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Sample records for grade serous carcinomas

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

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    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.

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

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    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.

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

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    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.

  5. KRAS/BRAF Analysis in Ovarian Low-Grade Serous Carcinoma Having Synchronous All Pathological Precursor Regions

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    Kohei Nakamura

    2016-04-01

    Full Text Available Ovarian low-grade serous carcinoma is thought to begin as a serous cystadenoma or adenofibroma that progresses in a slow stepwise fashion. Among the low-grade serous carcinomas, there is a high frequency of activating mutations in the KRAS or BRAF genes; however, it remains unclear as to how these mutations contribute to tumor progression. This is the first report to track the histopathological progression of serous adenofibroma to low-grade serous carcinoma. Each stage was individually analyzed by pathological and molecular genetic methods to determine what differences occur between the distinct stages of progression.

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

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    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).

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

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    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.

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

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    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

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

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    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.

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

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

    2018-02-01

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

  11. 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).

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    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

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

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    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.

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

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    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.

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

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    2014-10-01

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

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

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

    2018-01-01

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

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

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    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.

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

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    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.

  18. 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.

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    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.

  19. Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas

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    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...... of the primary tumor but rather the presence of extraovarian disease, specifically invasive implants. According to the terminology of the 2014 WHO Classification, typical SBTs are equivalent to APSTs and SBTs displaying micropapillary architecture are synonymous with niLGSC. In addition, "invasive implants" were...

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

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    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.

  1. Pancreatic Metastasis of High-Grade Papillary Serous Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report

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    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.

  2. 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.

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    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.

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

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    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

  4. 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

  5. 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.

  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. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Integrated analyses of microRNAs demonstrate their widespread influence on gene expression in high-grade serous ovarian carcinoma.

    Science.gov (United States)

    Creighton, Chad J; Hernandez-Herrera, Anadulce; Jacobsen, Anders; Levine, Douglas A; Mankoo, Parminder; Schultz, Nikolaus; Du, Ying; Zhang, Yiqun; Larsson, Erik; Sheridan, Robert; Xiao, Weimin; Spellman, Paul T; Getz, Gad; Wheeler, David A; Perou, Charles M; Gibbs, Richard A; Sander, Chris; Hayes, D Neil; Gunaratne, Preethi H

    2012-01-01

    The Cancer Genome Atlas (TCGA) Network recently comprehensively catalogued the molecular aberrations in 487 high-grade serous ovarian cancers, with much remaining to be elucidated regarding the microRNAs (miRNAs). Here, using TCGA ovarian data, we surveyed the miRNAs, in the context of their predicted gene targets. Integration of miRNA and gene patterns yielded evidence that proximal pairs of miRNAs are processed from polycistronic primary transcripts, and that intronic miRNAs and their host gene mRNAs derive from common transcripts. Patterns of miRNA expression revealed multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression across tumors showed a higher frequency of in silico predicted target sites in the mRNA 3'-untranslated region (with less frequency observed for coding sequence and 5'-untranslated regions). The miR-29 family and predicted target genes were among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR-29a in vitro repressed several anti-correlated genes (including DNMT3A and DNMT3B) and substantially decreased ovarian cancer cell viability. This study establishes miRNAs as having a widespread impact on gene expression programs in ovarian cancer, further strengthening our understanding of miRNA biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit high diversity reflecting the genomic heterogeneity within a clinically homogeneous disease population. Putative miRNA:mRNA interactions, as identified using integrative analysis, can be validated. TCGA data are a valuable resource for the identification of novel tumor suppressive miRNAs in ovarian as well as other cancers.

  14. 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

  15. Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan.

    Science.gov (United States)

    Chao, Kuan-Chong; Chen, Yi-Jen; Juang, Chi-Mou; Lau, Hei-Yu; Wen, Kuo-Chang; Sung, Pi-Lin; Fang, Feng-Ying; Twu, Nae-Fang; Yen, Ming-Shyen

    2013-03-01

    To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p statistic). PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ. Copyright © 2013. Published by Elsevier B.V.

  16. Akt2/ZEB2 may be a biomarker for exfoliant cells in ascitic fluid in advanced grades of serous ovarian carcinoma.

    Science.gov (United States)

    Liu, Changmei; Yang, Fangmei

    2015-09-01

    Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.

  17. Serous endometrial intraepithelial carcinoma: a case series and literature review

    International Nuclear Information System (INIS)

    Pathiraja, P; Dhar, S; Haldar, K

    2013-01-01

    Minimal uterine serous cancer (MUSC) or serous endometrial intraepithelial carcinoma (EIC) has been described by many different names since 1998. There have been very few cases reported in literature since EIC/MUSC was recognized as a separate entity. The World health Organization (WHO) Classification favors the term serous EIC. Although serous EIC is confined to the uterine endometrium at initial histology diagnosis, a significant number of patients could have distal metastasis at diagnosis, without symptoms. Serous EIC is considered as being the precursor of uterine serous cancer (USC), but pure serous EIC also has an aggressive behavior similar to USC. It is therefore prudent to have an accurate diagnosis and appropriate surgical staging. There are very few published articles in literature that discuss the pure form of serous EIC. The aim of this series is to share our experience and review evidence for optimum management of serous EIC. We report a series of five women treated in our institute in the last 3 years. We reviewed the relevant literature on serous EIC and various management strategies, to recommend best clinical practice. Pure serous EIC is a difficult histopathological diagnosis, which requires ancillary immunohistochemical staining. It can have an aggressive clinical behavior with early recurrence and poor survival. Optimum surgical staging, with appropriate adjuvant treatment, should be discussed when treating these patients

  18. 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.

  19. Normal-sized ovarian papillary serous carcinoma: a case report.

    Science.gov (United States)

    Wu, W C; Lai, C I; Huang, L C; Chiu, T H; Hung, Y C; Chang, W C

    2010-01-01

    A normal-sized ovarian papillary serous carcinoma is rare. We present the case of a 46-year-old woman with progressive abdominal fullness of one week's duration. The medical evaluation revealed abdominal carcinomatosis with normal-sized ovaries and an elevated serum CA-125 level of 147,365.8 U/ml. Cytoreductive surgery (hysterectomy, bilateral salpingo-oophorectomy, omentectomy, lymphadenectomy, infracolic omentectomy, peritoneal biopsy, washing cytology, and appendectomy) was performed. The histologic examination revealed an ovarian serous papillary carcinoma. Adjuvant chemotherapy was administered. The serum CA-125 level decreased after completion of treatment. Normal-sized ovarian serous surface papillary carcinomas should be kept in mind as an origin of disease in patients who have peritoneal carcinomatosis, which sometimes is a diagnostic dilemma of the disease source. We report this case to emphasize the clinical symptoms and importance of the early and accurate diagnosis of a normal-sized ovarian papillary serous carcinoma.

  20. 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.

  1. 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 ...

  2. Primary peritoneal serous carcinoma: A rare case and palliative approach

    Directory of Open Access Journals (Sweden)

    Viral M Bhanvadia

    2014-01-01

    Full Text Available Primary peritoneal serous carcinoma (PPSC is a rare primary malignancy that diffusely involves the peritoneum, indistinguishable clinically and histopathologically from primary serous ovarian carcinoma. The origin of PPSC has not been well characterized. Here we present a case of PPSC diagnosed in ultrasonography-guided fine needle aspiration cytology (FNAC in a 76- old female presenting with ascites, abdominal pain, distension and constipation. PPSC is an unusual tumour but cytomorphology is distinctive enough to diagnose preoperatively. In the case report hereby described PPSC is an inoperable malignancy, hence chemotherapy and palliative care are the only offered treatment.

  3. Low grade serious carcinoma of the peritoneum in a BRCA1 carrier previously diagnosed with a "low-grade serous tubal intra-epithelial carcinoma" (STIC) on risk reducing surgery.

    Science.gov (United States)

    Chay, Wen Yee; Horlings, Hugo M; Tinker, Anna V; Gelmon, Karen A; Gilks, C Blake

    2015-04-01

    •Conventional definitions of STIC do not capture all lesions associated with serous neoplasia and the presence of abnormal p53 expression may be helpful diagnostically.•The management of STICs and tubal atypias remain uncertain.•The POINT Project is a registry set up to address this critical gap in knowledge.

  4. Uterine Serous Papillary Carcinoma: A Retrospective Analysis of 22 Cases

    OpenAIRE

    Demir Özbasar; Serap Bozok; Taner Turan; İltac Küçükelçi; Gökhan Tulunay; Şadıman Altınbaş; Nurettin Boran; Ömer Faruk Demir; Mehmet Faruk Köse

    2008-01-01

    OBJECTIVE: The cases of 22 patients with uterine serous papillary carcinoma (USPC) were reviewed for this study. STUDY DESIGN: The data of 22 patients diagnosed with USPC was examined. 18 patients underwent formal staging surgery including type I hysterectomy, bilateral salphingo-oophorectomy, para-aortic and bilateral pelvic lymphadenectomy, appendectomy and omentectomy in our clinic. Four patients were sent to our clinic from other hospitals after primary surgery. Staging of the disease ...

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  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. 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.

  12. Prognostic Factors of Uterine Serous Carcinoma-A Multicenter Study.

    Science.gov (United States)

    Zhong, Xiaozhu; Wang, Jianliu; Kaku, Tengen; Wang, Zhiqi; Li, Xiaoping; Wei, Lihui

    2018-04-04

    The prognostic factors of uterine serous carcinoma (USC) vary among studies, and there is no report of Chinese USC patients. The aim of this study was to investigate the clinicopathological characteristics and prognostic factors in Chinese patients with USC. Patients with USC from 13 authoritative university hospitals in China and treated between 2004 and 2014 were retrospectively reviewed. Three-year disease-free survival rate (DFSR), cumulative recurrence, and cumulative mortality were estimated by Kaplan-Meier analyses and log-rank tests. Multivariate Cox regression analysis was used to model the association of potential prognostic factors with clinical outcomes. Data of a total of 241 patients were reviewed. The median follow-up was 26 months (range, 1-128 months). Median age was 60 years (range, 39-84 years), and 58.0% had stages I-II disease. The 3-year DFSR and cumulative recurrence were 46.8% and 27.7%. Advanced stage (III and IV) (P = 0.004), myometrial invasion (P = 0.001), adnexal involvement (P USC. Prospective studies are needed to confirm these results.

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

    Science.gov (United States)

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

    2015-06-01

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

  14. 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.

  15. 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

  16. 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.

  17. Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis.

    Science.gov (United States)

    Cheng, Jung-Chien; Chang, Hsun-Ming; Leung, Peter C K

    2017-10-17

    Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression. Transforming growth factor-β1 (TGF-β1) is a well-known molecule that can strongly up-regulate CTGF expression in different types of normal and cancer cells. Our previous study demonstrated that TGF-β1 induces apoptosis of LGSC cells. However, the effect of TGF-β1 on CTGF expression in LGSC needs to be defined. In addition, whether CTGF mediates TGF-β1-induced LGSC cell apoptosis remains unknown. In the present study, we show that TGF-β1 treatment up-regulates CTGF expression by activating SMAD3 signaling in two human LGSC cell lines. Additionally, siRNA-mediated CTGF knockdown attenuates TGF-β1-induced cell apoptosis. Moreover, our results show that the inhibitory effect of the CTGF knockdown on TGF-β1-induced cell apoptosis is mediated by down-regulating SMAD3 expression. This study demonstrates an important role for CTGF in mediating the pro-apoptotic effects of TGF-β1 on LGCS.

  18. Population-based treatment and outcomes of Stage I uterine serous carcinoma

    NARCIS (Netherlands)

    Putten, L.J.M. van der; Hoskins, P.; Tinker, A.; Lim, P.; Aquino-Parsons, C.; Kwon, J.S.

    2014-01-01

    OBJECTIVE: Uterine serous carcinoma (USC) is a rare type of endometrial cancer that often recurs in patients with Stage I disease. Our objective was to evaluate treatment and outcomes in Stage I USC in the context of a population-based study. METHODS: This was a population-based retrospective cohort

  19. Hypermethylated APC in serous carcinoma based on a meta-analysis of ovarian cancer.

    Science.gov (United States)

    Shen, Chunyan; Sheng, Qifang; Zhang, Xiaojie; Fu, Yuling; Zhu, Kemiao

    2016-09-26

    The reduced expression of the Adenomatous polyposis coli (APC) gene, a tumor suppressor gene, through promoter hypermethylation has been reported to play a key role in the carcinogenesis. However, the correlation between APC promoter hypermethylation and ovarian cancer (OC) remains to be clarified. A comprehensive literature search was carried out in related research databases. The overall odds ratio (OR) and corresponding 95 % confidence interval (CI) were used to evaluate the effects of APC promoter hypermethylation on OC and clinicopathological characteristics. Ultimately, 12 eligible studies were used in our study, including 806 OC samples, 429 normal controls, 109 benign lesions and 75 LMP samples. The pooled OR showed that APC promoter hypermethylation was significantly higher in OC than in normal and benign controls (OR = 6.18 and OR = 3.26, respectively). No significant correlation was observed between OC and low malignant potential (LMP) tumors (P = 0.436). In the comparison of OC and normal controls, subgroup analysis based on race showed that the overall OR of APC promoter hypermethylation was significant and similar in Asians and Caucasians (OR = 8.34 and OR = 5.39, respectively). A subgroup analysis based on sample type found that the pooled OR was significantly higher in blood than in tissue (OR = 18.71 and OR = 5.74, respectively). A significant association was not observed between APC promoter hypermethylation and tumor grade or tumor stage. The pooled OR indicated that APC promoter hypermethylation was significantly lower in serous carcinoma than in non-serous carcinoma (OR = 0.56, P = 0.02). No obvious publication bias was detected by Egger's test (all P > 0.05). APC promoter hypermethylation may be linked to the increased risk of OC. It was associated with histological type, but not with tumor grade or tumor stage. Moreover, hypermethylated APC may be a noninvasive biomarker using blood samples. Future

  20. Primary Papillary Serous Carcinoma of the Fallopian Tube Presenting as a Vaginal Mass: A Case Report and Review of the Literature.

    Science.gov (United States)

    Kadour-Peero, Einav; Sagi-Dain, Lena; Cohen, Gil; Korobochka, Roman; Agbarya, Abed; Bejar, Jacob; Sagi, Shlomi

    2018-05-07

    BACKGROUND There is now evidence to support that some cases of high-grade serous papillary carcinoma arise from the fallopian tubes rather than the ovaries. Common symptoms at presentation include abdominal pain and swelling, vomiting, altered bowel habit and urinary symptoms. To our knowledge, this is the first case of serous papillary carcinoma presenting as a vaginal mass lesion. CASE REPORT A 41-year-old woman was referred to the Bnai-Zion Medical Center with the main complaint of irregular vaginal bleeding, vaginal mucous discharge, and suspected pelvic mass. Physical examination showed a soft, painless mass, measuring about 10 cm in diameter located mainly in the recto-vaginal septum, but not involving the uterus. Ultrasound examination showed no abnormal ovarian or uterine findings. Transvaginal biopsies of the mass showed a poorly differentiated serous papillary carcinoma of ovarian, tubal, or peritoneal origin. The physical examination and imaging findings strongly indicated an inoperable tumor, and the patient was treated with neoadjuvant (pre-surgical) chemotherapy. Pre-operative computed tomography (CT) imaging showed the partial involvement of the colon, and so surgical treatment included total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, partial vaginectomy, anterior rectal resection, and lymph node dissection. Histopathology of the surgical specimens showed a poorly differentiated serous carcinoma originating from the fimbria of the right fallopian tube. CONCLUSIONS To the best of our knowledge, this is the first report to describe primary fallopian tube papillary serous carcinoma presenting as a vaginal mass. Therefore, physicians should be aware of this possible diagnosis.

  1. 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...

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

    Science.gov (United States)

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

    2015-12-29

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

  3. 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.

  4. Mucosal Proliferations in Completely Examined Fallopian Tubes Accompanying Ovarian Low-grade Serous Tumors: Neoplastic Precursor Lesions or Normal Variants of Benign Mucosa?

    Science.gov (United States)

    Wolsky, Rebecca J; Price, Matt A; Zaloudek, Charles J; Rabban, Joseph T

    2018-05-01

    Malignant transformation of the fallopian tube mucosa, followed by exfoliation of malignant cells onto ovarian and/or peritoneal surfaces, has been implicated as the origin of most pelvic high-grade serous carcinoma. Whether a parallel pathway exists for pelvic low-grade serous tumors [ovarian serous borderline tumor (SBT) and low-grade serous carcinoma (LGSC)] remains to be fully elucidated. The literature is challenging to interpret due to variation in the diagnostic criteria and terminology for cytologically low-grade proliferations of the fallopian tube mucosa, as well as variation in fallopian tube specimen sampling. Recently, a candidate fallopian tube precursor to ovarian SBT, so-called papillary tubal hyperplasia, was described in advanced stage patients. The current study was designed to identify fallopian tube mucosal proliferations unique to patients with low-grade serous ovarian tumors (serous cystadenoma, SBT, LGSC) and to determine if they may represent precursors to the ovarian tumors. Fallopian tubes were thinly sliced and entirely examined microscopically, including all of the fimbriated and nonfimbriated portions of the tubes, from patients with ovarian serous cystadenoma (35), SBT (61), and LGSC (11) and from a control population of patients with ovarian mucinous cystadenoma (28), mature cystic teratoma (18) or uterine leiomyoma (14). The slides of the fallopian tubes were examined in randomized order, without knowledge of the clinical history or findings in the ovaries or other organs. Alterations of the mucosa of the fallopian tube were classified as type 1: nonpapillary proliferation of cytologically bland tubal epithelium exhibiting crowding, stratification, and/or tufting without papillary fibrovascular cores or as type 2: papillary alterations consisting of a fibrovascular core lined by a cytologically bland layer of tubal epithelium. A third abnormality, type 3, consisted of detached intraluminal papillae, buds, or nests of epithelium that

  5. 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

  6. 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

  7. Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan

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    Kuan-Chong Chao

    2013-03-01

    Conclusion: PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ.

  8. 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.

  9. [Expansion of secretory cells in the fallopian tubal epithelium in the early stages of the pathogenesis of ovarian serous carcinomas].

    Science.gov (United States)

    Asaturova, A V; Ezhova, L S; Faizullina, N M; Adamyan, L V; Khabas, G N; Sannikova, M V

    to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC). The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test. The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (pepithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), β-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (pepithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 4) ALDH1 between the intact epithelium and SCE, between and SCE and STIC, and between STIC and HGOSC. SCE was shown to be an independent intraepithelial lesion. The incidence of this abnormality increased with age and significantly

  10. 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

  11. 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.

  12. 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

  13. Bilateral primary fallopian tube papillary serous carcinoma in postmenopausal woman: Report of two cases

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    Dipanwita Nag

    2016-01-01

    Full Text Available Primary carcinoma of the fallopian tube is rare and accounts for about 0.14-1.8% of all gynecological malignancies. Correct diagnosis is rarely made preoperatively as clinically tubal carcinoma closely resembles ovarian carcinoma. Here, we report two cases of bilateral primary fallopian tube carcinomas. Case 1: A 54-year-old female presented with postmenopausal bleeding, abdominal pain, and pervaginal watery discharge for 10 days. Ultrasonography (USG of pelvis showed endometrial thickening and multiple tiny echogenic foci in omentum suggestive of omental cake. With a provisional diagnosis of endometrial carcinoma, total abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy was done. On gross examination, small and rudimentary right ovary was adherent to the fimbrial end of the tube. Left-sided tubo-ovarian mass was present, cut section of which showed yellowish solid area in tubal wall and encroaching on ovarian surface. On histological examination, sections from the fimbrial end of both fallopian tubes showed features of papillary serous adenocarcinoma. Case 2: 70-year-old lady, 15 years postmenopausal presented with gradual onset pain and swelling of abdomen, urinary incontinence since 4 days. USG showed bulky uterus, 5 cm × 2 cm fibroid, bilateral tubes, and ovaries were not visualized. Serum cancer antigen-125 was raised (159.7 U/ml. Total hysterectomy and bilateral salpingo-oophorectomy with infracolic omentectomy was done. On gross examination, ovaries were firmly attached to tubes and no apparent solid area was noted. On microscopy, papillary serous adenocarcinoma arising from tubal wall was seen infiltrating focally into ovarian stroma; tubal epithelium showed dysplastic change. Sections from omentum showed numerous psammoma bodies.

  14. Immunohistochemical Expression of COX-2 in Uterine Serous Carcinoma Tissue

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    Joseph Menczer

    2016-03-01

    Material and methods. Cox-2 expression assessment by immunohistochemistry was performed on deparaffinized sections of paraffin-embedded tissue blocks of consecutive available USC uterine specimens of patients diagnosed from 2000 to 2014. Staining of more than 10% of the cells was considered positive. Staining intensity was graded on a 0 and ndash;3 scale. A scoring index was calculated by multiplying the intensity grade by the percentage of stained cells and considered low when it was equal to 1 or less and high when it was more than 1. Clinicopathological data were retrospectively abstracted from the records of the study group patients Results. The study comprised uterine specimens of 31 USC patients. Positive immunohistochemical staining was observed in 25 (80.6% USC specimens and a high score in 6 (19.4% of them. No association between immunohistochemical staining parameters and clinicopathological prognostic factors was observed. Conclusion. Although our findings should be verified in larger series, it seems that in view of the lack of association between immunohistochemical Cox-2 staining parameters in USC tissue and clinicopathological prognostic factors, this aggressive tumor is not a candidate for the use of selective Cox-2 inhibitors. Key words: Cox-2 expression, uterine carcinosarcoma, clinicopathological prognostic factors [J Interdiscipl Histopathol 2016; 4(1.000: 9-12

  15. Curative high dose rate vaginal apex brachytherapy in stage I papillary serous carcinoma of the endometrium

    International Nuclear Information System (INIS)

    Turner, B.C.; Kacinski, B.M.; Gumbs, A.; Peschel, R.E.; Haffty, B.G.; Wilson, L.D.

    1996-01-01

    Introduction: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, clinical understaging, and poor response to salvage treatment. We describe the presentation, local and distant control, survival, salvage rate, and complications for patients undergoing whole abdominal radiation therapy (WART), low dose rate (LDR) intracavitary brachytherapy, or high dose rate (HDR) vaginal brachytherapy in patients with stage I UPSC. Methods: Between 1976 and 1994 more than 1700 patients with endometrial carcinoma were treated with radiation therapy, 30 patients with stage I UPSC (1.8%) were treated with radiation before or following TAH/BSO. All patients underwent either preoperative Simon's packing or tandem and plaque which delivered 30-40 Gy to the serosa, WART, or HDR Ir-192 vaginal apex brachytherapy to a total dose of 21 Gy in 3 fractions at 0.5 cm from the vaginal mucosa. A total of 14 patients received HDR vaginal brachytherapy and (5(14)) patients received systemic chemotherapy. All patients presented with vaginal bleeding at a median age of 67 years (range 34-88). The group of 30 patients underwent TAH/BSO, 17 patients were completely staged pathologically (pelvic and para-aortic lymph nodes, omentectomy, and pelvic washings), and 2 patients underwent omental biopsy and pelvic washings only. All specimens revealed UPSC, nuclear grade 3, and lymphovascular invasion (23%). The pathologic stage was IA: 23% (7), IB: 67% (20), and IC: 10% (3). The median follow-up for all patients was 49 months (range 13-187 months). For the patients receiving postoperative HDR vaginal brachytherapy the median time from surgery to radiation was 42 days (range 29-91). Results: The 5-year actuarial disease free survival for Figo stage I UPSC patients treated with postoperative HDR vaginal brachytherapy and systemic chemotherapy was 100% compared to 74% for stage I UPSC patient

  16. Morphological and immunohistochemical pattern of tubo-ovarian dysplasia and serous tubal intraepithelial carcinoma.

    Science.gov (United States)

    Chene, Gautier; Cayre, Anne; Raoelfils, Ines; Lagarde, Nicole; Dauplat, Jacques; Penault-Llorca, Frederique

    2014-12-01

    Histopathological examination of material from prophylactic salpingo-oophorectomies performed in patients at genetic risk of ovarian cancer can reveal abnormalities interpreted as possible pre-cancerous "ovarian dysplasia" and tubal precursors lesions. We sought to study the morphological features and immunohistochemical expression patterns of neoplasia-associated markers in prophylactically removed ovaries and fallopian tubes (pBSO) in comparison with a group of serous tubal intraepithelial carcinoma (STIC) and non-cancerous controls. Morphological features and immunohistochemical expression patterns of Ki-67 (for proliferation biomarker), p53 (key pathway of mullerian serous tumorogenesis), Bcl2 (anti-apoptotic), γH2AX (a double-strand breaks marker) and ALDH1 (a stem cell marker significantly associated with early-stage ovarian cancer) were blindly evaluated by two pathologists in 111 pBSO, 12 STICs and 116 non-cancerous salpingo-oophorectomies (control group) (nBSO). Morphological ovarian and tubal dysplasia scores were significantly higher in the pBSO than in controls (respectively, 8.8 vs 3.12, pSTICs compared with the controls whereas expression patterns of Ki67, p53 and bcl2 were low to moderate in the pBSO group. STICs overexpressed Ki67 and p53 while bcl2 expression was low; Interestingly, ALDH1 expression was low in non dysplastic epithelium, high in dysplasia and constantly low in STICs. The morphological and immunohistochemical profile of tubo-ovarian dysplasia and STICs might be consistent with progression toward neoplastic transformation in the Serous Carcinogenesis Sequence. These changes may be pre-malignant and could represent an important phase in early neoplasia. ALDH1 activation in pBSO samples and its extinction in STICs should be considered as a target for prevention. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Monoclonal antibody DS6 detects a tumor-associated sialoglycotope expressed on human serous ovarian carcinomas.

    Science.gov (United States)

    Kearse, K P; Smith, N L; Semer, D A; Eagles, L; Finley, J L; Kazmierczak, S; Kovacs, C J; Rodriguez, A A; Kellogg-Wennerberg, A E

    2000-12-15

    A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium. CA6 has a limited distribution in normal adult tissues and is most characteristically detected in fallopian tube epithelium, inner urothelium and type 2 pneumocytes. Pre-treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase-sensitive and periodic acid-sensitive sialic acid glycoconjugate ("sialoglycotope"). SDS-PAGE of OVCAR5 cell lysates has revealed that the CA6 epitope is expressed on an 80 kDa non-disulfide-linked glycoprotein containing N-linked oligosaccharides. Two-dimensional non-equilibrium pH gradient gel electrophoresis indicates an isoelectric point of approximately 6.2 to 6.5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double-label, 2-color immunohistochemical studies. The DS6-detected CA6 antigen appears to be distinct from other well-characterized tumor-associated antigens, including MUC1, CA125 and the histo-blood group-related antigens sLea, sLex and sTn. Copyright 2000 Wiley-Liss, Inc.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

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    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. Expression of Hyaluronan Synthases (HAS1–3) and Hyaluronidases (HYAL1–2) in Serous Ovarian Carcinomas: Inverse Correlation between HYAL1 and Hyaluronan Content

    International Nuclear Information System (INIS)

    Nykopp, Timo K; Anttila, Maarit; Rilla, Kirsi; Sironen, Reijo; Tammi, Markku I; Tammi, Raija H; Hämäläinen, Kirsi; Heikkinen, Anna-Mari; Komulainen, Marja; Kosma, Veli-Matti

    2009-01-01

    Hyaluronan, a tumor promoting extracellular matrix polysaccharide, is elevated in malignant epithelial ovarian tumors, and associates with an unfavorable prognosis. To explore possible contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1 and HYAL2), correlated with hyaluronidase enzyme activity hyaluronan content and HAS1–3 immunoreactivity. Normal ovaries (n = 5) and 34 serous epithelial ovarian tumors, divided into 4 groups: malignant grades 1+2 (n = 10); malignant grade 3 (n = 10); borderline (n = 4) and benign epithelial tumors (n = 10), were analyzed for mRNA by real-time RT-PCR and compared to hyaluronidase activity, hyaluronan staining, and HAS1–3 immunoreactivity in tissue sections of the same specimens. The levels of HAS2 and HAS3 mRNA (HAS1 was low or absent), were not consistently increased in the carcinomas, and were not significantly correlated with HAS protein or hyaluronan accumulation in individual samples. Instead, the median of HYAL1 mRNA level was 69% lower in grade 3 serous ovarian cancers compared to normal ovaries (P = 0.01). The expression of HYAL1, but not HYAL2, significantly correlated with the enzymatic activity of tissue hyaluronidases (r = 0.5; P = 0.006). An inverse correlation was noted between HYAL1 mRNA and the intensity of hyaluronan staining of the corresponding tissue sections (r = -0.4; P = 0.025). The results indicate that in serous epithelial ovarian malignancies HAS expression is not consistently elevated but HYAL1 expression is significantly reduced and correlates with the accumulation of hyaluronan. (233 words)

  1. Serous Carcinoma of the Uterine Cervix, an Extremely Rare Aggressive Entity: A Literature Review.

    Science.gov (United States)

    Jonska-Gmyrek, Joanna; Zolciak-Siwinska, Agnieszka; Gmyrek, Leszek; Michalski, Wojciech; Poniatowska, Grazyna; Fuksiewicz, Malgorzata; Wiechno, Pawel; Kucharz, Jakub; Kowalska, Maria; Kotowicz, Beata

    2018-01-23

    Serous carcinoma of the uterine cervix (USCC) is an extremely rare subtype. To establish the treatment strategy in patients with USCC is an important issue. MEDLINE (PubMed) was searched for all articles published after the first publication by Lurie et al. [Eur J Obstet Gynecol Reprod Biol 1991; 40: 79-81], reporting woman diagnosed with USCC. Because of limited numbers of studies on the topic of the study, we could not keep a restriction of eliminating smaller sample sizes. A search of PubMed demonstrated that 113 cases of USCC have been reported in the literature since the first publication. The current treatment modality adopted for early cervical cancer is hysterectomy with bilateral iliac-obturator lymphadenectomy and postoperative radiotherapy (RT) or radiochemotherapy (RT-CT) if risk factors for cervical carcinoma appear. The treatment strategy for locally advanced USCC is preoperative RT-CT or chemotherapy (CHTH) with the intention to treat the patient surgically. The treatment option for disseminated disease is CHTH with paclitaxel and carboplatin. Risk factors and a more advanced clinical stage of USCC have an impact on poor outcomes despite the use of standard treatment methods, adapted for cervical cancer. The outside-pelvic failures tend to seek effective systemic treatment. © 2018 S. Karger AG, Basel.

  2. 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.

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

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    Shunfei Yan

    2017-01-01

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

  4. 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.

  5. 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.

  6. Adjuvant radiotherapy for uterine papillary serous carcinoma: Whole abdominopelvic or pelvic irradiation?

    International Nuclear Information System (INIS)

    Casey, W.; Chen, Y.; DuBeshter, B.; Angel, C.; Dawson, A.; Smudzin, T.; Rubin, P.

    1996-01-01

    Objective: The optimum adjuvant therapy for uterine papillary serous carcinoma (UPSC), a rare but clinically aggressive histologic variant of endometrial carcinoma, is a controversial issue. UPSC behaves in a pattern that resembles the papillary serous carcinoma of the ovary with a tendency to spread to the peritoneal surfaces. Whole abdominopelvic irradiation (WAI) has been advocated but it remains unclear if adjuvant pelvic irradiation alone is sufficient for early stage UPSC. We reviewed our experience in the adjuvant radiation treatment for UPSC treated at our institution. Materials and Methods: Between 1985 and 1995, a series of 351 cases of endometrial carcinoma were referred to the department of Radiation Oncology. There were a total of 26 UPSC cases with 25 medical records available for review. Except for one case which received irradiation alone, the remaining 24 cases were all surgically staged with TAH/BSO. These patients were treated with WAI or pelvic irradiation with or without a vaginal cuff boost using brachytherapy. The irradiation treatment fields, dose, the local/regional and distant disease status at last follow-up were recorded. The medium follow-up interval was four years with a range of one to eight years. Kaplan-Meier plots for disease specific survival and local/regional disease free survival were obtained. Results: Of the 25 surgically staged UPSC patients, the stage distribution was as follows: 9 stage I, 4 stage II, 10 stage III, and 2 stage IVB. Twelve patients received WAI (4 stage I disease, and 8 stage III disease), while the remaining patients were treated with pelvic irradiation (XRT). 1.) 13 patients were alive without disease and 3 were alive with disease. Seven patients died of either distant metastasis or abdominal recurrence and two died of intercurrent disease (5 year disease specific survival for the whole group was 43%). Two of 17 patients with stages IIIA and below vs. five of 8 patients with stages IIIB and above died of

  7. 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.

  8. Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

    Science.gov (United States)

    Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

    2018-05-01

    Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

  9. Primary peritoneal serous papillary carcinoma (PSPC involving ovary and colon: Management and Treatment

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    Leanza V

    2013-05-01

    Full Text Available We present a case report of a 47-year-old woman who was admitted to our University-Hospital following diagnosis of pelvic mass. Abdominal examination revealed a tender, palpable mass on the right iliac region. At the gynecological examination uterus was regular in size. On the left side of the uterus a mass of 9 cm was observed; its surface was irregular and no mobility was found. Abdominal CT and NMR revealed massive ascites, omental cake and increased volume of both ovaries. Patient underwent longitudinal suprombelical-pubic laparotomy. After opening abdominal cavity, a free-fluid sample was taken and the results were positive for malignant cells. Typical neoplastic localizations on both ovaries, Douglas’ peritoneum, rectum, sigmoid colon and omentum were observed. Extemporaneous histological examination diagnosed a peritoneal serous papillary carcinoma. Hysterectomy with salpingo oophorectomy, total omentectomy, appendectomy, pelvic and lumbo-aortic lymphadenectomy was performed. Retroperitoneal approach to remove the whole Douglas’ peritoneum together with the pouch malignant localizations was done. Sigmoid colon and rectum were resected. A latero-terminal anastomosis with stapler was performed. All the visible abdominal maligant lesions were cut out. No transfusion was necessary. The postoperative course was regular and after seven days the patient was discharged. Chemotherapy ended the therapeutic management (six cycles of carboplatin and paclitaxel. After one year the patient is in good health and instrumental investigations (Ultrasounds, TC and NMR are negative for recurrence. Such a case is very interesting for the discrepancy between slight symptoms and severity of the disease, the solution of which was very complex requiring a skillful polyspecialized oncological team.

  10. 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

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

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    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

  12. Analysis of p130 protein and mRNA expression in ten patients with uterine papillary serous carcinoma

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    Shao-ting XU

    2011-11-01

    Full Text Available Objective To examine p130 protein and mRNA expression in uterine papillary serous carcinoma(UPSC and their clinical and pathologic significance.Methods A total of 10 UPSC patients(Stage I were included,with 10 cases of high-level endometrial carcinoma of the same stage taken as the control group and 10 cases of normal proliferative stage endometrium(EM taken as the disease control group.The level of p130 protein expression was determined by hematoxylin and eosin staining,microscopic observation,and immunohistochemistry,whereas the p130 mRNA levels were examined through real-time quantitative reverse transcriptase polymerase chain reaction.The clinicopathologic analysis was carried out in combination with clinical data.Results The p130 protein and p130 mRNA expression levels in the UPSC group(0.46±0.01 and 0.56±0.06,respectively were apparently less than that of the normal proliferative stage endometrium group(0.91±0.04 and 2.81±0.40,respectively;P < 0.01 and also less than those in high-level endometrial carcinoma(P < 0.05.Clinicopathologic analysis shows that all patients are post-menopausal women with symptoms of irregular vaginal bleeding and the average tumor size was 7.5cm(range: 1.2-14.8cm.The pathologic features are same as that of high-level ovarian papillary serous carcinoma.Conclusion Reduced p130 protein and p130 mRNA expression in UPSC might correlate with poor prognosis in UPSC patients.

  13. Interest of the serous dosage of HER-2/neu, EGFr, VEGF, IL6 and Ac anti-P53 among patients damaged by an esophagus epidermoid carcinoma, type epidermoid carcinoma whom treatment was an exclusive chemoradiotherapy

    International Nuclear Information System (INIS)

    Metges, J.P.; Le Tallec-Jestin, V.; Mahlaire, J.P.; Pradier, O.; Guenet, D.; Volant, A.; Codet, J.P.

    2006-01-01

    The serous concentrations of EGFr and HER2/neu seem to have a potential interest in the framework of the assumption of esophagus epidermoid carcinomas. A next step consists in comparing the serous value of these markers with their tissue expression on biopsies. A prospective study in parallel of a therapeutic trial is starting up to validate these results on a bigger number of patients. (N.C.)

  14. Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.

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    Kuo, Ying-Ju; Weinreb, Ilan; Perez-Ordonez, Bayardo

    2013-07-01

    Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.

  15. Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

    NARCIS (Netherlands)

    Wouters, Maartje C. A.; Komdeur, Fenne L.; Workel, Hagma H.; Klip, Harry G.; Plat, Annechien; Kooi, Neeltje M.; Wisman, G. Bea A.; Mourits, Marian J. E.; Arts, Henriette J. G.; Oonk, Maaike H. M.; Yigit, Refika; de Jong, Steven; Melief, Cornelis J. M.; Hollema, Harry; Duiker, Evelien W.; Daemen, Toos; de Bruyn, Marco; Nijman, Hans W.

    2016-01-01

    Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address

  16. "Surface epithelial changes" in uterine endometrioid carcinoma mimicking micropapillary serous borderline tumor of ovary: report of two cases and review of the literature

    Directory of Open Access Journals (Sweden)

    Quddus M Ruhul

    2011-01-01

    Full Text Available Abstract We encountered two cases of endometrioid carcinoma of uterus with extensive surface epithelial changes (SECs mimicking serous borderline tumor (SBT of the ovary. The first case was a well-differentiated endometrioid carcinoma arising in a background of complex atypical hyperplasia. The second case was moderately-differentiated endometrioid carcinoma with squamous and mucinous differentiation. The SECs comprised of thin microapapillae without hierarchal branching, lined by cuboidal cells with eosinophilic cytoplasm and mild to moderate nuclear atypia. These areas were reminiscent of SBTs of ovary, micropapillary type. This report expands the existing spectrum of SECs. Serous borderline tumor of ovary like surface epithelial changes could be misleading if present in an endometrial biopsy or curettings. Therefore, knowledge of this morphologic variation is important.

  17. Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients

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    Gallagher Michael F

    2009-12-01

    Full Text Available Abstract Background Tumours with high proportions of differentiated cells are considered to be of a lower grade to those containing high proportions of undifferentiated cells. This property may be linked to the differentiation properties of stem cell-like populations within malignancies. We aim to identify molecular mechanism associated with the generation of tumours with differing grades from malignant stem cell populations with different differentiation potentials. In this study we assessed microRNA (miRNA regulation in two populations of malignant Embryonal Carcinoma (EC stem cell, which differentiate (NTera2 or remain undifferentiated (2102Ep during tumourigenesis, and compared this to miRNA regulation in ovarian serous carcinoma (OSC patient samples. Methods miRNA expression was assessed in NTera2 and 2102Ep cells in the undifferentiated and differentiated states and compared to that of OSC samples using miRNA qPCR. Results Our analysis reveals a substantial overlap between miRNA regulation in 2102Ep cells and OSC samples in terms of miRNA biosynthesis and expression of mature miRNAs, particularly those of the miR-17/92 family and clustering to chromosomes 14 and 19. In the undifferentiated state 2102Ep cells expressed mature miRNAs at up to 15,000 fold increased levels despite decreased expression of miRNA biosynthesis genes Drosha and Dicer. 2102Ep cells avoid differentiation, which we show is associated with consistent levels of expression of miRNA biosynthesis genes and mature miRNAs while expression of miRNAs clustering to chromosomes 14 and 19 is deemphasised. OSC patient samples displayed decreased expression of miRNA biosynthesis genes, decreased expression of mature miRNAs and prominent clustering to chromosome 14 but not 19. This indicates that miRNA biosynthesis and levels of miRNA expression, particularly from chromosome 14, are tightly regulated both in progenitor cells and in tumour samples. Conclusion miRNA biosynthesis and

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

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    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.

  19. Comparative evaluation of six cytological grading systems in breast carcinoma

    Directory of Open Access Journals (Sweden)

    Kaushik Saha

    2013-01-01

    Conclusions: Robinson′s grading system is simple, more objective and reproducible, and demonstrated the best concordance with histological grading. So, Robinson′s system should be used routinely for breast carcinoma aspirates.

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

    2015-09-22

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.

  1. Cediranib, a pan-VEGFR inhibitor, and olaparib, a PARP inhibitor, in combination therapy for high grade serous ovarian cancer.

    Science.gov (United States)

    Ivy, S Percy; Liu, Joyce F; Lee, Jung-Min; Matulonis, Ursula A; Kohn, Elise C

    2016-01-01

    An estimated 22,000 women are diagnosed annually with ovarian cancer in the United States. Initially chemo-sensitive, recurrent disease ultimately becomes chemoresistant and may kill ~14,000 women annually. Molecularly targeted therapy with cediranib (AZD2171), a vascular endothelial growth factor receptor (VEGFR)-1, 2, and 3 signaling blocker, and olaparib (AZD2281), a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, administered orally in combination has shown anti-tumor activity in the treatment of high grade serous ovarian cancer (HGSOC). This combination has the potential to change the treatment of HGSOC. Preclinical and clinical studies of single agent cediranib and olaparib or their combination are reviewed. Data are presented from peer-reviewed published manuscripts, completed and ongoing early phase clinical trials registered in ClinicalTrials.gov, National Cancer Institute-sponsored clinical trials, and related recent abstracts. Advances in the treatment of HGSOC that improve progression-free and overall survival have proven elusive despite examination of molecularly targeted therapy. HGSOC patients with deleterious germline or somatic mutations in BRCA1 or BRCA2 (BRCAm) are most responsive to PARP inhibitors (PARPi). PARPi combined with angiogenesis inhibition improved anti-cancer response and duration in both BRCAm and BRCA wild type HGSOC patients, compared to olaparib single agent treatment, demonstrating therapeutic chemical and contextual synthetic lethality.

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

    Science.gov (United States)

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

    2017-12-01

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

  3. Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

    Science.gov (United States)

    Zonta, Yohan Ricci; Martinez, Marcelo; Camargo, Isabel Cristina C.; Domeniconi, Raquel F.; Lupi Júnior, Luiz Antonio; Pinheiro, Patricia Fernanda F.; Reiter, Russel J.; Martinez, Francisco Eduardo; Chuffa, Luiz Gustavo A.

    2017-01-01

    Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFβ1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy. PMID:28398226

  4. Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo.

    Science.gov (United States)

    Schwab, Carlton L; English, Diana P; Roque, Dana M; Bellone, Stefania; Lopez, Salvatore; Cocco, Emiliano; Nicoletti, Roberta; Rutherford, Thomas J; Schwartz, Peter E; Santin, Alessandro D

    2014-10-01

    Uterine serous carcinoma (USC) represents an aggressive variant of endometrial cancer and accounts for a large proportion of deaths annually. HER2/neu amplification is associated with USC in approximately 30-35% of cases. The objective of this study was to determine the sensitivity of a panel of primary USC cell lines to the small tyrosine kinase inhibitor neratinib, an ErbB1 and HER2 inhibitor, both in vitro and in vivo. HER2/neu amplification was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 24 USC cell lines. Flow cytometry was used to determine the effects of neratinib on cell viability, cell cycle distribution and signaling in vitro. Mice harboring HER2/neu amplified xenografts were treated with neratinib to assess the efficacy of the drug in vivo. HER2/neu amplification was noted in 8/24 primary cell lines. Data regarding the efficacy of neratinib was determined using 4 HER2 amplified cell lines and 4 non-amplified cell lines with similar growth rates. Data revealed that cell lines with HER2/neu amplification were exquisitely more sensitive to neratinib compared to non-amplified cell lines (mean ± SEM IC50: 0.011μM ± 0.0008 vs. 0.312μM ± 0.0456 pNeratinib caused arrest in the G0/G1 phase of the cell cycle and resulted in decreased autophosphorylation of HER2 and activation of S6. Neratinib treated mice harboring xenografts of HER2/neu amplified USC showed delayed tumor growth and improved overall survival compared to vehicle (p=0.0019). Neratinib may be a potential treatment option for patients harboring HER2/neu amplified USC. Clinical trials for this subset of endometrial cancer patients are warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. A diagnostic dilemma following risk-reducing surgery for BRCA1 mutation – a case report of primary papillary serous carcinoma presenting as sigmoid cancer

    Directory of Open Access Journals (Sweden)

    Nash Guy F

    2007-09-01

    Full Text Available Abstract Background Women that carry germ-line mutations for BRCA1 or BRCA2 genes are at an increased risk of developing breast, ovarian and peritoneal cancer. Primary peritoneal carcinoma is a rare tumour histologically identical to papillary serous ovarian carcinoma. Risk-reducing surgery in the form of mastectomy and oophorectomy in premenopausal women has been recommended to prevent breast and ovarian cancer occurrence and decrease the risk of developing primary peritoneal cancer. Case presentation We present a case report of a woman with a strong family history of breast cancer who underwent risk-reducing surgery in the form of bilateral salpingo-oophorectomy following a mastectomy for a right-sided breast tumour. Following the finding of a BRCA1 mutation, a prophylactic left-sided mastectomy was performed. After remaining well for twenty-seven years, she presented with rectal bleeding and altered bowel habit, and was found to have a secondary cancer of the sigmoid colon. She was finally diagnosed with primary papillary serous carcinoma of the peritoneum (PSCP. Conclusion PSCP can present many years after risk-reducing surgery and be difficult to detect. Surveillance remains the best course of management for patients with known BRCA mutations.

