour specimens, originally diagnosed as primary ovarian mucinous carcinoma, using refined histological criteria. All patients were contacted to establish survival status. Clinicopathological characteristics and patient survival data were compared with a group of...

  5. Expression of Interactive Genes Associated with Apoptosis and Their Prognostic Value for Ovarian Serous Adenocarcinoma.

    Science.gov (United States)

    Shin, Kyusik; Kim, Ki Hyung; Yoon, Man Soo; Suh, Dong Soo; Lee, Ji Young; Kim, Ari; Eo, Wankyu

    2016-01-01

    Malignant ovarian tumor is one of the leading causes of worldwide cancer death. It is usually characterized by insidious onset and late diagnosis because of the absence of symptoms, allowing ovarian cancer cases to progress rapidly and become unresectable. The tumor suppressor, p53, plays an important role in regulating cell cycles and apoptosis. p53 is regulated by several molecules, and it interacts with other apoptotic proteins. To compare the prognosis of ovarian serous carcinoma and evaluate the expression of DNA-PKcs, Akt3, GSK-3β, and p53 in cancerous cells. DNA-PKcs, Akt3, GSK-3β, and p53 expression levels were scored using immunohistochemistry staining of tissue samples from 132 women with ovarian serous adenocarcinoma. Expression was confirmed by real-time RT-PCR. Analyses were stratified by age, tumor grades, cancer stages and serum CA 125 levels. Significant differences in DNA-PKcs, Akt3, and p53 expression were observed between participants with different stages and tumor grades of ovarian serous adenocarcinoma. DNA-PKcs and p53 expression increased along with increasing tumor grade. Meanwhile, DNA-PKcs, Akt3, and p53 expression increased along with increasing cancer stage, and with a decrease in 5-year overall survival rate. This study shows that elevated expression of DNA-PKcs, Akt3, and p53 in ovarian serous adenocarcinoma tissues are an indication of more advanced disease and worse prognosis.

  6. Serous cystadenocarcinoma of the pancreas: report of a case and management reflections

    Directory of Open Access Journals (Sweden)

    Bramis K

    2012-03-01

    Full Text Available Abstract Background Serous adenomas represent 1-2% of pancreatic neoplasms and typically are asymptomatic not requiring any treatment and simple observation is the option of choice. Although, they carry a realistic risk of malignancy despite the general view that they never become malignant. We report a case, which, according to our best knowledge is the 27th case reported in the literature. Methods We reviewed the literature by performing a search in Pub Med and Medline. Results A 86-year old patient known to have a serous cystadenoma of the pancreas treated conservatively through a close clinical and radiological follow up which was unattended for 4 years ending up to our emergency department suffering an acute abdomen. Exploratory laparotomy revealed a perforated prepyloric ulcer which was treated accordingly. Patient died some weeks later due to severe medical co morbidities. Conclusion Serous cystic neoplasms of the pancreas carry a realistic risk of malignancy despite the general view that they never become malignant. In our opinion the treatment strategy of serous cystic neoplasms of the pancreas should be aggressive even in cases of remote metastases since prognosis of the disease is satisfactory

  7. OCT Angiography Compared to Fluorescein and Indocyanine Green Angiography in Chronic Central Serous Chorioretinopathy

    NARCIS (Netherlands)

    Teussink, M.M.; Breukink, M.B.; Grinsven, M.J.J.P. van; Hoyng, C.B.; Klevering, B.J.; Boon, C.J.F.; Jong, E.K.; Theelen, T.

    2015-01-01

    PURPOSE: Abnormal choroidal blood flow is considered important in the pathogenesis of chronic central serous chorioretinopathy (CSC). Optical coherence tomography (OCT) angiography can image ocular blood cell flow and could thus provide novel insights in disease mechanisms of CSC. We evaluated

  8. Spontaneous Cerebrospinal Fluid Otorrhea from a Persistent Tympanomeningeal Fissure Presenting as Recurrent Serous Otitis Media

    DEFF Research Database (Denmark)

    Zakaryan, Arman; Poulsgaard, Lars; Hollander, Camilla

    2015-01-01

    We describe spontaneous cerebrospinal fluid (CSF) otorrhea through a patent tympanomeningeal (Hyrtl) fissure presenting as recurrent serous otitis media. The CSF leak was observed when a drain was placed through the tympanic membrane by an otologist. The diagnosis was then confirmed by computed...

  9. Serous Retinal Detachment in Dome-shaped Macula with 7 Years Follow-up.

    Science.gov (United States)

    Alakeely, Adel G; Alrashaed, Saba

    2016-01-01

    Dome-shaped macula (DSM) was first described by Gaucher et al . as a convex protrusion of macula within a staphyloma in highly myopic eyes that cause visual impairment associated with serous foveal detachment (SFD). We describe a patient with persistent SFD in DSM documented by serial spectral domain optical coherence tomography for 7 years with stable vision.

  10. Struma ovarii – a dermoid and serous form of ovarian cyst

    Directory of Open Access Journals (Sweden)

    Dobrosława Sikora-Szczęśniak

    2013-10-01

    Full Text Available Struma ovarii belongs to the class of monodermal and highly specialized teratomas. These tumors are detected mainly among mature teratomas, accounting for up to 3% of all ovarian teratomas. Besides dermoid cysts, thyroid tissue is also found in serous and mucous cysts within the ovary. The aim of the research was to analysis of the incidence of struma ovarii – a rare type of tumor – among dermoid and serous ovarian cysts. Medical documentation of female patients subjected to surgery in the Department of Gynecology and Obstetrics, Independent Public Health Care Institution in Lipsko over a period of 17 years was reviewed for cases of struma ovarii. Struma ovarii was detected in 4 out of 103 operated females with dermoid and serous cysts. Thyroid tissue and serous cyst with a double-twisted pedicle were detected in a 22-year-old patient in the 10th week of gestation within the left ovary. In three cases of patients aged 42, 46, and 51, thyroid tissue encapsulated in dermoid cells was also located on the left side. All diagnoses were made on the basis of histopathological assessments. In a 17-year observation period, gestational struma ovarii was identified in one out of 17,751 patients whose pregnancies led to delivery. This accounts for 0.0068% of pregnancies ending with delivery. Struma ovarii was detected in one half of the patients in whom dermoid cells were detected bilaterally.

  11. Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges

    OpenAIRE

    Rahmathulla G; Hovey EJ; Hashemi-Sadraei N; Ahluwalia MS

    2013-01-01

    Gazanfar Rahmathulla,1 Elizabeth J Hovey,2,3 Neda Hashemi-Sadraei,4 Manmeet S Ahluwalia4 1Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, 2Department of Medical Oncology, Prince of Wales Hospital, Sydney, NSW, Australia; 3School of Medicine, University of New South Wales, Sydney, NSW, Australia; 4Department of Medical Oncology, Neurological and Taussig Cancer Institutes, Cleveland Clinic, Cleveland, OH, USA Abstract: High-grade gliomas continue to have dismal prognosis d...

  12. 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.

  13. Augmentation cystoplasty and simultaneous ureteral reimplantation reduce high-grade vesicoureteral reflux in children with neurogenic bladder

    OpenAIRE

    Jen-Bin Wang; Chin-Su Liu; Shin-Lin Tsai; Chou-Fu Wei; Tai-Wai Chin

    2011-01-01

    Background: To compare the incidence of residual high-grade vesicoureteral reflux (HVUR) (≥Grade III) in neurogenic bladder patients receiving augmentation cystoplasty alone or with simultaneous ureteral reimplantation. Furthermore, we also tried to find the risk factors of residual VUR and febrile urinary tract infection. Methods: Between 1999 and 2009, urinary bladder augmentation was performed in 21 children with neurogenic bladder. Seventeen of these patients had VUR on preoperative vo...

  14. 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.

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

    Science.gov (United States)

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

    2018-01-01

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

  16. 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.)

  17. Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges.

    Science.gov (United States)

    Rahmathulla, Gazanfar; Hovey, Elizabeth J; Hashemi-Sadraei, Neda; Ahluwalia, Manmeet S

    2013-01-01

    High-grade gliomas continue to have dismal prognosis despite advances made in understanding the molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. Conventional treatment approaches, including surgery, radiotherapy, and cytotoxic chemotherapy, have been used with limited success. Therapeutic advances using molecular targeted therapy, immunotherapy, and others such as dietary treatments have not been able to halt tumor progression and disease-related death. High-grade gliomas (World Health Organization grades III/IV) are histologically characterized by cellular and nuclear atypia, neoangiogenesis, and necrosis. The expression of vascular endothelial growth factor, a molecular mediator, plays a key role in vascular proliferation and tumor survival. Targeting vascular endothelial growth factor has demonstrated promising results, with improved quality of life and progression-free survival. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, is approved by the Food and Drug Administration as a single agent in recurrent glioblastoma and is associated with manageable toxicity. This review discusses the efficacy, practical aspects, and response assessment challenges with the use of bevacizumab in the treatment of high-grade gliomas.

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

  19. Analysis of foot and ankle kinematics after operative reduction of high-grade intra-articular fractures of the calcaneus.

    Science.gov (United States)

    Hetsroni, Iftach; Nyska, Meir; Ben-Sira, David; Arnson, Yoav; Buksbaum, Chen; Aliev, Elchan; Mann, Gideon; Massarwe, Sabri; Rozenfeld, Gal; Ayalon, Moshe

    2011-05-01

    High-grade calcaneal fractures represent a complex injury, with limited data to support the advisability of open reduction. Restoration of foot and ankle kinematics during walking, which has been previously shown to be significantly limited after nonoperative treatment, has never been studied after the operation. This study was designed to address this lack of information to assess the advisability of the operation in this respect. Twenty patients with a minimum of 2 years after Open Reduction Internal Fixation (ORIF) for high-grade fractures were evaluated with a computerized gait analysis system, in addition to the radiographic assessment and functional questionnaires. Foot and ankle kinematic variables in the operated limbs were compared with contralateral limbs and with matched healthy control individuals. The kinematical gait analysis demonstrated recreation of normal ankle motions in operated patients. Subtalar motion demonstrated relative symmetry between operated and contralateral limbs, but it was still significantly limited compared with healthy controls. Bohler angle was between 15° and 35°. Functional questionnaires and rate of postoperative complications supported the generalizability of our operated group compared with previous literature assessing similar injuries. In high-grade calcaneal fractures, when recreation of gross calcaneal anatomy is obtained during the operation, walking ankle motion is recreated as well. However, subtalar motions, although recreated to a certain extent, still demonstrate limitations when compared with noninjured individuals. These results support the advisability of the operation in these complex injuries, but they demonstrate that subtalar motion is not completely normalized despite a favorable anatomic outcome.

  20. 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.

  1. Large-spot subthreshold transpupillary thermotherapy for chronic serous macular detachment

    Directory of Open Access Journals (Sweden)

    Giuseppe Lo Giudice

    2011-03-01

    Full Text Available Giuseppe Lo Giudice1, Valentina de Belvis2, Marco Tavolato1, Alessandro Galan11San Paolo Ophthalmic Center, San Antonio Hospital, Padova, Italy; 2Paediatric Low Vision Center, Paediatric Rare Eye Disease Center, Department of Paediatrics, University of Padova, ItalyPurpose: To report the effect of subthreshold transpupillary thermotherapy (TTT in treating serous detachment of the neurosensory retina secondary to chronic central serous chorioretinopathy (CCSC.Methods: Seven eyes from five patients with CCSC, persistent serous detachment of the neurosensory retina and a clinical course of between 12 and 60 months were treated. All eyes received large-spot TTT guided by indocyanine green angiography (ICGA. Subthreshold TTT was performed using an 810 nm diode laser with a spot size of 3.0 mm (power was set at 350 mW. Treatment was applied for 60 seconds to the areas of choroidal hyperfluorescence on ICGA.Results: The mean number of TTT sessions was 1.4 ± 0.5. All eyes were followed up for at least 6 months (mean 9.6 ± 3.2 standard deviation; range 6–12 months. The mean logarithm of the minimum angle of resolution best-corrected visual acuity was significantly better compared with baseline. All TTT-treated eyes had stable or improved vision (P < 0.001. Mean optical coherence tomography (OCT central foveal thickness was significantly lower in all patients (P < 0.001 compared with pretreatment OCT, with a reduction in subretinal fluid and resolution of serous detachment associated with anatomical fovea restoration. No patient had any treatment-related side effects.Conclusion: Modified subthreshold TTT appears to have a beneficial effect in treating patients with CCSC and persistent neurosensory detachment. The encouraging results and lack of visually significant complications suggest that further investigation is warranted.Keywords: central serous chorioretinopathy, indocyanine green angiography, neurosensory detachment, transpupillary

  2. Inhibition of Hedgehog signaling antagonizes serous ovarian cancer growth in a primary xenograft model.

    Directory of Open Access Journals (Sweden)

    Christopher K McCann

    Full Text Available Recent evidence links aberrant activation of Hedgehog (Hh signaling with the pathogenesis of several cancers including medulloblastoma, basal cell, small cell lung, pancreatic, prostate and ovarian. This investigation was designed to determine if inhibition of this pathway could inhibit serous ovarian cancer growth.We utilized an in vivo pre-clinical model of serous ovarian cancer to characterize the anti-tumor activity of Hh pathway inhibitors cyclopamine and a clinically applicable derivative, IPI-926. Primary human serous ovarian tumor tissue was used to generate tumor xenografts in mice that were subsequently treated with cyclopamine or IPI-926.Both compounds demonstrated significant anti-tumor activity as single agents. When IPI-926 was used in combination with paclitaxel and carboplatinum (T/C, no synergistic effect was observed, though sustained treatment with IPI-926 after cessation of T/C continued to suppress tumor growth. Hh pathway activity was analyzed by RT-PCR to assess changes in Gli1 transcript levels. A single dose of IPI-926 inhibited mouse stromal Gli1 transcript levels at 24 hours with unchanged human intra-tumor Gli1 levels. Chronic IPI-926 therapy for 21 days, however, inhibited Hh signaling in both mouse stromal and human tumor cells. Expression data from the micro-dissected stroma in human serous ovarian tumors confirmed the presence of Gli1 transcript and a significant association between elevated Gli1 transcript levels and worsened survival.IPI-926 treatment inhibits serous tumor growth suggesting the Hh signaling pathway contributes to the pathogenesis of ovarian cancer and may hold promise as a novel therapeutic target, especially in the maintenance setting.