  6. Comparison of Clinical Characteristic and Prognosis between Ovarian Clear Cell Carcinoma and Serous Carcinoma: A 10-Year Cohort Study of Chinese Patients.

    Science.gov (United States)

    Ye, Shuang; Yang, Jiaxin; You, Yan; Cao, Dongyan; Huang, Huifang; Wu, Ming; Chen, Jie; Lang, Jinghe; Shen, Keng

    2015-01-01

    To compare the clinicopathologic features and prognosis of Chinese patients with ovarian clear cell carcinoma (CCC) and serous carcinoma (SC). A retrospective cohort study was designed to investigate the clinicopathologic characteristic and prognosis of patients with CCC and SC who were diagnosed and treated in in a tertiary referral center (Peking Union Medical College Hospital) between 1999 and 2009. The Kaplan-Meier method and Cox regression were employed in the survival analysis. A total of 504 cases were included in the study, comprising 197 cases of CCC and 307 cases of SC. The mean age of the patients with SC was greater than of CCC patients (3.6±0.94, PPatients with CCC were more likely to be early-stage and optimally debulked (Ppatients with CCC had normal values, and the level was significantly lower than in patients with SC (Ppatients had platinum-resistant tumors compared with platinum-sensitive disease (45.7% in CCC vs. 61.0% in SC [P=0.008]). The 5-year survival rate was 51.2% in the CCC group vs. 49.8% in the SC group (P=0.428). Patients with advanced CCC had a statistically significant poorer overall survival (OS) compared with their SC counterparts (38.0 vs. 52.0 months; hazard ratio 1.584, 95% confidence interval [CI] 1.167-2.150, P=0.003). However, the advantage of improved progression-free survival (PFS) existed across all stages. Women with ovarian CCC presented at a younger age and early stage. Patients with ovarian CCC also had improved PFS, but they had similar OS compared to patients with SC. However, patients with advanced CCC had decreased survival.

  7. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    International Nuclear Information System (INIS)

    Press, Joshua Z; Smith, Margaret; Spellman, Paul T; Wang, Yuker; Miller, Dianne M; Horsman, Doug; Faham, Malek; Gilks, C Blake; Gray, Joe; Huntsman, David G; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E; Blood, Katherine A

    2008-01-01

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways

  8. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Gilks, C. Blake; Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray, Joe; Huntsman, David G.

    2008-05-02

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n=5), clear cell (n=4), or low grade serous (n=2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  9. Ovarian carcinomas with genetic and epigenetic BRCA1 loss havedistinct molecular abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray,Joe; Huntsman, David G.

    2007-07-23

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  10. [The WHO/ISUP grading system for renal carcinoma].

    Science.gov (United States)

    Moch, H

    2016-07-01

    Histological tumor grading is an accepted prognostic parameter of renal cell carcinoma (RCC). In 2012, the International Society of Urologic Pathologists (ISUP) proposed a novel grading system for RCC, mainly based on the evaluation of nucleoli: grade 1 tumors have nucleoli that are inconspicuous and basophilic at ×400 magnification; grade 2 tumors have nucleoli that are clearly visible at ×400 magnification and eosinophilic; grade 3 tumors have clearly visible nucleoli at ×100 magnification; and grade 4 tumors have extreme pleomorphism or rhabdoid and/or sarcomatoid morphology. This grading system was validated for clear cell renal cell carcinoma and papillary renal cell carcinoma. At the same time, the ISUP proposed not grading chromophobe renal cell carcinomas according to this system. At a consensus conference in Zurich the World Health Organization (WHO) recommended the ISUP grading system; thus, the WHO/ISUP grading system is now going to be implemented internationally. The ISUP/WHO grading system has not been validated as a prognostic parameter for other tumor subtypes, but can be used for descriptive purposes.

  11. Effective treatment of Stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy

    International Nuclear Information System (INIS)

    Turner, Bruce C.; Knisely, Jonathan P. S.; Kacinski, Barry M.; Haffty, Bruce G.; Gumbs, Andrew A.; Roberts, Kenneth B.; Frank, Alex H.; Peschel, Richard E.; Rutherford, Thomas J.; Edraki, Babak; Kohorn, Ernest I.; Chambers, Setsuko K.; Schwartz, Peter E.; Wilson, Lynn D.

    1998-01-01

    Purpose: Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC. Methods and Materials: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using 226 Ra or 137 Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using 192 Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy. Results: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94

  12. Role of cytologic grading in prognostication of invasive breast carcinoma

    Directory of Open Access Journals (Sweden)

    Khan Nazoora

    2009-01-01

    Full Text Available Background: Evaluation of cytologic features is indispensable in the preoperative diagnosis and grading of infiltrating ductal breast carcinoma (CA in fine-needle aspiration cytology (FNAC material and this method can also provide additional information regarding intrinsic features of the tumor as well as its prognosis. Aim: This study has been done to evaluate comparatively the cytologic and histomorphologic grading of infiltrating ductal carcinoma of breast with specific reference to lymph node metastasis and its role in prognostication. Materials and Methods: Forty three patients who underwent FNAC and mastectomy for infiltrating ductal carcinoma were cytologically and histologically graded (employing Robinson′s cytologic grading system and Elston′s modification of Bloom-Richardson system, respectively. Statistical analysis was done employing ′z′ test and c2 test to compare the two grading system and to examine the degree of correlation between the cytologic and histologic grades. Multiple regression analysis was done to assess the significance of every cytologic and histologic parameter. All 43 cases, graded cyto-histologically were also evaluated for presence or absence of metastasis to the regional lymph nodes employing c2 test. Results: With histologic grade taken as the standard, cytology was found to be fairly comparable, for grading breast carcinoma (overall sensitivity 89.1%, specificity 100%. Further comparison of the two grading systems by Z-test showed that difference between the cytologic and histologic grading was insignificant in all the three grade (p > 0.05. Of the six parameters studied, cell dissociation, nucleoli and chromatin pattern were the most influential features (p < 0.001. The statistically significant difference (p < 0.001 was found in incidences of axillary lymph node metastatic rate in three cytologic grades (15.4% in grade I vs. 83.3% in grade III as well. Conclusions: Apart from being simple and

  13. Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium.

    Directory of Open Access Journals (Sweden)

    Kate Lawrenson

    Full Text Available The molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses.We studied 10 cases of MT-EC (containing endometrioid and serous differentiation, 5 pure low-grade endometrioid adenocarcinoma (EAC and 5 pure uterine serous carcinoma (USC. Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006, H19 (P = 0.010, HOMER2 (P = 0.009 and TNNT1 (P = 0.006. Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035.Our data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future.

  14. Three-dimensional power doppler ultrasound is useful to monitor the response to treatment in a patient with primary papillary serous carcinoma of the peritoneum.

    Science.gov (United States)

    Su, Jen-Min; Huang, Yu-Fang; Chen, Helen H W; Cheng, Ya-Min; Chou, Cheng-Yang

    2006-05-01

    To date, this is the first report to monitor changes of intratumor vascularization and the response to radiation and Cyberknife therapy in a patient with recurrent primary papillary serous carcinoma of the peritoneum by three dimensional (3D) power Doppler ultrasonography (PDUS). Transvaginal 3D PDUS detected a recurrent presacral tumor with abundant intratumor vascularity. Serial examinations of the tumor volume and serum CA-125 level were studied before, during, and 6 mo after therapy. Meanwhile, the intratumor blood flow was measured and expressed as vascularity indices. All of the tumor volume, intratumor vascularity indices and serum CA-125 level decreased progressively following therapy. A remaining lesion with nearly absent intratumor power Doppler signals suggested a scarring lesion posttreatment. Indeed, CT-guided tissue biopsy confirmed fibrotic change. 3D PDUS is useful to monitor the response to treatments and to differentiate residual tumors from lesions of scarring change posttreatment. It provides more accurate posttreatment information than pelvic computed tomography.

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

    Science.gov (United States)

    2016-10-01

    Cancer Res, in press. PMID: 27590741 31. Ayhan A, Kuhn E, Wu RC, Ogawa H, Talbott AB, Mao TL, Sugimura H, Shih IM, Wang TL. CCNE1 copy number gain...most significant focal DNA somatic copy number alterations were shared between cases with and without STIC lesions. Class comparison of the RNA...significant effort has been placed on determining the menstrual status of samples collected – this included reviewing the endometrium of corresponding

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

    Science.gov (United States)

    2013-10-01

    the Affymetrix 6.0 SNP array instead of the oligonucleotide Agilent 1M CGH array for somatic copy number alterations, due to familiarity and reliable...epithelium. As a result, a significant effort has been placed on determining the menstrual status of samples collected – this has included reviewing the...HRT at time of surgery o Unknown menstrual cycle status at time of surgery The tissue microarray includes the following permutations (2 cores per

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

    Science.gov (United States)

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

    2013-01-01

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

  18. The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Varvara Vitiazeva

    Full Text Available Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer.In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSn. The LC-ESI-MSn of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes.The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC.Mucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from

  19. 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

  20. Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners.

    Science.gov (United States)

    Sarfstein, Rive; Friedman, Yael; Attias-Geva, Zohar; Fishman, Ami; Bruchim, Ilan; Werner, Haim

    2013-01-01

    Accumulating epidemiological evidence shows that obesity is associated with an increased risk of several types of adult cancers, including endometrial cancer. Chronic hyperinsulinemia, a typical hallmark of diabetes, is one of the leading factors responsible for the obesity-cancer connection. Numerous cellular and circulating factors are involved in the biochemical chain of events leading from hyperinsulinemia and insulin resistance to increased cancer risk and, eventually, tumor development. Metformin is an oral anti-diabetic drug of the biguanide family used for treatment of type 2 diabetes. Recently, metformin was shown to exhibit anti-proliferative effects in ovarian and Type I endometrial cancer, although the mechanisms responsible for this non-classical metformin action remain unclear. The insulin-like growth factors (IGFs) play a prominent role in cancer biology and their mechanisms of action are tightly interconnected with the insulin signaling pathways. Given the cross-talk between the insulin and IGF signaling pathways, the aim of this study was to examine the hypothesis that the anti-proliferative actions of metformin in uterine serous carcinoma (USC) are potentially mediated via suppression of the IGF-I receptor (IGF-IR) pathway. Our results show that metformin interacts with the IGF pathway, and induces apoptosis and inhibition of proliferation and migration of USC cell lines with both wild type and mutant p53. Taken together, our results suggest that metformin therapy could be a novel and attractive therapeutic approach for human USC, a highly aggressive variant of endometrial cancer.

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

    Directory of Open Access Journals (Sweden)

    Mortazavi Amir

    2008-09-01

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

  2. Interest of the serous dosage of HER-2/neu, EGFr, VEGF, IL6 and Ac anti-P53 among patients damaged by an esophagus epidermoid carcinoma, type epidermoid carcinoma whom treatment was an exclusive chemoradiotherapy; Interet du dosage serique de HER-2/neu, EGFr, VEGF, IL6 et Ac anti-P53 chez des patients atteints d'un carcinome epidermoide de l'oesophage de type carcinome epidermoide dont le traitement etait une chimioradiotherapie exclusive

    Energy Technology Data Exchange (ETDEWEB)

    Metges, J.P.; Le Tallec-Jestin, V.; Mahlaire, J.P.; Pradier, O. [Departement de Cancerologie, 29 - Brest (France); Guenet, D.; Volant, A. [Service d' anatomopathologie, 29 - Brest (France); Codet, J.P. [Service de Medecine Nucleaire, 29 - Brest (France)

    2006-11-15

    The serous concentrations of EGFr and HER2/neu seem to have a potential interest in the framework of the assumption of esophagus epidermoid carcinomas. A next step consists in comparing the serous value of these markers with their tissue expression on biopsies. A prospective study in parallel of a therapeutic trial is starting up to validate these results on a bigger number of patients. (N.C.)

  3. Increased intragenic IGF2 methylation is associated with repression of insulator activity and elevated expression in serous ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Zhiqing eHuang

    2013-05-01

    Full Text Available Overexpression of insulin-like growth factor-II (IGF2 is a prominent characteristic of many epithelial ovarian malignancies. IGF2 imprinting and transcription are regulated in part through DNA methylation, which in turn regulates binding of the insulator protein, CTCF, within the IGF2/H19 imprint center. We have shown that IGF2 overexpression in ovarian cancer is associated with hypermethylation of CTCF binding sites within the IGF2/H19 imprint center. The aim of this study was to investigate the methylation and binding capacity of a novel putative CTCF binding motif located intragenic to IGF2 and determine how this relates to IGF2 expression. In 35 primary serous epithelial ovarian cancer specimens, methylation of two CpGs, including one within the core binding motif and another adjacent to this motif, was higher in the 18 cancers with elevated IGF2 expression versus 10 with low expression (avg. 68.2% vs. 38.5%; p<0.0001. We also found that the CpG site within the CTCF binding motif is hypermethylated in male gametes (>92%; avg. 93.2%; N=16. We confirmed binding of CTCF to this region in ovarian cancer cells, as well as the paralog of CTCF, BORIS, which is frequently overexpressed in cancers. The unmethylated CTCF binding motif has insulator activity in cells that express CTCF or BORIS, but not in cells that express both CTCF and BORIS. These intragenic CpG dinucleotides comprise a novel paternal germline imprint mark and are located in a binding motif for the insulator protein CTCF. Methylation of the CpG dinucleotides is positively correlated with IGF2 transcription, supporting that increased methylation represses insulator function. These combined results suggest that methylation and CTCF binding at this region play important roles in regulating the level of IGF2 transcription. Our data have revealed a novel epigenetic regulatory element within the IGF2/H19 imprinted domain that is highly relevant to aberrant IGF2 expression in ovarian

  4. P-MAPA immunotherapy potentiates the effect of cisplatin on serous ovarian carcinoma through targeting TLR4 signaling.

    Science.gov (United States)

    de Almeida Chuffa, Luiz Gustavo; de Moura Ferreira, Grazielle; Lupi, Luiz Antonio; da Silva Nunes, Iseu; Fávaro, Wagner José

    2018-01-17

    Toll-like receptors (TLRs) are transmembrane proteins expressed on the surface of ovarian cancer (OC) and immune cells. Identifying the specific roles of the TLR-mediated signaling pathways in OC cells is important to guide new treatments. Because immunotherapies have emerged as the adjuvant treatment for patients with OC, we investigated the effect of a promising immunotherapeutic strategy based on protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) combined with cisplatin (CIS) on the TLR2 and TLR4 signaling pathways via myeloid differentiation factor 88 (MyD88) and TLR-associated activator of interferon (TRIF) in an in vivo model of OC. Tumors were chemically induced by a single injection of 100 μg of 7,12-dimethylbenz(a)anthracene (DMBA) directly under the left ovarian bursa in Fischer 344 rats. After the rats developed serous papillary OC, they were given P-MAPA, CIS or the combination P-MAPA+CIS as therapies. To understand the effects of the treatments, we assessed the tumor size, histopathology, and the TLR2- and TLR4-mediated inflammatory responses. Although CIS therapy was more effective than P-MAPA in reducing the tumor size, P-MAPA immunotherapy significantly increased the expressions of TLR2 and TLR4. More importantly, the combination of P-MAPA with CIS showed a greater survival rate compared to CIS alone, and exhibited a significant reduction in tumor volume compared to P-MAPA alone. The combination therapy also promoted the increase in the levels of the following OC-related proteins: TLR4, MyD88, TRIF, inhibitor of phosphorylated NF-kB alpha (p-IkBα), and nuclear factor kappa B (NF-kB p65) in both cytoplasmic and nuclear sites. While P-MAPA had no apparent effect on tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6, it seems to increase interferon-γ (IFN-γ), which may induce the Thelper (Th1)-mediated immune response. Collectively, our results suggest that P-MAPA immunotherapy combined with cisplatin

  5. Papillary Tubal Hyperplasia. The Putative Precursor of Ovarian Atypical Proliferative (Borderline) Serous Tumors, Noninvasive Implants and Endosalpingiosis

    Science.gov (United States)

    Kurman, Robert J.; Vang, Russell; Junge, Jette; Hannibal, Charlotte Gerd; Kjaer, Susanne K.; Shih, Ie-Ming

    2011-01-01

    In contrast to the controversy regarding the terminology and behavior of ovarian noninvasive low-grade serous tumors (atypical proliferative serous tumor [APST] and serous borderline tumor [SBT]), little attention has been directed to their origin. Similarly, until recently, proliferative lesions in the fallopian tube have not been extensively studied. The recent proposal that ovarian high-grade serous carcinomas are derived from intraepithelial carcinoma in the fallopian tube prompted us to evaluate the possible role of the fallopian tube in the genesis of low-grade serous tumors. We have identified a lesion, designated “papillary tubal hyperplasia (PTH)”, characterized by small rounded clusters of tubal epithelial cells and small papillae, with or without associated psammoma bodies, that are present within the tubal lumen and which are frequently associated with APSTs. Twenty-two cases in this study were selected from a population-based study in Denmark of approximately 1000 patients with low-grade ovarian serous tumors in whom implants were identified on the fallopian tube. Seven additional cases were seen recently in consultation at The Johns Hopkins Hospital (JHH). These 7 cases were not associated with an ovarian tumor. Papillary tubal hyperplasia was found in 20 (91%) of the 22 cases in the Danish study. Based on this association of PTH with APSTs with implants and the close morphologic resemblance of PTH, not only to the primary ovarian APSTs but also to the noninvasive epithelial implants and endosalpingiosis, we speculate that the small papillae and clusters of cells from the fallopian tubes implant on ovarian and peritoneal surfaces to produce these lesions. The 7 JHH cases of PTH that were not associated with an ovarian tumor support the view that PTH is the likely precursor lesion. We propose a model for the development of ovarian and extraovarian low-grade serous proliferations (APST, noninvasive epithelial implants and endosalpingiosis) that

  6. BRCA1 is expressed in uterine serous carcinoma (USC) and controls insulin-like growth factor I receptor (IGF-IR) gene expression in USC cell lines.

    Science.gov (United States)

    Amichay, Keren; Kidron, Debora; Attias-Geva, Zohar; Schayek, Hagit; Sarfstein, Rive; Fishman, Ami; Werner, Haim; Bruchim, Ilan

    2012-06-01

    The insulin-like growth factor I receptor (IGF-IR) and BRCA1 affect cell growth and apoptosis. Little information is available about BRCA1 activity on the IGF signaling pathway. This study evaluated the effect of BRCA1 on IGF-IR expression. BRCA1 and IGF-IR immunohistochemistry on archival tissues (35 uterine serous carcinomas [USCs] and 17 metastases) were performed. USPC1 and USPC2 cell lines were transiently cotransfected with an IGF-IR promoter construct driving a luciferase reporter gene and a BRCA1 expression plasmid. Endogenous IGF-IR levels were evaluated by Western immunoblotting. We found high BRCA1 and IGF-IR protein expression in primary and metastatic USC tumors. All samples were immunostained for BRCA1-71% strongly stained; and 33/35 (94%) were stained positive for IGF-IR-2 (6%) strongly stained. No difference in BRCA1 and IGF-IR staining intensity was noted between BRCA1/2 mutation carriers and noncarriers. Metastatic tumors stained more intensely for BRCA1 than did the primary tumor site (P = 0.041) and with borderline significance for IGF-IR (P = 0.069). BRCA1 and IGF-IR staining did not correlate to survival. BRCA1 expression led to 35% and 54% reduction in IGF-IR promoter activity in the USPC1 and USCP2 cell lines, respectively. Western immunoblotting showed a decline in phosphorylated IGF-IR and phosphorylated AKT in both transiently and stably transfected cells. BRCA1 and IGF-IR are highly expressed in USC tumors. BRCA1 suppresses IGF-IR gene expression and activity. These findings suggest a possible biological link between the BRCA1 and the IGF-I signaling pathways in USC. The clinical implications of this association need to be explored.

  7. T-DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo

    International Nuclear Information System (INIS)

    English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

    2014-01-01

    Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody–drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy

  8. Dual HER2\\PIK3CA targeting overcomes single-agent acquired resistance in HER2 amplified uterine serous carcinoma cell lines in vitro and in vivo

    Science.gov (United States)

    Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L.; English, Diana P.; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D.

    2015-01-01

    HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC), and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA mutated and PIK3CA-wild type HER2/neu amplified USC cell lines. Cell viability and cell cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC-xenografts. We found both single agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long lasting growth inhibition in both USC xenografts when compared to single agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA or pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild type PIK3CA resistant to chemotherapy. PMID:26333383

  9. Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo.

    Science.gov (United States)

    Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L; English, Diana P; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D

    2015-11-01

    HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu-amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0-G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy. ©2015 American Association for Cancer Research.

  10. 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

  11. The number of cycles of neoadjuvant chemotherapy is associated with prognosis of stage IIIc-IV high-grade serous ovarian cancer.

    Science.gov (United States)

    Xu, Xia; Deng, Fei; Lv, Mengmeng; Chen, Xiaoxiang

    2017-02-01

    No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc-IV high-grade serous ovarian cancer (HG-SOC). A total of 129 IIIc-IV stage HG-SOC cases were retrospectively analyzed. Cases were comprised of patients who underwent NAC followed by IDS and who achieved clinical complete response (CCR) at the end of primary therapy. Patients were recruited from the Jiangsu Institute of Cancer Research between 1993 and 2013. Optimal IDS-associated factors were explored with logistic regression. The association between progression-free survival (PFS), overall survival (OS) duration, and covariates was assessed by Cox proportional hazards model and log-rank test. The median number of NAC cycle was 3 (range 1-8). CA-125 decreasing kinetics (p = 0.01) was independently associated with optimal IDS. CA-125 decreasing kinetics, optimal IDS, and NAC cycles was independently associated with OS (p cycles was shorter than those of patients who underwent cycles (12.3 versus 17.2 months). The PFS and OS of patients who underwent cycles of adjuvant chemotherapy post-IDS were shorter than those of patients who underwent ≥5 cycles (14.2 and 20.3 versus 21.2 and 28.8 months). NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved CCR. The number of administered NAC cycles should not exceed 4.

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

    Science.gov (United States)

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

    2007-08-01

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

  13. The evolution of endometrial carcinoma classification through application of immunohistochemistry and molecular diagnostics: past, present and future.

    Science.gov (United States)

    Goebel, Emily A; Vidal, August; Matias-Guiu, Xavier; Blake Gilks, C

    2017-12-12

    Uterine cancer was first subclassified based on anatomic site, separating those tumours arising from the endometrium from cervical cancers. There was then further subclassification of endometrial cancers based on cell type, and this correlated with the Type I and Type II categories identified through the epidemiological studies of Bokhman, with endometrioid carcinoma corresponding (approximately) to Type I and serous carcinoma to Type II. These histotypes are not clearly separable in practice, however, with considerable interobserver variability in histotype diagnosis, especially for high-grade tumours. There followed studies of immunomarkers and then mutational studies of single genes, in attempts to improve subclassification. While these have revealed significant differences in protein expression and mutation profiles between endometrioid and serous carcinomas, there is also considerable overlap, so that there remain challenges in subclassification of endometrial carcinoma. Gene panel testing, using next-generation sequencing, was applied to endometrial cancers and highlighted that there are tumours that show genetic alterations intermediate between classic Type I/endometrioid and Type II/serous carcinomas. The Cancer Genome Atlas studies of endometrioid and serous carcinoma offered revolutionary insight into the subclassification of endometrial carcinoma, i.e. that there are four distinct categories of endometrial carcinoma, rather than two, based on genomic architecture. In this review, we provide an overview of immunohistochemical and molecular markers in endometrial carcinoma and comment on the important future directions in endometrial carcinoma subclassification arising from The Cancer Genome Atlas results.

  14. Association of a renal papillary carcinoma with a low grade tumour of the collecting ducts

    Science.gov (United States)

    Daniel, L; Zattara-Cannoni, H; Lechevallier, E; Pellissier, J

    2001-01-01

    This case report describes a 75 year old man who had a renal papillary carcinoma associated with a low grade tumour of the collecting ducts. These tumours showed different immunohistochemical patterns for epithelial membrane antigen, cytokeratin 19, and Ulex europaeus lectin expression. In addition, cytogenetic findings were 47, XY, +7 and 45, XY, -8, add(12)(q–ter) for the papillary renal carcinoma and the low grade tumour of the collecting ducts, respectively. This is the first report where these two types of tumour are associated and cytogenetically distinguished. Key Words: renal cell carcinoma • low grade tumour of the collecting ducts PMID:11477121

  15. Identification of the IGF1/PI3K/NF κB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Koti, Madhuri; Evans, Kenneth; Feilotter, Harriet E; Park, Paul C; Squire, Jeremy A; Gooding, Robert J; Nuin, Paulo; Haslehurst, Alexandria; Crane, Colleen; Weberpals, Johanne; Childs, Timothy; Bryson, Peter; Dharsee, Moyez

    2013-01-01

    Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer. The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with standard platinum-based chemotherapy. Twelve patient tumours demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumours from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using an Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumours from the resistant group and the sensitive group. Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NF κB/ERK gene signalling networks. This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. In addition, our results provide a pathway context for

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

    Directory of Open Access Journals (Sweden)

    Hamide Sayar

    2013-09-01

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

  17. Global miRNA expression analysis of serous and clear cell ovarian carcinomas identifies differentially expressed miRNAs including miR-200c-3p as a prognostic marker

    International Nuclear Information System (INIS)

    Vilming Elgaaen, Bente; Olstad, Ole Kristoffer; Haug, Kari Bente Foss; Brusletto, Berit; Sandvik, Leiv; Staff, Anne Cathrine; Gautvik, Kaare M; Davidson, Ben

    2014-01-01

    Improved insight into the molecular characteristics of the different ovarian cancer subgroups is needed for developing a more individualized and optimized treatment regimen. The aim of this study was to a) identify differentially expressed miRNAs in high-grade serous ovarian carcinoma (HGSC), clear cell ovarian carcinoma (CCC) and ovarian surface epithelium (OSE), b) evaluate selected miRNAs for association with clinical parameters including survival and c) map miRNA-mRNA interactions. Differences in miRNA expression between HGSC, CCC and OSE were analyzed by global miRNA expression profiling (Affymetrix GeneChip miRNA 2.0 Arrays, n = 12, 9 and 9, respectively), validated by RT-qPCR (n = 35, 19 and 9, respectively), and evaluated for associations with clinical parameters. For HGSC, differentially expressed miRNAs were linked to differentially expressed mRNAs identified previously. Differentially expressed miRNAs (n = 78) between HGSC, CCC and OSE were identified (FDR < 0.01%), of which 18 were validated (p < 0.01) using RT-qPCR in an extended cohort. Compared with OSE, miR-205-5p was the most overexpressed miRNA in HGSC. miR-200 family members and miR-182-5p were the most overexpressed in HGSC and CCC compared with OSE, whereas miR-383 was the most underexpressed. miR-205-5p and miR-200 members target epithelial-mesenchymal transition (EMT) regulators, apparently being important in tumor progression. miR-509-3-5p, miR-509-5p, miR-509-3p and miR-510 were among the strongest differentiators between HGSC and CCC, all being significantly overexpressed in CCC compared with HGSC. High miR-200c-3p expression was associated with poor progression-free (p = 0.031) and overall (p = 0.026) survival in HGSC patients. Interacting miRNA and mRNA targets, including those of a TP53-related pathway presented previously, were identified in HGSC. Several miRNAs differentially expressed between HGSC, CCC and OSE have been identified, suggesting a carcinogenetic role for these mi

  18. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

    Science.gov (United States)

    Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-10-13

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.

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

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    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

  20. MAL2 and tumor protein D52 (TPD52 are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

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    Fanayan Susan

    2010-09-01

    Full Text Available Abstract Background The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52, which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Methods Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. Results MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p Conclusions MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients.

  1. Serous Macular Detachments

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    Hakan Özdemir

    2012-03-01

    Full Text Available Serous macular detachment has only recently been recognized to occur in a significant number of eyes with macular pathology including diabetic retinopathy, retinal vein occlusion, Behçet disease, Irvine-Gass syndrome and pars planitis. These serous retinal detachments associated with retinal vascular leakage are not suspected clinically or angiographically but can be diagnosed with optical coherence tomography (OCT beneath the edematous neurosensory retina. The detection of shallow foveal detachment may be helpful in better understanding the pathogenesis of these disorders. In addition, the detection of serous macular detachment may also help to better guide and assess the results of therapy in the future. (Turk J Oph thal mol 2012; 42: 146-9

  2. 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)

  3. ALBI versus Child-Pugh grading systems for liver function in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Na, Seong K; Yim, Sun Y; Suh, Sang J; Jung, Young K; Kim, Ji H; Seo, Yeon S; Yim, Hyung J; Yeon, Jong E; Byun, Kwan S; Um, Soon H

    2018-04-01

    The prognostic performance of the albumin-bilirubin (ALBI) grade in hepatocellular carcinoma (HCC) as an objective method of assessing liver function was investigated. Data from 2099 patients with HCC in Korea were collected and analyzed retrospectively. The discriminative performance of ALBI grade was compared with Child-Pugh (C-P) grade for different stages or treatments. The median follow up duration was 16.2 months (range: 1.0-124.9). The median survival times were 49.7 months for C-P grade A (65.8%), 12.4 months for C-P grade B (25.5%), and 4.2 months for C-P grade C (8.6%) (P < 0.001). The median survival times were 84.2 months for ALBI grade 1 (32.8%), 25.5 months for ALBI grade 2 (53.5%), and 7.7 months for ALBI grade 3 (13.7%) (P < 0.001). In early UICC stages, ALBI grade showed better discriminative performance than C-P grade. In curative treatments, ALBI grade also showed better discriminative performance than C-P grade (Harrell's C: 0.624 (C-P grade) vs 0.667 [ALBI grade]). ALBI grade provided better prognostic performance in survival analysis and better distribution of the grades than C-P grade in HCC, suggesting that ALBI grade could be a good alternative grading system for liver function in patients with HCC. © 2018 Wiley Periodicals, Inc.

  4. Serous ovarian, fallopian tube and primary peritoneal cancers

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVE: The aim of this systematic review is to analyze data on risk factors, epidemiology, clinicopathology and molecular biology from studies comparing primary peritoneal cancer, fallopian tube cancer and ovarian cancer of serous histology, in order to achieve a greater understanding...... 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...... included. RESULTS: Twenty-eight studies were found eligible. Primary peritoneal cancer patients were older, had higher parity, were more often obese and had poorer survival compared to ovarian cancer patients. Differences in protein expression patterns of Her2/neu, estrogen and progestin receptors...

  5. Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy

    Directory of Open Access Journals (Sweden)

    Julian Arista-Nasr

    2016-04-01

    Full Text Available ABSTRACT Purpose The vast majority of urothelial carcinomas infiltrating the bladder are consistent with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. Materials and Methods We describe the clinicopathologic features of two patients with low-grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. Results Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12 and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. Conclusions The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients.

  6. MAL2 and tumor protein D52 (TPD52) are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

    International Nuclear Information System (INIS)

    Byrne, Jennifer A; Sutherland, Robert L; Fazio, Anna de; O'Brien, Philippa M; Maleki, Sanaz; Hardy, Jayne R; Gloss, Brian S; Murali, Rajmohan; Scurry, James P; Fanayan, Susan; Emmanuel, Catherine; Hacker, Neville F

    2010-01-01

    The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52), which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p < 0.001; n = 124) and was an independent predictor of survival in the overall carcinoma cohort (hazard ratio (HR), 0.498; 95% confidence interval (CI), 0.34-0.728; p < 0.001; n = 221), and in serous carcinomas (HR, 0.440; 95% CI, 0.294-0.658; p < 0.001; n = 182). MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients

  7. Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade

    Directory of Open Access Journals (Sweden)

    Kanika Gupta

    2018-01-01

    Full Text Available Context: Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Aims: Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. Settings and Design: A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Materials and Methods: Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR Breast Imaging Reporting and Data System (BI-RADS Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Statistical Analysis Used: Chi square test, ordinal regression, and Goodman and Kruskal tau test. Results: Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001. The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 as compared to masses with hypoechoic echotexture. Conclusions: Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

  8. Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade.

    Science.gov (United States)

    Gupta, Kanika; Kumaresan, Meenakshisundaram; Venkatesan, Bhuvaneswari; Chandra, Tushar; Patil, Aruna; Menon, Maya

    2018-01-01

    Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Chi square test, ordinal regression, and Goodman and Kruskal tau test. Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001 ). The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 ) in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs) with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 ) as compared to masses with hypoechoic echotexture. Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

  9. Evaluation of Tumor Heterogeneity of Prostate Carcinoma by Flow- and Image DNA Cytometry and Histopathological Grading

    Directory of Open Access Journals (Sweden)

    Naining Wang

    2000-01-01

    Full Text Available Background. Heterogeneity of prostate carcinoma is one of the reasons for pretreatment underestimation of tumor aggressiveness. We studied tumor heterogeneity and the probability of finding the highest tumor grade and DNA aneuploidy with relation to the number of biopsies. Material and methods. Specimens simulating core biopsies from five randomly selected tumor areas from each of 16 Böcking’s grade II and 23 grade III prostate carcinomas were analyzed for tumor grade and DNA ploidy by flow‐ and fluorescence image cytometry (FCM, FICM. Cell cycle composition was measured by FCM. Results. By determination of ploidy and cell cycle composition, morphologically defined tumors can further be subdivided. Heterogeneity of tumor grade and DNA ploidy (FCM was 54% and 50%. Coexistence of diploid tumor cells in aneuploid specimens represents another form of tumor heterogeneity. The proportion of diploid tumor cells decreased significantly with tumor grade and with increase in the fraction of proliferating cell of the aneuploid tumor part. The probability of estimating the highest tumor grade or aneuploidy increased from 40% for one biopsy to 95% for 5 biopsies studied. By combining the tumor grade with DNA ploidy, the probability of detecting a highly aggressive tumor increased from 40% to 70% and 90% for one and two biopsies, respectively. Conclusion. Specimens of the size of core biopsies can be used for evaluation of DNA ploidy and cell cycle composition. Underestimation of aggressiveness of prostate carcinoma due to tumor heterogeneity is minimized by simultaneous study of the tumor grade and DNA ploidy more than by increasing the number of biopsies. The biological significance of coexistent diploid tumor cell in aneuploid lesions remains to be evaluated.

  10. 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.

  11. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System.

    Science.gov (United States)

    Epstein, Jonathan I; Egevad, Lars; Amin, Mahul B; Delahunt, Brett; Srigley, John R; Humphrey, Peter A

    2016-02-01

    In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out

  12. The relation of serum PSA and Gleason's grade in patients with prostacic carcinoma

    Directory of Open Access Journals (Sweden)

    Živković Slađana

    2003-01-01

    Full Text Available The prostatic adenocarcinoma is one of the most frequent malignant tumors of men over 50 years of age. It is distinguished by agressive clinical course and heterogeneous multifocal hystomorphologic changes. PSA is the most reliable serum marker in diagnostics and observation of prostatic carcinoma and gleason's system of tumor-diferentiation grading is generally accepted way of determining the hystologic grade. Gleason's system is correlated with serum levels of PSA and with biological behaviour of the tumor. We presented 40 patients with verified ACP in whom the level of serum PSA, gleason's grade and score were compared. Highly significant correlation was found between serum level of PSA and the differentation grade of the tumor - Gleason's grade and score. Combination of PSA parameters and Gleason's score enables correct estimation of tumor's behaviour and correct therapeutic protocole.

  13. Comparative analysis among X-ray mammographic findings, nuclear and histologic grading, and TNM staging of breast carcinoma

    International Nuclear Information System (INIS)

    Park, Jin Sook; Sung, Ki Joon; Cho, Mee Yon; Hong, In Soo; Kim, Myung Soon; Oh, Ki Keun

    1996-01-01

    The purpose of this study was to evaluate the prognosis of breast carcinoma by comparison with X-ray mammographic findings, nuclear and histologic grade, and TNM staging. We retrospectively reviewed 114 cases (113 patients) of breast carcinoma, analysing X-ray mammographic findings of all cases with regard to mass, calcification, and spiculation. In 80 cases of scirrhous invasive ductal breast carcinoma. Black's nuclear and Bloom-Richardson's histologic grade were also evaluated. Mammographic findings and nuclear and histologic grade were compared with TNM staging which might suggest the prognosis of breast carcinoma. X-ray mammographic findings (mass, calcification and spiculation) did not significantly correlate with T staging, but the clinical staging of the spiculation was advanced. These X-ray findings did not significantly correlate with the nuclear grading and the histologic grading. Nuclear grade did not correlate with T and M staging, but correlated significantly with N staging and clinical stage(p < 0.05). Histologic grade did not significantly correlate with TNM staging. The clinical staging of spiculation was advanced and nuclear grade correlated significantly with N stage and clinical staging. X-ray mammographic findings did not directly correlate with nuclear and histologic grading, but combined studies of the evaluation of mammographic findings and nuclear and histologic grade were useful for prognosing breast carcinoma

  14. Large palpable ductal carcinoma in situ is Her-2 positive with high nuclear grade.

    Science.gov (United States)

    Monabati, Ahmad; Sokouti, Ali-Reza; Noori, Sadat Noori; Safaei, Akbar; Talei, Abd-Rasul; Omidvari, Shapoor; Azarpira, Negar

    2015-01-01

    Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group with variable clinical presentation. The exact molecular mechanism is not known why some ductal carcinomas may reach to such a large size but still remains in situ. Although, molecular classification of DCIS lesions and nuclear grading are important for identification of more aggressive lesions but it is not sufficient. Our aim was to examine the expression pattern of immunohistochemical (IHC) markers of ER, PR, HER-2 in palpable DCIS lesions and compare with clinicopathological findings. Our center is referral hospital from South of Iran. Samples were obtained from fifty four patients with a diagnosis of palpable DCIS. Equivocal (2+) case in HER-2 IHC testing was more characterized by chromogenic in situ hybridization. The positive frequency of HER2, ER, and PR was 92%, 48%, and 37% respectively. Palpable DCIS lesions were significantly more HER-2 positive (92%). The DCIS cases were more likely to be of high nuclear grade (grade III) and Her-2 positive cases were more likely to be of high nuclear grade than intermediate grade. All ER negative tumors had high nuclear grade. The Her-2 positivity is suggested as the most important factor responsible for marked in situ proliferation and production of palpable mass.

  15. Central serous chorioretinopathy

    DEFF Research Database (Denmark)

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

    2008-01-01

    are blurred vision, usually in one eye only and perceived typically by the patient as a dark spot in the centre of the visual field with associated micropsia and metamorphopsia. Normal vision often recurs spontaneously within a few months. The condition can be precipitated by psychosocial stress...... 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...

  16. Correlation between 3 T apparent diffusion coefficient values and grading of invasive breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cipolla, Valentina, E-mail: valentina.cipolla@yahoo.it [Department of Radiological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy); Santucci, Domiziana; Guerrieri, Daniele; Drudi, Francesco Maria [Department of Radiological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy); Meggiorini, Maria Letizia [Department of Gynaecological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy); Felice, Carlo de [Department of Radiological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy)

    2014-12-15

    Highlights: • Apparent diffusion coefficient is a quantitative parameter which reflects molecular water movement. • Grading is an independent prognostic factor which correlates with other histopathological features. • Apparent diffusion coefficient values were significantly different between G1 and G3 classes. - Abstract: Purpose: The aim of this study was to evaluate whether the apparent diffusion coefficient (ADC) provided by 3.0 T (3 T) magnetic resonance diffusion-weighted imaging (DWI) varied according to the grading of invasive breast carcinoma. Materials and methods: A total of 92 patients with 96 invasive breast cancer lesions were enrolled; all had undergone 3 T magnetic resonance imaging (MRI) for local staging. All lesions were confirmed by histological analysis, and tumor grade was established according to the Nottingham Grading System (NGS). MRI included both dynamic contrast-enhanced and DWI sequences, and ADC value was calculated for each lesion. ADC values were compared with NGS classification using the Mann–Whitney U and the Kruskal–Wallis H tests. Grading was considered as a comprehensive prognostic factor, and Rho Spearman test was performed to determine correlation between grading and tumor size, hormonal receptor status, HER2 expression and Ki67 index. Pearson's Chi square test was carried out to compare grading with the other prognostic factors. Results: ADC values were significantly higher in G1 than in G3 tumors. No significant difference was observed when G1 and G3 were compared with G2. Tumor size, hormonal receptor status, HER2 expression and Ki67 index correlated significantly with grading but there was a significant difference only between G1 and G3 related to the ER and PR status, HER2 expression and Ki67 index. There was no statistically significant difference in lesion size between the two groups. Conclusion: ADC values obtained on 3 T DWI correlated with low-grade (G1) and high-grade (G3) invasive breast carcinoma. 3

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

    Science.gov (United States)

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

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

  18. Determination of hepatocellular carcinoma grade by needle biopsy is unreliable for liver transplant candidate selection.

    Science.gov (United States)

    Court, Colin M; Harlander-Locke, Michael P; Markovic, Daniela; French, Samuel W; Naini, Bita V; Lu, David S; Raman, Steven S; Kaldas, Fady M; Zarrinpar, Ali; Farmer, Douglas G; Finn, Richard S; Sadeghi, Saeed; Tomlinson, James S; Busuttil, Ronald W; Agopian, Vatche G

    2017-09-01

    The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection. Of 965 patients undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to transplant. Grade by PNB had poor concordance to final explant pathology (κ = 0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%) in identifying poorly differentiated tumors. Vascular invasion was predicted by explant pathologic grade (r s = 0.24; P Liver Transplantation 23 1123-1132 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  19. Clear cell renal cell carcinoma: validation of World Health Organization/International Society of Urological Pathology grading.

    Science.gov (United States)

    Dagher, Julien; Delahunt, Brett; Rioux-Leclercq, Nathalie; Egevad, Lars; Srigley, John R; Coughlin, Geoffrey; Dunglinson, Nigel; Gianduzzo, Troy; Kua, Boon; Malone, Greg; Martin, Ben; Preston, John; Pokorny, Morgan; Wood, Simon; Yaxley, John; Samaratunga, Hemamali

    2017-12-01

    In 2012, the International Society of Urological Pathology (ISUP) introduced a novel grading system for clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma. This system is incorporated into the latest World Health Organization renal tumour classification, being designated WHO/ISUP grading. This study was undertaken to compare WHO/ISUP and Fuhrman grading and to validate WHO/ISUP grading as a prognostic parameter in a series of clear cell RCC. Analysis of 681 cases of ccRCC showed that 144 tumours could not be assigned a Fuhrman grade on the basis of ambiguous grading features. The application of WHO/ISUP grading resulted in a general down-grading of cases when compared with Fuhrman grading. In a sub-group of 374 cases, for which outcome data were available, 9.3% were WHO/ISUP grade 1, 50.3% were grade 2, 24.1% grade 3 and 16.3% grade 4, while the distribution of Fuhrman grades was 0.4% grade 1, 48.7% grade 2, 29.4% grade 3 and 21.5% grade 4. There were no recurrence/metastases amongst patients with WHO/ISUP grade 1 tumours and there was a significant difference in outcome for WHO/ISUP grades 2, 3 and 4. For Fuhrman grading the cancer-free survival was not significantly different for grade 2 and grade 3 tumours. On multivariate analysis WHO/ISUP grade and pT staging category were found to retain prognostic significance. The study demonstrates that FG cannot be applied in >20% of cases of ccRCC and the WHO/ISUP provides superior prognostic information. © 2017 John Wiley & Sons Ltd.

  20. 3D Texture Analysis in Renal Cell Carcinoma Tissue Image Grading

    Science.gov (United States)

    Cho, Nam-Hoon; Choi, Heung-Kook

    2014-01-01

    One of the most significant processes in cancer cell and tissue image analysis is the efficient extraction of features for grading purposes. This research applied two types of three-dimensional texture analysis methods to the extraction of feature values from renal cell carcinoma tissue images, and then evaluated the validity of the methods statistically through grade classification. First, we used a confocal laser scanning microscope to obtain image slices of four grades of renal cell carcinoma, which were then reconstructed into 3D volumes. Next, we extracted quantitative values using a 3D gray level cooccurrence matrix (GLCM) and a 3D wavelet based on two types of basis functions. To evaluate their validity, we predefined 6 different statistical classifiers and applied these to the extracted feature sets. In the grade classification results, 3D Haar wavelet texture features combined with principal component analysis showed the best discrimination results. Classification using 3D wavelet texture features was significantly better than 3D GLCM, suggesting that the former has potential for use in a computer-based grading system. PMID:25371701

  1. 3D Texture Analysis in Renal Cell Carcinoma Tissue Image Grading

    Directory of Open Access Journals (Sweden)

    Tae-Yun Kim

    2014-01-01

    Full Text Available One of the most significant processes in cancer cell and tissue image analysis is the efficient extraction of features for grading purposes. This research applied two types of three-dimensional texture analysis methods to the extraction of feature values from renal cell carcinoma tissue images, and then evaluated the validity of the methods statistically through grade classification. First, we used a confocal laser scanning microscope to obtain image slices of four grades of renal cell carcinoma, which were then reconstructed into 3D volumes. Next, we extracted quantitative values using a 3D gray level cooccurrence matrix (GLCM and a 3D wavelet based on two types of basis functions. To evaluate their validity, we predefined 6 different statistical classifiers and applied these to the extracted feature sets. In the grade classification results, 3D Haar wavelet texture features combined with principal component analysis showed the best discrimination results. Classification using 3D wavelet texture features was significantly better than 3D GLCM, suggesting that the former has potential for use in a computer-based grading system.