  3. CyberKnife® enhanced conventionally fractionated chemoradiation for high grade glioma in close proximity to critical structures

    Directory of Open Access Journals (Sweden)

    Oermann Eric

    2010-06-01

    Full Text Available Abstract Introduction With conventional radiation technique alone, it is difficult to deliver radical treatment (≥ 60 Gy to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma. Methods Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy. Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife® image-guided radiosurgical system. The majority of patients (88% received concurrent and/or adjuvant Temozolmide. Results During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients. Conclusion We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting

  4. Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas

    DEFF Research Database (Denmark)

    Vang, Russell; Hannibal, Charlotte G; Junge, Jette

    2017-01-01

    Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated...... "atypical proliferative serous tumor (APST)" and a small subset of SBTs with micropapillary architecture that have a poor outcome and are designated "noninvasive low-grade serous carcinoma (niLGSC)". It also has been argued that the difference in behavior between the 2 groups is not due to the subtype...... renamed "low-grade serous carcinoma" (LGSC). The argument as to whether it is the appearance of the primary tumor or the presence of extraovarian LGSC that determines outcome remains unsettled. The current study was initiated in 2004 and was designed to determine what factors were predictive of outcome...

  5. Poly(adenosine diphosphate-ribose) polymerase expression in serous ovarian carcinoma: correlation with p53, MIB-1, and outcome.

    Science.gov (United States)

    Brustmann, Hermann

    2007-04-01

    This study investigated the expression of poly(adenosine diphosphate-ribose) polymerase (PARP) in a cohort of ovarian serous carcinomas by immunohistochemistry with regard to outcome, clinicopathologic parameters, proliferation as assessed by MIB-1 labeling indices (LIs), and p53 immunoexpression. Formalin-fixed, paraffin-embedded archival tissues of 50 ovarian serous carcinomas were immunostained with antibodies to PARP, MIB-1, and p53. In addition, 10 benign serous cystadenomas and 10 typical serous borderline ovarian tumors were included in the PARP immunostudy. Immunostaining for PARP was scored with regard to quantity and intensity of positively stained nuclei as negative, low, or strong. The MIB-1 LIs were quantitated as the percentage of positively stained nuclei in 1000 nuclei. For p53, at least 10% of tumor cells had to display nuclear staining. The expression of PARP was scored negative in all serous cystadenomas and low in serous borderline ovarian tumors. Strong PARP expression was determined in 38 cases (76%), and low expression in 12 cases (12%) of ovarian serous carcinomas; MIB-1 staining was noted in all cases (mean, 44.2; range, 10.8-66.5), positivity for p53 in 39 cases (78%). The PARP immunoreactivity increased with the International Federation of Gynecology and Obstetrics stage (P = 0.0075), as well as p53 positivity (P = 0.0141) and MIB-1 LIs (P = 0.0102), with grade determined after Malpica et al. (P = 0.0445) but not with grade assessed after Shimizu et al. (P = 0.1495). A trend for poor outcome was observed in patients whose tumors displayed high levels of PARP immunoexpression (P = 0.0196, log-rank test). This study indicates that PARP expression is frequently upregulated in ovarian serous carcinomas, related with MIB-1 LIs and p53 expression, and may serve as a marker of aggressive behavior with prognostic value.

  6. 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

  7. In patients suffering from idiopathic central serous chorioretinopathy, anxiety scores are higher than in healthy controls, but do not vary according to sex or repeated central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Bazzazi N

    2015-04-01

    Full Text Available Nooshin Bazzazi,1 Mohammad Ahmadpanah,2 Siamak Akbarzadeh,1 Mohammad Ali Seif Rabiei,3 Edith Holsboer-Trachsler,4 Serge Brand4,5 1Department of Ophthalmology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; 2Research Center for Behavioral Disorders and Substance Abuse, Hamadan University of Medical Sciences; Hamadan, Iran; 3Department of Social Medicine, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; 4Psychiatric Clinics of the University of Basel, Center for Affective, Stress and Sleep Disorders, Basel, Switzerland; 5Department of Sport and Health Science, Sport Science Section, University of Basel, Basel, Switzerland Introduction: Idiopathic central serous chorioretinopathy (CSCR is a relatively common ophthalmic disorder characterized by the development of a serous detachment of the sensory retina. Psychophysiological factors may trigger or maintain CSCR, though, surprisingly, the association between CSCR and anxiety has yet to be studied. The aims of the present study were threefold: to determine whether 1 Iranian patients with CSCR have higher scores for anxiety, 2 anxiety is lower, if CSCR has been experienced twice, and whether 3 anxiety scores differ between sexes.Methods: A total of 30 patients with CSCR and 30 healthy age- and sex-matched controls took part in the study. A brief face-to-face interview was conducted covering demographic variables and history and occurrence of CSCR and assessing anxiety.Results: Compared to healthy controls, anxiety was significantly higher in both first-time and second-time CSCR patients. In CSCR patients, anxiety scores did not differ between sexes.Conclusion: Higher anxiety scores were observed in Iranian patients with CSCR, irrespective of whether this was the first or second occurrence of CSCR. This suggests there is no psychological adaptation in terms of reduced anxiety among patients with repeated CSCR. Keywords: idiopathic central

  8. Adenomas colorretais: fatores de risco associados à displasia de alto grau Colorectal adenomas: risk factors for high-grade dysplasia

    Directory of Open Access Journals (Sweden)

    Julia Schmidt Silva

    2009-06-01

    Full Text Available FUNDAMENTOS: O estudo dos pólipos, em especial os adenomatosos, é relevante devido à correlação direta com o carcinoma colorretal. Objetivo: Analisar quais são os fatores de risco para uma displasia de alto grau do pólipo adenomatoso retirados endoscopicamente. MÉTODOS: Avaliamos todas as colonoscopias realizadas pelo Serviço de Coloproctologia no período de janeiro de 2003 a dezembro de 2006. Foram incluídos os pacientes com diagnóstico de pólipos adenomatosos. Analisamos a existência da relação entre adenomas com displasia de alto grau e os fatores associados dos pacientes e pólipos. RESULTADOS: Foram realizados 1821 exames e encontramos 208 pacientes com 326 adenomas. 51,4% do sexo masculino e 69,2% tinham um único adenoma. Foram encontrados 28 pacientes (13,5% com, ao total, 34 adenomas (10,4%, com displasia de alto grau. Entre os adenomas com displasia de alto grau, 64,7% eram = 1cm, 61,8% eram sésseis, 29,4% vilosos e 70,6% estavam localizados no cólon esquerdo. Comparando as características do grupo dos adenomas com displasia de baixo grau com o de alto grau, foi estatisticamente significativo o tamanho = 1cm e o componente viloso (P BACKGROUND: The study of polyps, especially adenomatous, is justified because of the straight correlation among them with the incidence of CRC. Objective: To analyze the risk factors for high-grade dysplasia of adenomatous polyps removed endoscopically. METHODS: All consecutive colonoscopies performed by the Colorectal Department of the Hospital Nossa Senhora da Conceição, in Porto Alegre/RS, from January 2003 to December 2006, were evaluated. Patients diagnosed with adenomatous polyps were included. The relationship among tumors with high-grade dysplasia and the features of the patients and polyps were analyzed. RESULTS: Among the 1,821 exams, 326 adenomas were detected in 208 patients. 51.4% of the patients were male; 69,2% had only one adenoma. A total of 28 patients (13,5% with 34

  9. [The use of ProstaDoz in patients with benign prostatic hyperplasia and coexistent high-grade prostatic intraepithelial neoplasia].

    Science.gov (United States)

    Antonov, A G; Gordeev, V V; Fedorchuk, S B; Laptev, D O

    2017-10-01

    In recent years there has been an increasing interest in the drug treatment of benign prostatic hyperplasia (BPH) to improve the patients quality of life without surgical treatment. In this connection, phytotherapeutic drugs and biologically active dietary supplements (BADS), consisting of a combination of microelements, vitamins and plant extracts, have been increasingly used in addition to synthetic preparations. To investigate the clinical effectiveness of dietary supplement ProstaDoz in the treatment of BPH with coexistent high-grade prostatic intraepithelial neoplasia (PIN). The study group comprised 30 men with BPH and high-grade PIN who were diagnosed with primary biopsy and received ProstaDoz for three months. The control group included 18 patients with the same diagnosis who were treated with Tamsulosin. After a 3-month intake of the ProstaDoz, a statistically significant reduction was observed in symptom scores for BPH and the quality of life index by 18% (p<0.001) and 16.7% (p<0.001), respectively. The residual urine volume and total serum PSA decreased by 28.3% (p<0.001) and 46.8% (p<0.001), respectively. Unlike the control group, the rate of prostate cancer detection was 6.25 times lower in patients taking ProstaDoz, and 16% of them had lower grade PIN compared with baseline or no PIN at all. The findings suggest that using ProstaDoz in patients with BPH and high-grade PIN contributes to improving the quality of life (QoL) of patients and the regression of dysplasia.

  10. 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.)

  11. Adenomas with high-grade dysplasia and early adenocarcinoma are more likely to be sessile in the proximal colon.

    Science.gov (United States)

    Sawhney, M S; Dickstein, J; LeClair, J; Lembo, C; Yee, E

    2015-08-01

    Size and the sessile morphology of an adenoma may explain why colonoscopy is less effective in preventing proximal colonic cancer than distal cancers. We wanted to determine if advanced polypoid neoplasms (APNs, i.e. adenoma with high-grade dysplasia or early adenocarcinoma) are more likely to be sessile and/or smaller in the proximal colon. We searched our institution's pathology database from 2004 to 2012 and identified patients with APNs. Polyps were categorized by size, morphology and location in the colon. Average polyp size and morphology were determined for each location. During the study period, 564 patients with APNs were identified. Of these, adenocarcinoma was noted in 21.6% and high-grade dysplasia in 78.4%. The average patient age was 64.4 years and 54.9% were men. The proportion of APNs that were ≤ 5 mm was 1.7%, ≤ 10 mm 19.3% and ≤ 15 mm 39%. APNs in the proximal colon were larger than those in the distal colon, but the difference was not statistically significant (27 vs 24 mm; P = 0.06). Eighty-three per cent of APNs in the proximal colon were sessile vs 57% in the distal colon (P = 0.001). APNs in the proximal colon were almost four times more likely to be sessile than in the distal colon (OR = 3.7). A similar association was noted for polyps ≤ 20 mm or polyps with high-grade dysplasia. APNs in the proximal colon were almost four-times more likely to be sessile than those in the distal colon. No difference in the size of polyps was noted. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

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

    Science.gov (United States)

    Park, Juhyun; Cho, Sung Yong; Jeong, Seung-Hwan; Lee, Seung Bae; Son, Hwancheol; Jeong, Hyeon

    2016-08-01

    To investigate the relationship between low testosterone levels and prostate cancer detection risk in a biopsy population. In all, 681 men who underwent initial 12-core transrectal prostate biopsy at our institution were included in this retrospective study. Patients were divided into groups with low (levels (≥300 ng/dL). Clinical and pathological data were analysed. Among 681 men, 86 men (12.6%) had low testosterone levels, 143 (32.7%) had a positive biopsy, and 99 (14.5%) had high-grade prostate cancer. The mean age, prostate-specific antigen (PSA) level, PSA density, body mass index (BMI), number of abnormal digital rectal examination (DRE) findings, and diabetes mellitus (DM) history were significantly different between the low and normal level testosterone groups. A low testosterone level was significantly associated with a higher risk of detection of overall prostate cancer than a normal testosterone level in univariate analysis (odds ratio [OR] 2.545, P = 0.001), but not in multivariate analysis adjusting for parameters such as age, PSA, prostate volume, BMI, abnormal DRE findings and DM (OR 1.583, P = 0.277). Meanwhile, a low testosterone level was significantly related to a higher rate of high-grade prostate cancer compared with a normal testosterone level in univariate (OR 3.324, P level is an independent risk factor for high-grade prostate cancer detection at biopsy. Therefore, checking testosterone levels could help to determine whether prostate biopsy should be carried out. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

  13. Trends in peri-operative performance status following resection of high grade glioma and brain metastases: The impact on survival.

    Science.gov (United States)

    Patel, Chirag K; Vemaraju, Ravi; Glasbey, James; Shires, Joanne; Northmore, Tessa; Zaben, Malik; Hayhurst, Caroline

    2018-01-01

    Maximal surgical resection of high grade brain tumours is associated with improved overall survival (OS). It carries the risk of neurological deterioration leading to worsening performance status (PS), which may affect overall survival and preclude patients from adjuvant therapy. We aim to review the changes in performance status of patients undergoing resection of high grade tumours and metastases and the impact of changes on overall survival. A prospective study of the perioperative performance status of 75 patients who underwent primary resection of malignant primary brain tumour or solitary metastasis in a single centre. Data on patients' demographics, tumour histology and overall survival were also collected. WHO performance status was recorded pre-operatively and at intervals following surgery. Of the 75 patients (35 males, 40 females, median age 61 years at diagnosis), 50 had primary malignant brain tumours, 25 had metastasis. Although PS dropped at postoperative day 1 in 14 patients (18.7%), 28% improved by day 5 and there was significant improvement by day 14 (41%, p=0.02). The number of patients with PS 3 or worse changed from 4% pre-operatively (n=3) to 8% (n=6). Overall survival is better in those whose PS remained improved or unchanged at 2 weeks after surgery compared to those whose PS deteriorated; high grade glioma median survival 15.67 vs. 2.4 months (p=0.005) and metastasis median survival 8.53 vs.2.33 months (p=0.001). Our data demonstrates that although PS may deteriorate immediately after surgery, the majority of patients regain their baseline PS or improve by 2 weeks postoperatively; decisions on fitness for adjuvant treatment should therefore be delayed until then. In those patients whose PS declines following surgery overall survival is poor. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  14. Diagnostic yield of cardiovascular magnetic resonance in young-middle aged patients with high-grade atrio-ventricular block.