  2. ZEB1 overexpression associated with E-cadherin and microRNA-200 downregulation is characteristic of undifferentiated endometrial carcinoma.

    Science.gov (United States)

    Romero-Pérez, Laura; López-García, M Ángeles; Díaz-Martín, Juan; Biscuola, Michele; Castilla, M Ángeles; Tafe, Laura J; Garg, Karuna; Oliva, Esther; Matias-Guiu, Xavier; Soslow, Robert A; Palacios, José

    2013-11-01

    Undifferentiated endometrial carcinomas are very aggressive high-grade endometrial carcinomas that are frequently under-recognized. This study aimed to analyze the molecular alterations underlying the development of these endometrial carcinomas, focusing on those related to dedifferentiation. We assessed a series of 120 tumors: 57 grade 1 and 2 endometrioid endometrial carcinomas, 15 grade 3 endometrioid endometrial carcinomas, 27 endometrial serous carcinomas, and 21 undifferentiated endometrial carcinomas. We found a high frequency of DNA mismatch repair deficiency (38%) and moderate rate of p53 overexpression (∼33%) in undifferentiated carcinomas. In contrast to the characteristic endometrioid phenotype, there was a dramatic downregulation of E-cadherin expression in the undifferentiated subtype. Quantitative methylation studies dismissed CDH1 promoter hypermethylation as the mechanism responsible for this change in gene expression, while immunohistochemistry revealed that the E-cadherin repressor ZEB1 was frequently overexpressed (62%) in undifferentiated endometrial carcinomas. This finding was accompanied by a sharp downregulation in the expression of the miR-200 family of microRNAs, well-known targets of ZEB1. Furthermore, there was enhanced expression of epithelial-to-mesenchymal transition markers in undifferentiated endometrial carcinomas, such as N-cadherin, cytoplasmic p120, and osteonectin. In addition, HMGA2, a regulator of epithelial-to-mesenchymal transition that is expressed in aggressive endometrial tumors, such as endometrial serous carcinomas and carcinosarcomas, was expressed in >20% of undifferentiated carcinomas. These results suggest that ZEB1 overexpression, associated with E-cadherin and miR-200s downregulation, and the expression of mesenchymal markers might enhance the metastatic potential of undifferentiated endometrial carcinomas, leading to a poor prognosis. In addition, our observations suggest that the immnohistochemical analysis

  3. Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade.

    Science.gov (United States)

    Gu, Yi-Feng; Cohn, Shannon; Christie, Alana; McKenzie, Tiffani; Wolff, Nicholas; Do, Quyen N; Madhuranthakam, Ananth J; Pedrosa, Ivan; Wang, Tao; Dey, Anwesha; Busslinger, Meinrad; Xie, Xian-Jin; Hammer, Robert E; McKay, Renée M; Kapur, Payal; Brugarolas, James

    2017-08-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutations, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl ) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with PAX8, a transcription factor frequently overexpressed in ccRCC, led to ccRCC of different grades. Bap1 -deficient tumors were of high grade and showed greater mTORC1 activation than Pbrm1 -deficient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1 , in Pbrm1 -deficient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specific drivers of ccRCC and histologic grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCCs arise from Bowman capsule cells. Significance: Determinants of tumor grade and aggressiveness across cancer types are poorly understood. Using ccRCC as a model, we show that Bap1 and Pbrm1 loss drives tumor grade. Furthermore, we show that the conversion from low grade to high grade can be promoted by activation of mTORC1. Cancer Discov; 7(8); 900-17. ©2017 AACR. See related commentary by Leung and Kim, p. 802 This article is highlighted in the In This Issue feature, p. 783 . ©2017 American Association for Cancer Research.

  4. 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.

  5. The Fuhrman grading system has no prognostic value in patients with nonsarcomatoid chromophobe renal cell carcinoma.

    Science.gov (United States)

    Steffens, Sandra; Janssen, Martin; Roos, Frederik C; Becker, Frank; Steinestel, Julie; Abbas, Mahmoud; Steinestel, Konrad; Wegener, Gerd; Siemer, Stefan; Thüroff, Joachim W; Hofmann, Rainer; Stöckle, Michael; Schrader, Mark; Hartmann, Arndt; Hasenfus, Andrea; Kuczyk, Markus A; Junker, Kerstin; Schrader, Andres J

    2014-12-01

    The prognostic value of the Fuhrman nuclear grading system has been questioned for chromophobe renal cell carcinoma (chRCC) because this subtype frequently displays nuclear and nucleolar pleomorphism. The present study reevaluates this grading system in a series of patients with nonsarcomatoid chRCC. We identified 176 patients (3.6%) with nonsarcomatoid chRCC in a total of 4897 patients who underwent surgery for renal cell carcinoma at 5 centers in Germany between 1990 and 2010. The mean follow-up was 51.1 months. The 3 groups (G1 versus G2 versus G3/4) were comparable in terms of age, sex, tumor diameter, and lymph node metastasis. They only differed significantly in tumor stage (P = .01) and the incidence of synchronous visceral metastasis (P = .04). The 5-year cancer-specific survival rates were 84.4% for G1 (n = 32), 84.3% for G2 (n = 108), and 74.1% for G3/4 tumors (n = 33) (P = .58). Accordingly, multivariate analysis including age, sex, tumor stage, and metastatic disease did not identify Fuhrman grading as an independent predictor of cancer-specific survival in patients with chRCC (P = .4). We were able to demonstrate in a large multicenter cohort that the Fuhrman grading system does not qualify as a prognostic tool in patients with chRCC. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2011-03-01

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

  7. Ductal carcinoma of breast: nuclear grade as a predictor of S-phase fraction.

    Science.gov (United States)

    Dabbs, D J

    1993-06-01

    Nuclear grade (NG) and S-phase fraction (SPF) are established independent prognostic variables for ductal breast carcinomas. Nuclear grade can be assigned by a pathologist in a simple fashion during histopathologic evaluation of the tumor, while SPF requires flow cytometric evaluation of tumor samples. This prospective study was undertaken to determine whether elevated SPF could be predicted from NG alone and how NG and SPF correlate with c-erbB-2 expression. Eighty-two breast carcinomas of ductal type were assigned an NG of low (grade 1 or grade 2) or high (grade 3). S-phase fraction was recorded initially from fresh-frozen tissue samples and was designated as either low SPF (below the value designated as the cutoff for elevated SPF) or high SPF (a value at or greater than the cutoff value). On fresh tissue the NG predicted the range of SPF (low or high) in 89% of cases. Four percent of the cases that did not correlate could definitely be attributed to sample error. The remaining 7% that did not correlate could have been due to sample error, specimen quality, or tumor heterogeneity, as demonstrated by reversal of SPF range as performed on paraffin blocks of tumor. Eighty-eight percent of the tumors positive for c-erbB-2 were NG 3 and 12% were NG 2. All c-erbB-2 tumors were aneuploid. This study demonstrates the importance of carefully assigning NGs on tissue and indicates the importance of reviewing flow cytometric data side by side with histopathologic parameters to detect discrepancies between these two modalities. Careful nuclear grading assignment can accurately predict the range of SPF.

  8. Preoperative computed tomography for determining nodal status combined with histologic grading as a prognostic factor for patients with tongue carcinoma

    International Nuclear Information System (INIS)

    Ogura, Ichiro; Kurabayashi, Tohru; Amagasa, Teruo; Iwaki, Hiroshi; Sasaki, Takehito

    2001-01-01

    The purpose of this study was to evaluate the predictive value of preoperative neck computed tomography (CT) in combination with histologic grading as a prognostic factor for patients with tongue carcinoma. Fifty-five patients with squamous cell carcinoma of the tongue were examined by CT prior to radical neck dissection. The locoregional failure and survival rates of these patients were analyzed in relation to their clinical characteristics, histologic grading (World Health Organization, WHO) based on tongue biopsy, and imaging diagnoses prior to surgery. Logistic multivariate regression analysis showed that both histologic grading and number of metastatic lymph nodes on CT were significant and independent prognostic factors in locoregional failure (p=0.009 and p=0.009, respectively). When the numebr of metastatic lymph nodes detected on preoperative neck CT were combined with the histologic grading for the evaluation, the five-year overall survival rates of A group (0 node with any Grade, or 1 node with Grade I-II) and B group (1 node with Grade III, or 2 or more nodes with any Grade) were 74.5% and 37.5%, respectively (p=0.001). The difference was more significant than histologic grading alone or the number of metastatic lymph nodes seen on CT alone. The combination of preoperative neck CT with histologic grading of the primary tumor is useful as a prognostic indicator for patients with tongue carcinoma. (author)

  9. The Expression of the Zonula Adhaerens Protein PLEKHA7 Is Strongly Decreased in High Grade Ductal and Lobular Breast Carcinomas.

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Tille

    Full Text Available PLEKHA7 is a junctional protein, which participates in a complex that stabilizes E-cadherin at the zonula adhaerens. Since E-cadherin is involved in epithelial morphogenesis, signaling, and tumor progression, we explored PLEKHA7 expression in cancer. PLEKHA7 expression was assessed in invasive ductal and lobular carcinomas of the breast by immunohistochemistry, immunofluorescence and quantitative RT-PCR. PLEKHA7 was detected at epithelial junctions of normal mammary ducts and lobules, and of tubular and micropapillary structures within G1 and G2 ductal carcinomas. At these junctions, the localization of PLEKHA7 was along the circumferential belt (zonula adhaerens, and only partially overlapping with that of E-cadherin, p120ctn and ZO-1, as shown previously in rodent tissues. PLEKHA7 immunolabeling was strongly decreased in G3 ductal carcinomas and undetectable in lobular carcinomas. PLEKHA7 mRNA was detected in both ductal and lobular carcinomas, with no observed correlation between mRNA levels and tumor type or grade. In summary, PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas, and since PLEKHA7 protein but not mRNA expression is strongly decreased or lost in high grade ductal carcinomas and in lobular carcinomas, loss of PLEKHA7 is a newly characterized feature of these carcinomas.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  11. Computer approach to recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma.

    Science.gov (United States)

    Kruk, Michal; Osowski, Stanislaw; Markiewicz, Tomasz; Slodkowska, Janina; Koktysz, Robert; Kozlowski, Wojciech; Swiderski, Bartosz

    2014-06-01

    To present a computerized system for recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma on the basis of microscopic images of the neoplasm cells in application of hematoxylin and eosin staining. The applied methods use combined gradient and mathematical morphology to obtain nuclei and classifiers in the form of support vector machine to estimate their Fuhrman grade. The starting point is a microscopic kidney image, which is subject to the advanced methods of preprocessing, leading finally to estimation of Fuhrman grade of cells and the whole analyzed image. The results of the numerical experiments have shown that the proposed nuclei descriptors based on different principles of generation are well connected with the Fuhrman grade. These descriptors have been used as the diagnostic features forming the inputs to the classifier, which performs the final recognition of the cells. The average discrepancy rate between the score of our system and the human expert results, estimated on the basis of over 3,000 nuclei, is below 10%. The obtained results have shown that the system is able to recognize 4 Fuhrman grades of the cells with high statistical accuracy and agreement with different expert scores. This result gives a good perspective to apply the system for supporting and accelerating the research of kidney cancer.

  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. Joint multiple fully connected convolutional neural network with extreme learning machine for hepatocellular carcinoma nuclei grading.

    Science.gov (United States)

    Li, Siqi; Jiang, Huiyan; Pang, Wenbo

    2017-05-01

    Accurate cell grading of cancerous tissue pathological image is of great importance in medical diagnosis and treatment. This paper proposes a joint multiple fully connected convolutional neural network with extreme learning machine (MFC-CNN-ELM) architecture for hepatocellular carcinoma (HCC) nuclei grading. First, in preprocessing stage, each grayscale image patch with the fixed size is obtained using center-proliferation segmentation (CPS) method and the corresponding labels are marked under the guidance of three pathologists. Next, a multiple fully connected convolutional neural network (MFC-CNN) is designed to extract the multi-form feature vectors of each input image automatically, which considers multi-scale contextual information of deep layer maps sufficiently. After that, a convolutional neural network extreme learning machine (CNN-ELM) model is proposed to grade HCC nuclei. Finally, a back propagation (BP) algorithm, which contains a new up-sample method, is utilized to train MFC-CNN-ELM architecture. The experiment comparison results demonstrate that our proposed MFC-CNN-ELM has superior performance compared with related works for HCC nuclei grading. Meanwhile, external validation using ICPR 2014 HEp-2 cell dataset shows the good generalization of our MFC-CNN-ELM architecture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Kim, Ji Hoon; Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2015-05-01

    To identify the CT features in differentiating grade 3 neuroendocrine carcinomas from grade 1/2 neuroendocrine tumours. This study included 161 patients with surgically confirmed pancreatic neuroendocrine neoplasms. Pathology slides were reviewed to determine the tumour grade. CT image analysis included size, pattern, calcification, margin, pancreatic duct dilatation, bile duct dilatation, vascular invasion, arterial enhancement ratio, and portal enhancement ratio. We used 2 cm, 3 cm, and 4 cm as cutoff values of tumour size and 0.9 and 1.1 of enhancement ratio to determine the sensitivity and specificity. Pathology analysis identified 167 lesions in 161 patients. 154 lesions (92 %) were grade 1/2 and 13 (8 %) were grade 3. Portal enhancement ratio (< 1.1) showed high sensitivity and specificity 92.3 % and 80.5 %, respectively in differentiating grade 3 from grade 1/2. It showed the highest odds ratio (49.60), followed by poorly defined margin, size (> 3 cm), bile duct dilatation, and vascular invasion. When at least two of these five criteria were used in combination, the sensitivity and specificity for diagnosing grade 3 were 92.3 % (12/13) and 87.7 % (135/154), respectively. By using specific CT findings, grade 3 can be differentiated from grade 1/2 with a high diagnostic accuracy leading to an appropriate imaging staging. (orig.)

  16. Next Generation Sequencing of Tubal Intraepithelial Carcinomas

    Science.gov (United States)

    McDaniel, Andrew S.; Stall, Jennifer N.; Hovelson, Daniel H.; Cani, Andi K.; Liu, Chia-Jen; Tomlins, Scott A.; Cho, Kathleen R.

    2016-01-01

    Importance High-grade serous carcinoma (HGSC) is the most prevalent and lethal form of ovarian cancer. HGSCs frequently arise in the distal fallopian tubes rather than the ovary, developing from small precursor lesions called serous tubal intraepithelial carcinomas (TICs or more specifically STICs). While STICs have been reported to harbor TP53 mutations, detailed molecular characterizations of these lesions are lacking. Observations We performed targeted next generation sequencing (NGS) on formalin-fixed, paraffin- embedded tissue from four women, two with HGSC and two with uterine endometrioid carcinoma (UEC) who were diagnosed with synchronous STICs. We detected concordant mutations in both HGSCs with synchronous STICs, including TP53 mutations as well as assumed germline BRCA1/2 alterations, confirming a clonal relationship between these lesions. NGS confirmed the presence of a STIC clonally unrelated to one case of UEC. NGS of the other tubal lesion diagnosed as a STIC unexpectedly supported the lesion as a micrometastasis from the associated UEC. Conclusions and Relevance We demonstrate that targeted NGS can identify genetic lesions in minute lesions such as TICs, and confirm TP53 mutations as early driving events for HGSC. NGS also demonstrated unexpected relationships between presumed STICs and synchronous carcinomas, suggesting potential diagnostic and translational research applications. PMID:26181193

  17. Correlation between chondroitin sulfate iron colloid - enhanced MR imaging and the histological grade of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Suto, Y. [Dept. of Radiology, Tottori University School of Medcine, Yonago (Japan); Kodama, F. [Dept. of Radiology, Tottori University School of Medcine, Yonago (Japan); Kamba, M. [Dept. of Radiology, Tottori University School of Medcine, Yonago (Japan); Ohta, Y. [Dept. of Radiology, Tottori University School of Medcine, Yonago (Japan)

    1995-01-01

    The association between contrast enhancement by chondroitin sulfate iron colloid (CSIC) and the histological grade of hepatocellular carcinoma (HCC) was evaluated in 24 patients diagnosed by histological examination of surgical specimens (26 nodules: 11 well-differentiated and 15 poorly-moderately-differentiated nodules). In the well-differentiated HCC nodules, the tumor-liver contrast to noise ratio (CNR) was not significantly increased after i.v. CSIC injection on both T1-weighted and T2-weighted images. In the moderately-poorly-differentiated HCC, CNR was significantly increased after CSIC administration on both T1-weighted and T2-weighted images (p<0.01). MR imaging using CSIC may be useful for diagnosing the degree of HCC differentiation. (orig.).

  18. Correlation between chondroitin sulfate iron colloid - enhanced MR imaging and the histological grade of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Suto, Y.; Kodama, F.; Kamba, M.; Ohta, Y.

    1995-01-01

    The association between contrast enhancement by chondroitin sulfate iron colloid (CSIC) and the histological grade of hepatocellular carcinoma (HCC) was evaluated in 24 patients diagnosed by histological examination of surgical specimens (26 nodules: 11 well-differentiated and 15 poorly-moderately-differentiated nodules). In the well-differentiated HCC nodules, the tumor-liver contrast to noise ratio (CNR) was not significantly increased after i.v. CSIC injection on both T1-weighted and T2-weighted images. In the moderately-poorly-differentiated HCC, CNR was significantly increased after CSIC administration on both T1-weighted and T2-weighted images (p<0.01). MR imaging using CSIC may be useful for diagnosing the degree of HCC differentiation. (orig.)

  19. Massive Bilateral Serous Retinal Detachment in a Case of Hypertensive Chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Luis Villalba-Pinto

    2014-07-01

    Full Text Available Introduction: Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. Case Report: A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. Discussion: In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes.

  20. Massive Bilateral Serous Retinal Detachment in a Case of Hypertensive Chorioretinopathy

    Science.gov (United States)

    Villalba-Pinto, Luis; Hernández-Ortega, M. Ángeles; de los Mozos, F. Javier Lavid; Pascual-Camps, Isabel; Dolz-Marco, Rosa; Arevalo, J. Fernando; Gallego-Pinazo, Roberto

    2014-01-01

    Introduction Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. Case Report A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. Discussion In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes. PMID:25120474

  1. CARCINOMA PROSTATE HISTOPATHOLOGY IN NEEDLE BIOPSIES INCLUDING REVISED GLEASON’S GRADING AND ROLE OF IMMUNOHISTOCHEMICAL MARKERS

    Directory of Open Access Journals (Sweden)

    Rema Priyadarsini

    2017-05-01

    Full Text Available BACKGROUND Adenocarcinoma of prostate is the most common form of cancer in men accounting for 29% of cancers in developed nations and the incidence of prostatic cancer is 6.4% in males of Trivandrum District. MATERIALS AND METHODS All prostatic biopsies taken per rectally and stained by haematoxylin and eosin. In suspected cases of malignancy immunohistochemical markers, the AMACR P504S and high molecular weight cytokeratin 34E12 were done. RESULTS The total number of cases studied were 142. The final diagnosis with histomorphological features show that maximum cases were prostatic carcinoma constituting 45.5% of the samples received. CONCLUSION All prostatic carcinomas were graded by revised Gleason’s grade (ISUP 2005 and the use of immunohistochemical markers in arriving at a definite diagnosis in carcinoma prostate was confirmed.

  2. 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.

  3. Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy.

    Science.gov (United States)

    Pina, Christian; Khattab, Ahmed; Katzman, Philip; Bruckner, Lauren; Andolina, Jeffrey; New, Maria; Yau, Mabel

    2015-05-01

    A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. Because the patient was adrenalectomized, extra adrenal androgen production was suspected. Imaging studies including pelvic ultrasound and pelvic magnetic resonance imaging (MRI) were obtained to evaluate for adrenal rest tumors of the ovaries. Abdominal MRI was obtained to evaluate for residual adrenal tissue. A cystic lesion arising from her right ovary suspicious for ovarian neoplasm was noted on pelvic MRI. Right salpingo-oophorectomy was performed and histopathological examination revealed ovarian serous adenocarcinoma, low-grade, and well-differentiated. Tumor marker CA-125 was elevated and additional ovarian cancer staging workup confirmed stage IIIC due to one lymph node positive for carcinoma. The patient then developed a large left ovarian cyst, which led to a complete total abdominal hysterectomy and removal of the left ovary and fallopian tube. Pathology confirmed ovarian serous adenocarcinoma with microscopic focus of carcinoma in the left ovary. After numerous complications, the patient responded well to chemotherapy, CA-125 levels fell and no evidence of carcinoma was observed on subsequent imaging. To our knowledge, this is the first reported case of an ovarian serous adenocarcinoma in a patient with CAH. Although rare, we propose that the ovaries were the origin of androgen production and not residual adrenal tissue. The relationship between CAH and ovarian carcinomas has yet to be established, but further evaluation is needed given the poor survival rate of high-grade serous ovarian carcinoma.

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

    Directory of Open Access Journals (Sweden)

    Satoshi Takeuchi

    2011-05-01

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

  5. 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.

  6. Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma.

    Science.gov (United States)

    Andrici, Juliana; Jung, Jason; Sheen, Amy; D'Urso, Lisa; Sioson, Loretta; Pickett, Justine; Parkhill, Thomas R; Verdonk, Brandon; Wardell, Kathryn L; Singh, Arjun; Clarkson, Adele; Watson, Nicole; Toon, Christopher W; Gill, Anthony J

    2016-05-01

    Gynecologic and primary peritoneal serous carcinoma may be difficult to distinguish from abdominal mesotheliomas clinically, morphologically, and immunohistochemically. BAP1 double-hit inactivation and subsequent loss of protein expression have been reported in more than half of all abdominal mesotheliomas. We therefore sought to investigate the expression of BAP1 in serous carcinoma and explore its potential utility as a marker in the differential diagnosis with mesothelioma. We searched the computerized database of the Department of Anatomical Pathology, Royal North Shore Hospital, Australia, for all cases of gynecologic and peritoneal serous carcinomas and mesotheliomas diagnosed between 1998 and 2014. Immunohistochemistry for BAP1 was then performed on tissue microarray sections. Cases with completely absent nuclear staining in the presence of a positive internal control in nonneoplastic cells were considered negative. If staining was equivocal (eg, absent nuclear staining but no internal control), staining was repeated on whole sections. Loss of BAP1 expression was found in only 1 of 395 (0.3%) serous carcinomas but in 6 of 9 (67%) abdominal mesotheliomas (P < .001) and 131 of 277 (47%) thoracic mesotheliomas (P < .001). We conclude that BAP1 loss occurs extremely infrequently in gynecologic and peritoneal serous adenocarcinomas, whereas it is very common in mesotheliomas including abdominal mesothelioma. Therefore, although positive staining for BAP1 cannot be used to exclude a diagnosis of mesothelioma, loss of BAP1 expression can be used to very strongly support a pathological diagnosis of abdominal mesothelioma over serous carcinoma. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-08-01

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

  8. Next-Generation Sequencing of Tubal Intraepithelial Carcinomas.

    Science.gov (United States)

    McDaniel, Andrew S; Stall, Jennifer N; Hovelson, Daniel H; Cani, Andi K; Liu, Chia-Jen; Tomlins, Scott A; Cho, Kathleen R

    2015-11-01

    High-grade serous carcinoma (HGSC) is the most prevalent and lethal form of ovarian cancer. HGSCs frequently arise in the distal fallopian tubes rather than the ovary, developing from small precursor lesions called serous tubal intraepithelial carcinomas (TICs, or more specifically, STICs). While STICs have been reported to harbor TP53 mutations, detailed molecular characterizations of these lesions are lacking. We performed targeted next-generation sequencing (NGS) on formalin-fixed, paraffin-embedded tissue from 4 women, 2 with HGSC and 2 with uterine endometrioid carcinoma (UEC) who were diagnosed as having synchronous STICs. We detected concordant mutations in both HGSCs with synchronous STICs, including TP53 mutations as well as assumed germline BRCA1/2 alterations, confirming a clonal association between these lesions. Next-generation sequencing confirmed the presence of a STIC clonally unrelated to 1 case of UEC, and NGS of the other tubal lesion diagnosed as a STIC unexpectedly supported the lesion as a micrometastasis from the associated UEC. We demonstrate that targeted NGS can identify genetic alterations in minute lesions, such as TICs, and confirm TP53 mutations as early driving events for HGSC. Next-generation sequencing also demonstrated unexpected associations between presumed STICs and synchronous carcinomas, providing evidence that some TICs are actually metastases rather than HGSC precursors.

  9. Wide variation of prostate-specific antigen doubling time of untreated, clinically localized, low-to-intermediate grade, prostate carcinoma.

    Science.gov (United States)

    Choo, Richard; Klotz, Laurence; Deboer, Gerrit; Danjoux, Cyril; Morton, Gerard C

    2004-08-01

    To assess the prostate specific antigen (PSA) doubling time of untreated, clinically localized, low-to-intermediate grade prostate carcinoma. A prospective single-arm cohort study has been in progress since November 1995 to assess the feasibility of a watchful-observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The PSA doubling time was estimated from a linear regression of ln(PSA) against time, assuming a simple exponential growth model. As of March 2003, 231 patients had at least 6 months of follow-up (median 45) and at least three PSA measurements (median 8, range 3-21). The distribution of the doubling time was: 50 years, 56. The median doubling time was 7.0 years; 42% of men had a doubling time of >10 years. The doubling time of untreated clinically localized, low-to-intermediate grade prostate cancer varies widely.

  10. Bladder transitional cell carcinoma: correlation of contrast enhancement on computed tomography with histological grade and tumour angiogenesis

    International Nuclear Information System (INIS)

    Xie, Q.; Zhang, J.; Wu, P.-H.; Jiang, X.-Q.; Chen, S.-L.; Wang, Q.-L.; Xu, J.; Chen, G.-D.; Deng, J.-H.

    2005-01-01

    AIM: To investigate the correlation between the degree of contrast enhancement of bladder cancer in the early enhanced phase of helical computed tomography (CT) and microvessel density (MVD), vascular endothelial growth factor (VEGF) and histological grade. MATERIALS AND METHODS: Sixty-five patients with transitional cell carcinoma of the bladder were examined by incremental unenhanced CT and helical CT at 40-45 s after initiation of intravenous administration of contrast medium before surgery. The CT density in Hounsfield units of bladder carcinomas were measured in the middle of the maximum diameter section of the cancer lesions on unenhanced and enhanced CT. The degree of contrast enhancement of the tumour was determined as the absolute increase in Hounsfield units. Histological grade, VEGF and MVD were analysed for each cancer. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between CT enhancement and histological grade, VEGF expression and MVD. RESULTS: Different degrees of enhancement were observed in 91 cancers during the early enhanced phase of helical CT. Mean MVDs and mean CT enhancing values of different histological grade groups were statistically different (p<0.001). A positive correlation was found in the CT-enhancing value of bladder cancer and MVD (Pearson correlation test; r=0.938, p<0.001) and histological grade (Spearman rank correlation; r=0.734, p<0.001). VEGF of bladder cancer did not correlate with the change in CT attenuation (Spearman rank correlation; r=0.087, p=0.410) and MVD (Spearman rank correlation, r=0.103, p=0.330). CONCLUSION: In bladder cancer, the degree of contrast enhancement during the early enhanced helical CT is correlated with the MVD and histological grade of tumour. It is possible that MVD is the histopathological basis of early contrast enhancement of bladder cancer

  11. SPECIFICITIES OF ENDOMETRIAL PROLIFERATION/STEM CELL INDEX DISTRIBUTION IN ENDOMETRIOID CARCINOMA OF DIFFERENT GRADE OF MALIGNANCY.

    Science.gov (United States)

    Kikalishvili, N; Beriashvili, R; Muzashvili, T; Burkadze, G

    2018-03-01

    Endometrial neoplasia is the most common malignant tumor of female genital system in developed countries. The incidence of endometrial cancer has increased in the last years and despite advances in diagnosis and treatment, the death rates have steadily been increasing over the past 20 years. Therefore aspects of endometrial cancer development, pathogenesis and effective treatment is especially urgent to this day, as much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Endometrial stem cells take the special place among somatic stem cells of female reproductive system-the detection of them and identification of their location in the complex cellular hierarchy still remains challenging. Further study of endometrial stem cells will clarify their role in gynecologic pathologies associated with hyper-proliferative states of endometrium. The aim of our study was to explore the specificities of endometrial proliferative/stem cell index distribution under endometrioid carcinoma of different grade of malignancy. The study represents a retrospective research. The coded and depersonalized material data from Acad. N. Kipshidze Central University Clinic was used in the study. 3 study groups - 1st study group "Endometrioid Carcinoma Grade 1" (14 cases), 2nd study group "Endometrioid Carcinoma Grade 2" (23 cases) and 3rd study group "Endometrioid Carcinoma Grade 3" were selected from routine histopathology tissue specimens of uterus. Hematoxilyn-eosin technology and immunohistochemistry with proliferation marker ki67 and stem cell marker CD146 was performed. The proliferative/stem cell index was calculated by the ratio of Ki67-positive cell percentage value divided by CD146-positive cell percentage value. The study showed that in the 1st study group labeled as "Endometrioid Carcinoma Grade 1", the proliferative/stem cell index ranges between 21.7 and 25.5. Its mean average value in the age distribution subgroups accounts for: 1

  12. 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.

  13. Clinicopathologic features of sentinel node metastases predictive of positive axillary clearance in grade 1 invasive breast carcinoma.

    LENUS (Irish Health Repository)

    Hayes, B

    2012-02-01

    BACKGROUND: Sentinel node (SN) biopsy is widely used to stage breast carcinoma and, when positive, typically leads to axillary clearance (AC). AIMS: This study assesses clinicopathologic features of grade 1 breast carcinoma SNs with the aim of identifying a group of patients, who are likely to have a negative AC and can, therefore, safely be spared further surgery. RESULTS: Two hundred and forty-seven patients with grade 1 invasive carcinoma were identified, of whom 29 had a positive SN. Four patients (13.8%) had a positive AC. Positive AC occurred in 3 of 6 (50%) patients whose SN showed extranodal extension (EE), but in only 1 of 23 (4.3%) patients without EE. All patients were staged as pN1(sn) following SN biopsy: only one, who had a 5.27 mm metastasis with EE, was pN2 following AC. CONCLUSIONS: Extranodal extension is a significant predictor of a positive AC in this group. In its absence, AC did not alter the post-SN biopsy pN stage.

  14. Non-invasive, low-grade papillary urothelial carcinoma in the urachus

    DEFF Research Database (Denmark)

    Pedersen, Gyrithe Lynghøj; Dahl, Claus; Azawi, Nessn Htum

    2013-01-01

    urothelial carcinoma, and through a systematic literature search, we identified 12 additional cases of urachal urothelial carcinoma reported in English literature in the past 20 years. The cases were compared according to the Sheldon Staging System and the Mayo Staging System presented by Ashley et al...

  15. Comparative evaluation of the modified Scarff-Bloom-Richardson grading system on breast carcinoma aspirates and histopathology

    Directory of Open Access Journals (Sweden)

    Cherry Bansal

    2012-01-01

    Full Text Available Background: Fine needle aspiration (FNA is a quick, minimally invasive procedure for evaluation of breast tumors. The Scarff-Bloom-Richardson (SBR grade on histological sections is a well-established tool to guide selection of adjuvant systemic therapy. Grade evaluation is possible on cytology smears to avoid and minimize the morbidity associated with overtreatment of lower grade tumors. Aim : The aim was to test the hypothesis whether breast FNA from the peripheral portion of the lesion is representative of Scarff-Bloom-Richardson grade on histopathology as compared to FNA from the central portion. Materials and Methods : Fine-needle aspirates and subsequent tissue specimens from 45 women with ductal carcinoma (not otherwise specified were studied. FNAs were performed under ultrasound guidance from the central as well as the peripheral third of the lesion for each case avoiding areas of necrosis/calcification. The SBR grading was compared on alcohol fixed aspirates and tissue sections for each case. Results : Comparative analysis of SBR grade on aspirates from the peripheral portion and histopathology by the Pearson chi-square test (χ2 =78.00 showed that it was statistically significant (P<0.001 with 93% concordance. Lower mitotic score on aspirates from the peripheral portion was observed in only 4 out of 45 (9% cases. The results of the Pearson chi-square test (χ2 = 75.824 with statistically significant (P=0.000. Conclusion : This prospective study shows that FNA smears from the peripheral portion of the lesion are representative of the grading performed on the corresponding histopathological sections. It is possible to score and grade by SBR system on FNA smears.

  16. Ductal carcinoma in situ of the breast (DCIS with heterogeneity of nuclear grade: prognostic effects of quantitative nuclear assessment

    Directory of Open Access Journals (Sweden)

    Fu Yuejiao

    2007-09-01

    Full Text Available Abstract Background Previously, 50% of patients with breast ductal carcinoma in situ (DCIS had more than one nuclear grade, and neither worst nor predominant nuclear grade was significantly associated with development of invasive carcinoma. Here, we used image analysis in addition to histologic evaluation to determine if quantification of nuclear features could provide additional prognostic information and hence impact prognostic assessments. Methods Nuclear image features were extracted from about 200 nuclei of each of 80 patients with DCIS who underwent lumpectomy alone, and received no adjuvant systemic therapy. Nuclear images were obtained from 20 representative nuclei per duct, from each of a group of 5 ducts, in two separate fields, for 10 ducts. Reproducibility of image analysis features was determined, as was the ability of features to discriminate between nuclear grades. Patient information was available about clinical factors (age and method of DCIS detection, pathologic factors (DCIS size, nuclear grade, margin size, and amount of parenchymal involvement, and 39 image features (morphology, densitometry, and texture. The prognostic effects of these factors and features on the development of invasive breast cancer were examined with Cox step-wise multivariate regression. Results Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. For the pooled assessment with ~200 nuclei per patient, a discriminant function with one densitometric and two texture features was significantly (p Conclusion Image analysis provided reproducible assessments of nuclear features which quantitated differences in nuclear grading for patients. Quantitative nuclear image features indicated prognostically significant differences in DCIS, and may contribute additional information to prognostic assessments of which patients are likely to develop invasive disease.

  17. TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

    International Nuclear Information System (INIS)

    Sanlioglu, Ahter D.; Korcum, Aylin F.; Pestereli, Elif; Erdogan, Gulgun; Karaveli, Seyda; Savas, Burhan; Griffith, Thomas S.; Sanlioglu, Salih V.

    2007-01-01

    Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma

  18. Edmondson-Steiner grade: A crucial predictor of recurrence and survival in hepatocellular carcinoma without microvascular invasio.

    Science.gov (United States)

    Zhou, Li; Rui, Jing-An; Zhou, Wei-Xun; Wang, Shao-Bin; Chen, Shu-Guang; Qu, Qiang

    2017-07-01

    Microvascular invasion (MVI), an important pathologic parameter, has been proven to be a powerful predictor of long-term prognosis in hepatocellular carcinoma (HCC). However, prognostic factors in HCC without MVI remain unknown. The present study aimed to identify the risk factors of recurrence and poor post-resectional survival in this type of HCC. A total of 109 patients with MVI-absent HCC underwent radical hepatectomy were enrolled. The influence of clinicopathologic variables on recurrence and patient survival was assessed using univariate and multivariate analyses. Chi-square test found that Edmondson-Steiner grade and satellite nodule were significantly associated with recurrence, while the former was the single marker for early recurrence. Stepwise logistic regression analysis demonstrated the independent predictive role of Edmondson-Steiner grade for recurrence. On the other hand, Edmondson-Steiner grade, serum AFP level and satellite nodule were significant for overall and disease-free survival in univariate analysis, whereas tumor size was linked to disease-free survival. Of the variables, Edmondson-Steiner grade, serum AFP level and satellite nodule were independent indicators. Edmondson-Steiner grade, a histological classification, carries robust prognostic implications for all the endpoints for prognosis, thus being potential to be a crucial prognosticator in HCC without MVI. Copyright © 2017 Elsevier GmbH. All rights reserved.

  19. Malign mural nodules associated with serous ovarian tumor of borderline malignancy: a case report and literature review.

    Science.gov (United States)

    Gungor, Tayfun; Altinkaya, S Ozlem; Akbay, Serap; Bilge, Umit; Mollamahmutoglu, Leyla

    2010-03-01

    Cystic tumors of ovary, whether benign, borderline, or malignant may be associated with mural nodule of various types, including sarcomas, sarcoma-like mural nodules (SLMN), and foci of anaplastic carcinoma. Cases of serous borderline ovarian tumor with mural nodules of mixed type are very rare. A 54-year-old woman referred with abdominal swelling. Imaging studies revealed a huge mass localized in pelvis and lower abdomen and grade 1-2 left renal hydronephrosis. Preoperative Ca-125 was 798 U/ml. In exploratory laparotomy there was a 16 cm mass adherent to lateral abdominal wall and intestines. Adhesiolysis and de-bulking surgery were performed including bilateral pelvic, para-aortic lymphadenectomy, appendectomy and omentectomy. Left ureter was found to be dilated because of the infiltration of distal part by the tumor, so distal ureteral resection and neoureterocystostomy were performed. Final pathology revealed borderline serous ovarian tumor with mural nodules which were consisted of SLMNs, multiple and sharply demarcated from the adjacent tumor, and sarcomatous nodules showing infiltrative appearance in metastatic regions. Mural nodules showed a positive reaction for vimentin and SMA but were negative for cytokeratin and also necrosis, hemorrhage, and 10-15 mitoses in 10 high power fields were noted. She had postoperative chemotherapy and follow-up is going on without metastases in her first year. The existence of sarcomatous nodules combined with the SLMN necessitates a careful histologic analysis for treatment and the determination of prognosis. However, too few cases of mixed type mural nodules have been published to warrant a conclusion regarding their prognosis.

  20. Laparoscopic Diagnosis of Adenocarcinoma of the Appendix Mimicking Serous Papillary Adenocarcinoma of the Peritoneum

    OpenAIRE

    Yoshimura, Mayumi; Terai, Yoshito; Konishi, Hiromi; Tanaka, Yoshimichi; Tanaka, Tomohito; Sasaki, Hiroshi; Ohmichi, Masahide

    2013-01-01

    Primary carcinoma of the vermiform appendix is a rare disease with few clinical symptoms. Accordingly, preoperative diagnosis of appendiceal cancer is challenging because of the lack of specific symptoms. We herein report a case of appendicular adenocarcinoma found unexpectedly during laparoscopic surgery in a 69-year-old Japanese female patient diagnosed with serous papillary adenocarcinoma, in order to determine whether optimal cytoreduction could successfully be achieved at the time of pri...

  1. Ductal carcinoma in situ of the breast (DCIS) with heterogeneity of nuclear grade: prognostic effects of quantitative nuclear assessment

    International Nuclear Information System (INIS)

    Chapman, Judith-Anne W; Miller, Naomi A; Lickley, H Lavina A; Qian, Jin; Christens-Barry, William A; Fu, Yuejiao; Yuan, Yan; Axelrod, David E

    2007-01-01

    Previously, 50% of patients with breast ductal carcinoma in situ (DCIS) had more than one nuclear grade, and neither worst nor predominant nuclear grade was significantly associated with development of invasive carcinoma. Here, we used image analysis in addition to histologic evaluation to determine if quantification of nuclear features could provide additional prognostic information and hence impact prognostic assessments. Nuclear image features were extracted from about 200 nuclei of each of 80 patients with DCIS who underwent lumpectomy alone, and received no adjuvant systemic therapy. Nuclear images were obtained from 20 representative nuclei per duct, from each of a group of 5 ducts, in two separate fields, for 10 ducts. Reproducibility of image analysis features was determined, as was the ability of features to discriminate between nuclear grades. Patient information was available about clinical factors (age and method of DCIS detection), pathologic factors (DCIS size, nuclear grade, margin size, and amount of parenchymal involvement), and 39 image features (morphology, densitometry, and texture). The prognostic effects of these factors and features on the development of invasive breast cancer were examined with Cox step-wise multivariate regression. Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. For the pooled assessment with ~200 nuclei per patient, a discriminant function with one densitometric and two texture features was significantly (p < 0.001) associated with nuclear grading, and provided 78.8% correct jackknifed classification of a patient's nuclear grade. In multivariate assessments, image analysis nuclear features had significant prognostic associations (p ≤ 0.05) with the development of invasive breast cancer. Texture (difference entropy, p < 0.001; contrast, p < 0.001; peak transition probability, p = 0.01), densitometry (range density, p = 0.004), and measured margin (p = 0.05) were associated with

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

    Science.gov (United States)

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

    2015-08-01

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

  3. The distribution of ductal carcinoma in situ (DCIS) grade in 4232 women and its impact on overdiagnosis in breast cancer screening.

    Science.gov (United States)

    van Luijt, P A; Heijnsdijk, E A M; Fracheboud, J; Overbeek, L I H; Broeders, M J M; Wesseling, J; den Heeten, G J; de Koning, H J

    2016-05-10

    The incidence of ductal carcinoma in situ (DCIS) has rapidly increased over time. The malignant potential of DCIS is dependent on its differentiation grade. Our aim is to determine the distribution of different grades of DCIS among women screened in the mass screening programme, and women not screened in the mass screening programme, and to estimate the amount of overdiagnosis by grade of DCIS. We retrospectively included a population-based sample of 4232 women with a diagnosis of DCIS in the years 2007-2009 from the Nationwide network and registry of histopathology and cytopathology in the Netherlands. Excluded were women with concurrent invasive breast cancer, lobular carcinoma in situ and no DCIS, women recently treated for invasive breast cancer, no grade mentioned in the record, inconclusive record on invasion, and prevalent DCIS. The screening status was obtained via the screening organisations. The distribution of grades was incorporated in the well-established and validated microsimulation model MISCAN. Overall, 17.7 % of DCIS were low grade, 31.4 % intermediate grade, and 50.9 % high grade. This distribution did not differ by screening status, but did vary by age. Older women were more likely to have low-grade DCIS than younger women. Overdiagnosis as a proportion of all cancers in women of the screening age was 61 % for low-grade, 57 % for intermediate-grade, 45 % for high-grade DCIS. For women age 50-60 years with a high-grade DCIS this overdiagnosis rate was 21-29 %, compared to 50-66 % in women age 60-75 years with high-grade DCIS. Amongst the rapidly increasing numbers of DCIS diagnosed each year is a significant number of overdiagnosed cases. Tailoring treatment to the probability of progression is the next step to preventing overtreatment. The basis of this tailoring could be DCIS grade and age.

  4. Relationship of PCNA, C-erbB2 and CD44s expression with tumor grade and stage in urothelial carcinomas of the bladder

    Science.gov (United States)

    Yıldırım, Ayhan; Kösem, Mustafa; Sayar, İlyas; Gelincik, İbrahim; Yavuz, Alparslan; Bozkurt, Aliseydi; Erkorkmaz, Ünal; Bayram, İrfan

    2014-01-01

    In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas. PMID:25035774

  5. Pleomorphic lobular carcinoma: is it more similar to a classic lobular cancer or to a high-grade ductal cancer?

    Directory of Open Access Journals (Sweden)

    Costarelli L

    2017-12-01

    Full Text Available Leopoldo Costarelli, Domenico Campagna, Alessandra Ascarelli, Francesco Cavaliere, Maria Helena Colavito, Tatiana Ponzani, Laura Broglia, Massimo La Pinta, Elena Manna, Lucio Fortunato Breast Unit, San Giovanni-Addolorata Hospital, Rome, Italy Background: Pleomorphic invasive lobular carcinoma (P-ILC is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the literature regarding this topic.Materials and methods: We reviewed our experiences from 2010 to 2015 and compared 40 patients with P-ILC, 126 patients with classic-ILC (C-ILC and 574 cases of high-grade invasive ductal carcinoma (HG-IDC. We studied the histologic and immunohistochemical features, clinical presentation and surgical treatment.Results: P-ILC is diagnosed at the same age and tumor diameter as those of the other two histologic types. It is associated more frequently with multiple lymph node metastases and high proliferative index, and HER2/neu is amplified in 10% of cases. In spite of sharing some histologic characteristics with C-ILC (same growth pattern, loss of E-cadherin expression, same genetic pathway, its clinical and pathologic features define an autonomous entity. Its surgical treatment is similar to those of C-ILC and HG-IDC.Conclusion: This is the first review comparing these three pathologic entities. Our findings may be useful in understanding this variety of invasive lobular carcinoma, and further studies are certainly needed in this field. Keywords: breast cancer, lobular cancer, pleomorphic, mastectomy

  6. FUNDUS AUTOFLUORESCENCE LIFETIMES AND CENTRAL SEROUS CHORIORETINOPATHY.

    Science.gov (United States)

    Dysli, Chantal; Berger, Lieselotte; Wolf, Sebastian; Zinkernagel, Martin S

    2017-11-01

    To quantify retinal fluorescence lifetimes in patients with central serous chorioretinopathy (CSC) and to identify disease specific lifetime characteristics over the course of disease. Forty-seven participants were included in this study. Patients with central serous chorioretinopathy were imaged with fundus photography, fundus autofluorescence, optical coherence tomography, and fluorescence lifetime imaging ophthalmoscopy (FLIO) and compared with age-matched controls. Retinal autofluorescence was excited using a 473-nm blue laser light and emitted fluorescence light was detected in 2 distinct wavelengths channels (498-560 nm and 560-720 nm). Clinical features, mean retinal autofluorescence lifetimes, autofluorescence intensity, and corresponding optical coherence tomography (OCT) images were further analyzed. Thirty-five central serous chorioretinopathy patients with a mean visual acuity of 78 ETDRS letters (range, 50-90; mean Snellen equivalent: 20/32) and 12 age-matched controls were included. In the acute stage of central serous chorioretinopathy, retinal fluorescence lifetimes were shortened by 15% and 17% in the respective wavelength channels. Multiple linear regression analysis showed that fluorescence lifetimes were significantly influenced by the disease duration (P autofluorescence lifetimes, particularly in eyes with retinal pigment epithelial atrophy, were associated with poor visual acuity. This study establishes that autofluorescence lifetime changes occurring in central serous chorioretinopathy exhibit explicit patterns which can be used to estimate perturbations of the outer retinal layers with a high degree of statistical significance.