    Science.gov (United States)

    Baritussio, A; Ghosh Dastidar, A; Frontera, A; Ahmed, N; De Garate, E; Harries, I; Diab, I; Duncan, E; Thomas, G; Nisbet, A; Bucciarelli-Ducci, C

    2017-10-01

    Atrio-ventricular block (AVB) is a rare finding in young or middle-aged adults, often leading to pacemaker implantation (PM) without further investigation. We sought to assess the diagnostic role of cardiovascular magnetic resonance (CMR) in young and middle-aged adults with high-grade AVB. We consecutively enrolled young-middle aged (18-65years) patients with high grade AVB referred to CMR after standard clinical assessment (history, electrocardiogram and cardiac rhythm monitoring) prior to PM implantation. Cine and post-contrast imaging were performed in a 1.5T scanner. 34 patients (59% male, mean age 42±12years) with high grade AVB were referred to CMR for suspected ischemic heart disease (IHD)(n=4) and non-ischemic heart disease (NIHD)(n=20); no clear cause was found in 9 patients prior to CMR and 1 patient had suspected lung disease. A pathologic substrate was found on CMR in 15 patients (44%), while a structurally normal heart was reported in 18 (53%). Non-specific findings were reported in 1 patient (3%). There was a fair agreement between CMR and echocardiographic findings (Cohen's kappa 0.243), and CMR provided an entirely new diagnosis in 34% of patients. As compared to the standard clinical assessment, CMR had an additional role in 65% of patients and guided further testing (genetic testing, extra-cardiac imaging) in 9%. CMR found a pathologic substrate in 44% of patients, mainly NIHD (32%). Half of the patients (53%) had a structurally normal heart. When added to the standard clinical assessment, CMR had an incremental diagnostic role in two thirds of patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  15. Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges

    Directory of Open Access Journals (Sweden)

    Rahmathulla G

    2013-04-01

    Full Text Available Gazanfar Rahmathulla,1 Elizabeth J Hovey,2,3 Neda Hashemi-Sadraei,4 Manmeet S Ahluwalia4 1Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, 2Department of Medical Oncology, Prince of Wales Hospital, Sydney, NSW, Australia; 3School of Medicine, University of New South Wales, Sydney, NSW, Australia; 4Department of Medical Oncology, Neurological and Taussig Cancer Institutes, Cleveland Clinic, Cleveland, OH, USA Abstract: High-grade gliomas continue to have dismal prognosis despite advances made in understanding the molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. Conventional treatment approaches, including surgery, radiotherapy, and cytotoxic chemotherapy, have been used with limited success. Therapeutic advances using molecular targeted therapy, immunotherapy, and others such as dietary treatments have not been able to halt tumor progression and disease-related death. High-grade gliomas (World Health Organization grades III/IV are histologically characterized by cellular and nuclear atypia, neoangiogenesis, and necrosis. The expression of vascular endothelial growth factor, a molecular mediator, plays a key role in vascular proliferation and tumor survival. Targeting vascular endothelial growth factor has demonstrated promising results, with improved quality of life and progression-free survival. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, is approved by the Food and Drug Administration as a single agent in recurrent glioblastoma and is associated with manageable toxicity. This review discusses the efficacy, practical aspects, and response assessment challenges with the use of bevacizumab in the treatment of high-grade gliomas. Keywords: bevacizumab, antiangiogenesis, glioma, glioblastoma, vascular endothelial growth factor

  16. 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

  17. 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

  18. 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

    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......O2 mineral nanoparticles (formed, together with diaspore, during diagenesis) and Fe nanominerals (formed during epigenesis) were hitherto unknown not only for the allochthonous karst-type bauxite deposits of Greece, but also for the overall bauxite deposits, worldwide....

  19. 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

  20. Detection of high-grade neoplasia in air-dried cervical PAP smears by a microRNA-based classifier.

    Science.gov (United States)

    Ivanov, Mikhail K; Titov, Sergei E; Glushkov, Sergei A; Dzyubenko, Victoria V; Malek, Anastasia V; Arkhangelskaya, Polina A; Samsonov, Roman B; Mikhetko, Andrey A; Bakhidze, Elena V; Berlev, Igor V; Kolesnikov, Nikolay N

    2018-03-01

    Recent studies have shown that changes in the expression levels of certain microRNAs correlate with the degree of severity of cervical lesions. The aim of the present study was to develop a microRNA-based classifier for the detection of high-grade cervical intraepithelial neoplasia (CIN ≥2) in cytological samples from patients with different high-risk human papillomavirus (HR-HPV) viral loads. For this purpose, raw RT-qPCR data for 25 candidate microRNAs, U6 snRNA and human DNA in air-dried PAP smears from 174 women with different cervical cytological diagnoses, 144 of which were HR-HPV-positive [40 negative for intraepithelial lesion or malignancy (NILM), 34 low-grade squamous intraepithelial lesions (L-SIL), 57 high-grade squamous intraepithelial lesions (H-SIL), 43 invasive cancers], were statistically processed. The expression level changes of various individual microRNAs were found to be significantly correlated with the cytological diagnosis but the statistical significance of this correlation was critically dependent on the normalization strategy. We developed a linear classifier based on the paired ratios of 8 microRNA concentrations and cellular DNA content. The classifier determines the dimensionless coefficient (DF value), which increases with the severity of cervical lesion. The high- and low-grade CINs were better distinguished by the microRNA classifier than by the measurement of individual microRNA levels with the use of traditional normalization methods. The diagnostic sensitivity of detecting high-grade lesions (CIN ≥2) with the developed microRNA classifier was 83.4%, diagnostic specificity 81.2%, ROC AUC=0.913. The analysis can be performed with the same nucleic acid preparation as used for HPV testing. No statistically significant correlation of the DF value and HR-HPV DNA load was found. The DF value and the HR HPV presence and viral DNA load may be regarded as independent criteria that can complement each other in molecular

  1. 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.

  2. 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

  3. Ovarian serous carcinoma: relationship of p53 and bcl-2 with tumor angiogenesis and VEGF expression.

    Science.gov (United States)

    Crasta, Julian A; Mishra, Suniti; Vallikad, Elizabeth

    2011-11-01

    The aim of the study was to assess the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in ovarian serous carcinoma and to examine their relation with apoptosis.Paraffin-embedded specimens of 41 cases of ovarian serous carcinomas were evaluated by immunohistochemistry for VEGF, p53, and bcl-2 expression. MVD was assessed with CD31 staining. We investigated the association of tumor angiogenesis (MVD and VEGF) with clinicopathologic factors, p53 overexpression, and bcl-2 expression.There was a significant correlation between high MVD and suboptimal debulking and advanced stage disease. A significant negative correlation was expressed between bcl-2 and VEGF expression. In univariate analysis, only stage had a significant impact on disease-free survival.The results of this study suggest that higher degree of angiogenesis is associated with suboptimal debulking and advanced-stage disease. Expression of VEGF had negative association with VEGF expression.