  7. Endometrial intraepithelial carcinoma: A case report and brief review

    Directory of Open Access Journals (Sweden)

    Ram Manisha

    2008-10-01

    Full Text Available This case report describes the precursor lesion of uterine papillary serous carcinoma (UPSC. A 65-year-old post-menopausal female presented with prolapse and vaginal discharge and underwent a hysterectomy revealing an atrophic endometrium, highly atypical endometrial glands, the lining cells of which showed pseudostratification, hobnailing, a high nuclear to cytoplasmic ratio, and prominent nucleoli. A p53 immunoreactivity score of 8 and a MIB-1 index of 80% was obtained leading to a diagnosis of endometrial intraepithelial carcinoma (EIC. Since serous EIC is commonly associated with extra-uterine serous carcinoma, it is a uniquely aggressive precursor lesion. Molecular studies support the hypothesis that EIC is a precursor of both uterine and extra-uterine invasive serous carcinomas. This is why the treatment protocol for EIC cases is total abdominal hysterectomy (TAH, accompanied by a staging procedure. In our patient, EIC was limited to the endometrium; associated with an excellent clinical outcome.

  8. Gd-EOB-DTPA-enhanced magnetic resonance images of hepatocellular carcinoma: correlation with histological grading and portal blood flow

    Energy Technology Data Exchange (ETDEWEB)

    Kogita, Sachiyo; Imai, Yasuharu; Fukuda, Kazuto; Igura, Takumi; Sawai, Yoshiyuki [Ikeda Municipal Hospital, Department of Gastroenterology, Osaka (Japan); Okada, Masahiro; Murakami, Takamichi [Kinki University, School of Medicine, Department of Radiology, Osaka (Japan); Kim, Tonsok; Onishi, Hiromitsu; Hori, Masatoshi [Osaka University, Graduate School of Medicine, Department of Radiology, Osaka (Japan); Takamura, Manabu [Ikeda Municipal Hospital, Department of Radiology, Osaka (Japan); Morimoto, Osakuni [Ikeda Municipal Hospital, Department of Surgery, Osaka (Japan); Nagano, Hiroaki [Osaka University, Graduate School of Medicine, Department of Surgery, Osaka (Japan); Wakasa, Kenichi [Osaka City University, Graduate School of Medicine, Department of Diagnostic Pathology, Osaka (Japan); Hayashi, Norio [Osaka University, Graduate School of Medicine, Department of Gastroenterology and Hepatology, Osaka (Japan)

    2010-10-15

    To retrospectively investigate enhancement patterns of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI in relation to histological grading and portal blood flow. Sixty-nine consecutive patients with 83 histologically proven HCCs and DNs were studied. To assess Gd-EOB-DTPA uptake, we calculated the EOB enhancement ratio, which is the ratio of the relative intensity of tumorous lesion to surrounding nontumorous area on hepatobiliary phase images (post-contrast EOB ratio) to that on unenhanced images (pre-contrast EOB ratio). Portal blood flow was evaluated by CT during arterial portography. Post-contrast EOB ratios significantly decreased as the degree of differentiation declined in DNs (1.00 {+-} 0.14) and well, moderately and poorly differentiated HCCs (0.79 {+-} 0.19, 0.60 {+-} 0.27, 0.49 {+-} 0.10 respectively). Gd-EOB-DTPA uptake, assessed by EOB enhancement ratios, deceased slightly in DNs and still more in HCCs, while there was no statistical difference in the decrease between different histological grades of HCC. Reductions in portal blood flow were observed less frequently than decreases in Gd-EOB-DTPA uptake in DNs and well-differentiated HCCs. Reduced Gd-EOB-DTPA uptake might be an early event of hepatocarcinogenesis, preceding portal blood flow reduction. The hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI may help estimate histological grading, although difficulties exist in differentiating HCCs from DNs. (orig.)

  9. 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.

  10. Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women.

    Science.gov (United States)

    Correnti, Maria; Medina, Francisco; Cavazza, María Eugenia; Rennola, Antonieta; Avila, Maira; Fernándes, Andreína

    2011-06-01

    Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women. Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL=200; HSIL=100; CC=150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections. HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31. Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and -31 (prevalence, ~90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family

    Science.gov (United States)

    Geyer, Felipe C; Berman, Samuel H.; Marchiò, Caterina; Burke, Kathleen A; Guerini-Rocco, Elena; Piscuoglio, Salvatore; Ng, Charlotte K Y; Pareja, Fresia; Wen, Hannah Y; Hodi, Zoltan; Schnitt, Stuart J; Rakha, Emad A; Ellis, Ian O; Norton, Larry; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/deletions and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1–13) and 4.0 (1–7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12, or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions

  12. Expression of Stem Cell Markers in Preinvasive Tubal Lesions of Ovarian Carcinoma.

    Science.gov (United States)

    Chene, G; Ouellet, V; Rahimi, K; Barres, V; Meunier, L; De Ladurantaye, M; Provencher, D; Mes-Masson, A M

    2015-01-01

    In order to better understand the ovarian serous carcinogenic process with tubal origin, we investigated the expression of stem cell markers in premalignant tubal lesions (serous tubal intraepithelial carcinoma or STIC). We found an increased stem cell marker density in the normal fallopian tube followed by a high CD117 and a low ALDH and CD44 expression in STICs raising the question of the role of the stem cell markers in the serous carcinogenic process.

  13. Expression of Stem Cell Markers in Preinvasive Tubal Lesions of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    G. Chene

    2015-01-01

    Full Text Available In order to better understand the ovarian serous carcinogenic process with tubal origin, we investigated the expression of stem cell markers in premalignant tubal lesions (serous tubal intraepithelial carcinoma or STIC. We found an increased stem cell marker density in the normal fallopian tube followed by a high CD117 and a low ALDH and CD44 expression in STICs raising the question of the role of the stem cell markers in the serous carcinogenic process.

  14. Molecular targets in serous gynecologic cancers

    NARCIS (Netherlands)

    Groeneweg, J.W.

    2015-01-01

    In this thesis we describe a series of studies assessing the effectiveness of targeted therapeutics that inhibit Notch signaling or the HER2 receptor in serous gynecologic cancers. In the first part of the thesis, we have confirmed previous data by showing expression of Notch1 and Notch3 in ovarian

  15. Finasteride for chronic central serous chorioretinopathy.

    Science.gov (United States)

    Forooghian, Farzin; Meleth, Annal D; Cukras, Catherine; Chew, Emily Y; Wong, Wai T; Meyerle, Catherine B

    2011-04-01

    To evaluate the safety and efficacy of finasteride, an inhibitor of dihydrotestosterone synthesis, in the treatment of chronic central serous chorioretinopathy. Five patients with chronic central serous chorioretinopathy were prospectively enrolled in this pilot study. Patients were administered finasteride (5 mg) daily for 3 months, after which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity, central subfield macular thickness, and subretinal fluid volume as assessed by optical coherence tomography. Serum dihydrotestosterone, serum testosterone, and urinary cortisol were also measured. There was no change in mean best-corrected visual acuity. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months and rose to levels that were below baseline by 6 months. The changes in both optical coherence tomography parameters paralleled those in serum dihydrotestosterone level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased after discontinuation of finasteride. In the remaining patient, both optical coherence tomography parameters normalized with finasteride and remained stable when the study medication was discontinued. Finasteride may represent a novel medical treatment for chronic central serous chorioretinopathy. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of central serous chorioretinopathy.

  16. 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

  17. 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

  18. Qualitative analysis of connective tissue stroma in different grades of oral squamous cell carcinoma: A histochemical study

    Directory of Open Access Journals (Sweden)

    Smitha Kullage

    2017-01-01

    Full Text Available Background: Detection of oral cancer at an early stage is of utmost importance to decrease morbidity and mortality. Tumor stroma plays a critical role during carcinogenesis. There is lack of information regarding the characteristics of the stroma in relation to the invading malignant epithelial cells and the interdependence between stroma and tumor cells in different grades of oral squamous cell carcinoma (OSCC. Aim: The present study was aimed to analyze and compare the nature of stroma in the vicinity of invading tumor islands in different grades of OSCC, using a histochemical technique picrosirius-polarization method. The present study also evaluated and correlated the possible role of inflammatory response in determining the nature of the stroma. Subjects and Methods: The study included thirty cases of different grades of histologically diagnosed OSCC and ten sections of normal buccal mucosa as a control group. Nature of collagen was analyzed using picrosirius-polarization method, and intensity of inflammatory cell infiltrate was recorded using ImageJ software (1.42q, NIH, USA. The results were tabulated and analyzed statistically. Results: Normal oral mucosa showed predominantly reddish birefringence. All cases of well-differentiated OSCC showed reddish-orange color. Nearly 70% moderately differentiated cases showed yellowish-orange (YO and 60% of poorly differentiated cases, showed greenish-yellow (GY. The mean inflammatory cell count was highest in well-differentiated group. There was shift to YO and GY collagen when the cell differentiation and inflammatory cell count decreased in moderate and poorly differentiated cases. Conclusion: Both inflammatory cells and tumor cells have a role in determining the nature of the collagen fibers in tumor stroma of OSCC, probably with opposing effects on stromal behavior and hence both are significant in predicting prognosis.

  19. Unusual presentation of high-grade neuroendocrine carcinoma of the Urinary bladder with small-cell and large-cell features

    Directory of Open Access Journals (Sweden)

    Vitor Fiorin de Vasconcellos

    2013-10-01

    Full Text Available High-grade neuroendocrine carcinoma of the urinary bladder comprehends small-cell and large-cell variants. It is a rare and aggressive neoplasm, mostly diagnosed in advanced stages. It is more frequently encountered among Caucasian men in the sixth decade of life. Urinary symptoms are the most common clinical presentation. Diagnosis is generally not troublesome once the lesions are easily detectable by imaging exams and cystoscopy. This neoplasia is associated with tobacco smoking, and is frequently associated with other carcinomatous components such as urothelial carcinoma, adenocarcinoma, and sarcomatoid carcinoma. The authors report a case of an apparently healthy female patient who presented cervical lymph node enlargement not accompanied by systemic symptoms. The supraclavicular lymph node biopsy revealed metastatic small cell carcinoma. The computed tomography scan showed a bladder wall nodular thickening, enlarged lymph nodes along the iliac, periaortic, mediastinal, cervical and supraclavicular chains, as well as an insufflating lytic bone lesion in the right iliac wing. The positron emission tomography-fluorodeoxyglucose (PET-FDG added to these findings, the presence of a paraesophageal lymph node, lymphadenomegaly in the gluteal region and a vertebral lytic lesion in T10. Resected specimen of the bladder tumor revealed a high-grade neuroendocrine carcinoma with small-cell and large-cell features.

  20. Expression of p53 protein in high-grade gastroenteropancreatic neuroendocrine carcinoma

    DEFF Research Database (Denmark)

    Ali, Abir Salwa; Grönberg, Malin; Federspiel, Birgitte

    2017-01-01

    of immunoreactive p53 protein in GEP-NEC. Materials and methods Tumor tissues from 124 GEP-NEC patients with locally advanced or metastatic disease treated with platinum-based chemotherapy were collected from Nordic centers and clinical data were obtained from the Nordic NEC register. Tumor proliferation rate...... In this cohort of GEP-NEC patients, p53 expression could not be correlated with clinical outcome. However, in patients with colorectal NECs, p53 expression was correlated with shorter PFS and OS. Further studies are needed to establish the role of immunoreactive p53 as a prognostic marker for GEP-NEC patients.......Background Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are aggressive, rapidly proliferating tumors. Therapeutic response to current chemotherapy regimens is usually short lasting. The aim of this study was to examine the expression and potential clinical importance...

  1. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

    Science.gov (United States)

    Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

    2008-08-15

    The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

  2. The Oviduct and Serous Cancer Risk Assessment

    Science.gov (United States)

    2015-10-01

    such as transitional-like metaplasia [Walthard cell nests (WCNs), n= 5]; (3) serous tubal intraepithelial neo- plasms (STINs) (n= 18); and (4...catenin staining in type 2 SCOUTs, with a shift in distribution from the membrane to the cyto- plasm and nucleus, is unclear but it is emblematic ofWnt...6 BRCA). Clinical outcome data including the time to last follow-up, and clinical status at last follow-up were extracted from the electronic

  3. Impact of the ovarian microenvironment on serous cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0182 TITLE: Impact of the ovarian microenvironment on serous cancer PRINCIPAL INVESTIGATOR: Joanna E. Burdette...Impact of the ovarian microenvironment on serous cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0182 5c. PROGRAM ELEMENT NUMBER 6...for intervention that would block serous cancer while still confined to the fallopian tubes. Using a series of normal, modified, and tumorigenic tubal

  4. 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 collected...... data on POC (n=1443), PPC (n=268) and PFC (n=171) cases was obtained from the Danish Gynecological Cancer Database (2005-2013). Chi-square, Fisher's or Wilcoxon-Mann-Whitney test, multivariate logistic regression, Kaplan-Meier and multivariate Cox-regression were used as appropriate. Statistical tests...

  5. The 18F-FDG uptake in non small cell lung carcinoma correlates with the DNA-grading of malignancy

    International Nuclear Information System (INIS)

    Wu Jinchang

    2002-01-01

    In order to evaluate correlation of glucose metabolism and DNA ploidity of tumors, the uptake of 18 F-Deoxyglucose (FDG) by PET prior to surgery and the DNA content and DNA-grading of malignancy (DNA-MG) of Schiff-stained nuclei obtained from fresh tumor fragments by means of image cytometry were studied, and thereafter the correlation between standardized uptake value (SUV) and (DNA-MG) was analysed in forty-nine patients with histologically proven non-small cell lung carcinoma (NSCLC). As a result of the DNA histograms of these 49 patients, 46(93.88%) were aneuploidy and only 3(6.12%) were tetraploid. A linear correlation of the SUV versus the (DNA-MG) (r=0.336, p=0.024) was found, demonstrating that 18 F-FDG PET as a non-invasive metabolic imaging technique, may also provide information correlated to malignant DNA patterns which may be valuable in malignant differentiation and prognostic prediction

  6. Villous duodenal adenoma with II and III grade dysplasia and carcinoma in situ treated with cephalic duodenopancreatectomy

    Directory of Open Access Journals (Sweden)

    Čolović Radoje

    2006-01-01

    Full Text Available Background. Villous duodenal adenomas are rare, tend to malignant alteration and recurrence if surgical procedures are not sufficiently radical. They are mostly localized in the second portion of the duodenum and close to a papilla and are prone to malignant alteration. Case report. In this paper we presented a 79-year-old female patient already operated on twice elsewhere due to obstructive jaundice caused by villous duodenal adenoma, using, firstly, cholecystectomy and T-tube drainage of the choledoclus, and, then, an unsuccessful attempt of radical surgery − duodenopancreatectomy. The patient was some time wearing a T-tube drainage, and, then, submitted to endoscopic papillotomy, endoscopic stenting, and, finally to the insertion of a self-expandable metallic stent which got clogged three months later causing chalangitis. Three years following the first surgery, the patient presented to our institution and submitted to cephalic duodenopancreatectomy. Histology confirmed villous duodenal adenomas with II and III grade dysplasia and carcinoma in situ. The lymph nodes were tumour-free. The postoperative recovery was somewhat prolonged due to cardiologic difficulties and a mild infection of the wound. Conclusion. Villous duodenal adenoma is curable if treated correctly and in a proper time. Radical treatment delay increases the risk for malignant alteration which was the case with our patient who was submitted to it three years after the histologic confirmation of the diagnosis.

  7. CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC): towards the development of computer-assisted diagnostic method.

    Science.gov (United States)

    Huhdanpaa, Hannu; Hwang, Darryl; Cen, Steven; Quinn, Brian; Nayyar, Megha; Zhang, Xuejun; Chen, Frank; Desai, Bhushan; Liang, Gangning; Gill, Inderbir; Duddalwar, Vinay

    2015-10-01

    There are distinct quantifiable features characterizing renal cell carcinomas on contrast-enhanced CT examinations, such as peak tumor enhancement, tumor heterogeneity, and percent contrast washout. While qualitative visual impressions often suffice for diagnosis, quantitative metrics if developed and validated can add to the information available from standard of care diagnostic imaging. The purpose of this study is to assess the use of quantitative enhancement metrics in predicting the Fuhrman grade of clear cell RCC. 65 multiphase CT examinations with clear cell RCCs were utilized, 44 tumors with Fuhrman grades 1 or 2 and 21 tumors with grades 3 or 4. After tumor segmentation, the following data were extracted: histogram analysis of voxel-based whole lesion attenuation in each phase, enhancement and washout using mean, median, skewness, kurtosis, standard deviation, and interquartile range. Statistically significant difference was observed in 4 measured parameters between grades 1-2 and grades 3-4: interquartile range of nephrographic attenuation values, standard deviation of absolute enhancement, as well as interquartile range and standard deviation of residual nephrographic enhancement. Interquartile range of nephrographic attenuation values was 292.86 HU for grades 1-2 and 241.19 HU for grades 3-4 (p value 0.02). Standard deviation of absolute enhancement was 41.26 HU for grades 1-2 and 34.66 HU for grades 3-4 (p value 0.03). Interquartile range was 297.12 HU for residual nephrographic enhancement for grades 1-2 and 235.57 HU for grades 3-4 (p value 0.02), and standard deviation of the same was 42.45 HU for grades 1-2 and 37.11 for grades 3-4 (p value 0.04). Our results indicate that absolute enhancement is more heterogeneous for lower grade tumors and that attenuation and residual enhancement in nephrographic phase is more heterogeneous for lower grade tumors. This represents an important step in devising a predictive non-invasive model to predict the

  8. Enhancement pattern analysis of hypervascular hepatocellular carcinoma on dynamic MR imaging with histopathological correlation: Validity of portal phase imaging for predicting tumor grade

    International Nuclear Information System (INIS)

    Okamoto, Daisuke; Yoshimitsu, Kengo; Nishie, Akihiro; Tajima, Tsuyoshi; Asayama, Yoshiki; Ishigami, Kousei; Hirakawa, Masakazu; Ushijima, Yasuhiro; Kakihara, Daisuke; Nakayama, Tomohiro; Nishihara, Yunosuke; Aishima, Shinichi; Taketomi, Akinobu; Kishimoto, Junji; Honda, Hiroshi

    2012-01-01

    Purpose: To elucidate the correlation between hypervascular hepatocellular carcinoma (HCC) enhancement patterns on dynamic MR imaging and histological findings. Materials and methods: Surgically proven 46 hypervascular HCCs of forty-one patients were enrolled. For each HCC, the signal intensity in the portal phase (SIPP) was evaluated. In this study, high, iso-, or low intensity in the portal phase was hypothesized as late, moderate, or early washout pattern, respectively. The SIPP of each HCC was correlated to histological grade and architectural subtypes that represent degrees of trabecular structure. For the trabecular HCCs, the thickness of tumor plate was also correlated for indirect estimation of tumor sinusoid. Results: There was a significant correlation between the SIPP vs. histological grade and also vs. architectural subtypes, namely the degree of trabecular structure. Washout of hypervascular HCC occurred earlier as the histological grade advanced and the histological architecture got closer to pure trabecular HCC. For the trabecular HCCs, the thickness of tumor plate correlated significantly with SIPP or histological grade. Hypervascular HCCs with thicker tumor plates showed worse histological grade and earlier washout pattern. Conclusions: Histological grade of hypervascular HCC may be predicted using SIPP. The thickness of tumor plate, resultantly the size of sinusoid between tumor plates, can account for the relationship between washout pattern and histological grade in the trabecular HCCs.

  9. Histological grade of differentiation of hepatocellular carcinoma: comparison of the efficacy of diffusion-weighted MRI with T2-weighted imaging and angiography-assisted CT

    International Nuclear Information System (INIS)

    Saito, Kazuhiro; Nishio, Ryota; Saguchi, Toru; Akata, Soichi; Tokuuye, Koichi; Moriyasu, Fuminori; Sugimoto, Katsutoshi

    2012-01-01

    The purpose of this study is to determine the usefulness of diffusion-weighted imaging (DWI) for evaluating the histological grade of differentiation of hepatocellular carcinoma (HCC) compared with T2-weighted imaging (T2WI) and tumour haemodynamics. We retrospectively evaluated 32 patients with 42 pathologically confirmed HCC nodules. These patients underwent MRI, CT during arterial portography and CT hepatic arteriography. We evaluated the relationship between the histological grade of differentiation and the apparent diffusion coefficient (ADC) values, conspicuity of tumour on DWI, DWI and T2WI contrast-to-noise (C/N) ratios and tumour haemodynamics. There was no correlation between the histological grade of differentiation and the ADC values. The DWI C/N ratio was significantly different among all histological grades, but the T2WI C/N ratio was not. Tumour conspicuity on DWI correlated well with the histological grade of differentiation, but tumour haemodynamics only partially correlated with the histological grade of differentiation. DWI was useful for evaluating the histological grade of differentiation of HCC.

  10. The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

    Science.gov (United States)

    Pinato, D J; Sharma, R; Citti, C; Platt, H; Ventura-Cots, M; Allara, E; Chen, T-Y; Dalla Pria, A; Jain, M; Mínguez, B; Kikuchi, L; Kaufman West, E; Merli, M; Kaplan, D E; Hasson, H; Marks, K; Nelson, M; Núñez, M; Aytaman, A; Bower, M; Bräu, N

    2018-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm 3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC. © 2017 John Wiley & Sons Ltd.

  11. New hallmark of hepatocellular carcinoma, early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis: a new diagnostic algorithm.

    Science.gov (United States)

    Renzulli, Matteo; Biselli, Maurizio; Brocchi, Stefano; Granito, Alessandro; Vasuri, Francesco; Tovoli, Francesco; Sessagesimi, Elisa; Piscaglia, Fabio; D'Errico, Antonietta; Bolondi, Luigi; Golfieri, Rita

    2018-02-03

    Many improvements have been made in diagnosing hepatocellular carcinoma (HCC), but the radiological hallmarks of HCC have remained the same for many years. We prospectively evaluated the imaging criteria of HCC, early HCC and high-grade dysplastic nodules (HGDNs) in patients under surveillance for chronic liver disease, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and diffusion-weighted imaging. Our study population included 420 nodules >1 cm in 228 patients. The MRI findings of each nodule were collected in all sequences/phases. The diagnosis of HCC was made according to the American Association for the Study of Liver Diseases (AASLD) criteria; all atypical nodules were diagnosed using histology. A classification and regression tree was developed using three MRI findings which were independently significant correlated variables for early HCC/HCC, and the best sequence of their application in a new diagnostic algorithm (hepatobiliary hypointensity, arterial hyperintensity and diffusion restriction) was suggested. This algorithm demonstrated, both in the entire study population and for nodules ≤2 cm, higher sensitivity (96% [95% CI 93.5% to 97.6%] and 96.6% [95% CI 93.9% to 98.5%], P<0.001, respectively) and slightly lower specificity (91.8% [95% CI 88.6% to 94.1%], P=0.063, and 92.7% [95% CI 88.9% to 95.4%], P=0.125, respectively) than those of the AASLD criteria. Our new diagnostic algorithm also showed a very high sensitivity (94.7%; 95% CI 92% to 96.6%) and specificity (99.3%; 95% CI 97.7% to 99.8%) in classifying HGDN. Our new diagnostic algorithm demonstrated significantly higher sensitivity and comparable specificity than those of the AASLD imaging criteria for HCC in patients with cirrhosis evaluated using Gd-EOB-DTPA MRI, even for lesions ≤2 cm. Moreover, this diagnostic algorithm allowed evaluating other lesions which could arise in a cirrhotic liver, such as early HCC and HGDN. © Article author

  12. Histological Grading of Hepatocellular Carcinomas with Intravoxel Incoherent Motion Diffusion-weighted Imaging: Inconsistent Results Depending on the Fitting Method.

    Science.gov (United States)

    Ichikawa, Shintaro; Motosugi, Utaroh; Hernando, Diego; Morisaka, Hiroyuki; Enomoto, Nobuyuki; Matsuda, Masanori; Onishi, Hiroshi

    2018-04-10

    To compare the abilities of three intravoxel incoherent motion (IVIM) imaging approximation methods to discriminate the histological grade of hepatocellular carcinomas (HCCs). Fifty-eight patients (60 HCCs) underwent IVIM imaging with 11 b-values (0-1000 s/mm 2 ). Slow (D) and fast diffusion coefficients (D * ) and the perfusion fraction (f) were calculated for the HCCs using the mean signal intensities in regions of interest drawn by two radiologists. Three approximation methods were used. First, all three parameters were obtained simultaneously using non-linear fitting (method A). Second, D was obtained using linear fitting (b = 500 and 1000), followed by non-linear fitting for D * and f (method B). Third, D was obtained by linear fitting, f was obtained using the regression line intersection and signals at b = 0, and non-linear fitting was used for D * (method C). A receiver operating characteristic analysis was performed to reveal the abilities of these methods to distinguish poorly-differentiated from well-to-moderately-differentiated HCCs. Inter-reader agreements were assessed using intraclass correlation coefficients (ICCs). The measurements of D, D * , and f in methods B and C (Az-value, 0.658-0.881) had better discrimination abilities than did those in method A (Az-value, 0.527-0.607). The ICCs of D and f were good to excellent (0.639-0.835) with all methods. The ICCs of D * were moderate with methods B (0.580) and C (0.463) and good with method A (0.705). The IVIM parameters may vary depending on the fitting methods, and therefore, further technical refinement may be needed.

  13. Cytopathologic differential diagnosis of low-grade urothelial carcinoma and reactive urothelial proliferation in bladder washings: a logistic regression analysis.

    Science.gov (United States)

    Cakir, Ebru; Kucuk, Ulku; Pala, Emel Ebru; Sezer, Ozlem; Ekin, Rahmi Gokhan; Cakmak, Ozgur

    2017-05-01

    Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in urinary cytology. In cytologic preparations, the separation of low-grade urothelial carcinoma (LGUC) from reactive urothelial proliferation (RUP) can be exceedingly difficult. The bladder washing cytologies of 32 LGUC and 29 RUP were reviewed. The cytologic slides were examined for the presence or absence of the 28 cytologic features. The cytologic criteria showing statistical significance in LGUC were increased numbers of monotonous single (non-umbrella) cells, three-dimensional cellular papillary clusters without fibrovascular cores, irregular bordered clusters, atypical single cells, irregular nuclear overlap, cytoplasmic homogeneity, increased N/C ratio, pleomorphism, nuclear border irregularity, nuclear eccentricity, elongated nuclei, and hyperchromasia (p ˂ 0.05), and the cytologic criteria showing statistical significance in RUP were inflammatory background, mixture of small and large urothelial cells, loose monolayer aggregates, and vacuolated cytoplasm (p ˂ 0.05). When these variables were subjected to a stepwise logistic regression analysis, four features were selected to distinguish LGUC from RUP: increased numbers of monotonous single (non-umbrella) cells, increased nuclear cytoplasmic ratio, hyperchromasia, and presence of small and large urothelial cells (p = 0.0001). By this logistic model of the 32 cases with proven LGUC, the stepwise logistic regression analysis correctly predicted 31 (96.9%) patients with this diagnosis, and of the 29 patients with RUP, the logistic model correctly predicted 26 (89.7%) patients as having this disease. There are several cytologic features to separate LGUC from RUP. Stepwise logistic regression analysis is a valuable tool for determining the most useful cytologic criteria to distinguish these entities. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  14. [Pancreatic serous cystadenoma associated with pancreatic heterotopia].

    Science.gov (United States)

    Mohamed, Hedfi; Dorra, Belghachem; Hela, Bouhafa; Cherif, Abdelhedi; Azza, Sridi; Karim, Sassi; Khadija, Bellil; Adnen, Chouchene

    2016-01-01

    Pancreatic heterotopias (HP) are rare. They can occur at any age with a slight male predominance. These lesions are usually asymptomatic and they are often found incidentally during upper or lower GI endoscopy or during the anatomo-pathological examination of an organ which was resected for other reasons; they can be isolated or associated with a digestive pathology. We report, through observation, the association of HP with serous cystadenoma of the pancreas discovered during examinations to identify the etiology of isolated abdominal pain. The aim of this study is to analyse clinical and histological features of this rare pathology.

  15. Albumin-Bilirubin and Platelet-Albumin-Bilirubin Grades Accurately Predict Overall Survival in High-Risk Patients Undergoing Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma.

    Science.gov (United States)

    Hansmann, Jan; Evers, Maximilian J; Bui, James T; Lokken, R Peter; Lipnik, Andrew J; Gaba, Ron C; Ray, Charles E

    2017-09-01

    To evaluate albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades in predicting overall survival in high-risk patients undergoing conventional transarterial chemoembolization for hepatocellular carcinoma (HCC). This single-center retrospective study included 180 high-risk patients (142 men, 59 y ± 9) between April 2007 and January 2015. Patients were considered high-risk based on laboratory abnormalities before the procedure (bilirubin > 2.0 mg/dL, albumin 1.2 mg/dL); presence of ascites, encephalopathy, portal vein thrombus, or transjugular intrahepatic portosystemic shunt; or Model for End-Stage Liver Disease score > 15. Serum albumin, bilirubin, and platelet values were used to determine ALBI and PALBI grades. Overall survival was stratified by ALBI and PALBI grades with substratification by Child-Pugh class (CPC) and Barcelona Liver Clinic Cancer (BCLC) stage using Kaplan-Meier analysis. C-index was used to determine discriminatory ability and survival prediction accuracy. Median survival for 79 ALBI grade 2 patients and 101 ALBI grade 3 patients was 20.3 and 10.7 months, respectively (P  .05). ALBI and PALBI grades are accurate survival metrics in high-risk patients undergoing conventional transarterial chemoembolization for HCC. Use of these scores allows for more refined survival stratification within CPC and BCLC stage. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  16. Chylaskos as a presentation of serous papillary adenocarcinoma of the endometrium: a case report

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    Maria Inês Sequeira

    2017-06-01

    Full Text Available A 77-year-old female was presented to the emergency department with intense anorexia, weight loss despite progressive abdominal distension, and dyspnea. Abdomen imagiology workup reveled moderate-volume ascites and a hepatic occupying lesion. Diagnostic paracentesis allowed the drainage of a chylous effusion and cytology analysis identified adenocarcinoma cells. Hepatic metastasis of papillary serous adenocarcinoma of the endometrium was confirmed after tomography-guided biopsy. Endometrial carcinoma is the most common malignant gynecological neoplasm in developed countries and is often classified in types I with endometrioid histology (estrogen-dependent and non endometrioid types II (non-estrogen-dependent. Chylous ascites or chylaskos is a rare presentation on hospital admission. Several etiologies have been described. In adults, solid malignancy is expected to be identified in less than 20% of the cases. A systematic review has found only one case of endometrial carcinoma presenting with chylous ascite. As far as we know, this is the first case report of a serous papillary adenocarcinoma of the endometrium presenting with chylaskos.

  17. Identification and Characterization of Genomic Amplifications in Ovarian Serous Carcinoma

    Science.gov (United States)

    2009-07-01

    electron microscopy further revealed that NAC-1 was localized to discrete nuclear bodies, tentatively termed ‘‘NAC-1 bodies’’, with a diameter ranging...bodies, we applied ImmunoGold labeling on NAC-1-expressing- RK3E cells, followed by electron microscopy. Coimmunoprecipitation and Double...diseases, as well as malignant neo- plasms (22–24). Cytologic examination is routinely done to distinguish malignant from benign diseases. Although the

  18. Uterine Serous Papillary Carcinoma: A Retrospective Analysis of 22 Cases

    Directory of Open Access Journals (Sweden)

    Demir Özbasar

    2008-04-01

    CONCLUSIONS: Staging surgery should be performed on patients with USPC. Invasion of omentum and positive cytology were poor prognostic factors. The effect of adjuvant therapy on prognosis is not clear.

  19. B-cell lymphoma 2 is associated with advanced tumor grade and clinical stage, and reduced overall survival in young Chinese patients with colorectal carcinoma.

    Science.gov (United States)

    Wang, Jiasheng; He, Gan; Yang, Qiang; Bai, Lian; Jian, Bin; Li, Qugang; Li, Zhongfu

    2018-06-01

    The development of biomarkers that accurately and reliably detect colorectal cancer is a promising approach for colorectal cancer screening. Therefore, the objective of the present study was to evaluate the protein expression of α-methylacyl-CoA racemase (P504S/AMACR), tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2) and Ki-67/mindbomb E3 ubiquitin protein ligase 1 (MIB-1) in a population of Chinese patients with colorectal carcinoma. Colorectal tumors with matched normal tissue margins were collected from 148 surgical patients, and the demographic and clinical characteristics were collected. Immunohistochemical staining and western blot analysis of P504S/AMACR, p53, Bcl-2 and Ki-67/MIB-1 were conducted. Statistical analyses were used to compare protein expression in the colorectal tumors and matched normal tissue margins and to identify any associations between them and various clinicopathological parameters. Survival analyses were performed using the Kaplan-Meier method. In the present study, immunohistochemistry and western blot analysis revealed significantly higher expression of all four proteins in colorectal tumors compared with matched normal tissue margins (Pcolorectal carcinoma [relative risk (95% CI), 0.703 (0.552-0.895); P55 years) and reduced overall survival (Pcolorectal carcinoma. In conclusion, low expression of Bcl-2 is significantly correlated with advanced pathological grade and TNM stage and is a prognostic indicator of reduced overall survival in young Chinese patients with colorectal carcinoma.

  20. Prognostic significance of epithelial/stromal caveolin‐1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density

    Directory of Open Access Journals (Sweden)

    Dareen A. Mohammed

    2017-03-01

    Full Text Available Caveolin-1 may play a role in cancer development and progression. The aim was to record the expression and localization of caveolin-1 in benign prostatic hyperplasia (BPH, high grade prostatic intraepithelial neoplasia (HGPIN and prostatic carcinoma (PCa. Microvessel density was evaluated with CD34 immunostain. Correlations with known prognostic factors of PCa were recorded. Immunohistochemical expression of caveolin-1 and the MVD was evaluated in 65 cases; BPH (25, HGPIN (20 and PCa (20. Stromal caveolin-1expression was significantly higher in BPH than HGPIN and PCca. There was significant inverse relation between stromal caveolin-1 expression and extension to lymph node and seminal vesicle in carcinoma cases. Epithelial caveolin-1 was significantly higher in carcinomas than in BPH and HGPIN. Epithelial expression in carcinoma was significantly associated with preoperative PSA, Gleason score and lymph node extension. MVD was significantly higher in PCa than in BPH and HGPIN. There were significant relations between MVD and preoperative PSA, Gleason score, lymph node and seminal vesicle extension. Stromal caveolin-1 was associated with low MVD while epithelial caveolin-1 with high MVD. Conclusions: Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis.

  1. Application of ADC measurement in characterization of renal cell carcinomas with different pathological types and grades by 3.0 T diffusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xiaoduo, E-mail: yxd98@yahoo.com.cn [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Lin, Meng, E-mail: linmeng77xp@yahoo.com.cn [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Ouyang, Han, E-mail: hbybj@sohu.com [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Zhou, Chunwu, E-mail: cjr.zhouchunwu@163.vip.com [Department of Diagnostic Radiology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China); Zhang, Hongtu, E-mail: zhanghongtu1010@yahoo.com.cn [Department of Pathology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing (China)

    2012-11-15

    Purpose: To test the feasibility of apparent diffusion coefficient (ADC) value obtained with 3.0 T diffusion-weighted imaging (DWI) in the characterization of renal cell carcinomas (RCC) with different pathological subtypes and grades. Materials and methods: A total of 137 patients who were diagnosed with RCC and underwent DWI were included in this study. The diagnosis was confirmed by pathological examination of surgical specimens. Images of DWI were obtained with b values of 0 and 800 s/mm{sup 2}. The ADC values in the solid area of tumors and in the corresponding regions of contralateral normal renal parenchyma were measured and analyzed statistically. Results: The mean ADC value was significantly lower in RCC (1.381 {+-} 0.444 Multiplication-Sign 10{sup -3} mm{sup 2}/s) than in normal renal parenchyma (2.232 {+-} 0.221 Multiplication-Sign 10{sup -3} mm{sup 2}/s) (P < 0.001). The ADC value was also statistically different between clear cell RCC (CCRCC) and non-CCRCC, and between different grades of CCRCC except grade I vs II and grade III vs IV. Conclusion: ADC measurement on 3.0 T DWI provides useful information in diagnostic work-up of RCC in terms of differentiation of RCC and normal renal parenchyma, and characterization of RCC with different pathological subtypes and grades.

  2. Primary peritoneal clear cell carcinoma versus ovarian carcinoma versus malignant transformation of endometriosis: a vexing issue.

    Science.gov (United States)

    Insabato, Luigi; Natella, Valentina; Somma, Anna; Persico, Marcello; Camera, Luigi; Losito, Nunzia Simona; Masone, Stefania

    2015-05-01

    Peritoneum is a site for both primary and secondary tumors. Primary peritoneal tumors are fairly rare. The most common primary tumors of the peritoneum are malignant mesothelioma and serous papillary adenocarcinoma. Clear cell carcinoma of the peritoneum is extremely rare and often misdiagnosed as mesothelioma, serous carcinoma, or metastatic adenocarcinoma, so it represents a diagnostic challenge for both clinicians and pathologists. Up to date, to the best of our knowledge, only 11 cases of primary peritoneal clear cell carcinoma have been reported in the English literature. Distinguishing this tumor of the peritoneum versus ovarian carcinoma can be problematic. Herein, we report a rare case of primary peritoneal clear cell carcinoma occurring in a 49-year-old woman, along with a review of the literature. © The Author(s) 2015.

  3. Expression of Tissue Factor in Epithelial Ovarian Carcinoma Is Involved in the Development of Venous Thromboembolism.

    Science.gov (United States)

    Sakurai, Manabu; Matsumoto, Koji; Gosho, Masahiko; Sakata, Akiko; Hosokawa, Yoshihiko; Tenjimbayashi, Yuri; Katoh, Takashi; Shikama, Ayumi; Komiya, Haruna; Michikami, Hiroo; Tasaka, Nobutaka; Akiyama-Abe, Azusa; Nakao, Sari; Ochi, Hiroyuki; Onuki, Mamiko; Minaguchi, Takeo; Yoshikawa, Hiroyuki; Satoh, Toyomi

    2017-01-01

    Our 2007 study of 32 patients with ovarian cancer reported the possible involvement of tissue factor (TF) in the development of venous thromboembolism (VTE) before treatment, especially in clear cell carcinoma (CCC). This follow-up study further investigated this possibility in a larger cohort. We investigated the intensity of TF expression (ITFE) and other variables for associations with VTE using univariate and multivariate analyses in 128 patients with epithelial ovarian cancer initially treated between November 2004 and December 2010, none of whom had received neoadjuvant chemotherapy. Before starting treatment, all patients were ultrasonographically screened for VTE. The ITFE was graded based on immunostaining of surgical specimens. Histological types were serous carcinoma (n = 42), CCC (n = 12), endometrioid carcinoma (n = 15), mucinous carcinoma (n = 53), and undifferentiated carcinoma (n = 6). The prevalence of VTE was significantly higher in CCC (34%) than in non-CCC (17%, P = 0.03). As ITFE increased, the frequencies of CCC and VTE increased significantly (P epithelial ovarian cancer may involve TF expression in cancer tissues.

  4. Impact of MRI on high grade Ductal Carcinoma Insitu (HG DCIS) management, are we using the full scope of MRI?

    Science.gov (United States)

    Hajaj, Mohamad; Karim, Ahmed; Pascaline, Sana; Noor, Lubna; Patel, Shivali; Dakka, Mahmoud

    2017-10-01

    Preoperative assessment of pure Ductal Carcinoma Insitu (DCIS) is essential in the surgical planning. The role of Magnetic resonance imaging (MRI) has long been debated. The impact of MRI on the management of High Grade (HG) DCIS was assessed, whether it accurately captures the true size of this entity in comparison to conventional imaging, and, if MRI use would reduce the number of re-excision surgery. Ninety-one consecutive patients with HG DCIS, who were identified from a prospectively collected data at Kettering General Hospital between April 2011 and December 2015. All patients had preoperative MRI scan in addition to the standard breast imaging. This was compared to a control group of consecutive patients (n=52) which was obtained from a period just before 2011. Impact on surgical planning and number of surgeries for each patient was compared. The size of HG DCIS estimated by MRI was compared to the final histological size. Secondary outcomes included change of initial surgical plan and detection of occult contralateral breast cancer. MRI group had 91 patients with median age of 63. Seventy percent of which presented through the screening program. The overall sensitivity of MRI to detect HG DCIS was 77% (70/91) with a false negative rate FNR of 23% (21/91). Therefore, 70 patients only were included in the data analysis. The control group included 52 screening patients with comparable baseline characteristics. Re-excision (or completion mastectomy) rates were higher in the control group 26% compared to 8% in the MRI group (P-value 0.012). MRI use correctly converted the initial plan of breast conservation to mastectomy in 9 patients (13%). Five patients had additional ipsilateral malignant features (7%).Occult contra lateral disease, was diagnosed in 2 patients (3%). This study suggests that MRI could be an important tool in reducing the re-excision rates in the surgical management of HG DCIS. Although still controversial, selective MRI imaging can be useful

  5. Central serous choroidopathy in the Hallermann-Streiff Syndrome.

    Science.gov (United States)

    Blair, N P; Brockhurst, R J; Lee, W

    1981-08-01

    Central serous choroidopathy was observed in a young patient with the Hallermann-Streiff syndrome. Typical features of this syndrome include microphthalmos, proportionate dwarfism, dyscephaly with birdlike facies, dental abnormalities, and hypotrichosis. Exceptional aspects of this case include age of onset (11 years), high hyperopic refractive error (+ 13.00 sphere), and multiple recurrences caused by six separate documented leaks from the choroid. Fundus changes previously reported in the Hallermann-Streiff syndrome, interpreted as chorioretinal pigmentary changes, may have been secondary to previous undiagnosed central serous choroidopathy. Periodic ophthalmoscopy should be performed and may detect unrecognized episodes of central serous choroidopathy for which photocoagulation would be beneficial.

  6. An uncommon manifestation of paraneoplastic cerebellar degeneration in a patient with high grade urothelial, carcinoma with squamous differentiation: A case report and literature review

    International Nuclear Information System (INIS)

    Zhu, Yaofeng; Chen, Shouzhen; Chen, Songyu; Song, Jing; Chen, Fan; Guo, Hu; Shang, Zhenhua; Wang, Yong; Zhou, Changkuo; Shi, Benkang

    2016-01-01

    Paraneoplastic neurological syndromes (PNS) are rare disorders associated with malignant tumours, which are triggered by autoimmune reactions. Paraneoplastic cerebellar degeneration (PCD) is the PNS type most commonly associated with ovarian and breast cancer. Two bladder cancers manifesting in PCD were previously reported. However, the cancers in these cases had poor outcomes. Here, we present a 68-year old man with history of high-grade papillary urothelial carcinoma of the bladder. The patient suffered from persistent cerebellar ataxia accompanied by bladder cancer recurrence five months after transurethral resection of the bladder tumour (TURBt). Laboratory screening for the specific antibodies of paraneoplastic neurological syndromes revealed no positive results. Symptoms were not remitted after a 7-day-course of high-dose glucocorticoid therapy. To our surprise, the patient recovered fully after laparoscopic radical cystectomy. Postoperative pathology revealed that surgical specimens were urothelial carcinoma in situ (CIS) and squamous cell carcinoma of the bladder. The patient remained asymptomatic and there was no evidence of recurrence after the followup period of 11 months. To our knowledge, this is the third report of PCD in a patient with bladder cancer. This case showed that tumour resection cured the PCD. To assist clinical evaluation and management, literature regarding basic PNS characteristics and bladder cancers was reviewed

  7. Evaluation of renal cell carcinoma histological subtype and fuhrman grade using {sup 18}F-fluorodeoxyglucose-positron emission tomography/computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Reiko; Nozaki, Sayumi; Abe, Koichiro; Sakai, Shuji [Tokyo Women' s Medical University, Department of Diagnostic Imaging and Nuclear Medicine, Tokyo (Japan); Kondo, Tsunenori [Tokyo Women' s Medical University, Department of Urology, Tokyo (Japan); Nagashima, Yoji [Tokyo Women' s Medical University, Department of Surgical Pathology, Tokyo (Japan)

    2017-11-15

    We evaluated {sup 18}F-fluorodeoxyglucose (FDG) uptake by renal cell carcinomas (RCCs) to determine whether different histological subtypes and Fuhrman grades can be distinguished. We retrospectively reviewed the records and maximum standardised uptake value (SUVmax) of 147 patients with 154 RCCs who underwent FDG-positron emission tomography (PET)/computed tomography (CT) prior to tumour resection. The SUVmax was significantly lower in chromophobe RCC (chRCC) tumours than in clear cell RCC (ccRCC; p = 0.003) and papillary RCC (pRCC; p = 0.034) tumours. The mean tumour SUVmax was 4.58 ± 4.1 (range, 1.29-30.4) for ccRCC, 3.98 ± 1.9 (range, 0.49-6.72) for pRCC, and 1.93 ± 0.9 (range, 0.89-3.41) for chRCC. The SUVmax was not significantly different between the ccRCC and pRCC groups. In ccRCC and pRCC tumours, high-grade tumours had a significantly greater SUVmax (p < 0.001 and p < 0.05) than low-grade tumours by analysis of variance (ANOVA) and the Mann-Whitney U test. In ccRCC, multivariate regression analysis indicated that the SUVmax was a significant indicator of Fuhrman grade. No significant differences in uptake were observed between high- and low-grade chRCC tumours. The SUVmax obtained using FDG-PET/CT may be an important indicator for predicting tumour grade in ccRCC and pRCC. (orig.)

  8. Appendectomy with cytoreductive surgery for ovarian and type 2 endometrial carcinoma.

    Science.gov (United States)

    Wong, L F A; Wahab, N A; Gleeson, N

    2014-01-01

    There is considerable variation within and between cancer centers in the practice of appendectomy as part of cytoreductive surgery for ovarian carcinoma and in the surgical staging of endometrial carcinoma. The purpose of this study was to determine the prevalence and the type of appendiceal pathology, the morbidity associated with appendectomy in gynaecologic cancer surgery. This is a retrospective review of all cytoreductive surgery for ovarian carcinoma and surgical staging for endometrial carcinoma with appendectomy over a four year period. Two hundred and fifty-one patients (38 patients for endometrial carcinoma surgery and 213 patients for ovarian cytoreduction) had an appendectomy performed. Metastases to the appendix was present in 46 (23.2%) of primary ovarian carcinoma and one (2.6%) primary endometrial carcinosarcoma. The appendix was more likely to be involved in advanced stage ovarian cancer with positive peritoneal washings, omental deposits, grade 3 differentiation, and papillary serous histology. Sixteen (6.4%) co-incidental primary appendiceal tumours were detected. No postoperative morbidity specific to appendectomy was identified. One case of ovarian carcinoma was upstaged from IC to IIIA by the appendiceal metastases. There was no upstaging of disease in the endometrial carcinoma group. Appendectomy is an integral part of ovarian cytoreductive surgery but the authors found it did not upstage the disease in a clinically significant manner. The incidence of co-incidental appendiceal primary tumours was high in this series and may add value to the procedure in preventing further surgeries. The absence of procedure related morbidity is reassuring. The authors recommend appendectomy for all ovarian staging surgery and its consideration in type 2 endometrial cancer.

  9. Prognostic significance of epithelial/stromal caveolin-1 expression in prostatic hyperplasia, high grade prostatic intraepithelial hyperplasia and prostatic carcinoma and its correlation with microvessel density.

    Science.gov (United States)

    Mohammed, Dareen A; Helal, Duaa S

    2017-03-01

    Caveolin-1 may play a role in cancer development and progression. The aim was to record the expression and localization of caveolin-1 in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostatic carcinoma (PCa). Microvessel density was evaluated with CD34 immunostain. Correlations with known prognostic factors of PCa were recorded. Immunohistochemical expression of caveolin-1 and the MVD was evaluated in 65 cases; BPH (25), HGPIN (20) and PCa (20). Stromal caveolin-1expression was significantly higher in BPH than HGPIN and PCca. There was significant inverse relation between stromal caveolin-1 expression and extension to lymph node and seminal vesicle in carcinoma cases. Epithelial caveolin-1 was significantly higher in carcinomas than in BPH and HGPIN. Epithelial expression in carcinoma was significantly associated with preoperative PSA, Gleason score and lymph node extension. MVD was significantly higher in PCa than in BPH and HGPIN. There were significant relations between MVD and preoperative PSA, Gleason score, lymph node and seminal vesicle extension. Stromal caveolin-1 was associated with low MVD while epithelial caveolin-1 with high MVD. Caveolin-1 plays an important role in prostatic carcinogenesis and metastasis. Stromal expression of caveolin-1 in PCa is lowered in relation to BPH and HGPIN. In PCa; stromal caveolin-1 was associated with good prognostic parameters. Epithelial caveolin-1 is significantly increased in PCa than BPH and HGPIN. It is associated with clinically aggressive disease. Caveolin-1 may play a role in angiogenesis. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  10. Laparoscopic diagnosis of adenocarcinoma of the appendix mimicking serous papillary adenocarcinoma of the peritoneum.

    Science.gov (United States)

    Yoshimura, Mayumi; Terai, Yoshito; Konishi, Hiromi; Tanaka, Yoshimichi; Tanaka, Tomohito; Sasaki, Hiroshi; Ohmichi, Masahide

    2013-01-01

    Primary carcinoma of the vermiform appendix is a rare disease with few clinical symptoms. Accordingly, preoperative diagnosis of appendiceal cancer is challenging because of the lack of specific symptoms. We herein report a case of appendicular adenocarcinoma found unexpectedly during laparoscopic surgery in a 69-year-old Japanese female patient diagnosed with serous papillary adenocarcinoma, in order to determine whether optimal cytoreduction could successfully be achieved at the time of primary surgery. We performed diagnostic laparoscopic surgery in order to make a correct diagnosis based on the histological tissue. The vermiform appendix was found to contain a tumor measuring 1.5 cm wide and 4.5 cm long. Laparoscopic appendectomy, partial omentectomy, and partial resection of the lesion in the peritoneum were performed. The histological diagnosis was mucinous adenocarcinoma of the vermiform appendix, and the stage was T4NxM1. The patient received adjuvant chemotherapy with mFOLFOX 6 (5FU, leucovorin, and oxaliplatin). She achieved stable disease and was alive with disease eleven months after surgery. We therefore recommend that gynecologists should not rule out the possibility of appendiceal cancer, even in cases with preoperative findings similar to those of serous papillary adenocarcinoma of the peritoneum with peritoneal disseminated tumors.

  11. Smoking increased the risk of prostate cancer with grade group ≥ 4 and intraductal carcinoma in a prospective biopsy cohort.

    Science.gov (United States)

    Tang, Bo; Han, Cheng-Tao; Gan, Hua-Lei; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Zhu, Yao; Ye, Ding-Wei

    2017-06-01

    To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men. We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence. A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group ≥ 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR = 2.29, 95%CI: 1.14-4.59). Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa. © 2017 Wiley Periodicals, Inc.

  12. Inflammation-regulating factors in ascites as predictive biomarkers of drug resistance and progression-free survival in serous epithelial ovarian cancers

    International Nuclear Information System (INIS)

    Lane, Denis; Matte, Isabelle; Garde-Granger, Perrine; Laplante, Claude; Carignan, Alex; Rancourt, Claudine; Piché, Alain

    2015-01-01

    Platinum-based combination therapy is the standard first-line treatment for women with advanced serous epithelial ovarian carcinoma (EOC). However, about 20 % will not respond and are considered clinically resistant. The availability of biomarkers to predict responses to the initial therapy would provide a practical approach to identify women who would benefit from a more appropriate first-line treatment. Ascites is an attractive inflammatory fluid for biomarker discovery as it is easy and minimally invasive to obtain. The aim of this study was to evaluate whether six selected inflammation-regulating factors in ascites could serve as diagnostic or drug resistance biomarkers in patients with advanced serous EOC. A total of 53 women with stage III/IV serous EOC and 10 women with benign conditions were enrolled in this study. Eleven of the 53 women with serous EOC were considered clinically resistant to treatment with progression-free survival < 6 months. Ascites were collected at the time of the debulking surgery and the levels of cytokines were measured by ELISA. The six selected cytokines were evaluated for their ability to discriminate serous EOC from benign controls, and to discriminate platinum resistant from platinum sensitive patients. Median ascites levels of IL-6, IL-10 and osteoprotegerin (OPG) were significantly higher in women with advanced serous EOC than in controls (P ≤ 0.012). There were no significant difference in the median ascites levels of leptin, soluble urokinase plasminogen activator receptor (suPAR) and CCL18 among serous EOC women and controls. In Receiver Operator curve (ROC) analysis, IL-6, IL-10 and OPG had a high area under the curve value of 0.905, 0.832 and 0.825 respectively for distinguishing EOC from benign controls. ROC analysis of individual cytokines revealed low discriminating potential to stratify patients according to their sensitivity to first-line treatment. The combination of biomarkers with the highest discriminating

  13. High-grade poorly differentiated neuroendocrine carcinoma of the breast with low oncotype Dx recurrence score: A case report.

    Science.gov (United States)

    Munoz-Zuluaga, Carlos A; Kotiah, Sandy; Studeman, Kimberley D

    2017-01-01

    Primary neuroendocrine carcinoma of the breast (NECB) is a rare malignant tumor with controversial biological behavior and a lack of data guiding treatment decisions due to its scarcity. Cancer gene-expression profiling tests provide a better indication of clinical prognosis and help determine the best clinical management versus the traditional clinical and pathological parameters. This is a report of a NECB with a genetic assay that showed a low-risk tumor despite high-grade and poorly differentiated histopathological features. Patient outcomes correlate with the low risk classification without the need for adjuvant chemotherapy despite the standard clinical-pathologic approach. Analysis of cancer related genes expression and outcomes in historical NECB may elucidate new insight of this rare disease.

  14. Bap1 and Pbrm1: Determinants of Tumor Grade and mTOR Activation in VHL-Deficient Mouse Models of Renal Cell Carcinoma.

    Science.gov (United States)

    Leung, Janet Y; Kim, William Y

    2017-08-01

    Large genome sequencing efforts have identified frequent mutations in the histone-modifying and chromatin-remodeling genes BAP1 and PBRM1 in clear cell renal cell carcinoma (ccRCC). In this issue of Cancer Discovery , Gu and colleagues model these genetic events in mice and report that dual inactivation of Vhl with either Bap1 or Pbrm1 results in faithful genetically engineered murine models of ccRCC. Moreover, their work establishes that Bap1 and Pbrm1 are determinants of tumor grade and mTORC1 activation and provocatively suggests that the cell of origin of ccRCC may lie in PAX8-expressing Bowman capsule cells. Cancer Discov; 7(8); 802-4. ©2017 AACR See related article by Gu et al., p. 900 . ©2017 American Association for Cancer Research.

  15. 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.

  16. Transconjunctival drainage of serous and hemorrhagic choroidal detachment.

    Science.gov (United States)

    Rezende, Flávio A; Kickinger, Mônica C; Li, Gisèle; Prado, Renata F; Regis, Luiz Gustavo T

    2012-02-01

    To describe a novel surgical technique for drainage of bullous serous and hemorrhagic choroidal detachments. A prospective, consecutive case series of 6 eyes with serous and/or hemorrhagic choroidal detachments secondary to intraocular surgery was documented to evaluate the feasibility of using the 25-gauge and 20-gauge transconjunctival trocar/cannula systems to drain choroidal detachments. Two eyes had expulsive hemorrhagic choroidal detachments and 4 eyes had serous choroidal detachments after glaucoma surgeries. A 25-gauge infusion line was placed in the anterior chamber. A 20-gauge (in eyes with hemorrhagic choroidal detachments) or a 25-gauge (in eyes with serous detachments) trocar/cannula system was inserted into the suprachoroidal space 7.0 mm from limbus. After drainage, the cannulas were removed and no sutures were placed. Pars plana vitrectomy was performed only in eyes with concomitant pathology that demanded the additional procedure. The primary outcome measure was presence of choroidal detachment at 1 week, 2 weeks, and 1 month postoperatively. Secondary outcome measures were visual acuity at 6 months and intraocular pressure at 1 week and 1, 3, and 6 months postoperatively. Drainage of hemorrhagic choroidal detachments resulted in resolution of the detachments by 1 month postoperatively. In eyes with serous detachments, resolution was achieved by 1 week postdrainage. In both groups, intraocular pressure increased to at least 10 mmHg by postoperative Week 1. The visual acuity improved in all eyes. No complications related to the transconjunctival technique were noted. Transconjunctival drainage of serous and hemorrhagic choroidal detachments seems to be a feasible and simple surgical option with minimal scleral and conjunctival damage. Pars plana vitrectomy may not be necessary when draining choroidal detachments in this manner.

  17. Diagnosed a Patient with Central Serous Chorioretinopathy? Now What?: Management of Central Serous Chorioretinopathy.

    Science.gov (United States)

    Goldhagen, Brian E; Goldhardt, Raquel

    2017-06-01

    The goal of this paper is to provide a comprehensive review of the management options for central serous chorioretinopathy (CSCR). The majority of cases of acute CSCR may be managed with observation and cessation of corticosteroids, if possible, as well as life-style modifications including stress reduction and control of hypertension. The management of chronic disease is more challenging and may include either medication or laser-based treatment. Management of CSCR necessitates an individualized and selective treatment approach. There is overall poor evidence for the use of systemic and intravitreal medications. From this class of treatments, mineralocorticoid receptor antagonists appear to have the greatest potential. Although conventional thermal photocoagulation may be used in select cases, the most promising treatment options at this time for chronic CSCR are photodynamic therapy, either half-dose or half-fluence, and non-damaging (subthreshold) retinal laser therapy.

  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. 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 ...

  20. Pathways to Genome-targeted Therapies in Serous Ovarian Cancer.

    Science.gov (United States)

    Axelrod, Joshua; Delaney, Joe

    2017-07-01

    Genome sequencing technologies and corresponding oncology publications have generated enormous publicly available datasets for many cancer types. While this has enabled new treatments, and in some limited cases lifetime management of the disease, the treatment options for serous ovarian cancer remain dismal. This review summarizes recent advances in our understanding of ovarian cancer, with a focus on heterogeneity, functional genomics, and actionable data.

  1. Serous Effusions: An attempt at a clinical pathological correlation ...

    African Journals Online (AJOL)

    One hundred and three serous fluid examinations were analysed to try to discover a simple formula whereby a pathological and/or aetiological diagnosis may be made without recourse to multiple, invasive, sophisticated QC expensive procedures. It was hoped also to find features which would identify effusions arising from ...

  2. Chondroitin sulfate iron colloid-enhanced MR imaging of hepatocellular carcinoma; Correlation between histologic grade and detectability

    Energy Technology Data Exchange (ETDEWEB)

    Kamba, Masayuki; Suto, Yuji; Kodama, Fumiko; Kato, Terumi; Ohta, Yoshio; Horie, Yasushi; Hamazoe, Ryuichi; Kawasaki, Hironaka (Tottori Univ., Yonago (Japan). School of Medicine)

    1994-03-01

    We applied chondroitin sulfate iron colloid (CSIC) as an MR contrast agent to detect hepatocellular carcinoma (HCC). The MR and pathologic findings of 25 HCCs in 21 patients were analyzed. MR imaging was performed with a superconducting system operating at 1.5 T. Proton density-weighted (PDW), T[sub 2]-weighted (T[sub 2]W) and T[sub 1]-weighted (T[sub 1]W) images were obtained before and after an intravenous injection of 23.6 [mu]mol Fe/kg of CSIC. In moderately to poorly differentiated and moderately differentiated HCCs (n=15), all the lesions except a 5-mm satellite nodule were detectable with unenhanced T[sub 2]W images as well as CSIC-enhanced PDW, T[sub 2]W and T[sub 1]W images. In well to moderately differentiated HCCs (n=6), two to four lesions were detectable with unenhanced images. All the lesions except a 3-mm satellite nodule were detectable with CSIC-enhanced PDW, T[sub 2]W and T[sub 1]W images. In well differentiated HCCs (n=4), one or two lesions were detectable with unenhanced images. All the lesions were detectable with CSIC-enhanced T[sub 1]W images, while only two lesions were detectable with CSIC-enhanced PDW or T[sub 2]W images. CSIC administration improves detection rates, and is especially useful in detecting small foci of well to moderately or well differentiated HCC. (author).

  3. 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.

  4. BILATERAL SEROUS MACULAR DETACHMENT IN A PATIENT WITH NEPHROTIC SYNDROME.

    Science.gov (United States)

    Bilge, Ayse D; Yaylali, Sevil A; Yavuz, Sara; Simsek, İlke B

    2018-01-01

    The purpose of this study was to report a case of a woman with nephrotic syndrome who presented with blurred vision because of bilateral serous macular detachment. Case report and literature review. A 55-year-old woman with a history of essential hypertension, diabetes, and nephrotic syndrome was presented with blurred vision in both eyes. Her fluorescein angiography revealed dye leakage in the early and subretinal pooling in the late phases, and optical coherence tomography scans confirmed the presence of subretinal fluid in the subfovel area. In nephrotic syndrome cases especially with accompaniment of high blood pressure, fluid accumulation in the retina layer may occur. Serous macular detachment must be kept in mind when treating these patients.

  5. 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

  6. Statistical clustering of parametric maps from dynamic contrast enhanced MRI and an associated decision tree model for non-invasive tumour grading of T1b solid clear cell renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Yin; Yuan, Qing; Zhang, Yue; Fulkerson, Michael [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Madhuranthakam, Ananth J. [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); UT Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); Margulis, Vitaly; Cadeddu, Jeffrey A. [UT Southwestern Medical Center, Department of Urology, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); Brugarolas, James [UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); UT Southwestern Medical Center, Department of Internal Medicine, Dallas, TX (United States); Kapur, Payal [UT Southwestern Medical Center, Department of Urology, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States); UT Southwestern Medical Center, Department of Pathology, Dallas, Texas (United States); Pedrosa, Ivan [UT Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); UT Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); UT Southwestern Medical Center, Kidney Cancer Program, Simmons Comprehensive Cancer Center, Dallas, TX (United States)

    2018-01-15

    To apply a statistical clustering algorithm to combine information from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) into a single tumour map to distinguish high-grade from low-grade T1b clear cell renal cell carcinoma (ccRCC). This prospective, Institutional Review Board -approved, Health Insurance Portability and Accountability Act -compliant study included 18 patients with solid T1b ccRCC who underwent pre-surgical DCE MRI. After statistical clustering of the parametric maps of the transfer constant between the intravascular and extravascular space (K{sup trans}), rate constant (K{sub ep}) and initial area under the concentration curve (iAUC) with a fuzzy c-means (FCM) algorithm, each tumour was segmented into three regions (low/medium/high active areas). Percentages of each region and tumour size were compared to tumour grade at histopathology. A decision-tree model was constructed to select the best parameter(s) to predict high-grade ccRCC. Seven high-grade and 11 low-grade T1b ccRCCs were included. High-grade histology was associated with higher percent high active areas (p = 0.0154) and this was the only feature selected by the decision tree model, which had a diagnostic performance of 78% accuracy, 86% sensitivity, 73% specificity, 67% positive predictive value and 89% negative predictive value. The FCM integrates multiple DCE-derived parameter maps and identifies tumour regions with unique pharmacokinetic characteristics. Using this approach, a decision tree model using criteria beyond size to predict tumour grade in T1b ccRCCs is proposed. (orig.)

  7. Statistical clustering of parametric maps from dynamic contrast enhanced MRI and an associated decision tree model for non-invasive tumour grading of T1b solid clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Xi, Yin; Yuan, Qing; Zhang, Yue; Fulkerson, Michael; Madhuranthakam, Ananth J.; Margulis, Vitaly; Cadeddu, Jeffrey A.; Brugarolas, James; Kapur, Payal; Pedrosa, Ivan

    2018-01-01

    To apply a statistical clustering algorithm to combine information from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) into a single tumour map to distinguish high-grade from low-grade T1b clear cell renal cell carcinoma (ccRCC). This prospective, Institutional Review Board -approved, Health Insurance Portability and Accountability Act -compliant study included 18 patients with solid T1b ccRCC who underwent pre-surgical DCE MRI. After statistical clustering of the parametric maps of the transfer constant between the intravascular and extravascular space (K trans ), rate constant (K ep ) and initial area under the concentration curve (iAUC) with a fuzzy c-means (FCM) algorithm, each tumour was segmented into three regions (low/medium/high active areas). Percentages of each region and tumour size were compared to tumour grade at histopathology. A decision-tree model was constructed to select the best parameter(s) to predict high-grade ccRCC. Seven high-grade and 11 low-grade T1b ccRCCs were included. High-grade histology was associated with higher percent high active areas (p = 0.0154) and this was the only feature selected by the decision tree model, which had a diagnostic performance of 78% accuracy, 86% sensitivity, 73% specificity, 67% positive predictive value and 89% negative predictive value. The FCM integrates multiple DCE-derived parameter maps and identifies tumour regions with unique pharmacokinetic characteristics. Using this approach, a decision tree model using criteria beyond size to predict tumour grade in T1b ccRCCs is proposed. (orig.)

  8. 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

    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...

  9. Comparison on imaging features of central serous chorioretinopathy fundus

    Directory of Open Access Journals (Sweden)

    Ji-Jin Zhang

    2014-10-01

    Full Text Available AIM: To explore and analyze the image features, diagnosis and treatment of the central serous chorioretinopathy(CSCRfundus. METHODS: From May 2008 to May 2014, 97 cases of 121 eyes with central serous chorioretinopathy were treated in in our hospital. The imaging features were compared and analyzed through different methods. RESULTS: Sixty-one cases(61 eyeswere ≤45 years, including 13 case with disease in both eyes, single stove leak accounted for 48.6%, multifocal leakage(25.7%, atypical leakage accounted for 25.7%. Thirty-six cases(47 eyeswere >45 years, 11 cases with disease in both eyes, single focal leakage(8.5%, multifocal leakage(48.9%, atypical leakage accounted for 42.6%. FFA results showed acute hairstyle at the beginning of 89 eyes, chronic deferment type 32 eyes. OCT examination showed that the main features were neuroepithelial detachment, as well as the change of the retinal pigment epithelium(RPElayer, which was divided into RPE layer detachment 93 eyes, accounting for 76.9%, rough and RPE little ridges in 28 cases, accounting for 23.1%. The average thickness of macular center concave on the cortex of microns was 137.87±19.21μm, and there was no significant difference conpared with normal(137.32±4.98μmmicrons(t=0.30, P>0.05. The closer leakage area to macular fovea, the worse of eyesight.. CONCLUSION: Different imaging examination on central serous chorioretinopathy can show different features. For clinical diagnosis and treatment it had different and complementary roles, but were given significant help for diseases treatment.

  10. Dowsing in a case of recurrent central serous Chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Apoorva Ayachit

    2017-01-01

    Full Text Available We present a case of a 34-year-old male with diminution of vision in his left eye. He was diagnosed as a case of central serous chorioretinopathy (CSCR on clinical examination and optical coherence tomography (OCT. The episode resolved in 1 month. Nine months later, the patient had a recurrence. This time, the CSCR was imaged using spectral domain-OCT, enhanced depth imaging-OCT, fundus autofluorescence, and fundus fluorescein angiography. The patient was noted to have an associated extrafoveal subretinal fluid pocket with a focal choroidal excavation.

  11. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

    International Nuclear Information System (INIS)

    Bacman, David; Merkel, Susanne; Croner, Roland; Papadopoulos, Thomas; Brueckl, Wolfgang; Dimmler, Arno

    2007-01-01

    Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM) on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta) signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited. Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4) in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2) vs. high-grade (i.e. grade 3 and 4)), lymph node metastasis, distant metastasis, 5 year cancer related survival) using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed. High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and shorter survival. Stromal TGF-beta receptor 2

  12. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study

    Directory of Open Access Journals (Sweden)

    Papadopoulos Thomas

    2007-08-01

    Full Text Available Abstract Background Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophages (TAM on histological grade of differentiation in colon carcinoma. Disruption of transforming growth factor beta (TGF-beta signalling in tumour cells is related to more aggressive clinical behaviour. Expression data of components of this pathway in tumour-associated stroma is limited. Methods Tissue micro arrays of 310 colon carcinomas from curatively resected patients in UICC stage II and III were established. In a first step we quantified amount of CD68 positive TAMs and expression of components of TGF-beta signalling (TGF-beta1, TGF-beta receptors type 1 and 2, Smad 3 and 4 in tumour and associated stroma. Further we analyzed correlation to histological and clinical parameters (histological grade of differentiation (low-grade (i.e. grade 1 and 2 vs. high-grade (i.e. grade 3 and 4, lymph node metastasis, distant metastasis, 5 year cancer related survival using Chi-square or Fisher's exact test, when appropriate, to compare frequencies, Kaplan-Meier method to calculate 5-year rates of distant metastases and cancer-related survival and log rank test to compare the rates of distant metastases and survival. To identify independent prognostic factors Cox regression analysis including lymph node status and grading was performed. Results High-grade tumours and those with lymph node metastases showed higher rates of TAMs and lower expression of TGF-beta1. Loss of nuclear Smad4 expression in tumor was associated with presence of lymph node metastasis, but no influence on prognosis could be demonstrated. Decrease of both TGF-beta receptors in tumour-associated stroma was associated with increased lymph node metastasis and

  13. DNA damage signaling and apoptosis in preinvasive tubal lesions of ovarian carcinoma.

    Science.gov (United States)

    Chene, Gautier; Ouellet, Veronique; Rahimi, Kurosh; Barres, Veronique; Caceres, Katia; Meunier, Liliane; Cyr, Louis; De Ladurantaye, Manon; Provencher, Diane; Mes Masson, Anne Marie

    2015-06-01

    High-grade serous ovarian cancer (HGSC) is the most life-threatening gynecological malignancy despite surgery and chemotherapy. A better understanding of the molecular basis of the preinvasive stages might be helpful in early detection and diagnosis. Genetic instability is 1 of the characteristics shared by most human cancers, and its level is variable through precancerous lesions to advanced cancer. Because DNA damage response (DDR) has been described as 1 of the first phases in genomic instability, we investigated the level of DDR activation and the apoptosis pathway in serous tubal intraepithelial carcinoma (STIC), the potential precursor of HGSC. A tissue microarray including 21 benign fallopian tubes, 21 STICs, 17 HGSCs from patients with STICs (associated ovarian cancer [AOC]) from the same individuals, and 30 HGSCs without STICs (non-AOC) was used in this study.Immunohistochemistry was performed to evaluate the level of DDR proteins (pATM, pChk2, γH2AX, 53BP1, and TRF2), apoptosis proteins (Bcl2, BAX, and BIM), and cyclin E. The expression of all DDR proteins increased from benign fallopian tubes to STICs. The level of expression of pATM, pChk2, γH2AX, and TRF2 was also increased in STICs in comparison with AOC. BAX, BIM, and cyclin E expressions were high in STICs, whereas Bcl2 expression was low. Immunohistochemical profiles of AOC and non-AOC were also different. These results suggest an activation of the DDR and apoptosis pathways in STICs, indicating that genomic instability may occur early in the precancerous lesions of HGSC.

  14. 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.

  15. CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

    Science.gov (United States)

    Conway, Mandi D; Noble, Jason A; Peyman, Gholam A

    2017-01-01

    Central serous chorioretinopathy (CSR) is a serous detachment of the neurosensory retina commonly associated with male sex, Type-A personality and corticosteroid use. Exogenous administration of androgens and development of CSR in men has been reported. Only one case of CSR in a postmenopausal woman receiving exogenous androgen therapy has been reported. The authors describe three cases of chronic CSR in postmenopausal women receiving exogenous testosterone therapy. Diagnosis was based on characteristic clinical, fluorescein angiographic, and optical coherence tomography findings. The three women were being treated with exogenous testosterone and progesterone therapy for symptoms of menopause and libido loss. Average age at presentation was 54.7 years (53-56 years), average duration of exogenous androgen use was 61 months (36-87 months), with average 19.7-month follow-up. Resolution of symptoms seemed correlated with cessation of androgen use despite treatment with oscillatory photodynamic therapy and intravitreal pharmacotherapy with antivascular endothelial growth factor agents. Exogenous testosterone is increasingly prescribed for menopausal symptoms and libido loss. Treatment with oscillatory photodynamic therapy, supplemental bevacizumab intravitreal pharmacotherapy, and cessation of exogenous androgen therapy was successful in three cases of chronic, therapy-resistant CSR. Ophthalmologists should inquire about androgen usage in patients who present with CSR, especially in the setting of therapy resistance.

  16. High-dose-rate intracavitary brachytherapy (HDR-IC) in treatment of cervical carcinoma: 5-year results and implication of increased low-grade rectal complication on initiation of an HDR-IC fractionation scheme

    International Nuclear Information System (INIS)

    Wang Chongjong; Wan Leung, Stephen; Chen Huichun; Sun Limin; Fang Fumin; Changchien Chanchao; Huang Engyen; Wu Jiaming; Chen Chuhnchih

    1997-01-01

    Purpose: To report the treatment results and rectal/bladder complications of cervical carcinoma radically treated with high-dose-rate intracavitary brachytherapy (HDR-IC). The current policy of using three-fraction scheme was examined. Methods and Materials: Between November 1987 and August 1990, 173 patients with cervical carcinoma were treated with curative-intent radiation therapy. Whole pelvic irradiation was administered with 10-MV X ray. Dose to the central cervix was 40-44 Gy in 20-22 fractions, following by pelvic wall boost 6-14 Gy in three to seven fractions with central shielding. 60 Co sources were used for HDR-IC, and 7.2 Gy was given to Point A for three applications, 1-2 weeks apart. Duration of follow-up was 5-7.8 years. Results: Twenty-eight patients (16%) developed central-regional recurrences. Overall 5-year actuarial pelvic control rate was 83%. By stage, 5-year actuarial pelvic control rates were 94%, 87%, and 72% for Stages IB + IIA, IIB + IIIA, and IIIB + IVA, respectively. Thirty-one patients (18%) developed distant metastasis. Overall 5-year actuarial survival rate was 58%. By stage, 5-year actuarial survival rates were 79%, 59%, and 41% for Stages IB + IIA, IIB + IIIA, and IIIB + IVA, respectively. Sixty-six (38%) and 19 patients (11%) developed rectal and bladder complications, respectively. For rectal complication, the overall actuarial rate was 38% at 5 years. By grade, 5-year actuarial rectal complication rates were 24%, 15%, 4%, and 3% for Grades 1-4, respectively. Overall prevalence of rectal complications was 37% and 14% at 2 and 5 years, respectively. Prevalence of low-grade rectal complication (Grades 1 and 2) was dominant at 2 years (30%), but declined to 8% at 5 years. Prevalence of high-grade, severe rectal complication (Grades 3 and 4) remained steady at 2 and 5 years (7% and 6%, respectively). Five-year actuarial bladder complication was 9%. Five-year prevalence of bladder complication was 2%. Conclusion: Using a three

  17. 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.

  18. Acute lymphoblastic leukemia presenting with bilateral serous macular detachment

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    Luisa Vieira

    2015-12-01

    Full Text Available ABSTRACT Acute lymphoblastic leukemia is a malignant hematopoietic neoplasia, which is rare in adults. Although ocular fundus alterations may be commonly observed in the course of the disease, such alterations are rarely the presenting signs of the disease. Here we describe the case of a patient with painless and progressive loss of visual acuity (right eye, 2/10; left eye, 3/10 developing over two weeks, accompanied by fever and cervical lymphadenopathy. Fundus examination showed bilateral macular serous detachment, which was confirmed by optical coherence tomography. Fluorescein angiography revealed hyperfluorescent pinpoints in the posterior poles. The limits of the macular detachment were revealed in the late phase of the angiogram. The results of blood count analysis triggered a thorough, systematic patient examination. The diagnosis of acute lymphoblastic leukemia B (CD10+ was established, and intensive systemic chemotherapy was immediately initiated. One year after the diagnosis, the patient remains in complete remission without any ophthalmologic alterations.

  19. Utility of early dynamic and delayed post-diuretic 18F-FDG PET/CT SUVmax in predicting tumour grade and T-stage of urinary bladder carcinoma: results from a prospective single centre study.

    Science.gov (United States)

    Sharma, Abhishek; Mete, Uttam K; Sood, Ashwani; Kakkar, Nandita; Gorla, Arun K R; Mittal, Bhagwant R

    2017-04-01

    Accurate pre-treatment grading and staging of bladder cancer are vital for better therapeutic decision and prognosis. The aim of the present study was to evaluate the correlation between maximum standardized uptake value (SUV max ) calculated during early dynamic and post-diuretic fluorine-18 fludeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT studies with grade and pT-stage of bladder cancer. 39 patients with suspected/proven bladder carcinoma underwent 10-min early dynamic pelvic imaging and delayed post-diuretic whole-body FDG PET/CT imaging. SUV max of the lesions derived from both studies was compared with grade and pT-stage. Relationship of SUV max with grade and pT-stage was analyzed using independent sample t-test and analysis of variance. SUV max of the early dynamic imaging showing tumour perfusion was independent from the SUV max of delayed imaging. High-grade tumours showed higher SUV max than low-grade tumours in the early dynamic imaging (5.4 ± 1.4 vs 4.7 ± 1.6; p-value 0.144) with statistically significant higher value in Stage pT1 tumours (6.8 ± 0.8 vs 5.5 ± 1.2; p-value 0.04). Non-invasive pTa tumours had significantly less SUV max than higher stage tumours during early dynamic imaging [F(4,29) = 6.860, p 0.001]. Early dynamic imaging may have a role in predicting the grade and aggressiveness of the bladder tumours and thus can help in treatment planning and prognostication. Advances in knowledge: Dynamic PET/CT is a limitedly explored imaging technique. This prospective pilot study demonstrates the utility of this modality as a potential adjunct to standard FDG PET/CT imaging in predicting the grade and aggressiveness of the bladder tumours and thus can impact the patient management.

  20. Fibrotic scar formation in central serous chorioretinopathy developed during systemic treatment with corticosteroids

    NARCIS (Netherlands)

    Hooymans, JMM

    1998-01-01

    Background: The purpose of the study is to demonstrate the development of subretinal fibrotic scar formation in central serous chorioretinopathy (CSCR) that developed during systemic corticosteroid treatment. Methods: The clinical and photographic records of a patient in whom an unusual

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

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    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.

  2. The value of blood oxygenation level-dependent (BOLD MR imaging in differentiation of renal solid mass and grading of renal cell carcinoma (RCC: analysis based on the largest cross-sectional area versus the entire whole tumour.

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    Guang-Yu Wu

    Full Text Available To study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade.Ninety-five patients with 139 renal masses (93 malignant and 46 benign who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*largest and from the whole tumour (R2*whole. Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis.The intra-observer agreement was very good for R2*largest and R2*whole (all > 0.8. The inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79 was good and was significantly improved compared with the R2*largest (0.61, 95% confidence interval: 0.52~0.68, as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*whole (AUC=0.79/0.78[observer1/observer2] and R2*largest (AUC=0.75[observer1] was good and significantly higher (p=0.01 for R2*largest[observer2] vs R2*whole[observer2], p 0.7 and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1].BOLD MRI could provide a feasible parameter for differentiating renal cell carcinoma from benign renal masses and for predicting clear-cell renal cell carcinoma grading. Compared with the largest cross

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

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    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.

  4. Risk of serous retinal detachment in patients with end-stage renal disease on dialysis.

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    Yuh-Shin Chang

    Full Text Available The aim of this retrospective, nationwide, matched cohort study was to investigate the association of serous retinal detachment with having end-stage renal disease (ESRD while on dialysis. The cohort study included 94,024 patients with ESRD on dialysis registered between January 2000 to December 2009 in the Taiwan National Health Insurance Research Database. An age- and sex-matched control group comprised 94,024 patients selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. Twenty-seven ESRD patients and 11 controls developed serous retinal detachment (P < 0.001 during follow-up, demonstrating a significantly increased risk of serous retinal detachment in patients with ESRD on dialysis compared with controls (incidence rate ratio = 3.39, 95% confidence interval [CI] = 1.68-6.83. After adjustment for potential confounders, patients were 3.86 times more likely to develop serous retinal detachment than the full cohort (adjusted HR = 3.86, 95% CI = 1.15-12.96. In conclusion, patients with ESRD on dialysis demonstrate an increased risk of serous retinal detachment. Interdisciplinary collaboration between nephrologists and ophthalmologists is important to deal with serous retinal detachment in patients with ESRD on dialysis and prevent impairments of visual acuity.

  5. Detection of HPV-DNA by a PCR-based method in formalin-fixed, paraffin-embedded tissue from rare endocervical carcinoma types.

    Science.gov (United States)

    Nofech-Mozes, Sharon; Khalifa, Mahmoud M; Ismiil, Nadia; Dubé, Valerie; Saad, Reda S; Sun, Peizhu; Seth, Arun; Ghorab, Zeina

    2010-01-01

    High-risk human papilloma virus (HPV) seems to play a role in the pathogenesis of cervical squamous neoplasia and adenocarcinomas of the mucinous and endometrioid cell types. Cervical serous, clear cell, and small cell carcinomas differ from the conventional endocervical adenocarcinoma in their clinical characteristics. The data on the role of HPV in their pathogenesis are limited. In this study, we examined the presence of high-risk HPV-DNA in rare types of cervical carcinoma using polymerase chain reaction-based test. In-house cervical serous, clear cell, and small cell carcinoma cases accessioned between 2000 and 2008 were tested for HPV by polymerase chain reaction amplification of DNA extracted from deparaffinized sections using Roche AMPLICOR HPV Amplification Detection and Control Kits. The kit detects all 13 high-risk HPV-DNA genotypes. The positive cut-off point for AMPLICOR HPV Test was A450 = 0.2. We identified 4 serous, 3 clear cell, 1 mixed clear cell and serous, and 5 small cell carcinomas. High-risk HPV-DNA tested positive in 3 out of 4 serous carcinomas, 2 out of 3 cervical clear cell carcinomas, and all 5 cases of small cell carcinoma and the mixed cell type. Our report documents HPV status in a series of archival unusual types of adenocarcinoma of the uterine cervix. It suggests a robust association between high-risk HPV and these rare subtypes. Despite their unique clinical setting and morphologic appearance, the majority of these tumors likely share a common HPV-mediated carcinogenic pathway. Our observation is particularly significant in cervical cancer prevention as we enter the HPV vaccination era.

  6. The value of contrast-enhanced 64-row CT in differentiating benign from malignant serous ovarian neoplasms

    International Nuclear Information System (INIS)

    Dong Tianfa; Wu Meixian; Zhang Jiayun; Song Ting

    2009-01-01

    Objective: To assess the diagnostic value of contrast-enhanced 64-row CT scanning in deciding benign or malignant serous ovarian tumors. Methods: Fifty-eight cases of serous ovarian tumors proved pathologically were reviewed, including 25 malignant tumors, 25 benign, 8 borderline tumors. All patients underwent 64-row CT scanning, including plain scanning and contrast-enhance scanning. The tumors' shape, density, blood supply and enhancement features were evaluated. Results: Twenty-five cases of benign serous cystic adenoma were mostly unicameral, and showed a moderate mural enhancement only in 4 cases (16%) due to chronic pelvic infection and the others (21/25, 84%) had no of slight enhancement. Malignant tumors were cystic-solid mass with unclear margin, irregular shape and septa. Twenty-two cases of serous cystadenocarcinoma out of 25 cases (88%) appeared obvious enhancement and other 3 cases no enhancement. And 7 cases out of 8 (87.5%) borderlined serous cystadenomas showed different enhancement patterns. Conclusion: Benign ovarian serous neoplasms were mostly unicameral and no strong mural enhancement, suggesting a lack of blood supply. While, there were obvious enhancement in the ovarian serous cystadenocarcinoma and borderline serous cystadenoma with malignant potential. The 64-row CT is helpful for differentiating the nature of the serous ovarian neoplasm. (authors)

  7. Microsecond yellow laser for subfoveal leaks in central serous chorioretinopathy

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    Ambiya V

    2016-08-01

    Full Text Available Vikas Ambiya, Abhilash Goud, Annie Mathai, Padmaja Kumari Rani, Jay Chhablani Srimati Kanuri Santhamma Retina Vitreous Center, Kallam Anji Reddy Campus, L. V. Prasad Eye Institute, Hyderabad, India Purpose: To evaluate the role of navigated yellow microsecond laser in treating subfoveal leaks in nonresolving central serous chorioretinopathy (CSC. Methods: This prospective study included ten eyes of ten consecutive patients with nonresolving CSC with subfoveal leaks. All eyes were treated with 577 nm navigated yellow microsecond laser (5% duty cycle. Key inclusion criteria include a vision loss for a duration of minimum 3 months duration due to focal subfoveal leak on fluorescein angiography. Key exclusion criteria include prior treatment for CSC and any signs of chronic CSC. Comprehensive examination, in addition to low-contrast visual acuity assessment, microperimetry, autofluorescence, spectral domain optical coherence tomography, and fundus fluorescein angiography, was done at baseline, 1, 3, and 6 months after treatment. Rescue laser was performed as per predefined criteria at 3 months. Results: The average best-corrected visual acuity improved from 73.3±16.1 letters to 75.8±14.0 (P=0.69 at 3 months and 76.9±13.0 (P=0.59 at 6 months, but was not statistically significant. Low-contrast visual acuity assessment (logMAR improved from 0.41±0.32 to 0.35±0.42 (P=0.50 at 3 months and 0.28±0.33 (P=0.18 at 6 months. Average retinal sensitivity significantly improved from baseline 18.93±7.19 dB to 22.49±6.67 dB (P=0.01 at 3 months and 21.46±8.47 dB (P=0.04 at 6 months. Rescue laser was required only in one eye at 3 months; however, laser was required in three eyes at 6 months. Conclusion: Microsecond laser is a safe and effective modality for treating cases of nonresolving CSC with subfoveal leaks. Keywords: CSC, central serous chorioretinopathy, Navilas®, navigated laser, microsecond yellow laser

  8. Ten-year outcome including patterns of failure and toxicity for adjuvant whole abdominopelvic irradiation in high-risk and poor histologic feature patients with endometrial carcinoma

    International Nuclear Information System (INIS)

    Stewart, Kimberly D.; Martinez, Alvaro A.; Weiner, Sheldon; Podratz, Karl; Stromberg, Jannifer S.; Schray, Mark; Mitchell, Christina; Sherman, Alfred; Chen, Peter; Brabbins, Donald A.