  4. A case of endometrioid adenocarcinoma originating from the serous surface of the small intestine

    Directory of Open Access Journals (Sweden)

    Natsuko Makihara

    2015-09-01

    Full Text Available Malignant transformation of endometriosis has been extensively described in the literature. However, extragonadal endometrioid adenocarcinoma, either de novo or arising from malignant transformation of endometriosis, is rare. The present case report describes a patient with endometrioid adenocarcinoma on the serous surface of the small intestine. A 25- year-old female with no history of endometriosis was referred to our hospital with an intrapelvic tumor. An internal examination, ultrasound, and magnetic resonance imaging revealed a round mass approximately 80 mm in diameter; however, identification of the affected organ was difficult. Because we could not rule out malignancy based on the non-specific radiologic findings, laparotomy was performed. A mass with ileal adhesions was detected intraoperatively. In addition, the uterus and bilateral adnexa appeared normal. The tumor was resected with part of the ileum. Histopathology confirmed a diagnosis of endometrioid adenocarcinoma originating from the serous surface of the small intestine.

  5. [Serous macular detachment associated with circumscribed choroidal hemangioma: a case report].

    Science.gov (United States)

    Munteanu, M; Giuri, Stela; Rosca, C; Boruga, O; Chercota, V; Stanca, H T

    2013-01-01

    Choroidal hemangiomas are benign vascular hamartomas that typically present from second to fourth decade of life, when they can cause visual disturbance due to exudative retinal detachment. They represent uncommon benign choroidal vascular tumors, usually occuring sporadically in the absence of systemic disease. We report the case of a young female patient, presenting a juxtapapillary circumscribed choroidal haemangioma complicated with serous macular detachment. The patient underwent photodynamic therapy with verteporfin (PDT). Systematic follow-up using ophthalmoscopy, ultrasonography, Fluorescein angiography and Indocyanine green angiography was performed. The patient presented regression with flattening of tumour, resolution of the subretinal fluid, and significant improvement of vision. Mostly asymptomatic, the choroidal hemangiomas can be associated with serous retinal detachment, leading to reduced vision and metamorphopsia; in those cases, the long term visual prognosis is poor, even in adequately treated patients. PDT is effective in eliminating the subretinal fluid and improving vision in patients with circumscribed choroidal hemangioma.

  6. Spectral CT imaging in differential diagnosis of pancreatic serous oligocystic adenoma and mucinous cystic neoplasms

    International Nuclear Information System (INIS)

    Lin Xiaozhu; Chen Kemin; Wu Zhiyuan; Tao Ran; Guo Yan; Zhang Jing; Li Jianying; Shen Yun

    2011-01-01

    Objective: To investigate the CT spectral imaging features of pancreatic serous oligocystic adenoma and mucinous cystic neoplasms and to assess the value of spectral CT in differentiating between pancreatic serous oligocystic adenoma and mucinous cystic neoplasms. Methods: From Feb. 2010 to Dec. 2010, 27 patients with cystic neoplasms of the pancreas (group one with 15 serous oligocystic adenomas and group two with 12 mucinous cystic neoplasms) underwent dual-phase CT spectral imaging followed by surgery. Quantitative values (age, tumor size, CT value change as function of photon energy, effective-Z, iodine-water concentration, and calcium-water concentration) were compared with independent samples t test and Mann-Whitney test and non-quantitative parameters (gender, symptom, and tumor location) were compared with Chi-square test (Fisher exact). The parameters with significant differences between two groups were analyzed further and the performance of multiple parameters for joint differential diagnosis was evaluated with discriminant analysis. Results: Compared to patients with mucinous cystic neoplasms, patients with serous oligocystic adenoma had younger age, lower frequency of being symptomatic and smaller tumor size. The CT values on 40 keV to 60 keV (with 10 keV increment) in late arterial phase [(36±13) HU vs. (62±23) HU, (26±8) HU vs. (40±15) HU, and (19±6) HU vs. (27±10) HU respectively] and 40 keV to 50 keV (with 10 keV increment) in portal venous phase [(43±14) HU vs. (61±25) HU and (30±10) HU vs. (40±16) HU respectively], effective-Z (late arterial phase 7.80± 0.16 vs. 8.05±0.21, and portal venous phase 7.87±0.15 vs 8.02±0.22), concentration of calcium (water) [late arterial phase (5±3) g/L vs. (11±4) g/L, t=-3.836, P=0.001 and portal venous phase (7±3) g/L vs. (10±5) g/L, t=-2.071, P=0.049] and iodine (water) [late arterial phase (0.38±0.24) g/L vs. (0.78±0.32) g/L, t=-3.755, P=0.001 and portal venous phase (0.48± 0.24) g/L vs. (0

  7. Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment

    Science.gov (United States)

    2004-08-01

    Co[ýVr/ lgbt t A eic , n Sc t 1t’.jar lni ttItrtii, I’alogy Review Ovarian Tumorigenesis A Proposed Model Based on Morphological and Molecular...without cytologic atypia ( right inset). B: Epithelial cells lining the cystadenoma (between arrows) were isolated using laser capture microdissection with...specimen. Right panel (case F) shows a point mutation in the BRAF gene in both the serous borderline tumor and the corresponding cystadenoma. Fig. 3

  8. Collision tumor: serous cystadenocarcinoma and dermoid cyst in the same ovary

    DEFF Research Database (Denmark)

    Bige, Ozgur; Demir, Ahmet; Koyuncuoglu, Meral

    2008-01-01

    INTRODUCTION: Collision tumor means the coexistence of two adjacent, but histologically distinct tumors without histologic admixture in the same tissue or organ. Collision tumors involving ovaries are extremely rare. CASE: We present a case of 45-year-old parous woman with a left dermoid cyst......, with unusual imaging findings, massive ascites and peritoneal carcinomatosis. The patient underwent cytoreductive surgery. The histopathology revealed a collision tumor consisting of an invasive serous cystadenocarcinoma and a dermoid cyst....

  9. Mixed endometrioid and serous carcinoma developing in abdominal wall endometriosis following Cesarean section

    International Nuclear Information System (INIS)

    Da Ines, David; Montoriol, Pierre Francois; Petitcolin, Virginie; Garcier, Jean-Marc; Bourdel, Nicolas; Canis, Michel; Charpy, Cecile

    2011-01-01

    Abdominal wall endometriosis is unusual and mostly occurs in scars following Cesarean section. Although malignant transformation is rare, it must be recognized in order to benefit from radical resection. We report a very rare case of mixed endometrioid and serous carcinoma developing in a Cesarean section endometriosis scar and the way we managed it using surgery and chemotherapy. 18-FDG PET-CT imaging was performed to correctly stage the disease

  10. Mixed endometrioid and serous carcinoma developing in abdominal wall endometriosis following Cesarean section

    Energy Technology Data Exchange (ETDEWEB)

    Da Ines, David; Montoriol, Pierre Francois; Petitcolin, Virginie; Garcier, Jean-Marc (Dept. of Radiology and Medical Imaging, CHU Clermont-Ferrand, CHU Estaing, Clermont-Ferrand (France)), email: ddaines@chu-clermontferrand.fr; Bourdel, Nicolas; Canis, Michel (Dept. of Obstetrics and Gynecology, CHU Clermont-Ferrand, CHU Estaing, Clermont-Ferrand (France)); Charpy, Cecile (Dept. of Pathology, CHU Clermont-Ferrand, CHU Estaing, Clermont-Ferrand (France))

    2011-06-15

    Abdominal wall endometriosis is unusual and mostly occurs in scars following Cesarean section. Although malignant transformation is rare, it must be recognized in order to benefit from radical resection. We report a very rare case of mixed endometrioid and serous carcinoma developing in a Cesarean section endometriosis scar and the way we managed it using surgery and chemotherapy. 18-FDG PET-CT imaging was performed to correctly stage the disease

  11. Apical atrophy of retinal pigment epithelial detachments in central serous chorioretinopathy

    DEFF Research Database (Denmark)

    Pryds, Anders; Hamann, Steffen; Larsen, Michael

    2012-01-01

    compatible with CSC. RESULTS: A juxtafoveal retinal pigment epithelial detachment with apical atrophy of the retinal pigment epithelium with corresponding severe attenuation of the pigmentation of the retinal pigment epithelium was observed in both patients. One of the patients presented with a serous...... neurosensory retinal detachment with smokestack leakage 7 years after first being seen. The other patient was never seen with a neurosensory detachment. CONCLUSION: Isolated pigment epithelial detachment with apical retinal pigment epithelial atrophy may represent a precursor stage of CSC....

  12. CIAPIN1 and ABCA13 are markers of poor survival in metastatic ovarian serous carcinoma.

    Science.gov (United States)

    Nymoen, Dag Andre; Holth, Arild; Hetland Falkenthal, Thea E; Tropé, Claes G; Davidson, Ben

    2015-02-18

    The objective of this study was to investigate the expression and clinical role of 14 genes previously shown to be associated with chemotherapy response and/or progression-free survival in a smaller series of ovarian serous carcinoma effusions. Advanced-stage serous ovarian carcinoma effusions (n = 150) were analyzed for mRNA expression of AKR1C1, ABCA4, ABCA13, ABCB10, BIRC6, CASP9, CIAPIN1, FAS, MGMT, MUTYH, POLH, SRC, TBRKB and XPA using quantitative real-time PCR. mRNA expression was studied for association with clinicopathologic parameters, including chemotherapy response and survival. ABCA4 mRNA expression was significantly related to better (complete) chemotherapy response at diagnosis in the entire cohort (p = 0.018), whereas higher POLH mRNA levels were significantly related to better chemoresponse at diagnosis in analysis to 58 patients with pre-chemotherapy effusions treated with standard chemotherapy (carboplatin + paclitaxel; p = 0.023). In univariate survival analysis for patients with pre-chemotherapy effusions (n = 77), CIAPIN1 mRNA expression was significantly related to shorter overall (p = 0.007) and progression-free (p = 0.038) survival, whereas ABCA13 mRNA expression was significantly related to shorter OS (p = 0.024). Higher CIAPIN1 mRNA expression was an independent marker of poor overall survival in Cox multivariate analysis (p = 0.044). Our data identify ABCA4 and POLH as markers of better chemotherapy response in metastatic serous carcinoma. CIAPIN1 and ABCA13 may be novel markers of poor outcome in pre-chemotherapy serous carcinoma effusions.

  13. Comparison of Plasma Osteopontin Levels between Patients with Borderline Ovarian Tumours and Serous Ovarian Carcinoma.

    Science.gov (United States)

    Živný, J H; Leahomschi, S; Klener, P; Živný, J; Haluzík, M; Cibula, D

    2016-01-01

    Osteopontin (OPN) is a novel biomarker of various cancers including ovarian carcinoma. OPN is a promising adjunct to a major biomarker of ovarian cancer, CA125, in diagnosis, differential diagnosis and prognosis. The aim of our study was to measure the plasma level of OPN and CA125 in patients with borderline ovarian tumours (BOTs), serous ovarian carcinoma, and controls to determine its potential role in the differential diagnosis between serous ovarian carcinoma and BOT. The plasma samples of 66 women were analysed using Luminex technology, designed to simultaneously measure multiple specific protein targets. The mean OPN plasma level for the control group was 23.3 ng/ml; for BOT 26.3 ng/ml; and for patients with serous ovarian carcinoma 59.5 ng/ml. Specifically, there was a significant difference between the OPN levels in patients with ovarian carcinoma and BOT (P ovarian carcinoma. The area under the ROC curve (AUC) for OPN was 0.793 (95% confidence interval (CI) 0.669-0.917, P ovarian carcinoma and BOT.

  14. Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma

    International Nuclear Information System (INIS)

    Hamilton, Chad A.; Liou, W.-S.; Osann, Kathryn; Berman, Michael L.; Husain, Amreen; Teng, Nelson N.; Kapp, Daniel S.; Chan, John K.

    2005-01-01

    Purpose: To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma. Methods and Materials: Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods. Results: Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival. Conclusion: Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma

  15. Pharmacological study of radioactive-gold colloid transport by blood and by serous exudate

    International Nuclear Information System (INIS)

    Rousselet, J.

    1966-06-01

    After giving the essential physico-chemical properties of the colloids, the author considers the biological role of these substances and, in connection with their transport by the blood, their capture by elements of the reticula-endothelial system. A summary is given of present knowledge concerning the role of serous proteins in the transport of substances, particularly that of radio-active colloidal gold. The blood fractions which can take part in colloidal gold transport are the red blood corpuscles, the leukocytes and histiocytic elements as well as the plasma. The radioactive distribution in these various fractions is obtained by autoradiography of blood sediments. After showing the importance of the role of the plasma in radioactive particle transport, the author, describes the attempts made to detect a possible of colloidal gold 198 on the various serous proteins using various methods of separation. The ''in vitro'' and ''in vivo'' bonds between colloidal gold-198 particles and either the serous proteins or healthy specimens or the effusion liquids of pathological origin in man, or due to an experimental inflammation with carregenin in the rat, have been studied. The bonding appears to be effective because of the protective macromolecular layer formed by the gelatine. The different positions of the colloidal grains on the electrophoregram can only be explained by their different physico-chemical characteristics. Gold in the ionic form, on the other hand, is combined only with the albumen is the amount metal present does not exceed a certain value. (author) [fr

  16. Chronic central serous choroidopathy with severe visual loss in hyperopic microphthalmic identical twins

    Directory of Open Access Journals (Sweden)

    Fabry, Annelies

    2011-01-01

    Full Text Available Objective: To report chronic central serous choroidopathy with severe visual loss in hyperopic microphthalmic identical twins. Methods: The index patient was first examined in 1994, at age 31, and has been followed up closely for 17 years. He had repeated fluorescein and indocyanine green angiograms, OCT, ultrasound biometry, and recently also autofluorescence and EDI OCT. His twin brother was first examined in 2010, at age 47, and had a similar extensive exploration. Results: The index patient had a mean refractive error of +6 D OU and VA was 20/32++ in the RE and 20/200 in the LE in 1994. Vision slowly went down to 20/800+ in the RE and 20/600 in the LE in 2011. His twin brother has a mean refractive error of +6 D OU and VA 20/400 OU. Both have a short axial length of the eye, a thick choroid with dilated vessels, and central serous choroidopathy with cystic degeneration of the macula and retina in the posterior pole. Conclusions: We add to the reported complications of microphthalmos, chronic central serous choroidopathy.