    2002-01-01

    Purpose: To evaluate the long-term results of treatment using adjuvant whole abdominal irradiation (WAPI) with a pelvic/vaginal boost in patients with Stage I-III endometrial carcinoma at high risk of intra-abdominopelvic recurrence, including clear cell (CC) and serous-papillary (SP) histologic features. Methods and Materials: In a prospective nonrandomized trial, 119 patients were treated with adjuvant WAPI between November 1981 and April 2000. All patients were analyzed, including those who did not complete therapy. The mean age at diagnosis was 66 years (range 39-88). Thirty-eight patients (32%) had 1989 FIGO Stage I-II disease and 81 (68%) had Stage III. The pathologic features included the following: 64 (54%) with deep myometrial invasion, 48 (40%) with positive peritoneal cytologic findings, 69 (58%) with high-grade lesions, 21 (18%) with positive pelvic/para-aortic lymph nodes, and 44 (37%) with SP or CC histologic findings. Results: The mean follow-up was 5.8 years (range 0.2-14.7). For the entire group, the 5- and 10-year cause-specific survival (CSS) rate was 75% and 69% and the disease-free survival (DFS) rate was 58% and 48%, respectively. When stratified by histologic features, the 5- and 10-year CSS rate for adenocarcinoma was 76% and 71%, and for serous papillary/CC subtypes, it was 74% and 63%, respectively (p=0.917). The 5- and 10-year DFS rate for adenocarcinoma was 60% and 50% and was 54% and 37% serous papillary/CC subtypes, respectively (p=0.498). For surgical Stage I-II, the 5-year CSS rate was 82% for adenocarcinoma and 87% for SP/CC features (p=0.480). For Stage III, it was 75% and 57%, respectively (p=0.129). Thirty-seven patients had a relapse, with the first site of failure the abdomen/pelvis in 14 (38%), lung in 8 (22%), extraabdominal lymph nodes in 7 (19%), vagina in 6 (16%), and other in 2 (5%). When stratified by histologic variant, 32% of patients with adenocarcinoma and 30% with the SP/CC subtype developed recurrent disease. Most

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

    Science.gov (United States)

    2013-10-01

    Acknowledgements The authors wish to thank Drs Scott Tanner, Olga Ornatsky, Dmitry Bandura , Mitch Winnik and Mark Nitz for their critical reading of this...Quality assurance for polychromatic flow cytometry using a suite of calibration beads. Nat Protoc 2012, 7:2067-2079. 23. Baranov VI, Quinn Z, Bandura ... Bandura DR, Tanner SD, Dick J: Multiple cellular antigen detection by ICP-MS. J Immunol Methods 2006, 308:68-76. 25. Ornatsky OI, Kinach R, Bandura DR

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

    Science.gov (United States)

    2014-10-01

    Bendall SC, Sung P, Nolan GP, Arvin AM. Single-cell mass cytometry analysis of human tonsil T cell remodeling by varicella zoster virus. Cell Rep...Perspectives on Flow Cytometry 2013, September 20, 2013, Mass Cytometry and Cell Cycle, Mexico City, Mexico (by Web Conference) Nolan: Nuclear

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

    Science.gov (United States)

    2015-10-01

    about more informed changes to treatment modalities. To accomplish this vision with HG-SOC, we are using a single cell technology , mass cytometry... extracted from the composite MST. Clusters are represented as bubbles, the size of which corresponds to the number of cells in the cluster. The level of...Fantl WJ, Nolan GP. Transient partial permeabilization with saponin enables cellular barcoding prior to surface marker staining. Cytometry A. 2014 Dec;85

  12. Diagnostic value of p53 and M67 immunostaining for distinguishing benign from malignant serous effusions

    International Nuclear Information System (INIS)

    Hafez, N.H.; Tahoun, N.S.

    2011-01-01

    The differentiation of benign mesothelial cells from malignant tumor cells, primary, or metastatic, in serous effusions based on cytomorphologic features alone can be problematic. Purpose: This study was conducted to evaluate the utility of p53 and ki67 imrminocytochemical markers in differentiating benign from malignant tumor cells in serous effusions. Patients and methods: Archival Papanicolaou-stained smears of 91 pleura and peritoneal effusions were retrieved from Cytology Unit, Pathology Department, NCI, Cairo University between 2008 and 2010. Forty-one cases were positive for malignant cells and 50 cases were benign based on cytomorphologic features. Cases having doubt were excluded from the study. The slides were de stained and subjected to immunocytochemical staining for p53 and ki67. Histologic sections of colonic carcinoma and tonsillar tissue were used as positive control for p53 and ki67, respectively. Smears having > 5% positively stained nuclei for p53 were taken as positive and labeling index 10% of ki67 was considered positive. Frequencies of the individual immunocytochemical stains; p53 and ki67, in benign and malignant effusion as well as the combination of both stains were calculated. Results: p53 immunostaining showed nuclear positivity in 31 out of 41 malignant effusions (75.6%) and in 3 out of 50 benign effusions (6%), p < 0.005. p53 had 75.6% sensitivity, 94% specificity, 91.2% PPV, and 82.5% NPV. ki67 immunostaining was positive in 30 out of 41 malignant effusions (73.2%) and in 17 out of 50 benign effusions (34%), p < 0.05. ki67 had 73.2% sensitivity, 66% specificity, 63.8% PPV, and 75% NPV. Cases were then analyzed for combined immuno profile of p3 and ki67. Among the 24 cases that coexpressed both antigens, 22 cases (91.7%) were malignant. Thirty two out of 34 cases (94.1%) that showed negative results for both antigens were benign. For the cases that showed p53 immunostaining only, 9 out of 10 cases (90%) were malignant. Fifteen out of

  13. Treatment of juxtafoveal central serous chorioretinopathy by compound anisodine injection

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    Jian-Feng Xu

    2014-04-01

    Full Text Available AIM: To investigate the efficiency and security of compound anisodine injection in the treatment of juxtafoveal central serous chorioretinopathy(CSC. METHODS: Sixty patients(60 eyeswho were diagnosed of juxtafoveal CSC were assigned randomly into 2 groups: 32 cases(32 eyes, therapeutic groupwere injected subcutaneously compound anisodine injection for 2mL q.d around superficial temporal arteries in the affected eyes; 28 cases(28 eyes, control groupreceived only traditional oral medication. Both groups received therapy for 2 to 4 courses of treatment. The main observations were the best corrected visual acuity(BCVA, subjective symptom, visual field, average light sensitivity and optical coherent topography(OCT.RESULTS: There was no significant difference between the therapeutic group and the control group before treatment(P>0.05, but all the outcome measures at 1, 3mo in the treatment group were significantly improved as compared with control group(PP>0.05. No severe adverse reaction was noted except mild ones such as temporary dry mouth, dizziness and palpitation in a few cases.CONCLUSION: Compound anisodine injection has remarkable effects in the treatment of juxtafoveal CSC. It can shorten the course, improved the visual function and decreased the recurrence rate of CSC.

  14. MRI appearances of pure epithelial papillary serous borderline ovarian tumours

    International Nuclear Information System (INIS)

    Naqvi, J.; Nagaraju, E.; Ahmad, S.

    2015-01-01

    Borderline epithelial ovarian tumours (BOT) represent 15–20% of all non-benign ovarian epithelial neoplasms. Compared to malignant ovarian tumours, they usually present at a younger age and carry a far superior prognosis. Fertility-conserving surgery is an important treatment option for patients with BOT. Ultrasound and CT are both widely available and play roles in the initial investigation and staging of BOT, respectively. However, lack of soft-tissue contrast limits their ability to characterize BOT. MRI can facilitate recognition of pure epithelial serous BOT (SBOT), including the cystic papillary and surface papillary subtypes. An abundance of hyperintense papillary projections with low signal internal branching and ovarian stroma preservation with a hypointense ovarian capsular margin on T2-weighted imaging are features strongly suggestive of SBOT. In this review we will discuss the general morphological features of SBOT, the benefits and drawbacks of ultrasound and CT in the initial work-up, and the principal MRI features enabling recognition of surface papillary and cystic papillary SBOT

  15. Fundus Autofluorescence and Spectral Domain OCT in Central Serous Chorioretinopathy

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    Luiz Roisman

    2011-01-01

    Full Text Available Background. To describe the standard autofluorescence (FAF, the near infrared autofluorescence (NIA and optical coherence tomography (OCT patterns in central serous chorioretinopathy, correlating them with fluorescein angiography. Methods. Cross-sectional observational study, in which patients with at least seven months of CSC underwent ophthalmologic examination, fundus photography, FAF, NIA, fluorescein angiography (FA, and spectral-domain OCT. Results. Seventeen eyes of thirteen patients were included. The presentation features were a mottled hyperFAF in the detached area and areas with pigment mottling. NIA images showed areas of hyperNIA similar to FAF and localized areas of hypoNIA, which correlated with the points of leakage in the FA. OCT showed pigment epithelium detachment at the location of these hypoNIA spots. Discussion. FAF showed increased presence of fluorophores in the area of retinal detachment, which is believed to appear secondary to lipofuscin accumulation in the RPE or the presence of debris in the subretinal fluid. NIA has been related to the choroidal melanin content and there were areas of both increased and decreased NIA, which could be explained by damage ahead the retina, basically RPE and choroid. These findings, along with the PEDs found in the areas of hypoNIA, support the notion of a primary choroidal disease in CSC.

  16. Flat choroidal melanoma masquerading as central serous chorioretinopathy

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    Timothy Patrick Higgins

    2016-01-01

    Full Text Available There are several mimickers of choroidal melanoma. We report a patient with recent family stress who developed blurred vision to 20/50 OD and was found to have unilateral central serous chorioretinopathy and a coincidental choroidal nevus. After 1 year without resolution of the subretinal fluid, the patient was referred for our opinion. On examination, visual acuity was 20/50 in the right eye and 20/20 in the left eye. The left eye was normal. Evaluation of the right eye showed a small, pigmented submacular choroidal lesion measuring 4 mm Χ 3 mm. Ultrasonography documented an isoechoic mass measuring 1.71 mm in thickness. Optical coherence tomography showed subretinal fluid with shaggy photoreceptors and hyper-reflective material within the subretinal fluid, likely indicative of lipofuscin within macrophages. Autofluorescence revealed orange pigment overlying the lesion. These features were strongly suggestive of small choroidal melanoma with five risk factors for tumor growth. Treatment with Iodine-125 plaque brachytherapy was performed on the patient. The readers should keep in mind that choroidal melanoma can manifest as a tiny choroidal mass with related multimodal imaging features of subretinal fluid and orange pigment.

  17. The relationship between the percentage of lung shunting on Tc-99m macroaggregated albumin (Tc-99m MAA scan and the grade of hepatocellular carcinoma vascularity

    Directory of Open Access Journals (Sweden)

    Rania Refaat

    2014-06-01

    Conclusion: Tc-99m MAA scan is fundamental prior to Y-90 microsphere SIRT as it minimizes the risk of post-radioembolization complications, hence, enhancing the safety of Y-90 microsphere subsequent administration. Moreover, the percentage of lung shunting varies considerably among patients with HCC relying on the grade of tumor vascularity.

  18. Expression of the glioma-associated oncogene homolog 1 (gli1 in advanced serous ovarian cancer is associated with unfavorable overall survival.

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    Alessandra Ciucci

    Full Text Available Recent evidence links aberrant activation of Hedgehog (Hh signaling with the pathogenesis of several cancers including medulloblastoma, glioblastoma, melanoma as well as pancreas, colorectal, and prostate carcinomas. Here we investigated the role of the transcription factor Gli1 in ovarian cancer. To this end, the expression profile of Gli1 was examined in normal ovaries, ovarian tumors, and ovarian cancer cell lines, and the in vitro effects of a specific Hh-pathway blocker, KAAD-cyclopamine, or a specific Gli1 inhibitor (GANT58 on cell proliferation and on Hh target gene expression were also assessed. Results obtained showed that epithelial cells in ovarian cancer tissue express significantly higher levels of nuclear Gli1 than in normal ovarian tissue, where the protein was almost undetectable. In addition, multivariate analysis showed that nuclear Gli1 was independently associated to poor survival in advanced serous ovarian cancer patients (HR = 2.2, 95%CI 1.0-5.1, p = 0.04. In vitro experiments demonstrated Gli1 expression in the three ovarian carcinoma cell lines tested, A2780, SKOV-3 and OVCAR-3. Remarkably, although KAAD-cyclopamine led to decreased cell proliferation, this treatment did not inhibit hedgehog target gene expression in any of the three ovarian cancer cell lines, suggesting that the inhibition of cell proliferation was a nonspecific or toxic effect. In line with these data, no differences on cell proliferation were observed when cell lines were treated with GANT58. Overall, our clinical data support the role of Gli1 as a prognostic marker in advanced serous ovarian cancer and as a possible therapeutic target in this disease. However, our in vitro findings draw attention to the need for selection of appropriate experimental models that accurately represent human tumor for testing future therapies involving Hh pathway inhibitors.

  19. Atypical vitelliform macular dystrophy misdiagnosed as chronic central serous chorioretinopathy: case reports

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    Lee Young

    2012-07-01

    Full Text Available Abstract Background To report two cases of atypical vitelliform macular dystrophy misdiagnosed as chronic central serous chorioretinopathy. Case presentation Two patients with incidentally discovered abnormalities of the retina without specific symptoms were referred to our hospital for consultation. Bilateral macula atrophic lesions were observed and optical coherence tomography revealed serous retinal detachment in the macula. Fluorescein angiography showed multiple leakages around the central hypofluorescent area and indocyanine green angiography showed partially dilated choroidal vessels. Fundus autofluorescence (FAF showed a decreasing pattern of autofluorescence in the subretinal fluid area, and increasing autofluorescence at the border of the serous retinal detachment. Both patients were diagnosed with chronic central serous chorioretinopathy. Photodynamic therapy and intravitreal bevacizumab injection were administered for engorged choroidal vessels during follow-up, but neither patient showed improvement in symptoms or ophthalmologic findings. Based on re-evaluation by fundus photography, optical coherence tomography, fluorescein angiography, and comparison of the results of FAF with the first visit, vitelliform macular dystrophy was suspected and a definite diagnosis was made by electrooculography and genetic testing. Conclusion In patients with continuous serous retinal detachment without response to photodynamic therapy or intravitreal bevacizumab injection, careful fundus exam and FAF can be used to diagnose atypical vitelliform macular dystrophy.

  20. Hypoxia-Activated Alkylating Agents in BRCA1-Mutant Ovarian Serous Carcinoma.

    Science.gov (United States)

    Conroy, Michael; Borad, Mitesh J; Bryce, Alan H

    2017-07-26

    Breast cancer 1 antigen (BRCA 1) and breast cancer 2 antigen (BRCA2) genes play a significant role in deoxyribonucleic acid (DNA) repair by means of interstrand crosslink repair, and deleterious germline mutations of these are responsible for most hereditary breast and ovarian cancers. Therapeutic strategies which specifically target interstrand crosslink repair can therefore be helpful in patients with harmful mutations. We describe two patients with advanced ovarian cancer and deleterious BRCA1 mutations who were treated with TH-302, a hypoxia-activated alkylating agent.

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

    Science.gov (United States)

    2006-08-01

    Trope§, Ben Davidson§, and Tian-Li Wang*† *Departments of Pathology, Gynecology, and Oncology, ‡Department of Biostatistics , The Johns Hopkins University...Medicine and Dentistry of New Jersey, Piscataway, NJ) was used in the immunohistochemistry study. Immunohistochemistry was performed by standard...Eksir, 4 Daniel Egger, 2 James Geyer, 4 Brad H. Nelson, 5 Brad Stone, 6 Herbert A. Fritsche, 7 and Richard B.S. Roden 8 1Department of Biostatistics and

  2. Primary peritoneal serous papillary carcinoma (PSPC) involving ovary and colon: Management and Treatment

    OpenAIRE

    Leanza V; Coco L; Leanza G; Scilletta B; Zanchì G; Vecchio R; Zarbo G

    2013-01-01

    We present a case report of a 47-year-old woman who was admitted to our University-Hospital following diagnosis of pelvic mass. Abdominal examination revealed a tender, palpable mass on the right iliac region. At the gynecological examination uterus was regular in size. On the left side of the uterus a mass of 9 cm was observed; its surface was irregular and no mobility was found. Abdominal CT and NMR revealed massive ascites, omental cake and increased volume of both ovaries. Patient underwe...

  3. Expression of CA125 in Tissue and Serum of Uterine Serous Carcinoma Patients

    Directory of Open Access Journals (Sweden)

    Joseph Menczer

    2015-09-01

    Conclusion: The higher proportion of USC patients with positive CA125 immunohistochemical tissue staining than with elevated serum CA125 levels indicates the presence of some mechanism that prevents the access of CA125 into the circulation. [J Interdiscipl Histopathol 2015; 3(3.000: 102-104

  4. 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...surface epithelium. We tested muliplex detection of antibodies to candidate ovarian TAAs and statistical modeling for discrimination of sera of ovarian...cancer patients and controls. The best model generated an AUC of 0.86 (0.78-0.90) for discrimination of sera of EOC patients and healthy patients using

  5. Assessment of Myometrial Invasion in Premenopausal Grade 1 Endometrial Carcinoma: Is Magnetic Resonance Imaging a Reliable Tool in Selecting Patients for Fertility-Preserving Therapy?

    Science.gov (United States)

    Sakane, Makoto; Hori, Masatoshi; Onishi, Hiromitsu; Tsuboyama, Takahiro; Ota, Takashi; Tatsumi, Mitsuaki; Ueda, Yutaka; Kimura, Toshihiro; Kimura, Tadashi; Tomiyama, Noriyuki

    The aim of this study was to evaluate the diagnostic ability of magnetic resonance imaging (MRI) in premenopausal women with G1 endometrial carcinoma. Twenty-six patients underwent T2W, diffusion weighted, and dynamic contrast-enhanced 3-T MRI. The degree of myometrial invasion was pathologically classified into no invasion, shallow (3 mm or less), and more. Two radiologists assessed myometrial invasion on MRI. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values, AUC, and interobserver agreement were analyzed. For assessing myometrial invasion, mean accuracy, sensitivity, specificity, positive predictive values, negative predictive values, and AUC, respectively, were as follows: 63%, 42%, 85%, 79%, 47%, and 0.75. Mean interobserver agreement was fair (k = 0.36). Shallow invasions were underestimated as no invasion on MRI in all 6 cases. Magnetic resonance imaging produced false-negative result on half of patients. The misjudgments tended to happen in patients with shallow invasion.

  6. Primary peritoneal anaplastic giant cell carcinoma: case report of an unusual and highly malignant müllerian neoplasm.

    Science.gov (United States)

    Lu, Xian; Zhang, Cunxian; Liu, Fang; Sung, C James; Steinhoff, Margaret M; Lawrence, W Dwayne

    2008-01-01

    Virtually all primary peritoneal carcinomas (PPCs) are of serous papillary type. We report an unusual histologic type of PPC composed of anaplastic giant cells, which exhibited an aggressive clinical course. A 72-year-old woman presented with lower abdominal pain. Computed tomography showed a diffuse omental thickening. The patient underwent an exploratory laparotomy with omentectomy, total hysterectomy, bilateral salpingo-oophorectomy, and appendectomy. Pathologic examination revealed extensive omental replacement by tumor but only superficial surface cortical involvement of both ovaries, a disease distribution consistent with a typical müllerian-derived PPC. However, this neoplasm was composed of diffuse anaplastic tumor giant cells, rather than serous carcinoma, which is the usual histologic type encountered in PPC. The patient died within 1 month after surgery. We report this unusual histologic variant of PPC to raise awareness that anaplastic giant cell carcinoma may arise in the pelvic peritoneum as a primary tumor.

  7. The utility of serum N-ERC/mesothelin as a biomarker of ovarian carcinoma.

    Science.gov (United States)

    Saeki, Harumi; Hashizume, Akane; Izumi, Hiroshi; Suzuki, Fujihiko; Ishi, Kazuhisa; Nojima, Michio; Maeda, Masahiro; Hino, Okio

    2012-10-01

    Ovarian carcinoma has been difficult to diagnose at an early stage. Recently, it has been recognized that the measurement of blood N-ERC/mesothelin levels aids early detection in and postoperative therapeutic monitoring of patients with mesothelioma, who have been exposed to asbestos. ERC/mesothelin has also been reported to be expressed in ovarian carcinoma. We determined serum N-ERC/mesothelin levels in patients with ovarian carcinoma using an enzyme-linked immunosorbent assay (ELISA). In addition, we immunohistochemically evaluated surgically resected specimens for C-ERC/mesothelin expression. As a result, of the 32 patients with ovarian tumors (18 carcinoma, 2 borderline tumors), one patient with serous adenocarcinoma showed increased N-ERC/ mesothelin levels. Immunohistochemically, of the 20 ovarian tumor (carcinoma and borderline tumor) specimens evaluated for serum N-ERC/mesothelin, 9 (45.0%) were positive for C-ERC/mesothelin. The C-ERC/mesothelin-positive specimens were found to be serous and clear cell adenocarcinomas. If serum N-ERC/mesothelin, which is considered useful for early detection in and therapeutic monitoring of patients with mesothelioma, may also be used for ovarian carcinoma monitoring, it may be a valuable serum tumor marker for the early detection of ovarian carcinoma.

  8. 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.

  9. 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.

  10. 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.

  11. A case of a temporal bone meningioma presenting as a serous otitis media

    International Nuclear Information System (INIS)

    Nicolay, Simon; De Foer, Bert; Bernaerts, Anja; Van Dinther, Joost; Parizel, Paul M

    2014-01-01

    We report the imaging features of a case of a temporal bone meningioma extending into the middle ear cavity and clinically presenting as a serous otitis media. Temporal bone meningioma extending in the mastoid or the middle ear cavity, however, is very rare. In case of unexplained or therapy-resistant serous otitis media and a nasopharyngeal tumor being ruled out, a temporal bone computed tomography (CT) should be performed. If CT findings are suggestive of a temporal bone meningioma, a magnetic resonance imaging (MRI) examination with gadolinium will confirm diagnosis and show the exact extension of the lesion

  12. 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.

  13. Chronic Central Serous Chorioretinopathy in a Patient with Pigment Dispersion Syndrome: A Possible Correlation.

    Science.gov (United States)

    Kourkoutas, Dimitrios; Tsakonas, George; Karamaounas, Aristotelis; Karamaounas, Nikolaos

    2017-01-01

    Chronic central serous chorioretinopathy (CSCR) is a progressive chorioretinopathy with widespread atrophic RPE abnormalities and serous retinal detachments (SRDs) present for 6 months or longer. We report a case of CSCR in a 38-year-old patient with Pigment Dispersion Syndrome (PDS). In the presented case of CSCR, the chronic course of the disease may in part be associated with an underlying generalized degenerative dysfunction of the pigmented cells of the eye on grounds of PDS. We suggest that a chronic course of disease may be suspected in the setting of CSCR with concurrent RPE pathology, such as what is found in PDS.

  14. Chronic Central Serous Chorioretinopathy in a Patient with Pigment Dispersion Syndrome: A Possible Correlation

    Directory of Open Access Journals (Sweden)

    Dimitrios Kourkoutas

    2017-01-01

    Full Text Available Chronic central serous chorioretinopathy (CSCR is a progressive chorioretinopathy with widespread atrophic RPE abnormalities and serous retinal detachments (SRDs present for 6 months or longer. We report a case of CSCR in a 38-year-old patient with Pigment Dispersion Syndrome (PDS. In the presented case of CSCR, the chronic course of the disease may in part be associated with an underlying generalized degenerative dysfunction of the pigmented cells of the eye on grounds of PDS. We suggest that a chronic course of disease may be suspected in the setting of CSCR with concurrent RPE pathology, such as what is found in PDS.

  15. Interventions for central serous chorioretinopathy: a network meta-analysis

    Science.gov (United States)

    Salehi, Mahsa; Wenick, Adam S; Law, Hua Andrew; Evans, Jennifer R; Gehlbach, Peter

    2016-01-01

    Background Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy. Objectives To compare the relative effectiveness of interventions for central serous chorioretinopathy. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015. Selection criteria Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control. Data collection and analysis Two

  16. 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

  17. [Preneoplasias of ovarian carcinoma: biological and clinical aspects of different pathways of tumorigenesis].

    Science.gov (United States)

    Staebler, A

    2011-11-01

    Ovarian carcinomas consist of a heterogeneous group of malignant epithelial neoplasms with specific pathogenic mechanisms. This review provides a brief introduction to the different pathways of tumor progression and the associated molecular changes. However, the main focus will be on two areas with major paradigm shifting developments in recent years. Mutational analysis of ovarian clear cell carcinomas, endometrioid carcinomas and endometriotic lesions identified mutations in the ARID1A gene as common and early genetic changes in carcinomas with associated endometriosis and in atypical endometriosis itself. Extensive pathological work-up of the fallopian tubes of BRCA1/2 mutation carriers have demonstrated the existence of serous tubal intraepithelial carcinomas (STIC). Further studies showed that this lesion can also be found in 50-60% of patients with serous ovarian carcinomas without BRCA1/2 germline mutations. Pre-precursors which share the p53 mutations with STICs but proliferate very little are called p53-signatures and provide conclusive evidence that STICs develop in the fallopian tubes.

  18. 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

    PURPOSE: To report atypical central serous chorioretinopathy and choroidal thickening in a patient with heritable pulmonary arterial hypertension. METHODS: A 40-year-old man with heritable pulmonary arterial hypertension presented with blurred vision in his left eye and was followed up for 1 year...

  19. Serous otitis media and immunological reactions in the middle ear mucosa

    NARCIS (Netherlands)

    van der Baan, S.; Seldenrijk, C. A.; Henzen-Logmans, S. C.; Drexhage, H. A.

    1988-01-01

    An immunohistochemical study was performed on the middle ear mucosa of 21 children with chronic serous otitis media (SOM). In 86% of the patients a highly organized lymphatic tissue was found in the middle ear mucosa which can be regarded as part of the mucosa associated lymphoid tissue (MALT).

  20. 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...

  1. Expression profiling identifies genes involved in neoplastic transformation of serous ovarian cancer

    International Nuclear Information System (INIS)

    Merritt, Melissa A; Parsons, Peter G; Newton, Tanya R; Martyn, Adam C; Webb, Penelope M; Green, Adèle C; Papadimos, David J; Boyle, Glen M

    2009-01-01

    The malignant potential of serous ovarian tumors, the most common ovarian tumor subtype, varies from benign to low malignant potential (LMP) tumors to frankly invasive cancers. Given the uncertainty about the relationship between these different forms, we compared their patterns of gene expression. Expression profiling was carried out on samples of 7 benign, 7 LMP and 28 invasive (moderate and poorly differentiated) serous tumors and four whole normal ovaries using oligonucleotide microarrays representing over 21,000 genes. We identified 311 transcripts that distinguished invasive from benign tumors, and 20 transcripts that were significantly differentially expressed between invasive and LMP tumors at p < 0.01 (with multiple testing correction). Five genes that were differentially expressed between invasive and either benign or normal tissues were validated by real time PCR in an independent panel of 46 serous tumors (4 benign, 7 LMP, 35 invasive). Overexpression of SLPI and WNT7A and down-regulation of C6orf31, PDGFRA and GLTSCR2 were measured in invasive and LMP compared with benign and normal tissues. Over-expression of WNT7A in an ovarian cancer cell line led to increased migration and invasive capacity. These results highlight several genes that may play an important role across the spectrum of serous ovarian tumorigenesis

  2. 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

  3. 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

  4. 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.

  5. Failure to recognize preoperatively high-risk endometrial carcinoma is associated with a poor outcome.

    Science.gov (United States)

    Di Cello, Annalisa; Rania, Erika; Zuccalà, Valeria; Venturella, Roberta; Mocciaro, Rita; Zullo, Fulvio; Morelli, Michele

    2015-11-01

    To evaluate the misdiagnosis between endometrial biopsy and definitive surgical pathology and to assess whether the failure in recognizing preoperatively high-risk endometrial carcinoma (EC) can impact oncological outcomes. A retrospective study was conducted to evaluate patients with EC diagnosed by preoperative endometrial biopsy who subsequently underwent surgical staging between 2006 and 2013 at our institution. In patients with a surgical diagnosis of high-risk EC, histotype and grade change between the endometrial biopsy and surgical specimen (discordance diagnosis) were evaluated and correlated to survival outcomes. Cox's regression model for multivariable analysis was used to evaluate the effect of several variables (age, stage, discordance in diagnosis, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy) on the survival rate. Data from 447 patients were reviewed. Among 109 women with surgical diagnosis of high-risk EC, 35 (32.1%) were preoperatively misdiagnosed. Of these 35 women, 24 (68.6%) cases were upgraded to grade 3, and 11 (3.4%) were upgraded to serous or clear cell type in the definitive specimen. The 5-year overall survival (OS; 70.2 vs. 86.8%; p=0.029), disease-specific survival (DSS; 72.5 vs. 88.2%; p=0.039) and recurrence free survival (RFS; 62.6 vs. 82.5%; p=0.024) were significantly lower in the high-risk EC patients who were preoperatively undiagnosed in the endometrial biopsy compared with patients with an appropriate preoperative histological diagnosis. Controlling for age, stage, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy, multivariable analysis revealed that discordance in diagnosis was associated with poorer survival outcomes. Failure to recognize preoperatively high-risk ECs is associated with worse outcomes. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  6. 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

  7. 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.

  8. Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics.

    Science.gov (United States)

    Gamwell, Lisa F; Gambaro, Karen; Merziotis, Maria; Crane, Colleen; Arcand, Suzanna L; Bourada, Valerie; Davis, Christopher; Squire, Jeremy A; Huntsman, David G; Tonin, Patricia N; Vanderhyden, Barbara C

    2013-02-21

    The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer. The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested. BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. Spectral karyotyping revealed a largely normal diploid karyotype (in greater than 95% of cells) with a visibly shorter chromosome 20 contig. High density SNP array analysis also revealed few genomic anomalies in BIN-67 cells, which included loss of heterozygosity of an estimated 16.7 Mb interval on chromosome 20. SNP array analyses of four SCCOHT samples also indicated a low frequency of genomic anomalies in the majority of cases. Although resistant to platinum chemotherapeutic drugs, BIN-67 cell viability in vitro was reduced by > 75% after infection with oncolytic viruses. These results show that SCCOHT differs from high-grade serous carcinomas by exhibiting few chromosomal anomalies and lacking TP53 mutations. Although BIN-67 cells are

  9. Clinically-inspired automatic classification of ovarian carcinoma subtypes

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    Aicha BenTaieb

    2016-01-01

    Full Text Available Context: It has been shown that ovarian carcinoma subtypes are distinct pathologic entities with differing prognostic and therapeutic implications. Histotyping by pathologists has good reproducibility, but occasional cases are challenging and require immunohistochemistry and subspecialty consultation. Motivated by the need for more accurate and reproducible diagnoses and to facilitate pathologists′ workflow, we propose an automatic framework for ovarian carcinoma classification. Materials and Methods: Our method is inspired by pathologists′ workflow. We analyse imaged tissues at two magnification levels and extract clinically-inspired color, texture, and segmentation-based shape descriptors using image-processing methods. We propose a carefully designed machine learning technique composed of four modules: A dissimilarity matrix, dimensionality reduction, feature selection and a support vector machine classifier to separate the five ovarian carcinoma subtypes using the extracted features. Results: This paper presents the details of our implementation and its validation on a clinically derived dataset of eighty high-resolution histopathology images. The proposed system achieved a multiclass classification accuracy of 95.0% when classifying unseen tissues. Assessment of the classifier′s confusion (confusion matrix between the five different ovarian carcinoma subtypes agrees with clinician′s confusion and reflects the difficulty in diagnosing endometrioid and serous carcinomas. Conclusions: Our results from this first study highlight the difficulty of ovarian carcinoma diagnosis which originate from the intrinsic class-imbalance observed among subtypes and suggest that the automatic analysis of ovarian carcinoma subtypes could be valuable to clinician′s diagnostic procedure by providing a second opinion.

  10. Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma.

    Science.gov (United States)

    Chao, Angel; Lai, Chyong-Huey; Wang, Tzu-Hao; Jung, Shih-Ming; Lee, Yun-Shien; Chang, Wei-Yang; Yang, Lan-Yang; Ku, Fei-Chun; Huang, Huei-Jean; Chao, An-Shine; Wang, Chin-Jung; Chang, Ting-Chang; Wu, Ren-Chin

    2018-05-03

    We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.

  11. Maspin and MCM2 immunoprofiling in salivary gland carcinomas

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    Helmy Iman M

    2011-09-01

    Full Text Available Abstract Background The pathogenesis of salivary gland carcinomas is very complex and prognostic markers are difficult to find in these carcinomas of which the different subtypes have varying malignant potential. The study was conducted to examine the cellular distribution of maspin and MCM2 in salivary gland carcinomas and their value to predict lymph node metastasis. Materials and methods Fifty three paraffin blocks of different lesions (15 muco-epidermoid carcinoma, 14 adenoid cystic carcinoma, 3 epi-myoepithelial carcinoma, 5 salivary duct carcinoma, 5 malignant pleomorphic adenoma, 6 polymorphous low grade adenocarcinoma and 5 acinic cell carcinoma were prepared for immunohistochemical staining with maspin and MCM2 antibodies. ANOVA and Pearson correlation tests were used for the statistical analysis of the results. Results All salivary gland carcinomas express maspin and MCM2 with variable cellular localization. There was a significant difference in the expression of each antibody between mucoepidermoid carcinoma, adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. No association was found between examined markers and lymph node metastasis. Conclusions Salivary gland carcinomas express maspin and MCM2 with variable levels and cellular localization, consisting important markers of biological behavior in these tumors. The level of MCM2 expression can be used in the differential diagnosis of adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. Further study with large sample size is recommended to assess their value in prediction of lymph node metastasis.

  12. SAVED BY THE APPENDIX – A CASE OF SEROUS CYSTADENOCARCINOMA OF OVARY DETECTED ON ACCOUNT OF ACUTE APPENDICITIS

    OpenAIRE

    Avijeet; Naveen; Manohar; Gopal

    2013-01-01

    ABSTRACT: Ovarian cancer accounts for 5% of all cancers among women and causes more deaths than any other female genital tract cancer. The majority (85-90%) of ovarian cancers is epithelial in origin and arises typically in postmenopa usal patients. An ovarian serous cystadenocarcinoma forms the malignant end of ovari an serous tumours. It is the most common malignant ovarian tumor and is derived from glandul ar epithelium, in which cystic accumulations of ret...

  13. 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

  14. A case of endometrioid adenocarcinoma originating from the serous surface of the small intestine

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    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.

  15. 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

  16. Simultaneous serous cystadenoma of the pancreas and mucinous cystadenoma of the appendix.

    Science.gov (United States)

    Alrefaie, Waddah; Katz, Matthew H; Easter, David W; Yi, Eunhee S; Weidner, Noel; Savides, Thomas J; Moossa, Abdool R; Bouvet, Michael

    2004-03-01

    Serous cystadenoma of the pancreas and mucinous tumors of the vermiform appendix are rare. To our knowledge, the simultaneous occurrence of these two tumors has not been reported. Here, we report an adult female who presented with signs and symptoms of appendicitis. A preoperative CT scan confirmed the findings of appendicitis and also showed an incidental large mass in the head of the pancreas. The patient underwent uneventful appendectomy. Her pathology revealed an acutely inflamed appendix with a benign mucinous cystadenoma at the tip. Several months after her recovery, a Whipple procedure was performed. Pathologic examination showed a 5x5 cm serous cystadenoma of the head of the pancreas without evidence of malignancy. Two years later, the patient is alive and well without evidence of tumor recurrence. Cystadenomas of the pancreas and appendix are unusual and their simultaneous occurrence is a rare event.

  17. CLINICAL AND LIQUOR DIFFERENCES IN CASES OF SEROUS AND PURULENT MENINGITIS IN CHILDREN OF DIFFERENT AGE

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    E. M. Mazayeva

    2014-01-01

    Full Text Available The article presents features of clinical course and composition of cerebrospinal liquid in cases of purulent and serous meningitis depending on the age of the patients and the disease etiology. 40 children with bacterial purulent meningitis of meningococcal, hemophilic and unknown aetiology and 40 children with serous meningitis predominantly of enteroviral etiology were examined. The differences in duration and intensity of clinical symptoms, total protein concentration, and liquor cytosis were detected. The highest liquor indicators were revealed in the case of hemophilic meningitis in children of early age and in the case of meningococcal meningitis in children over seven years old. This fact can be explained by various pathogenic features of the causative agent and different compensatory reactions in children of different age. 

  18. Simultaneous Serous Cystadenoma of the Pancreas and Mucinous Cystadenoma of the Appendix

    OpenAIRE

    Alrefaie W; Katz MH; Easter DW; Yi ES; Weidner N; Savides TS; Moossa AR; Bouvet M

    2004-01-01

    CONTEXT: Serous cystadenoma of the pancreas and mucinous tumors of the vermiform appendix are rare. To our knowledge, the simultaneous occurrence of these two tumors has not been reported. CASE REPORT: Here, we report an adult female who presented with signs and symptoms of appendicitis. A preoperative CT scan confirmed the findings of appendicitis and also showed an incidental large mass in the head of the pancreas. The patient underwent uneventful appendectomy. Her pathology revealed an acu...

  19. 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....

  20. Calcification of peritoneum and peritoneal fluid perfusion malfunction in carcinomatosis of serous membranes of peritoneal cavity

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    Gantsev SK

    2016-09-01

    Full Text Available The article describes the peritoneal calcification in peritoneal carcinomatosis, as well as its possible role in the development of carcinomatosis within the frames of the authors’ alternative theory. The analysis of the "serous-lymph hatches" condition of the intact peritoneum and peritoneum in carcinomatosis was carried out. Also the elemental quantitative calcium determination in the intact peritoneum and the peritoneum in peritoneal carcinomatosis was carried out using the atomic emission spectrometry.

  1. Descolamento de retina seroso em paraganglioma: relato de caso Serous retinal detachment in paraganglioma: case report

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    Oscar Villas Boas

    2008-02-01

    Full Text Available Os autores descrevem um caso de uma paciente gestante com hipertensão arterial resistente ao tratamento e descolamento seroso bilateral de retina. Confirmou-se, pelo exame anátomo-patológico, ser um paraganglioma.The authors describe a case of a pregnant patient with arterial hypertension that resists to the treatment and retinal bilateral serous detachment. It was confirmed to be a paraganglioma by anatomicopathological examination.

  2. 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

  3. Chronic central serous choroidopathy with severe visual loss in hyperopic microphthalmic identical twins

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    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.

  4. 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.

    Science.gov (United States)

    Bazzazi, Nooshin; Ahmadpanah, Mohammad; Akbarzadeh, Siamak; Seif Rabiei, Mohammad Ali; Holsboer-Trachsler, Edith; Brand, Serge

    2015-01-01

    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. 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. 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. 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.

  5. Squamous Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

  6. Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    D. Ben Sellem

    2011-01-01

    Full Text Available Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii generate statistical models capable of classifying borderline tumors and (iii establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using 1H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate and mucinous (N-acetyl-lysine carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients.

  7. Recent Concepts of Ovarian Carcinogenesis: Type I and Type II

    Directory of Open Access Journals (Sweden)

    Masafumi Koshiyama

    2014-01-01

    Full Text Available Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may develop de novo from the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT. With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the “tubal peritoneal junction” (TPJ, undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells.

  8. Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR).

    Science.gov (United States)

    McCluggage, W Glenn; Judge, Meagan J; Clarke, Blaise A; Davidson, Ben; Gilks, C Blake; Hollema, Harry; Ledermann, Jonathan A; Matias-Guiu, Xavier; Mikami, Yoshiki; Stewart, Colin J R; Vang, Russell; Hirschowitz, Lynn

    2015-08-01

    A comprehensive pathological report is essential for optimal patient management, cancer staging and prognostication. In many countries, proforma reports are used but these vary in their content. The International Collaboration on Cancer Reporting (ICCR) is an alliance formed by the Royal College of Pathologists of Australasia, the Royal College of Pathologists of the United Kingdom, the College of American Pathologists, the Canadian Partnership Against Cancer and the European Society of Pathology, with the aim of developing an evidence-based reporting data set for each cancer site. This will reduce the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish and maintain standardised cancer reporting data sets. The resultant standardisation of cancer reporting will benefit not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets. We describe the development of a cancer data set by the ICCR expert panel for the reporting of primary ovarian, fallopian tube and peritoneal carcinoma and present the 'required' and 'recommended' elements to be included in the report with an explanatory commentary. This data set encompasses the recent International Federation of Obstetricians and Gynaecologists staging system for these neoplasms and the updated World Health Organisation Classification of Tumours of the Female Reproductive Organs. The data set also addresses issues about site assignment of the primary tumour in high-grade serous carcinomas and proposes a scoring system for the assessment of tumour response to neoadjuvant chemotherapy. The widespread implementation of this data set will facilitate consistent and accurate data collection, comparison of epidemiological and pathological parameters between different populations, facilitate research and hopefully will result in improved patient management.

  9. [Reproducibility of Fuhrman nuclear grade: advantages of a two-grade system].

    Science.gov (United States)

    Letourneux, Hervé; Lindner, Véronique; Lang, Hervé; Massfelder, Thierry; Meyer, Nicolas; Saussine, Christian; Jacqmin, Didier

    2006-06-01

    The Fuhrman nuclear grade is the reference histoprognostic grading system routinely used all over the world for renal cell carcinoma. Studies measuring the inter-observer and intra-observer concordance of Fuhrman grade show poor results in terms of reproducibility and repeatability. These variations are due to a certain degree of subjectivity of the pathologist in application of the definition of tumour grade, particularly nuclear grade. Elements able to account for this subjectivity in renal cell carcinoma are identified from a review of the literature. To improve the reliability of nuclear grade, the territory occupied by the highest grade must be specified and the grades should probably be combined. At the present time, regrouping of grade 1 and 2 tumours as low grade and grade 3 and 4 tumours as high grade would achieve better reproducibility, while preserving the prognostic: value for overall survival. The development of new treatment modalities and their use in adjuvant situations will imply the use of reliable histoprognostic factors to specify, indications.

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Serum protein profile at remission can accurately assess therapeutic outcomes and survival for serous ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Jinhua Wang

    Full Text Available BACKGROUND: Biomarkers play critical roles in early detection, diagnosis and monitoring of therapeutic outcome and recurrence of cancer. Previous biomarker research on ovarian cancer (OC has mostly focused on the discovery and validation of diagnostic biomarkers. The primary purpose of this study is to identify serum biomarkers for prognosis and therapeutic outcomes of ovarian cancer. EXPERIMENTAL DESIGN: Forty serum proteins were analyzed in 70 serum samples from healthy controls (HC and 101 serum samples from serous OC patients at three different disease phases: post diagnosis (PD, remission (RM and recurrence (RC. The utility of serum proteins as OC biomarkers was evaluated using a variety of statistical methods including survival analysis. RESULTS: Ten serum proteins (PDGF-AB/BB, PDGF-AA, CRP, sFas, CA125, SAA, sTNFRII, sIL-6R, IGFBP6 and MDC have individually good area-under-the-curve (AUC values (AUC = 0.69-0.86 and more than 10 three-marker combinations have excellent AUC values (0.91-0.93 in distinguishing active cancer samples (PD & RC from HC. The mean serum protein levels for RM samples are usually intermediate between HC and OC patients with active cancer (PD & RC. Most importantly, five proteins (sICAM1, RANTES, sgp130, sTNFR-II and sVCAM1 measured at remission can classify, individually and in combination, serous OC patients into two subsets with significantly different overall survival (best HR = 17, p<10(-3. CONCLUSION: We identified five serum proteins which, when measured at remission, can accurately predict the overall survival of serous OC patients, suggesting that they may be useful for monitoring the therapeutic outcomes for ovarian cancer.

  12. Rate of Appendiceal Metastasis with Non-Serous Epithelial Ovarian Cancer in Manitoba.

    Science.gov (United States)

    Altman, Alon D; Lefas, Georgia; Power, Laura; Lambert, Pascal; Lotocki, Robert; Dean, Erin; Nachtigal, Mark W

    2018-02-01

    This study sought to evaluate the rate of appendiceal involvement in non-serous mucinous and endometrioid-associated epithelial ovarian cancers. The Manitoba Cancer Registry and CancerCare database were used to find all women with non-serous epithelial ovarian, fallopian tube, or primary peritoneal cancer between 1995 and 2011. All patients with an appendectomy were then identified, and their final pathology findings were reviewed. Women who did not receive treatment or lacked follow-up were excluded. We identified 338 patients from 1995-2011 with no prior appendectomy. Of these, 16.6% received an appendectomy, and 22.8% were clinically evaluated. Most cases within this cohort were mucinous (62%) and stage 1 (63%). Four appendiceal metastases were identified (7.2%), and one half appeared clinically normal at the time of surgery (3.6%). Within the mucinous histologic type, 32.7% of patients received an appendectomy, with a metastatic rate of 5.7%. Of the 127 endometrioid cases, only 10 patients received an appendectomy, and 2 were found to have metastases. No metastases were found in the 85 patients in the clear cell cohort, only 5 of whom received an appendectomy. Routine appendectomy or clinical assessment of the appendix is valuable for all non-serous ovarian cancers. The rate of involvement for endometriosis-associated ovarian cancers may be significantly higher than expected, and further studies need to be conducted. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

  13. THE EFFECT OF PHOTOPIGMENT BLEACHING ON FUNDUS AUTOFLUORESCENCE IN ACUTE CENTRAL SEROUS CHORIORETINOPATHY.

    Science.gov (United States)

    Choi, Kwang-Eon; Yun, Cheolmin; Kim, Young-Ho; Kim, Seong-Woo; Oh, Jaeryung; Huh, Kuhl

    2017-03-01

    To evaluate the effect of photobleaching on fundus autofluorescence (FAF) images in acute central serous chorioretinopathy. We obtained prephotobleaching and postphotobleaching images using an Optomap 200Tx, and photobleaching was induced with a Heidelberg Retina Angiograph 2. Degrees of photobleaching were assessed as grayscale values in Optomap images. Concordances among the three kinds of images were analyzed. Hyper-AF lesions in prephotobleaching images were classified as Type 1 (changed to normal-AF after photobleaching) and Type 2 (unchanged after photobleaching). The FAF composite patterns of central serous chorioretinopathy lesions were classified as diffuse or mottled. Initial and final best-corrected visual acuity, central retinal thickness, and disease duration were compared according to fovea FAF type. Forty-one eyes of 41 patients were analyzed. The lesion brightness of postphotobleaching Optomap FAF showed greater concordance with Heidelberg Retina Angiograph 2 FAF (94.74%) than the prephotobleaching Optomap FAF (80.49%). Eyes with Type 1 fovea had greater initial and final best-corrected visual acuity (20/23 vs. 20/41, 20/21 vs. 20/32, P < 0.0001, P = 0.001, respectively) and shorter disease duration (19.68 ± 12.98 vs. 51.55 ± 44.98 days, P = 0.043) than those with Type 2 fovea. However, eyes with diffuse Type 2 fovea had only lower initial and final best-corrected visual acuity (20/23 vs. 20/45, 20/21 vs. 20/36, P < 0.0001, P < 0.0001, respectively) than those with Type 1 fovea. Understanding the photobleaching effect is necessary for the accurate interpretation of FAF images. Furthermore, comparing prephotobleaching and postphotobleaching FAF images may be helpful for estimation of lesion status in central serous chorioretinopathy.