  17. External validation suggests Integrin beta 3 as prognostic biomarker in serous ovarian adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Sundfeldt Karin

    2009-09-01

    Full Text Available Abstract Background The majority of women with ovarian cancer are diagnosed in late stages, and the mortality rate is high. The use of biomarkers as prognostic factors may improve the treatment and clinical outcome of these patients. We performed an external validation of the potential biomarkers CLU, ITGB3, CAPG, and PRAME to determine if the expression levels are relevant to use as prognostic factors. Methods We analysed the gene expression of CLU, ITGB3, CAPG, and PRAME in 30 advanced staged serous adenocarcinomas with quantitative real-time polymerase chain reaction (QPCR and the protein levels were analysed in 98 serous adenocarcinomas with western blot for semiquantitative analysis. Statistical differences in mRNA and protein expressions between tumours from survivors and tumours from deceased patients were evaluated using the Mann-Whitney U test. Results The gene and protein ITGB3 (Integrin beta 3 were significantly more expressed in tumours from survivors compared to tumours from deceased patients, which is in concordance with our previous results. However, no significant differences were detected for the other three genes or proteins CLU, CAPG, and PRAME. Conclusion The loss of ITGB3 expression in tumours from deceased patients and high expression in tumours from survivors could be used as a biomarker for patients with advanced serous tumours.

  18. The relationship between fundus fluorescein angiographic findings and serous macular detachment in diabetic macular edema.

    Science.gov (United States)

    Gungel, Hulya; Altan, Cigdem

    2013-10-01

    To investigate whether the serous macular detachment (SMD) shown by optical coherence tomography is associated with types of maculopathy, severity of retinopathy, the effect of macular and retinal photocoagulation, and retinal circulation times in diabetic macular edema. Patients were grouped as SMD+ (Group 1) and SMD- (Group 2). Fundus photography and fluorescein angiography were evaluated regarding the type of maculopathy; severity of retinopathy and also arm-retina time, arteriovenous transit time, and venous filling time; and the applied macular and panretinal laser treatment. Diffuse maculopathy was seen more frequently in eyes with SMD, whereas ischemic maculopathy was more frequent in eyes without SMD. There was no significant difference regarding severity of retinopathy and retinal circulation times between groups. The frequency of patients with complete panretinal photocoagulation and grid laser photocoagulation was found to be higher in Group 2. Serous macular detachment can occur in eyes with increased vascular permeability in macula. Serous macular detachment may be an important finding in terms of the possible existence of diffuse maculopathy and the need of additional panretinal photocoagulation, but absence of SMD may point at ischemic maculopathy.

  19. Expression of autocrine motility factor mRNA is a poor prognostic factor in high-grade astrocytoma.

    Science.gov (United States)

    Tanizaki, Yoshinori; Sato, Yuichi; Oka, Hidehiro; Utsuki, Satoshi; Kondo, Koji; Miyajima, Yoshiteru; Nagashio, Ryo; Fujii, Kiyotaka

    2006-09-01

    It has been reported that tumor infiltration is correlated with the expression of autocrine motility factor (AMF) and its receptor 78 kDa glycoprotein (gp78). The purpose of the present study was to detect AMF and gp78 mRNA expression levels and their localization in high-grade astrocytomas (glioblastoma and anaplastic astrocytoma) and to determine whether AMF and gp78 are important prognostic factors. A total of 32 formalin-fixed and paraffin-embedded glioblastomas and 23 formalin-fixed and paraffin-embedded anaplastic astrocytomas was used. The expressions of AMF and gp78 mRNA were detected using the highly sensitive in situ hybridization method. The expression of AMF mRNA was detected in 27 of 32 glioblastomas (84.4%) and 11 of 23 anaplastic astrocytomas (47.8%). The positivity of AMF mRNA was significantly higher in glioblastomas than in anaplastic astrocytomas (P = 0.0094), but gp78 mRNA was detected in most cases and no statistical significance was observed. The overall survival of patients with AMF expression was significantly shorter than patients without AMF expression (P = 0.0175). In anaplastic astrocytomas, the overall survival of patients with AMF expression was also significantly shorter than in patients without AMF expression (P = 0.0058). This study demonstrated that AMF is a poor prognostic factor in high-grade astrocytomas.

  20. The Necessity of a High-grade Telescope for Education and Future Research Activities in the Phillipines

    Science.gov (United States)

    Celebre, C. P.

    Astronomy has been practiced in the Philippines for the past century. However, the study of celestial objects in the country is confined to its observation and publication of data. There is no course on astronomy in the tertiary level while it is briefly covered in the general science curriculum of the elementary and high schools in the country. No serious research activity has been conducted primarily due to the lack of necessary research instruments such as a high-grade telescope and the required formal education or training of staff in astronomy to perform such an activity. The possible donation of a 45-cm high-grade telescope with its accessories by the Government of Japan, through its Cultural Grant-aid Program, to the Philippines will upgrade the capability of the Astronomical Observatory of the Philippine Atmospheric, Geophysical and Astronomical Services Administration (PAGASA) to observe and study astronomical objects and phenomena. Likewise, it will improve services in the promotion of the science of astronomy in the country, especially in the education and training of science teachers.

  1. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-07-01

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

  3. 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.

  4. Sacral neuromodulation for persistent faecal incontinence after laparoscopic ventral rectopexy for high-grade internal rectal prolapse.

    Science.gov (United States)

    Mishra, A; Prapasrivorakul, S; Gosselink, M P; Gorissen, K J; Hompes, R; Jones, O; Cunningham, C; Matzel, K E; Lindsey, I

    2016-03-01

    Internal rectal prolapse is recognized as an aetiological factor in faecal incontinence. Patients found to have a high-grade internal rectal prolapse on routine proctography are offered a laparoscopic ventral rectopexy after failed maximum medical therapy. Despite adequate anatomical repair, faecal incontinence persists in a number of patients. The aim of this study was to evaluate the outcome of sacral neuromodulation in this group of patients. Between August 2009 and January 2012, 52 patients who underwent a laparoscopic ventral rectopexy for faecal incontinence associated with high-grade internal rectal prolapse had persistent symptoms of faecal incontinence and were offered sacral neuromodulation. Symptoms were evaluated before and after the procedure using the Fecal Incontinence Severity Index (FISI) and the Gastrointestinal Quality of Life Index (GIQLI). Temporary test stimulation was successful in 47 (94%) of the patients who the