  14. Cadherin 5 is Regulated by Corticosteroids and Associated with Central Serous Chorioretinopathy

    DEFF Research Database (Denmark)

    Schubert, Carl; Pryds, Anders; Zeng, Shemin

    2014-01-01

    Central serous chorioretinopathy (CSC) is characterized by leakage of fluid from the choroid into the subretinal space and, consequently, loss of central vision. The disease is triggered by endogenous and exogenous corticosteroid imbalance and psychosocial stress and is much more prevalent in men...... endothelium, was downregulated by corticosteroids which may increase permeability of choroidal vasculature, leading to fluid leakage under the retina. We found a significant association of four common CDH5 SNPs with CSC in male patients in both cohorts. Two common intronic variants, rs7499886:A>G and rs...

  15. Emotional profiles to the Rorschach test in subjects affected by Central Serous Chorioretinopathy: preliminary observations

    Directory of Open Access Journals (Sweden)

    Giovanna Gioffrè

    2013-05-01

    Full Text Available Psychological variables could be related to disorders of vision with particular interest of depressive feautures, but with little attention to dimensions such as stress and anxiety. Psychological stress associated with hyperactivation of the sympathetic autonomic nervous system, is considered the most important risk factor of a rare disorder of vision, the Central Serous Chorioretinopathy (CSC, whose etiology has not yet been clarified. This study to examine the psychological literature regarding to CSC and explore in a preliminary the projective methods of the Rorschach test, any correlations between personality variables and predisposition to CSC.

  16. Serous retinal detachment accompanied by MEWDS in a myopic patient with dome-shaped macula.

    Science.gov (United States)

    Shin, Min Kyu; Byon, Ik Soo; Park, Sung Who; Lee, Ji Eun

    2014-01-01

    Macular serous retinal detachment (MSRD) is a rare complication in highly myopic patients with an inferior staphyloma, tilted disc, or dome-shaped macula. Multiple evanescent white dot syndrome (MEWDS) presents with sudden visual loss and multiple yellowish dots that resolve spontaneously within several weeks. The authors report the development and spontaneous resolution of subretinal fluid accompanied by MEWDS in a myopic patient with a dome-shaped macula. Dysfunction of the retinal pigment epithelium due to MEWDS likely induced temporary MSRD in this patient. Copyright 2014, SLACK Incorporated.

  17. Hep par-1: a novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma

    International Nuclear Information System (INIS)

    Hanif, R.

    2014-01-01

    To evaluate the diagnostic utility of Hep par-1 in differentiating hepatocellular carcinoma from metastatic carcinoma taking histopathology as a gold standard. Study Design: Comparative cross-sectional study. Place and Duration of Study: Pathology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from April 2007 to February 2008. Methodology: Hep par-1 immunohistochemical stain was performed on 60 cases of liver carcinoma, 30 cases each of metastatic and hepatocellular carcinoma. Information regarding patient age, gender, sign and symptoms, radiographic findings, histological grade of tumour, and expression of Hep par-1 on hepatocellular and metastatic carcinoma were recorded on proforma sheet. Sensitivity, specificity, positive and negative predictive values, and accuracy of Hep par-1 were calculated using the formulas. Results: Hep par-1 expression was noted in 25 out of 30 cases of hepatocellular carcinoma (83%). Out of 30 cases of metastatic carcinoma, only one case expressed staining in < 5% tumour cells and remaining 29 cases showed no reactivity. The age of the patients with hepatocellular carcinoma ranged from 40 to 76 years with a median age of 60.5 years and 40 - 75 years for metastatic carcinomas with a median age of 57.5 years. Conclusion: Hep par-1 is a reliable immunohistochemical marker for cases of hepatocellular carcinoma (HCC). It can be used along with other markers in morphologically difficult cases when differential diagnosis lies between poorly differentiated HCC and metastatic carcinoma of liver. (author)

  18. Morphologic, Immunophenotypic, and Molecular Features of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Ramalingam, Preetha

    2016-02-01

    Epithelial ovarian cancer comprises a heterogeneous group of tumors. The four most common subtypes are serous, endometrioid, clear cell, and mucinous carcinoma. Less common are transitional cell tumors, including transitional cell carcinoma and malignant Brenner tumor. While in the past these subtypes were grouped together and designated as epithelial ovarian tumors, these tumor types are now known to be separate entities with distinct clinical and biologic behaviors. From a therapeutic standpoint, current regimens employ standard chemotherapy based on stage and grade rather than histotype. However, this landscape may change in the era of personalized therapy, given that most subtypes (with the exception of high-grade serous carcinoma) are relatively resistant to chemotherapy. It is now well-accepted that high-grade and low-grade serous carcinomas represent distinct entities rather than a spectrum of the same tumor type. While they are similar in that patients present with advanced-stage disease, their histologic and molecular features are entirely different. High-grade serous carcinoma is associated with TP53 mutations, whereas low-grade serous carcinomas are associated with BRAF and KRAS mutations. Endometrioid and clear cell carcinomas typically present as early-stage disease and are frequently associated with endometriosis. Mucinous carcinomas typically present as large unilateral masses and often show areas of mucinous cystadenoma and mucinous borderline tumor. It must be emphasized that primary mucinous carcinomas are uncommon tumors, and metastasis from other sites such as the appendix, colon, stomach, and pancreaticobiliary tract must always be considered in the differential diagnosis. Lastly, transitional cell tumors of the ovary, specifically malignant Brenner tumors, are quite uncommon. High-grade serous carcinoma often has a transitional cell pattern, and adequate sampling in most cases shows more typical areas of serous carcinoma. Immunohistochemical

  19. Prostate carcinomas

    International Nuclear Information System (INIS)

    Toledano, A.; Chauveinc, L.; Flam, T.; Thiounn, N.; Solignac, S.; Timbert, M.; Rosenwald, J.C.; Cosset, J.M.; Ammor, A.; Bonnetain, F.; Brenier, J.P.; Maingon, P.; Peignaux, K.; Truc, G.; Bosset, M.; Crevoisier, R. de; Tucker, S.; Dong, L.; Cheung, R.; Kuban, D.; Azria, D.; Llacer Moscardo, C.; Ailleres, N.; Allaw, A.; Serre, A.; Fenoglietto, P.; Hay, M.H.; Thezenas, S.; Dubois, J.B.; Pommier, P.; Perol, D.; Lagrange, J.L.; Richaud, P.; Brune, D.; Le Prise, E.; Azria, D.; Beckendorf, V.; Chabaud, S.; Carrie, C.; Bosset, M.; Bosset, J.F.; Maingon, P.; Ammor, A.; Crehangen, G.; Truc, G.; Peignaux, K.; Bonnetain, F.; Keros, L.; Bernier, V.; Aletti, P.; Wolf, D.; Marchesia, V.; Noel, A.; Artignan, X.; Fourneret, P.; Bacconier, M.; Shestaeva, O.; Pasquier, D.; Descotes, J.L.; Balosso, J.; Bolla, M.; Burette, R.; Corbusier, A.; Germeau, F.; Crevoisier, R. de; Dong, L.; Bonnen, M.; Cheung, R.; Tucker, S.; Kuban, D.; Crevoisier, R. de; Melancon, A.; Kuban, D.; Cheung, R.; Dong, L.; Peignaux, K.; Brenier, J.P.; Truc, G.; Bosset, M.; Ammor, A.; Barillot, I.; Maingon, P.; Molines, J.C.; Berland, E.; Cornulier, J. de; Coulet-Parpillon, A.; Cohard, C.; Picone, M.; Fourneret, P.; Artignan, X.; Daanen, V.; Gastaldo, J.; Bolla, M.; Collomb, D.; Dusserre, A.; Descotes, J.L.; Troccaz, J.; Giraud, J.Y.; Quero, L.; Hennequin, C.; Ravery, V.; Desgrandschamps, F.; Maylin, C.; Boccon-Gibod, L.; Salem, N.; Bladou, F.; Gravis, G.; Tallet, A.; Simonian, M.; Serment, G.; Salem, N.; Bladou, F.; Gravis, G.; Simonian, M.; Rosello, R.; Serment, G.

    2005-01-01

    Some short communications on the prostate carcinoma are given here. The impact of pelvic irradiation, conformation with intensity modulation, association of radiotherapy and chemotherapy reduction of side effects, imaging, doses escalation are such subjects studied and reported. (N.C.)

  20. Anaplastic carcinoma

    International Nuclear Information System (INIS)

    Parikh, D.M.; Agarwal, S.; Rao, R.S.

    1999-01-01

    Thyroid carcinoma (TC) is a slow growing tumor with an indolent course and has an excellent prognosis. However, a sharp contrast exists in the biological behavior of TC, which in its well-differentiated form is associated with long-term survival, but in its undifferentiated form is one of the most lethal neoplasms known. The anaplastic carcinoma (ANC) form has a fulminanat course with poor prognosis and almost invariably, a fatal outcome

  1. Basal Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  2. Merkel Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Merkel cell carcinoma Overview Merkel cell carcinoma: This rare skin ... hard patch (1) or firm bump (2). Merkel cell carcinoma: Overview What is Merkel cell carcinoma? Merkel ...

  3. Multifocal pancreatic serous cystadenoma with atypical cells and focal perineural invasion.

    Science.gov (United States)

    Kamei, K; Funabiki, T; Ochiai, M; Amano, H; Kasahara, M; Sakamoto, T

    1991-10-01

    A case of multifocal pancreatic serous cystadenoma with atypical cells is reported. The patient was a 72-yr-old female who complained of jaundice. The distal common bile duct was obstructed, and the proximal bile duct was remarkably dilated on cholangiography. The main portal vein was obstructed and collateral vessels had developed on portal angiography. Total pancreatectomy was performed. The resected specimen contained one tumor in the head of the pancreas, five in the body, and one in the tail. The tumors of the head and body were morphologically the same. Microscopically, both contained spongelike multilocular cysts on their cut surfaces. These cysts were covered with low cuboid epithelium containing clear cytoplasm and abundant glycogen. Neural invasion was also found. The tumor cells exhibited an increased N/C ratio, variable nuclear size, irregular nuclear margins, and coarse nuclear chromatin. These tumors had aneuploid nuclear DNA with a DNA index of 1.9 and a proliferation index of 0.28. We feel that it is necessary to reconsider the biological concept of serous cystadenoma.

  4. Is MRI a useful tool to distinguish between serous and mucinous borderline ovarian tumours?

    International Nuclear Information System (INIS)

    Bazot, M.; Haouy, D.; Daraï, E.; Cortez, A.; Dechoux-Vodovar, S.; Thomassin-Naggara, I.

    2013-01-01

    Aim: To analyse the morphological magnetic resonance imaging (MRI) features of borderline ovarian tumours (BOT) and to evaluate whether MRI can be used to distinguish serous from mucinous subtypes. Materials and methods: A retrospective study of 72 patients who underwent BOT resection was undertaken. MRI images were reviewed blindly by two radiologists to assess MRI features: size, tumour type, grouped and irregular thickened septa, number of septa, loculi of different signal intensity, vegetations, solid portion, signal intensity of vegetations, normal ovarian parenchyma, and pelvic ascites. Statistical analysis was performed using Mann–Whitney and Fisher's exact tests. Logistic regression analysis was used to assess the predictive value of the MRI findings for histological subtypes. Results: At histology, there were 33 serous BOT (SBOT) and 39 mucinous BOT (MBOT). Predictive MRI criteria for SBOT were bilaterality, predominantly solid tumour, and the presence of vegetations, especially exophytic or with a high T2 signal (p < 0.01), whereas predictive MRI criteria for MBOT were multilocularity, number of septa, loculi of different signal intensity, and grouped and irregular thickened septa (p < 0.01). Using multivariate analysis, vegetations were independently associated with SBOT [odds ratio (OR) = 29.5] and multilocularity with MBOT (OR = 3.9). Conclusion: Vegetations and multilocularity are two independent MRI features that can help to distinguish between SBOT and MBOT.

  5. [MANIFESTATIONS OF EPIDEMIC PROCESS AND TRANSMISSION ROUTES OF CAUSATIVE AGENT OF ENTEROVIRUS SEROUS MENINGITIS].

    Science.gov (United States)

    Sergevnin, V I; Tryasolobova, M A; Kudrevatykh, E V; Kuzovnikova, E Zh

    2015-01-01

    Study the manifestations of epidemic process and leading transmission routes of causative agents of enterovirus serous meningitis (SM) by results of laboratory studies and epidemiologic examination of epidemic nidi. During 2010 - 2014 a study for enterovirus was carried out in cerebrospinal fluid in 743 patients, hospitalized into medical organizations of Perm with primary diagnosis "serous meningitis", feces of 426 individuals, that had communicated with patients with SM of enterovirus etiology; 827 water samples from the distribution network, 295 water samples from open water and 57 washes from surface of vegetables and fruits. All the samples were studied in polymerase chain reaction, part--by a virological method. Epidemiologic examination of 350 epidemic nidi of SM was carried out. Enterovirus and (or) its RNA were detected in 62.0% of patients and 61.9% of individuals that had communicated with patients with enteroviris SM. ECHO 6 serotype enterovirus dominated among the causative agents. Maximum intensity of epidemic process of enterovirus SM, based on data from laboratory examination of patients, was detected in a group of organized pre-school and school age children during summer-autumn period. . Examination of epidemic nidi and laboratory control of environmental objects have shown that CV causative agent transmission factors are, in particular, unboiled water from decentralized sources (boreholes, wells, springs), water from open waters during bathing, as well as fresh vegetables, fruits, berries and meals produced from them. .

  6. Increase in Central Retinal Edema after Subthreshold Diode Micropulse Laser Treatment of Chronic Central Serous Chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Maciej Gawęcki

    2015-01-01

    Full Text Available Purpose. Subthreshold diode micropulse laser (SDM treatment is believed to be safe method of treating clinical entities involving retinal edema. We present a case of serous edematous reaction of the retina to SDM treatment. Methods. Case report. Results. A patient with chronic central serous chorioretinopathy (CSCR was treated with SDM Yellow multispot laser. Procedure had been preceded by careful titration of the laser power, which after achieving of the threshold parameter was decreased by 50%. The follow-up visit two days after treatment revealed significant central retinal edema and subretinal fluid. Fundus autofluorescence image showed thermal reaction from the RPE in the form of small spots of hyperfluorescence corresponding to the laser multispot pattern used for treatment. Retinal edema resolved after topical bromfenac and single intravitreal bevacizumab injection. Slight pigmentary reaction from the RPE persisted. Conclusion. In the treatment of CSCR, there is a need to significantly reduce threshold SDM power parameters or simply use very low power without titration.

  7. [Long-term follow-up after tympanostomy tube insertion in children with serous otitis media].

    Science.gov (United States)

    Fekete-Szabó, Gabriella; Kiss, Fekete; Rovó, László

    2015-11-15

    The authors report about the efficacy of inserted tympanostomy tube in children with serous otitis media. The aim of the authors was to assess the status of eardrum, the function of Eustachian tube and hearing level 10 years after the use of tympanostomy tube. Patients filled out a questionnaire and microscopic examination of tympanic membrane, tympanometry, Eustachian tube function examination, and audiometry tests were performed. In the period of 2003-2004, ventilation tube insertion was performed in 711 patients in the ENT Department of Pediatric Health Center of University of Szeged. In 349 patients adenotomy and tympanostomy tube insertion, in 18 cases tonsillectomy and grommet insertion and in 344 patients only typmanostomy tube insertion were performed. Due to objective difficulties (address change, no phone number) 453 patients were asked for control test and 312 persons accepted the invitation. Normal hearing level was found in 84.6% of patients and normal tympanometry result occurred in 82%. Tympanic ventilation disorder, perforation of tympanic membrane, sensorineural hearing loss and sensorineural hearing loss due to noise exposure were diagnosed. Application of tympanostomy tube is effective in the treatment of serous otitis media resulting from ventilation disorder. The authors draw attention to the importance of tympanometry examination to prevent the adhesive processes and cholesteatoma in chronic ventilation disorder of the middle ear.

  8. Cushing disease revealed by bilateral atypical central serous chorioretinopathy: case report.

    Science.gov (United States)

    Giovansili, Iama; Belange, Georeges; Affortit, Aude

    2013-01-01

    We report the case of a patient with Cushing disease revealed by bilateral central serous chorioretinopathy (CSCR). We present the clinical history, physical findings, laboratory results, and imaging studies of a 53-year-old Chinese woman with a Cushing disease revealed by bilateral CSCR. The association with CSCR and the pertinent literature are reviewed. A 53-year-old patient initially presented to the Department of Ophthalmology with a 4-week history of decreased vision in the left eye. Standard ophthalmologic examination and fluorescein angiography established the diagnosis of bilateral CSCR. Systemic clinical signs and biochemical analysis indicated hypercortisolism. Magnetic resonance imaging (MRI) of the pituitary gland showed a left-side lesion compatible with a microadenoma. The diagnosis of Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome secondary to a pituitary microadenoma was selected. Endoscopic endonasal transsphenoidal surgery was performed and the pituitary adenoma was successfully removed. The histology confirmed the presence of ACTH-immunopositive pituitary adenoma. Early postoperative morning cortisol levels indicated early remission. At 6 weeks postoperatively, the patient's morning cortisol remains undetectable, and serous retinal detachments had regressed. CSCR is an uncommon manifestation of endogenous Cushing syndrome. It can be the first presentation of hypercortisolism caused by Cushing disease. CSCR should be considered when assessing patients with Cushing syndrome complaining of visual disorders. On the other hand, it is useful in patients with an atypical form of CSCR to exclude Cushing's syndrome.

  9. Endometrioid carcinoma of the upper urinary tract

    Directory of Open Access Journals (Sweden)

    Kulkarni Jagdeesh

    2010-01-01

    Full Text Available Herein, we report a second case of endometrioid carcinoma of the upper urinary tract presenting 17 years after hysterectomy for high grade adenocarcinoma of ovary. A 51-year-old nullipara presented to us with a complaint of hematuria. After complete work up, she underwent right radical nephro-ureterectomy with bladder cuff excision. The histology showed endometrioid carcinoma of upper urinary tract without any evidence of endometriosis.

  10. 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

    Subtask 1: Submit documents for local IRB and Animal Ethics review. • Submission of institution approved animal protocols and related material for DoD’s...laboratories have submitted animal ethics protocols and received approval from their respective Animal Ethics Committees (Appendix B & Appendix C...targeted ES cells identified positive clones as indicated by the black arrows; (B) chimera mice identified successful germline transmission as

  11. Unusual manifestations of secondary urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Chaohui Lisa Zhao

    2016-03-01

    Full Text Available High-grade papillary urothelial carcinoma regularly invades the bladder wall, adjacent prostate, seminal vesicles, ureters, vagina, rectum, retroperitoneum, and regional lymph nodes. In advanced stages, it may disseminate to the liver, lungs, and bone marrow. On rare occasions, unusual metastatic foci like skin have been reported. The incidence of urothelial carcinoma has increased with associated rise in variants of urothelial carcinoma and unusual metastatic foci. It is imperative that urologists and pathologists are aware of the unusual variants and unusual metastatic locations to expedite the diagnostic process. Hereby we report an unusual case of secondary involvement of spinal nerve by conventional urothelial carcinoma. Also a second case of rhabdoid variant of urothelial carcinoma showing synchronous involvement of bladder and subcutaneous tissue of upper extremity is presented.

  12. Evolution and pathology of colorectal carcinoma

    International Nuclear Information System (INIS)

    Hermanek, P.

    1986-01-01

    Numerous clinical, epidemiological, histological and experimental observations favour the adenoma-carcinoma sequence. Metastases occur only after invasion of the submucosa. The elevated rate of synchronous lesions (carcinomas and adenomas) is emphasized. In the rule, lymphatic spread precedes distant metastasis. Typing and grading should be performed according to the rules of WHO. The present UICC staging system will be replaced by a new 4th edition 1987. Early carcinoma (limited to the submucosa) has an excellent prognosis and may be treated by limited procedures (polypectomy, local excision) in the most cases. The modern concept of histology- and stage-adapted cancer therapy requires the pre-, intra- and postoperative cooperation with the pathologist. (Author)

  13. Appendectomy in the surgical staging of ovarian carcinoma.

    Science.gov (United States)

    Beşe, T; Kösebay, D; Kaleli, S; Oz, A U; Demirkiran, F; Gezer, A

    1996-06-01

    Extensive debulking is accepted as the primary method of operative management for carcinoma of the ovary. However, there is no consensus regarding the role of appendectomy in primary surgical treatment. The aim of this study was to assess the role of appendectomy in the surgical staging and cytoreduction of ovarian carcinoma. The study was a retrospective review of 90 primary malignant ovarian carcinoma patients who had an appendectomy in addition to primary cytoreductive surgery. Out of 90 patients, 10 (11.1%) had metastasis to the appendix. The rate of metastasis to the appendix was 11.5% (9/78) in malignant epithelial ovarian carcinomas and 8.3% (1/12) in non-epithelial ovarian tumors. Of the patients with metastasis in the appendix, malignant epithelial ovarian tumors were identified in 90% (serous: 70%; clear cell: 20%), and non-epithelial malignant ovarian tumor were disclosed in 10% (granulosa cell carcinoma). There were no metastases to the appendix in the other histological types. Although metastasis to the appendix was not observed in early stage ovarian carcinomas, it was detected in 21.4% (9/42) of stage III and 50% (1/2) of stage IV. Macroscopic tumor metastasis in the abdomen was noted in all patients with metastasis to the appendix. Appendectomy for stage I and II patients was not beneficial and did not affect final staging. As a result, for the proper staging of ovarian carcinoma there is no advantage to the addition of routine appendectomy to primary cytoreductive surgery in early stage (stage I and II) malignant epithelial ovarian tumors. Appendectomy would contribute to the cytoreduction of advanced stage disease if it is macroscopically involved.

  14. Postoperative radiotherapy for merkel cell carcinoma

    International Nuclear Information System (INIS)

    Inoue, Kazuya; Asakawa, Isao; Katayama, Emiko; Kajitani, Chikae; Tamamoto, Tetsuro; Hasegawa, Masatoshi; Fukumoto, Takaya; Asada, Hideo

    2014-01-01

    Seven patients with Merkel cell carcinoma (MCC) who visited our department of radiation oncology from February 2005 to July 2011 received postoperative radiotherapy (50-60 Gy). All patients were alive without recurrence (median follow-up period: 47.6 (14.7-88.4) months). All of them had grade 2 dermatitis, and one grade 2 oral mucositis and three grade 2 lymphedema were observed. No adverse event grade 3 (CTCAE v4.0) or over was observed. In our hospital, clinical results of postoperative radiotherapy for MCC were fairly good, and adverse events were acceptable during the follow-up period. (author)

  15. Serous otitis media (S.O.M.). A bacteriological study of the ear canal and the middle ear

    NARCIS (Netherlands)

    Cabenda, S. I.; Peerbooms, P. G.; van Asselt, G. J.; Feenstra, L.; van der Baan, S.

    1988-01-01

    A bacteriological study of the middle-ear effusions and the ear canals in children with chronic serous otitis media (S.O.M.) was performed. Sixty-eight children (127 ears) were investigated. From this study it appeared that cleansing of the ear canal with 0.5% chlorhexidine in 70% ethanol for 30 s

  16. Pilot study of oral administration of a curcumin-phospholipid formulation for treatment of central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Mazzolani F

    2012-05-01

    Full Text Available Fabio MazzolaniPrivate Practice, Milan, ItalyBackground: The purpose of this open-label study was to investigate the effect of a curcumin-phospholipid (lecithin, Meriva® formulation (Norflo® tablet on visual acuity and retinal thickness in patients with acute or chronic central serous chorioretinopathy.Methods: Visual acuity was assessed by ophthalmologic evaluation, and optical coherence tomography was used to measure retinal thickness. Norflo tablets were administered twice a day to patients affected by central serous chorioretinopathy. The study included 18 eyes from 12 patients who completed a 6-month follow-up period. Visual acuity before and after Norflo treatment was the primary endpoint. The secondary endpoints were neuroretinal or pigment epithelial detachment, as measured by optical coherence tomography.Results: After 6 months of therapy, 0% of eyes showed reduction in visual acuity, 39% showed stabilization, and 61% showed improvement. The improvement was statistically significant (P = 0.08. After 6 months of therapy, 78% of eyes showed reduction of neuroretinal or retinal pigment epithelium detachment, 11% showed stabilization, and 11% showed an increase.Conclusion: Our results, albeit preliminary, show that curcumin administered as Norflo tablets is efficacious for the management of central serous chorioretinopathy, a relapsing eye disease, and suggest that bioavailable curcumin is worth considering as a therapeutic agent for the management of inflammatory and degenerative eye conditions, including those that activate the retinal microglia.Keywords: curcumin, central serous chorioretinopathy, retinal pigment epithelium detachment, Norflo®, Meriva®

  17. Somatic mutations in breast and serous ovarian cancer young patients : a systematic review and meta-analysis

    NARCIS (Netherlands)

    Encinas, Giselly; Maistro, Simone; Pasini, Fatima Solange; Hirata Katayama, Maria Lucia; Brentani, Maria Mitzi; de Bock, Geertruida Hendrika; Azevedo Koike Folgueira, Maria Aparecida

    2015-01-01

    Objective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC) or serous ovarian cancer (SOC). Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of

  18. Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Amankwah, Ernest K; Wang, Qinggang; Schildkraut, Joellen M

    2011-01-01

    Alterations in stromal tissue components can inhibit or promote epithelial tumorigenesis. Decorin (DCN) and lumican (LUM) show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We hypothesized that common variants in these genes associate with risk. Associations with sEOC among...

  19. Review of Topical Treatment of Upper Tract Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Kenneth G. Nepple

    2009-01-01

    Full Text Available A select group of patients with upper tract urothelial carcinoma may be appropriate candidates for minimally invasive management. Organ-preserving endoscopic procedures may be appropriate for patients with an inability to tolerate major surgery, solitary kidney, bilateral disease, poor renal function, small tumor burden, low-grade disease, or carcinoma in situ. We review the published literature on the use of topical treatment for upper tract urothelial carcinoma and provide our approach to treatment in the office setting.

  20. The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Jun-jun [Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011 (China); Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032 (China); Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011 (China); Wang, Yan [Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong' an Road, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong' an Road, Shanghai 200032 (China); Ding, Jing-xin; Jin, Hong-yan [Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011 (China); Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032 (China); Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011 (China); Yang, Gong, E-mail: yanggong@fudan.edu.cn [Cancer Institute, Fudan University Shanghai Cancer Center, 270 Dong' an Road, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong' an Road, Shanghai 200032 (China); Hua, Ke-qin, E-mail: huakeqin@126.com [Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011 (China); Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032 (China); Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, 413 Zhaozhou Road, Shanghai 200011 (China)

    2015-05-01

    HOX transcript antisense RNA (HOTAIR) is a well-known long non-coding RNA (lncRNA) whose dysregulation correlates with poor prognosis and malignant progression in many forms of cancer. Here, we investigate the expression pattern, clinical significance, and biological function of HOTAIR in serous ovarian cancer (SOC). Clinically, we found that HOTAIR levels were overexpressed in SOC tissues compared with normal controls and that HOTAIR overexpression was correlated with an advanced FIGO stage and a high histological grade. Multivariate analysis revealed that HOTAIR is an independent prognostic factor for predicting overall survival in SOC patients. We demonstrated that HOTAIR silencing inhibited A2780 and OVCA429 SOC cell proliferation in vitro and that the anti-proliferative effects of HOTAIR silencing also occurred in vivo. Further investigation into the mechanisms responsible for the growth inhibitory effects by HOTAIR silencing revealed that its knockdown resulted in the induction of cell cycle arrest and apoptosis through certain cell cycle-related and apoptosis-related proteins. Together, these results highlight a critical role of HOTAIR in SOC cell proliferation and contribute to a better understanding of the importance of dysregulated lncRNAs in SOC progression. - Highlights: • HOTAIR overexpression correlates with an aggressive tumour phenotype and a poor prognosis in SOC. • HOTAIR promotes SOC cell proliferation both in vitro and in vivo. • The proliferative role of HOTAIR is associated with regulation of the cell cycle and apoptosis.

  1. PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study, pre-operative recognition of high risk endometrial carcinoma: a multicentre prospective cohort study

    International Nuclear Information System (INIS)

    Visser, Nicole C. M.; Bulten, Johan; Wurff, Anneke A. M. van der; Boss, Erik A.; Bronkhorst, Carolien M.; Feijen, Harrie W. H.; Haartsen, Joke E.; Herk, Hilde A. D. M. van; Kievit, Ineke M. de; Klinkhamer, Paul J. J. M.; Pijlman, Brenda M.; Snijders, Marc P. M. L.; Vandenput, Ingrid; Vos, M. Caroline; Wit, Peter E. J. de; Poll-Franse, Lonneke V. van de; Massuger, Leon F.A.G.; Pijnenborg, Johanna M. A.

    2015-01-01

    Endometrial carcinoma is the most common gynaecologic malignancy in industrialised countries and the incidence is still rising. Primary treatment is based on preoperative risk classification and consists in most cases of hysterectomy with bilateral salpingo-oophorectomy. In patients with serous and clear cell histology a complete surgical staging is mandatory. However, in routine clinical practice final histology regularly does not correspond with the preoperative histological diagnosis. This results in both over and under treatment. The aim of this multicentre, prospective cohort study is to select a panel of prognostic biomarkers to improve preoperative diagnosis of endometrial carcinoma in order to identify those patients that need extended surgery and/or additional treatment. Additionally, we will determine whether incorporation of cervical cytology and comorbidity could improve this preoperative risk classification. All patients treated for endometrial carcinoma in the participating hospitals from September 2011 till December 2013 are included. Patient characteristics, as well as comorbidity are registered. Patients without preoperative histology, history of hysterectomy and/or endometrial carcinoma or no surgical treatment including hysterectomy are excluded. The preoperative histology and final pathology will be reviewed and compared by expert pathologists. Additional immunohistochemical analysis of IMP3, p53, ER, PR, MLH1, PTEN, beta-catenin, p16, Ki-67, stathmin, ARID1A and L1CAM will be performed. Preoperative histology will be compared with the final pathology results. Follow-up will be at least 24 months to determine risk factors for recurrence and outcome. This study is designed to improve surgical treatment of endometrial carcinoma patients. A total of 432 endometrial carcinoma patients were enrolled between 2011 and 2013. Follow-up will be completed in 2015. Preoperative histology will be evaluated systematically and background endometrium will be

  2. Mammary Analog Secretory Carcinoma of the Nasal Cavity

    DEFF Research Database (Denmark)

    Baneckova, Martina; Agaimy, Abbas; Andreasen, Simon

    2018-01-01

    Secretory carcinoma, originally described as mammary analog secretory carcinoma (MASC), is a low-grade salivary gland tumor characterized by a t(12;15)(p13;q25) translocation, resulting in an ETV6-NTRK3 gene fusion. Most MASCs are localized to the parotid gland and intraoral minor salivary glands...

  3. Verrucous Carcinoma of the Foot - Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Lalošević Jovan

    2016-09-01

    Full Text Available Verrucous carcinoma (VC is a rare variant of a well-differentiated squamous cell carcinoma (SCC with a low grade of malignancy. Epithelioma cuniculatum (EC is a subtype of VC, usually found on the sole of the foot.

  4. Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

    DEFF Research Database (Denmark)

    Kar, Siddhartha P; Tyrer, Jonathan P; Li, Qiyuan

    2015-01-01

    BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified...... in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). RESULTS: Gene set enrichment analysis...

  5. Carcinoma multiplex

    International Nuclear Information System (INIS)

    Shah, S. A.; Riaz, U.; Zahoor, I.; Jalil, A.; Zubair, M.

    2013-01-01

    Multiple primaries in a single patient are uncommon, though not very rare. The existence of such cancers in two un-related, non-paired organs is even more un-common. Here, we present a case of 55 years old male who presented to us with a mucoepidermoid carcinoma of the parotid gland and was operated. Later on, he presented with a large cystic swelling in the pelvis which turned out to be pseudomyxoma peritonei. A review of slides and immunohistochemistry indicated it to be adenocarcinoma colon. He presented again with recurrent mucoepidermoid carcinoma of the parotid which was operated successfully with the use of myocutaneous flap for wound closure. He is currently undergoing chemotherapy. In order to establish a separate mono-clonal etiology of both tumours, immunohistochemistry was performed. To the best of our knowledge, carcinoma multiplex in the colon and the parotid has never been reported before. (author)

  6. Serous 'Effusions

    African Journals Online (AJOL)

    1974-04-27

    Apr 27, 1974 ... The fluid is indeterminate where the specific gravity and the protein level are discordant. A probable diagnosis is based on strong collateral evidence, a definite diagnosis on pathological proof. RESULTS. Forty-nine examinations of ascites alone or associated with pleurisy and/or pericarditis are shown in ...

  7. Follicular carcinoma

    International Nuclear Information System (INIS)

    Shah, D.H.; Samuel, A.M.

    1999-01-01

    Follicular thyroid carcinoma (FTC) is considered as a disease of the elderly with a higher incidence in females as compared to papillary thyroid carcinoma (PTC). Some studies have reported its occurrence at an early age, which may be attributed to early diagnosis because of the availability of advanced techniques. The prognosis of the disease is considered poor as compared to that of PTC. The conclusions drawn in this review are based on 663 cases in whom adequate data was available for meaningful analysis followed for a mean period of 9.2 years, median, 7.8 years; range, 1-32 years

  8. GALLBLADDER CARCINOMA

    OpenAIRE

    Blaž Trotovšek; Valentin Sojar; Dragan Stanisavljevič; Aleš Tomažič

    2003-01-01

    Background. Carcinoma of the gallbladder is a tumour with a dismal prognosis and 5-years overall survival rate less than 5%. Among the tumours of the gastrointestinal tract it is fifth in the row and its incidence is approximately 1.2/105. Tumour occurs more often (2–6 times) in women and in people over 50 years old (90%). According to the Slovenian Registry of Cancer for year 1998 the incidence of gallbladder carcinoma was 2.7/105 and it occurred 4 times more often among women. The most impo...

  9. Typing and grading of cytological category C5 breast lesions

    International Nuclear Information System (INIS)

    Zafar, N.; Jamal, S.; Mamoon, N.; Luqman, M.; Anwar, M.

    2005-01-01

    Objective: To determine the tumour type, cytological grade and nuclear grade on fine-needle aspiration smears in cytological category C5 breast lesions and compare them with histopathological findings. Subjects and Methods: Out of all patients referred to AFIP, Rawalpindi for fine-needle aspiration of breast masses, those adjudged C5 (malignant) were chosen for this study. History, clinical details and mammographic findings were noted. Aspirated smears were examined and an attempt was made to ascertain tumour type, cytological grade and nuclear grade. On excision of these lesions, the cytological findings were compared with those on paraffin-embedded histological sections. Results: A total of 71 patients were included in this study. Of these, 64 (90.14%) were cytologically diagnosed as ductal carcinoma, 4 (5.63%) lobular carcinoma, 2 (2.82%) mucinous carcinoma and 1 (1.41%) as medullary carcinoma. Seventy (98.60%) tumours were correctly typed on aspiration smears. Sixty-eight (95.77%) cases were cytologically graded with accuracy. Nuclear grading was even better on cytology and, excluding one malignant lymphoma, all 70 (100%) smears were assessed correctly. Conclusion: Overall efficiency of the tumour typing, cytological grading and nuclear grading on aspirated material turned out to be quite accurate. In expert hands, cytological examination can be of great help in pre-operative planning and in cases where tumour morphology in paraffin-embedded material has been distorted by neo-adjuvant therapy prior to excision. (author)

  10. 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...... as noninvasive or invasive. Medical records were collected from hospital departments and reviewed. Data were analyzed using Kaplan-Meier and relative survival was estimated with follow-up through September 2, 2013. RESULTS: A cohort of 1042 women with a confirmed SBT diagnosis was identified. Women with stage I...... had an overall survival similar to the overall survival expected from the general population (p=0.3), whereas women with advanced stage disease had a poorer one (pwomen with noninvasive (pwomen with advanced stage...

  11. Serous Retinal Detachments Complicating Interferon-α and Ribavirin Treatment in Patients with Hepatitis C

    Directory of Open Access Journals (Sweden)

    Giulio Modorati

    2011-03-01

    Full Text Available Purpose: To report the cases of two patients with chronic hepatitis C infection showing serous retinal detachments similar to Vogt-Koyanagi-Harada (VKH disease. Methods: We reviewed the clinical records of two patients who were diagnosed with VKH-like disease during combined interferon-α (IFNα and ribavirin treatment. Results: Interruption of IFNα and ribavirin treatment in association with oral corticosteroids resulted in a favorable visual outcome in the case of diffuse retinal detachment (case 1. On the contrary, visual acuity did not improve when late cicatricial stage disease was already present (case 2. Conclusion: There is increasing evidence of a link between hepatitis C virus infection treated with pegylated IFNα-2b and the development of VKH-like disease. Knowing the potential side effects of IFNα and ribavirin administration is fundamentally important, as is the need to closely follow up those patients that need to undergo this treatment.

  12. Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci

    DEFF Research Database (Denmark)

    Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan

    2017-01-01

    BACKGROUND: Genome-wide association studies (GWAS) have identified 18 loci associated with serous ovarian cancer (SOC) susceptibility but the biological mechanisms driving these findings remain poorly characterised. Germline cancer risk loci may be enriched for target genes of transcription factors...... (TFs) critical to somatic tumorigenesis. METHODS: All 615 TF-target sets from the Molecular Signatures Database were evaluated using gene set enrichment analysis (GSEA) and three GWAS for SOC risk: discovery (2196 cases/4396 controls), replication (7035 cases/21 693 controls; independent from discovery...... to interact with PAX8 in the literature to the PAX8-target set and applying an alternative to GSEA, interval enrichment, further confirmed this association (P=0.006). Fifteen of the 157 genes from this expanded PAX8 pathway were near eight loci associated with SOC risk at P

  13. Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors

    DEFF Research Database (Denmark)

    Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian

    2017-01-01

    OBJECTIVE: Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. METHODS: This nationwide case-control study included all women with an SBT...... diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy...... or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p

  14. Serous papillary cystadenofibroma of the fallopian tube: A case report and short review of literature

    Directory of Open Access Journals (Sweden)

    Yasmeen Khatib

    2015-01-01

    Full Text Available Serous papillary cystadenofibromas (SPCAFs of the fallopian tube are very rare benign tumors of the female genital tract. They are usually asymptomatic and are found incidentally. Until now, only 18 cases of this tumor have been reported in the world literature. We report a case of SPCAF of the left fallopian tube in a 30-year-old female who presented with a large abdominal mass and pain. On computed tomography, a diagnosis of ovarian neoplasm was given. However, during surgery the tumor was found to arise from the fallopian tube and was treated with tubal cystectomy with sparing of the ovary. We present this unique case on account of its rarity, unusual presentation, and huge size along with a short review of literature.

  15. A Postmenopausal Woman with Giant Ovarian Serous Cyst Adenoma: A Case Report with Brief Literature Review

    Directory of Open Access Journals (Sweden)

    Nishat Fatema

    2018-01-01

    Full Text Available Giant (>10 cm ovarian cyst is a rare finding. In the literature, a few cases of giant ovarian cysts have been mentioned sporadically, especially in elderly patients. We report a 57-year-old postmenopausal woman with a giant left ovarian cyst measuring 43 × 15 × 9 cm. She was referred to us from the local health center in view of palpable pelvic mass for six-month period. Considering the age and menopausal state, we performed a total abdominal hysterectomy and bilateral salpingo-oophorectomy with excision of the giant left ovarian cyst intact and successfully without any significant complication. On histopathological examination, the cyst was confirmed as benign serous cystadenoma of the ovary. During the management of these high-risk cases of multidisciplinary approach, intraoperative and postoperative strict vigilance is necessary to avoid unwanted complications.

  16. [Selective retina therapy in central serous chorioretinopathy with detachment of the pigmentary epithelium].

    Science.gov (United States)

    Klatt, C; Elsner, H; Pörksen, E; Brinkmann, R; Bunse, A; Birngruber, R; Roider, J

    2006-10-01

    Selective Retina Therapy (SRT) is a new and innovative laser treatment modality that selectively treats the retinal pigmentary epithelium while sparing the photoreceptors. This therapeutic concept appears to be particularly suitable for treating patients with acute or chronic central serous chorioretinopathy (CSC). We present preliminary results obtained in five patients who had CSC associated with pigmentary epithelium detachment (PED) and serous subretinal fluid (SRF) and who were treated with SRT. This case series was made up of five male patients (mean age 47 years) with chronic CSC and SRF resulting from PED. Examinations performed before and at 1 month and 3 months after the treatment were: BCVA, FLA, OCT (Zeiss OCT III). For SRT, confluent treatment of the PED (area of leakage) was carried out using a pulsed frequency-doubled, Q-switched Nd-YLF prototype laser (lambda=527 nm, t= 1.7 s, 100 Hz, energy = 150-250 J). Best corrected visual acuity at baseline was 0.53, while after 4 weeks it was 0.56 and after 12 weeks, 0.5. At baseline leakage was seen at the PED on fluorescein angiography in all patients. After 4 weeks leakage activity was no longer noted on angiography in 4 of 5 patients. OCT at baseline showed SRF at the edge of the PED in all patients, but in 4 of the 5 patients this was no longer detectable after 4 weeks. SRT is a safe and effective treatment for patients with CSC in which PED has caused SRF. Not a single case of rip syndrome was observed in this study, even though the PED was treated confluently. Since SRT spares the photoreceptors it is particularly suitable for the treatment of CSC, especially when the origin of leakage is located close to the fovea. The results indicate that SRT leads to reconstruction of the outer blood-retina barrier.

  17. MUS81 is associated with cell proliferation and cisplatin sensitivity in serous ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Suhong; Zheng, Hui [Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Wen, Xuemei [Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Sun, Jiajun; Wang, Yanchun; Gao, Xiang; Guo, Lin [Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Lu, Renquan, E-mail: lurenquan@126.com [Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China)

    2016-08-05

    The dysfunction of DNA damage repair (DDR) pathway contributes to tumorigenesis and drug-resistance in cancer. MUS81 is a member of the conserved xeroderma pigmentosum group F (XPF) family protein of endonucleases, which is important to the DDR pathway. However, the role of MUS81 in the development of ovarian cancer remains uncertain. To explore the expression of MUS81 and its association to serous ovarian cancer (SOC), 43 biopsies of SOC patients were detected by qRT-PCR, and 29 specimens were further performed by immunohistochemistry analysis. Here, we observed that MUS81 was over-expressed in SOC tissues at both transcript and protein levels, and the expression level of MUS81 protein in ovarian cancer cell lines was also higher than that in human normal ovarian surface epithelial cell line (HOSEpiC). We also found that down-regulation of MUS81 expression in ovarian cancer cells inhibited cell proliferation and colony formation ability, and influenced cell cycle progression. Moreover, inhibition of MUS81 expression induced cellular senescence and enhanced the antitumor effect of cisplatin. Down-regulation of MUS81 expression could suppress the growth and development of SOC. These results indicate that MUS81 might play important roles in the progression of SOC and influence the antitumor effect of cisplatin. - Highlights: • MUS81 was overexpression in serous ovarian cancer (SOC). • Meanwhile down-regulation of inhibited cell proliferation and influenced cell cycle progression. • Inhibition of MUS81 induced cell cellular senescence and enhanced the antitumor effect of cisplatin. • Down-regulation of MUS81 expression could suppress the growth and development of SOC.

  18. MUS81 is associated with cell proliferation and cisplatin sensitivity in serous ovarian cancer

    International Nuclear Information System (INIS)

    Xie, Suhong; Zheng, Hui; Wen, Xuemei; Sun, Jiajun; Wang, Yanchun; Gao, Xiang; Guo, Lin; Lu, Renquan

    2016-01-01

    The dysfunction of DNA damage repair (DDR) pathway contributes to tumorigenesis and drug-resistance in cancer. MUS81 is a member of the conserved xeroderma pigmentosum group F (XPF) family protein of endonucleases, which is important to the DDR pathway. However, the role of MUS81 in the development of ovarian cancer remains uncertain. To explore the expression of MUS81 and its association to serous ovarian cancer (SOC), 43 biopsies of SOC patients were detected by qRT-PCR, and 29 specimens were further performed by immunohistochemistry analysis. Here, we observed that MUS81 was over-expressed in SOC tissues at both transcript and protein levels, and the expression level of MUS81 protein in ovarian cancer cell lines was also higher than that in human normal ovarian surface epithelial cell line (HOSEpiC). We also found that down-regulation of MUS81 expression in ovarian cancer cells inhibited cell proliferation and colony formation ability, and influenced cell cycle progression. Moreover, inhibition of MUS81 expression induced cellular senescence and enhanced the antitumor effect of cisplatin. Down-regulation of MUS81 expression could suppress the growth and development of SOC. These results indicate that MUS81 might play important roles in the progression of SOC and influence the antitumor effect of cisplatin. - Highlights: • MUS81 was overexpression in serous ovarian cancer (SOC). • Meanwhile down-regulation of inhibited cell proliferation and influenced cell cycle progression. • Inhibition of MUS81 induced cell cellular senescence and enhanced the antitumor effect of cisplatin. • Down-regulation of MUS81 expression could suppress the growth and development of SOC.

  19. Carcinoma vulvar

    Directory of Open Access Journals (Sweden)

    Yamit Peñas Zayas

    2015-11-01

    Full Text Available El carcinoma de la vulva tiene una incidencia de aproximadamente un 3-5% dentro de todas las enfermedades ginecológicas malignas. El 90% de los tumores malignos de la vulva está constituido por carcinoma epidermoide, el resto son adenocarcinomas, carcinomas de células basales y melanomas. Se realiza la presentación de un caso de una paciente femenina de 25 años de edad con antecedentes  de Diabetes Mellitus tipo II y trombopatia, que ingresa en el servicio de ginecología con un cuadro cutáneo polimorfo, localizado en labios mayores y menores, dado por lesiones eritematoerosivas y vegetante, sospechándose clínicamente el diagnóstico  de un carcinoma epidermoide, corroborándose el mismo histológicamente al realizarse biopsia de piel. Se indicó tratamiento con quimioterapia. Por la edad de la paciente y ser menos frecuente en mucosa que en la piel,  motivo la presentación del caso.

  20. Clinicopathologic significance of HLA-G and HLA-E molecules in Tunisian patients with ovarian carcinoma.

    Science.gov (United States)

    Babay, Wafa; Ben Yahia, Hamza; Boujelbene, Nadia; Zidi, Nour; Laaribi, Ahmed Baligh; Kacem, Dhikra; Ben Ghorbel, Radhia; Boudabous, Abdellatif; Ouzari, Hadda-Imene; Rizzo, Roberta; Rebmann, Vera; Mrad, Karima; Zidi, Inès

    2018-06-01

    The human leukocyte antigen (HLA)-G and HLA-E, non classical HLA class I molecules, have been highly implicated in immune tolerance. HLA-G and HLA-E molecules were proposed as putative markers of several advanced cancers. As a step towards a better understanding of ovarian carcinoma, we evaluated the expression of both HLA-G and HLA-E molecules and explored their prognostic implication. HLA-G and HLA-E expression were studied by immunohistochemistry on ovarian carcinoma tissues. This expression was semi-quantitatively scored into four expression groups and correlated to clinicopathological parameters and patients' survival. HLA-G and HLA-E have been found to be highly expressed in ovarian carcinoma tissues (Respectively, 72.4% and 96.8%). They are frequently co-expressed. Univariate and multivariate analysis revealed that a positive HLA-G expression status in tumor tissue is a promising candidate parameter to predict disease recurrence in addition to the disease status in Tunisian patients with ovarian carcinoma. Moreover, the elevated HLA-E expression was associated with serous ovarian carcinoma subtype as well as with advanced stages of ovarian carcinoma. HLA-G and HLA-E are highly represented in ovarian carcinoma suggesting a potential association with progressive disease mechanism. HLA-G and HLA-E molecules might be new candidates' markers for ovarian carcinoma progression. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  1. Histopathological evaluation of carcinoma of breast

    Directory of Open Access Journals (Sweden)

    R Pathak

    2016-03-01

    Full Text Available Background: Carcinoma of breast has become the major public health problem among females in developing as well as developed countries. InNepal it comprises 6% of total cancers cases and often diagnosed at advanced stage. Surgical removal or modified radical mastectomy (MRM is the most commonly used tools for disease management. The objective of this study is to identify the clinical, macroscopic and microscopic features of MRM specimens.Materials and methods: This prospective cross-sectional study was carried out at Department of Pathology, Bhaktapur Cancer Hospital, Bhaktapur, Nepal. Macroscopic and microscopic examination provided the tumor size, stage, grade, lymph node status, lympho-vascular invasion and perineural invasion. Data were collected and analyzed using SPSS 16.Results: The study comprised 112 breast cancer patients of which 109 (97.3% were females and 3 (2.7% were males. Invasive ductal carcinoma no specific type was the most common type of breast carcinoma. (84 cases accounting 75% of total cases. Carcinoma with medullary features was second most common (6 cases comprising 5.4% cases followed by lobular, papillary, apocrine, mucinious and NST mixed types. Grade II tumors were most frequent grade observed in 76.79% cases followed by Grade I (12.50% and Grade III (10.71%.Conclusion: As a conclusion invasive ductal carcinoma was the most common histological type breast cancer and the tumors were found at T2 and N3 stage i.e maximum at grade II. Our study provides prognostic significance of histo-pathological information in breast cancer management.

  2. Survival analysis and prognosis for patients with serous and mucinous borderline ovarian tumors: 14-year experience from a tertiary center in Iran.

    Directory of Open Access Journals (Sweden)

    Katayoun Ziari

    2015-04-01

    Full Text Available The aim of this study was to determine the prognosis and survival for patients with borderlineovarian tumor (BOT. A retrospective review of 30 patients with serous andmucinous BOT treated at or referred to our institution was performed. Fifteenpatients (50% had serous, and the others had mucinous BOT. About 86% of allpatients in both groups were in stage I of the disease. The recurrent disease occurredin 7% and 21% of serous and mucinous tumors, respectively. All recurrences,except one in mucinous tumors, were found in advance stage disease. After amean of 37 and 52 months follow-up, the overall survival was 100% and 93%, anddisease-free survival was 93% and 79% for serous and mucinous tumors,respectively. In this series, advanced stage was associated with poorprognosis. However, to obtain more accurate information further studies withnumber of patients and longer follow-up is recommended.

  3. Early chest tube removal after video-assisted thoracic surgery lobectomy with serous fluid production up to 500 ml/day

    DEFF Research Database (Denmark)

    Bjerregaard, Lars S; Jensen, Katrine; Petersen, Rene Horsleben

    2014-01-01

    In fast-track pulmonary resections, we removed chest tubes after video-assisted thoracic surgery (VATS) lobectomy with serous fluid production up to 500 ml/day. Subsequently, we evaluated the frequency of recurrent pleural effusions requiring reintervention....

  4. A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation

    International Nuclear Information System (INIS)

    Wiegand, Kimberly C; Lu, Yiling; Zhang, Fan; Anglesio, Michael S; Gilks, Blake; Mills, Gordon B; Huntsman, David G; Carey, Mark S; Hennessy, Bryan T; Leung, Samuel; Wang, Yemin; Ju, Zhenlin; McGahren, Mollianne; Kalloger, Steve E; Finlayson, Sarah; Stemke-Hale, Katherine

    2014-01-01

    Ovarian cancer is now recognized as a number of distinct diseases primarily defined by histological subtype. Both clear cell ovarian carcinomas (CCC) and ovarian endometrioid carcinomas (EC) may arise from endometriosis and frequently harbor mutations in the ARID1A tumor suppressor gene. We studied the influence of histological subtype on protein expression with reverse phase protein array (RPPA) and assessed proteomic changes associated with ARID1A mutation/BAF250a expression in EC and CCC. Immunohistochemistry (IHC) for BAF250a expression was performed on 127 chemotherapy-naive ovarian carcinomas (33 CCC, 29 EC, and 65 high-grade serous ovarian carcinomas (HGSC)). Whole tumor lysates were prepared from frozen banked tumor samples and profiled by RPPA using 116 antibodies. ARID1A mutations were identified by exome sequencing, and PIK3CA mutations were characterized by MALDI-TOF mass spectrometry. SAM (Significance Analysis of Microarrays) was performed to determine differential protein expression by histological subtype and ARID1A mutation status. Multivariate logistic regression was used to assess the impact of ARID1A mutation status/BAF250a expression on AKT phosphorylation (pAKT). PIK3CA mutation type and PTEN expression were included in the model. BAF250a knockdown was performed in 3 clear cell lines using siRNA to ARID1A. Marked differences in protein expression were observed that are driven by histotype. Compared to HGSC, SAM identified over 50 proteins that are differentially expressed in CCC and EC. These included PI3K/AKT pathway proteins, those regulating the cell cycle, apoptosis, transcription, and other signaling pathways including steroid hormone signaling. Multivariate models showed that tumors with loss of BAF250a expression showed significantly higher levels of AKT-Thr 308 and AKT-Ser 473 phosphorylation (p < 0.05). In 31 CCC cases, pAKT was similarly significantly increased in tumors with BAF250a loss on IHC. Knockdown of BAF250a by siRNA in

  5. Papillary carcinoma

    International Nuclear Information System (INIS)

    Shah, D.H.; Samuel, A.M.

    1999-01-01

    Papillary carcinoma of the thyroid (PTC) constitutes a major proportion of all thyroid cancers and is generally believed to be a slow growing tumor with an indolent course. The diagnosis of PTC often makes the physician overly optimistic and complacent and yet this tumor can be aggressive in a subset of patients leading to death in a few months. The fundamental but subtle differences underlying the extremes in biologic behaviour of this complex and fascinating tumor remain poorly understood. Although there is a general agreement among the investigators regarding prognostic factors, controversy exists about the management of the disease. There is divided opinion with respect to the type and extent of surgery and the need for radioiodine (1 31 I) treatment in case of PTC. The experiences at Radiation Medicine Centre (RMC) of 1904 cases of differentiated thyroid carcinoma (DTC) registered during the period 1963-1990 are reviewed

  6. Thyroid carcinoma

    International Nuclear Information System (INIS)

    Lambertini, Roberto; Dalurzo, Liliana; Jaen, Ana del V.

    2008-01-01

    In this document the case of a 66-year old woman is presented, with record of multi nodular goiter of 5 year of evolution, which is derived to scan ultrasound office to make a puncture-aspiration with thin needle because of the growth of nodular thyroid injuries. The ultrasound scan examination made before the puncture determine multiple dominant nodules of hyperplasia aspect between 15 and 25 mm of diameter and a small nodule of 6 mm suspected proliferate process. Despite its size, it was decided to include small nodule in injuries to a biopsy. The cytological study reveals nodular hyperplasia with carcinoma in the small nodule of 6 mm. A thyroidectomy is practiced on the patient. The deferred histological study of the thyroid gland confirms the finding of multi-nodular goiter with a small focus of papillar carcinoma. The ganglions examined were negative in the deferred examination [es

  7. Rectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fossati, V; Antognoni, P; Villa, E and others

    1985-01-01

    Records of 135 patients with rectal carcinoma were reviewed and correlations between survival rate, extent of tumor and radiotherapy were investigated. The survival rate at 5 years was 16% for C Astler Coller's stage patients and without metastases, but the prognosis was much less favourable for advanced tumors and/or subjects with distant metastases. Preliminary results of another series of patients treated with adjuvant radiotherapy are discussed.

  8. Mutational analysis of BRAF and KRAS in ovarian serous borderline (atypical proliferative) tumours and associated peritoneal implants

    DEFF Research Database (Denmark)

    Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G

    2014-01-01

    There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced......), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST-implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST-implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11...... SBT/APST-implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST-implant (non-invasive and invasive) pairs (p identical KRAS or BRAF...

  9. Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Vance, Sean; Suri, Jaipreet S. [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Mahan, Meredith [Public Health Science, Henry Ford Hospital, Detroit, Michigan (United States); Munkarah, Adnan [Division of Gynecologic Oncology, Department of Women' s Health Services, Henry Ford Hospital, Detroit, Michigan (United States)

    2014-02-01

    Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years. All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial carcinoma

  10. Megamitochondria in the serous acinar cells of the submandibular gland of the neotropical fruit bat, Artibeus obscurus.

    Science.gov (United States)

    Tandler, B; Nagato, T; Phillips, C J

    1997-05-01

    As part of a continuing investigation of the comparative ultrastructure of chiropteran salivary glands, we examined the submandibular glands of eight species of neotropical fruit bats in the genus Artibeus. We previously described secretory granules of unusual substructure in the seromucous demilunar cells of this organ in some species in this genus. In the present study, we turned our attention to the serous acinar cells in the same glands. Specimens of eight species of Artibeus were collected in neotropical localities. Salivary glands were extirpated in the field and thin slices were fixed by immersion in triple aldehyde-DMSO or in modified half-strength Karnovsky's fixative. Tissues were further processed for electron microscopy by conventional means. In contrast to seromucous cells, which exhibit species-specific diversification in bats of this genus, the secretory apparatus and secretory granules in the serous acinar cells are highly conserved across all seven species. The single exception involves the mitochondria in one species. In this instance, some of the serous cell mitochondria in Artibeus obscurus are modified into megamitochondria. Such organelles usually have short, peripheral cristae; a laminar inclusion is present in the matrix compartment of every outsized organelle. Inclusions of this nature never are present in normal-size mitochondria in the serous cells. None of the megamitochondria were observed in the process of degeneration. The giant mitochondria in A. obscurus have a matrical structure that is radically different from that of the only other megamitochondria reported to occur in bat salivary glands. The factors that lead to variation in megamitochondrial substructure in different species, as well as the functional capacities of such giant organelles, are unknown.

  11. Gene Expression Signature TOPFOX Reflecting Chromosomal Instability Refines Prediction of Prognosis in Grade 2 Breast Cancer

    DEFF Research Database (Denmark)

    Szasz, A.; Li, Qiyuan; Sztupinszki, Z.

    2011-01-01

    Purpose: To assess the ability of genes selected from those reflecting chromosomal instability to identify good and poor prognostic subsets of Grade 2 breast carcinomas. Methods: We selected genes for splitting grade 2 tumours into low and high grade type groups by using public databases. Patient...

  12. Verrucoid Variant of Invasive Squamous Cell Carcinoma in Oral Submucous Fibrosis: A Clinicopathological Challenge.

    Science.gov (United States)

    Ramani, Priya; Krithika, C; Ananthalakshmi, R; Singaram, Mamta; Jagdish, Praveena; Janardhanan, Sunitha; Jeevakarunyam, Sathiyajeeva

    2016-11-04

    Verrucous carcinoma (VC) is an exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. It is described as a lesion appearing in the sixth or seventh decade of life that has minimal aggressive potential and, in long-standing cases, has been shown to transform into squamous cell carcinoma. Oral submucous fibrosis (OSMF) is a potentially malignant disorder, and about one-third of the affected population develop oral squamous cell carcinoma. The histopathological diagnosis of verrucous carcinoma is challenging, and the interpretation of early squamous cell carcinoma requires immense experience. Here we present a rare case of a 24-year-old male with OSMF transforming to verrucous carcinoma with invasive squamous cell carcinoma. Even though the case had a straightforward clinical diagnosis, the serial sectioning done for pathological diagnosis disclosed the squamous cell carcinoma.

  13. Comparison of a sentinel lymph node mapping algorithm and comprehensive lymphadenectomy in the detection of stage IIIC endometrial carcinoma at higher risk for nodal disease.

    Science.gov (United States)

    Ducie, Jennifer A; Eriksson, Ane Gerda Zahl; Ali, Narisha; McGree, Michaela E; Weaver, Amy L; Bogani, Giorgio; Cliby, William A; Dowdy, Sean C; Bakkum-Gamez, Jamie N; Soslow, Robert A; Keeney, Gary L; Abu-Rustum, Nadeem R; Mariani, Andrea; Leitao, Mario M

    2017-12-01

    To determine if a sentinel lymph node (SLN) mapping algorithm will detect metastatic nodal disease in patients with intermediate-/high-risk endometrial carcinoma. Patients were identified and surgically staged at two collaborating institutions. The historical cohort (2004-2008) at one institution included patients undergoing complete pelvic and paraaortic lymphadenectomy to the renal veins (LND cohort). At the second institution an SLN mapping algorithm, including pathologic ultra-staging, was performed (2006-2013) (SLN cohort). Intermediate-risk was defined as endometrioid histology (any grade), ≥50% myometrial invasion; high-risk as serous or clear cell histology (any myometrial invasion). Patients with gross peritoneal disease were excluded. Isolated tumor cells, micro-metastases, and macro-metastases were considered node-positive. We identified 210 patients in the LND cohort, 202 in the SLN cohort. Nodal assessment was performed for most patients. In the intermediate-risk group, stage IIIC disease was diagnosed in 30/107 (28.0%) (LND), 29/82 (35.4%) (SLN) (P=0.28). In the high-risk group, stage IIIC disease was diagnosed in 20/103 (19.4%) (LND), 26 (21.7%) (SLN) (P=0.68). Paraaortic lymph node (LN) assessment was performed significantly more often in intermediate-/high-risk groups in the LND cohort (P<0.001). In the intermediate-risk group, paraaortic LN metastases were detected in 20/96 (20.8%) (LND) vs. 3/28 (10.7%) (SLN) (P=0.23). In the high-risk group, paraaortic LN metastases were detected in 13/82 (15.9%) (LND) and 10/56 (17.9%) (SLN) (%, P=0.76). SLN mapping algorithm provides similar detection rates of stage IIIC endometrial cancer. The SLN algorithm does not compromise overall detection compared to standard LND. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Serous goblet cells: the protein secreting cells in the oral cavity of a catfish, Rita rita (Hamilton, 1822) (Bagridae, Siluriformes).

    Science.gov (United States)

    Yashpal, Madhu; Mittal, Ajay Kumar

    2014-02-01

    Serous goblet cells in the oral epithelium of Rita rita are characterized by the presence of distinct eosinophilic granules occupying large parts of the cytoplasm. In R. rita, a range of histochemical results reveal that these cells are involved in proteinaceous secretions, and thus likely contribute to various functions analogous to those of mammalian saliva. The secretions of these cells have also been associated with specific functions and are discussed in relation to their physiological importance with special reference to their roles in lubrication, alteration in viscosity, various functions of mucus such as handling, maneuvering and driving of food items toward the esophagus, maintaining taste sensitivity and protection of the oral epithelium. In addition, the serous goblet cells may also be considered as the primary defensive cell of the oral epithelium of R. rita. The results significantly add to very limited set of literature on the serous goblet cells and provide noteworthy information on the mucous secretions in the oral cavity of fish. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease

    Directory of Open Access Journals (Sweden)

    Skirnisdottir Ingiridur

    2012-09-01

    Full Text Available Abstract Background Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Methods Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. Results The most significant differences (p  Conclusions The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome.

  16. PRESENTATION OF CENTRAL SEROUS CHORIORETINOPATHY IN TWO HUSBAND AND WIFE COUPLES.

    Science.gov (United States)

    Kanesa-Thasan, Aditya; Fawzi, Amani A; Gill, Manjot K

    2018-01-01

    Central serous chorioretinopathy (CSC) is a disease in which serous detachment of the neurosensory retina occurs over an area of leakage from the choriocapillaris through the retinal pigment epithelium. Associations have been drawn between high-stress personality types and steroid exposure. This article aims to describe a unique case series of two husband and wife couples with CSC. All methods were approved by the authors' institution's institutional review board. History, physical examination, and imaging data were obtained from the electronic medical records of the patients in question and from the providers who cared for these patients. Couple 1: A 35-year-old man presented with "dark spots" in his right eye. He reported no recent steroid use. Visual acuity at presentation was 20/30 in the right eye and 20/20 in the left eye. On fundus examination, there was subretinal fluid in the right eye. His wife presented on the same day with a "wavy section" in the right eye for 6 weeks. She also had no recent steroid use. Visual acuity at presentation was 20/20 in both eyes with blunting of the foveal reflex in the right eye. Optical coherence tomography showed a thick choroid with a pigment epithelial detachment in the right eye. Couple 2: A 34-year-old man presented with "blurry vision" in his right eye for one month. He was taking oral and nasal steroids for chronic sinusitis. Visual acuity was 20/30 in the right eye and 20/20 in the left eye. Fluorescein angiography and indocyanine green confirmed the diagnosis of CSC. After 3 months of persistent subretinal fluid, he received photodynamic therapy in the right eye. Three days after his photodynamic therapy, his 38-year-old wife presented with subjective blurring in both eyes. Visual acuity was 20/20 in both eyes, but optical coherence tomography showed thick choroid in both eyes, a large central pigment epithelial detachment in the right eye, and 3 small pigment epithelial detachments in the left eye. She had no

  17. Photodynamic therapy combined with antivascular endothelial growth factor treatment for recalcitrant chronic central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Asahi MG

    2017-11-01

    Full Text Available Masumi G Asahi,1 Andrew T Chon,1 Esmeralda Gallemore,1 Ron P Gallemore1,2 1Clinical Research Department, Retina Macula Institute, Torrance, CA, USA; 2Jules Stein Eye Institute, University of California, Los Angeles, CA, USA Purpose: To determine whether combination photodynamic therapy (PDT and antivascular endothelial growth factor (VEGF therapy is effective in the management of chronic central serous chorioretinopathy (CSC recalcitrant to conventional therapy. Methods: This was a retrospective analysis of eight patients with chronic CSC unresponsive to topical nonsteroidal anti-inflammatory drugs, focal photocoagulation, anti-VEGF alone, or PDT alone. All patients were evaluated with a full ophthalmic examination, spectral-domain optical coherence tomography (OCT, fluorescein angiography (FA, and most with indocyanine green angiography (ICGA followed by treatment with half-fluence PDT and intravitreal anti-VEGF injection (seven bevacizumab, one aflibercept. Patients were seen in follow-up 1 month after treatment. Results: All eight patients achieved complete resolution in subretinal fluid following combination treatment. Average duration of CSC prior to initiation of combination therapy was 7.5 months. Mean central macular thickness on OCT decreased significantly from 401.2±52.7 µm to 297.9±18.2 µm (p=0.0010 by 4 months after treatment (1.63±1.18 months. Seven of eight patients were followed up for an average of 13 months with no recurrence during that time. One case recurred at 8 months and was treated with repeat combination at that time. Frank choroidal neovascularization (CNV was not identified in these cases on FA or ICGA studies. Eight of eight patients showed significant improvement in vision from a logMAR of 0.1125±0.099 to 0.0125±0.064 (p=0.019. Conclusion: Combination PDT and anti-VEGF is effective for chronic CSC which has failed conventional therapy. Associated CNV and/or inflammation may be reasons for greater success in

  18. The effect of eradicating Helicobacter pylori on idiopathic central serous chorioretinopathy patients

    Directory of Open Access Journals (Sweden)

    Dang Y

    2013-09-01

    Full Text Available Yalong Dang,1,2,* Yalin Mu,2,* Manli Zhao,2 Lin Li,3 Yaning Guo,4 Yu Zhu1,2 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China; 2Department of Ophthalmology and Visual Science, Yellow River Hospital of Henan University of Science and Technology, Sanmenxia City, Henan, People's Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang City, Henan, People's Republic of China; 4Gu-Cheng Eye Hospital, Xi'an City, Shanxi, People's Republic of China *These authors contributed equally to this work Purpose: To evaluate the effect of Helicobacter pylori (H. pylori eradication on the remission of acute idiopathic central serous chorioretinopathy (ICSCR. Study design: A prospective, randomized, placebo-controlled study of 53 participants. Main outcome measure: Twenty-seven acute ICSCR patients tested positive for H. pylori were given an eradication H. pylori therapy, and another 26 patients with the same diagnosis received matching placebo medication. All participants were tested for the following items: (1 disappearance rate of subretinal fluid (SRF; (2 best-corrected visual acuity (BCVA; and (3 central retinal sensitivity at baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after treatment. The difference between the two groups was analyzed by PASW statistics version 18.0. Results: At each follow-up, the disappearance rate of SRF in the active treatment group seemed slightly better than in the control group, but no statistically significant differences were observed (P > 0.05 at each follow-up. The BCVA between the two groups also did not demonstrate statistically significant differences (P > 0.05 at each follow-up. Unlike the BCVA and the disappearance rate of SRF, we compared the change in central retinal sensitivity at 12 weeks after treatment; a statistical difference was observed (P = 0

  19. Clear cell carcinomas of the ovary have poorer outcomes compared with serous carcinomas: Results from a single-center Taiwanese study

    Directory of Open Access Journals (Sweden)

    Fei-Chun Ku

    2018-02-01

    Conclusion: The clinical outcomes of CCC are generally poorer than SC. Complete cytoreduction to no gross residual disease should be ideally achieved in CCC patients. A greater understanding of the molecular pathogenesis of CCC may lead to tailored therapies, ultimately optimizing outcomes.

  20. Oral Rigosertib for Squamous Cell Carcinoma

    Science.gov (United States)

    2017-06-22

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  1. Hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Farooqi, J.I.; Farooqi, R.J.

    2001-01-01

    Hepatocellular carcinoma (HCC) is a common cause of cancer mortality. Hepatitis B and C viruses, aflatoxin and alga toxin in the contaminated drinking water are the major etiological factors. Rapidly progressing medical imaging has resulted in the improved treatment results. Surgical resection has a major role for influencing prognosis of HCC. Local cancer therapies based on the advances in early diagnosis are progressing rapidly. Multimodality combination and sequential treatment has proved effective, unfortunately systemic chemotherapy for HCC remains disappointed. All of these have resulted in the improved prognosis of HCC. (author)

  2. Parotid carcinoma

    DEFF Research Database (Denmark)

    Godballe, Christian; Schultz, Joyce H; Krogdahl, Annelise

    2003-01-01

    -year recurrence-free survival of the entire study group was 63%, disease-specific survival was 69%, and crude survival was 52%. In univariate analysis, tumor size, histological appearance, T status, stage, the presence of lymph node metastases, distant metastases, pain, and facial nerve dysfunction had...... a significant influence on survival. CONCLUSIONS: A thorough histological revision is pivotal in retrospective parotid carcinoma studies, and tumor size; histological appearance; T, N, and M status; stage; facial nerve dysfunction; and pain from the face and/or neck seem to be significant prognostic indicators...

  3. Carcinoma Basocelular

    Directory of Open Access Journals (Sweden)

    Inês Alencar de Castro

    2008-03-01

    Full Text Available Vemos na região frontal de um paciente masculino, fototipo II de Fitzpatrick, lesão ulcerada com bordas papulosas róseas e peroladas, correspondendo a Carcinoma Basocelular. É lesão maligna originária das células não- queratinizadas da camada basal da epiderme, sendo a forma mais comum de câncer em humanos. Estima-se em torno de 100.000 casos/ano no Brasil. Ocorre predominantemente em pele exposta de indivíduos com pouca capacidade de se bronzear. Pode se tornar invasivo, mas raramente metastatiza.

  4. Gene expression analysis of early stage endometrial cancersreveals unique transcripts associated with grade and histologybut not depth of invasion

    Directory of Open Access Journals (Sweden)

    John eRisinger

    2013-06-01

    Full Text Available Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least 4-fold (univariate t-test, p <0.001 between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis.

  5. Inhibition of the Receptor Tyrosine Kinase AXL Restores Paclitaxel Chemosensitivity in Uterine Serous Cancer.

    Science.gov (United States)

    Palisoul, Marguerite L; Quinn, Jeanne M; Schepers, Emily; Hagemann, Ian S; Guo, Lei; Reger, Kelsey; Hagemann, Andrea R; McCourt, Carolyn K; Thaker, Premal H; Powell, Matthew A; Mutch, David G; Fuh, Katherine C

    2017-12-01

    Uterine serous cancer (USC) is aggressive, and the majority of recurrent cases are chemoresistant. Because the receptor tyrosine kinase AXL promotes invasion and metastasis of USC and is implicated in chemoresistance in other cancers, we assessed the role of AXL in paclitaxel resistance in USC, determined the mechanism of action, and sought to restore chemosensitivity by inhibiting AXL in vitro and in vivo We used short hairpin RNAs and BGB324 to knock down and inhibit AXL. We assessed sensitivity of USC cell lines to paclitaxel and measured paclitaxel intracellular accumulation in vitro in the presence or absence of AXL. We also examined the role of the epithelial-mesenchymal transition (EMT) in AXL-mediated paclitaxel resistance. Finally, we treated USC xenografts with paclitaxel, BGB324, or paclitaxel plus BGB324 and monitored tumor burden. AXL expression was higher in chemoresistant USC patient tumors and cell lines than in chemosensitive tumors and cell lines. Knockdown or inhibition of AXL increased sensitivity of USC cell lines to paclitaxel in vitro and increased cellular accumulation of paclitaxel. AXL promoted chemoresistance even in cells that underwent the EMT in vitro Finally, in vivo studies of combination treatment with BGB324 and paclitaxel showed a greater than 51% decrease in tumor volume after 2 weeks of treatment when compared with no treatment or single-agent treatments ( P USC. Mol Cancer Ther; 16(12); 2881-91. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. A novel mutation of sgk-1 gene in central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Mahmut Akyol

    2015-02-01

    Full Text Available AIM: To investigate the association of serum glucocorticoid kinase gene-1 (SGK-1 DNA variants with chronic central serous chorioretinopathy (CSC. METHODS: We enrolled 32 eyes of 32 patients who were diagnosed with chronic CSC and composed 32 normal eyes as a control group. Peripheral blood was used for DNA extraction and polymerase chain reaction (PCR amplification. SGK1 gene was sequenced by using BigDye® Terminator v3.1 cycle sequencing KIT (Applied Biosystems, Foster City, CA, USA. The SGK1 gene and its variants were investigated in CSC patient group and control group. RESULTS: We identified a new polymorphism M32V in two person in the patient group (Minor allele frequency (MAF=0.009 on the region of 1-60 amino acids. The rs1057293 was located in the encoder region of the SGK 1 gene but not associated with CSC (P=0.68. An intrinsic rs1743966 is also not associated (P=0.28. CONCLUSIONS: The new polymorphism M32V is located on the region of 1-60 amino acids which is necessary for localization to the mitochondria in CSC patient. This mutation is probably important for the energy metabolism and plays an important role in the cellular response to hyperosmotic stress and other stress stimuli. Both rs1057293 and rs1743966 are not associated with CSC.

  7. The relation of somatotypes and stress response to central serous chorioretinopathy.

    Science.gov (United States)

    Schwartz, Roy; Rozenberg, Assaf; Loewenstein, Anat; Goldstein, Michaella

    2017-12-01

    To investigate a possible relationship between central serous chorioretinopathy (CSC) and specific body types and compositions (somatotypes), and to examine the cortisol stress response among CSC patients of different somatotypes in comparison with healthy subjects. Prospective case-control study. A group of 28 patients with a previous or current diagnosis of CSC was compared with a group of 26 healthy subjects. Anthropometric measurements were used to estimate somatotype ratings in all subjects. Serum cortisol was measured at rest and following a stress-inducing computerized test in order to estimate response to stress in both groups. The main outcome measures included somatotype categorization and the change in serum cortisol following stress in both groups. No significant difference in somatotype composition was found between the groups. There was no statistically significant difference between the groups in the elevation of cortisol following the stress-inducing test. The sample size was too small to exclude or find any significant difference between the different 13 subgroups of somatotype composition in the elevation of cortisol. Our study did not show a typical somatotype related to CSC. While previous studies showed higher cortisol values in CSC patients, we did not see a higher elevation in blood cortisol following a stress response in this group in comparison with healthy subjects.

  8. Cushing's Syndrome and Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy.

    Science.gov (United States)

    van Haalen, Femke M; van Dijk, Elon H C; Dekkers, Olaf M; Bizino, Maurice B; Dijkman, Greet; Biermasz, Nienke R; Boon, Camiel J F; Pereira, Alberto M

    2018-01-01

    Central serous chorioretinopathy (CSC), a specific form of macular degeneration, has been reported as presenting manifestation of Cushing's syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing's syndrome. It is important to know whether CSC patients should be screened for Cushing's syndrome. Although hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing's syndrome prevalence is increased among chronic CSC (cCSC) patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis. Cross-sectional study. 86 cCSC patients and 24 controls. Prevalence of Cushing's syndrome, HPA axis activity. None of the cCSC patients met the clinical or biochemical criteria of Cushing's syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires. No case of Cushing's syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing's syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

  9. MRI findings of serous atrophy of bone marrow and associated complications

    Energy Technology Data Exchange (ETDEWEB)

    Boutin, Robert D. [Department of Radiology, Sacramento, CA (United States); White, Lawrence M. [University of Toronto, Joint Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada); Laor, Tal [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Spitz, Damon J. [New England Baptist Hospital, Department of Radiology, Boston, MA (United States); Lopez-Ben, Robert R. [Carolinas HealthCare System, Charlotte Radiology, Diagnostic Radiology, Charlotte, NC (United States); Stevens, Kathryn J. [Stanford University, Department of Radiology, Stanford, CA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States)

    2015-09-15

    To report the MRI appearance of serous atrophy of bone marrow (SABM) and analyse clinical findings and complications of SABM. A retrospective search of MRI examinations of SABM was performed. Symptoms, underlying conditions, MRI findings, delay in diagnosis and associated complications were recorded. We identified 30 patients (15 male, 15 female; mean age: 46 ± 21 years) with MRI findings of SABM. Underlying conditions included anorexia nervosa (n = 10), cachexia from malignant (n = 5) and non-malignant (n = 7) causes, massive weight loss after bariatric surgery (n = 1), biliary atresia (n = 1), AIDS (n = 3), endocrine disorders (n = 2) and scurvy (n = 1). MRI showed mildly hypointense signal on T1- weighted and hyperintense signal on fat-suppressed fluid-sensitive images of affected bone marrow in all cases and similar signal abnormalities of the adjacent subcutaneous fat in 29/30 cases. Seven patients underwent repeat MRI due to initial misinterpretation of bone marrow signal as technical error. Superimposed fractures of the hips and lower extremities were common (n = 14). SABM occurs most commonly in anorexia nervosa and cachexia. MRI findings of SABM are often misinterpreted as technical error requiring unnecessary repeat imaging. SABM is frequently associated with fractures of the lower extremities. (orig.)

  10. MRI findings of serous atrophy of bone marrow and associated complications

    International Nuclear Information System (INIS)

    Boutin, Robert D.; White, Lawrence M.; Laor, Tal; Spitz, Damon J.; Lopez-Ben, Robert R.; Stevens, Kathryn J.; Bredella, Miriam A.

    2015-01-01

    To report the MRI appearance of serous atrophy of bone marrow (SABM) and analyse clinical findings and complications of SABM. A retrospective search of MRI examinations of SABM was performed. Symptoms, underlying conditions, MRI findings, delay in diagnosis and associated complications were recorded. We identified 30 patients (15 male, 15 female; mean age: 46 ± 21 years) with MRI findings of SABM. Underlying conditions included anorexia nervosa (n = 10), cachexia from malignant (n = 5) and non-malignant (n = 7) causes, massive weight loss after bariatric surgery (n = 1), biliary atresia (n = 1), AIDS (n = 3), endocrine disorders (n = 2) and scurvy (n = 1). MRI showed mildly hypointense signal on T1- weighted and hyperintense signal on fat-suppressed fluid-sensitive images of affected bone marrow in all cases and similar signal abnormalities of the adjacent subcutaneous fat in 29/30 cases. Seven patients underwent repeat MRI due to initial misinterpretation of bone marrow signal as technical error. Superimposed fractures of the hips and lower extremities were common (n = 14). SABM occurs most commonly in anorexia nervosa and cachexia. MRI findings of SABM are often misinterpreted as technical error requiring unnecessary repeat imaging. SABM is frequently associated with fractures of the lower extremities. (orig.)

  11. [Features of psycho-emotional state of patients with central serous chorioretinopathy].

    Science.gov (United States)

    Shchuko, A A; Yureva, T N; Zlobina, A N

    to investigate peculiarities of psycho-emotional reactions in patients with central serous chorioretinopathy (CSCR). The study involved 35 patients with CSCR (mean age of 47.7±8.5 years) and 26 volunteers without visual impairment (mean age of 35.8±4.5 years). Their psycho-emotional state was studied using the SCL-90-R questionnaire (the severity of psychopathological symptomatology), TOBOL method (the type of attitude to the disease), Ways of Coping Questionnaire (WCQ) (strategies for controlling behavior), Spielberger-Hanin method (the level of anxiety), and the VFQ-25 questionnaire (quality of life). The psycho-emotional state of CSCR patients is characterized by elevated levels of depressive and paranoiac symptoms, obsessions, compulsions, and anxiety. Such patients tend to show supernatural, sthenic desire to maintain their professional status. They tend to try to resolve the conflict by denying the problem, imagining things and distracting oneself. They also show reactive and personal anxiety. In this study, their quality of life was significantly lower than that in healthy volunteers, vision-related criteria particularly concerned. Patients with CSCR demonstrate certain psycho-emotional features that can aggravate their general medical condition as well as the ophthalmic status.

  12. THE IMPORTANCE OF THE PERIPHERAL RETINA IN PATIENTS WITH CENTRAL SEROUS CHORIORETINOPATHY.

    Science.gov (United States)

    Oztas, Zafer; Akkin, Cezmi; Ismayilova, Nergiz; Nalcaci, Serhad; Afrashi, Filiz

    2018-03-01

    This research investigated the peripheral retinas of patients with central serous chorioretinopathy (CSCR). Sixty patients with CSCR and 60 age- and gender-matched controls were included in this prospective cross-sectional study. All 120 participants underwent ocular examinations and peripheral retinal evaluations using a Goldmann three-mirror lens. The examinations demonstrated peripheral retinal degeneration, atrophic or hyperplastic retinal pigment epithelial changes, and retinal breaks. The peripheral retinal degeneration rate was 39% in the CSCR group and 15% in the control group, and the CSCR group reported significantly more lattice degeneration than the control group (22 vs. 3%) (P = 0.004, odds ratio = 1.97, confidence interval = 0.68-5.65 and P = 0.002, odds ratio = 4.55, confidence interval = 0.77-26.83, respectively). Symptomatic U-shaped retinal breaks were found in three eyes (5%) in the CSCR group, and the rate of peripheral retinal degeneration was higher in the patients with chronic CSCR (vs. acute CSCR). However, this difference was not significant (P = 0.244). This study showed that peripheral retinal abnormalities, particularly lattice degeneration, are more common in patients with CSCR. Therefore, the authors recommend regular retinal examinations, with the inclusion of peripheral retinal assessments, for patients with CSCR.

  13. Single-gene prognostic signatures for advanced stage serous ovarian cancer based on 1257 patient samples.

    Science.gov (United States)

    Zhang, Fan; Yang, Kai; Deng, Kui; Zhang, Yuanyuan; Zhao, Weiwei; Xu, Huan; Rong, Zhiwei; Li, Kang

    2018-04-16

    We sought to identify stable single-gene prognostic signatures based on a large collection of advanced stage serous ovarian cancer (AS-OvCa) gene expression data and explore their functions. The empirical Bayes (EB) method was used to remove the batch effect and integrate 8 ovarian cancer datasets. Univariate Cox regression was used to evaluate the association between gene and overall survival (OS). The Database for Annotation, Visualization and Integrated Discovery (DAVID) tool was used for the functional annotation of genes for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The batch effect was removed by the EB method, and 1257 patient samples were used for further analysis. We selected 341 single-gene prognostic signatures with FDR matrix organization, focal adhesion and DNA replication which are closely associated with cancer. We used the EB method to remove the batch effect of 8 datasets, integrated these datasets and identified stable prognosis signatures for AS-OvCa.

  14. Temperament and Character Personality Profile and Illness-Related Stress in Central Serous Chorioretinopathy

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    Rupert Conrad

    2014-01-01

    Full Text Available Psychological stress is a risk factor as well as a consequence of central serous chorioretinopathy (CSC. Impulsiveness, overachievement, emotional instability, and hard-driving competitiveness have been discussed as personality features in CSC patients. We investigated 57 consecutive CSC patients and 57 age- and gender-matched controls by means of the Symptom Checklist 90-R and the Temperament and Character Inventory. Somatic risk factors, illness characteristics, subjective assessment of severity of illness, and illness-related stress in different areas of life (work, private life were evaluated. CSC patients showed significantly higher emotional distress as measured by the Global Severity Index. The CSC personality was characterized by lower scoring on the character dimension cooperativeness and the temperament dimension reward dependence. Cooperativeness as well as subjective assessment of severity of CSC has been recognized as significant predictors of illness-related work stress accounting for 30% of variance. Implicating competitiveness, hostility and emotional detachment, lower level of cooperativeness, and reward dependence support the existence of specific aspects of type A behaviour in CSC patients. Low perceived social support and loss of control may explain the significant contribution of this personality dimension to illness-related work stress. Treatment of CSC should thus incorporate psychoeducation about factors contributing to illness-related stress.

  15. Hypervascular solid-appearing serous cystic neoplasms of the pancreas: Differential diagnosis with neuroendocrine tumours

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    Park, Hye Sun; Kim, So Yeon; Park, Seong Ho; Lee, Seung Soo; Byun, Jae Ho; Kim, Jin Hee; Kim, Hyoung Jung; Lee, Moon-Gyu [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Hong, Seung-Mo [University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, Seoul (Korea, Republic of)

    2016-05-15

    To describe imaging findings of arterial hypervascular solid-appearing serous cystic neoplasms (SCNs) of the pancreas on CT and MR and determine imaging features differentiating them from neuroendocrine tumours (NETs). We retrospectively identified 15 arterial hypervascular solid-appearing SCNs and randomly chose 30 size-matched pancreatic NETs. On CT, two radiologists in consensus assessed the size, morphology, and CT attenuation. On MR, predominant signal intensity and the amount of the cystic component on T2-weighted images and ADC maps were evaluated and compared using Fisher's exact and Student's t-test. The mean SCN size was 2.6 cm (range, 0.8-8.3). The CT findings were similar between the two tumours: location, shape, margin, and enhancement pattern. SCNs were significantly more hypodense on non-enhanced CT images than NETs (P =.03). They differed significantly on MR: bright signal intensity (P =.01) and more than a 10 % cystic component on T2-weighted images (P =.01) were more common in SCNs than in NETs. All SCNs showed a non-restrictive pattern on the ADC map, while NETs showed diffusion restriction (P <.01). Arterial hypervascular solid-appearing SCNs and NETs share similar imaging features. Non-enhanced CT and MR images with T2-weighted images and ADC maps can facilitate the differentiation. (orig.)

  16. Choriocapillary blood propagation in normal volunteers and in patients with central serous chorioretinopathy.

    Science.gov (United States)

    Komatsu, Hideki; Young-Devall, Josephine; Peyman, Gholam A; Yoneya, Shin

    2010-03-01

    To evaluate early choroidal vascular dye-filling and dye propagation patterns in normal subjects and in patients with central serous chorioretinopathy (CSC) using indocyanine green (ICG) angiography. Seventeen healthy volunteers (21-81 years old) and six patients with CSC were included. ICG angiography was performed using a modified Topcon ICG video-camera system. Subtracted images were made using the early ICG frames at a time interval of 0.12 s. Ninety frames of time-sequential images for 3 s starting from the initial dye appearance in the choroid were prepared to construct an animated video. The animated video demonstrated dye-filling and propagation patterns at the level of the choroid-choriocapillaris. In normal young volunteers, the initial phase of dye filling appeared as a uniform patchy fluorescence in the sub-foveal area, and then spread evenly in a centrifugal manner in all directions in a wave-like, pulsed fashion towards the equator. In normal older volunteers, the initial phase was similar to that in young volunteers, but centrifugal flow propagation of fluorescence towards the periphery showed an uneven progression and border. In patients with CSC, the initial dye showed a multiple patchy dye appearance with a significant time delay and loss of the centrifugal extension pattern. Using this new approach, various choroidal dye propagation patterns were observed in normal volunteers and in patients with CSC. A video of subtracted images allowed evaluation of the dynamics of dye propagation in the choroid-choriocapillaris.

  17. Serous Macular Detachment Associated with Dome-Shaped Macula and Tilted Disc

    Directory of Open Access Journals (Sweden)

    Diamar Pardo-López

    2011-03-01

    Full Text Available Introduction: An entirely new type of staphyloma has been recently described as dome-shaped macula (DSM. It is characterized by an abnormal convex macular contour within the concavity of a posterior staphyloma. We found DSM associated with serous macular detachment (SMD and tilted disc in two consecutive cases. Case Reports: Case 1: A 37-year-old female presented to our department because of sudden onset blurred vision in her right eye (OD. The best-corrected visual acuity (BCVA was 0.5 in both eyes. Funduscopy evidenced bilateral tilted disc associated with posterior staphyloma. Optical coherence tomography (OCT demonstrated a DSM with SMD in her OD. After 15 months of follow-up, BCVA of her OD remained stable with chronic SMD. Case 2: A 32-year-old female presented to our department because of blurred vision in her OD. The BCVA was 0.4 in the OD and 1.0 in the left eye (OS. Bilateral tilted disc and posterior staphyloma were evidenced in the funduscopy. OCT demonstrated a bilateral DSM with SMD in her OD. After 45 months of follow-up, two further episodes of transient SMD were observed in her OD and seven in her OS. The final BCVA was 0.63 in the OD and 0.8 in the OS. Discussion: SMD associated with tilted disc constitutes a potential cause of subretinal fluid accumulation in myopic patients. OCT is essential for the detection of both SMD and DSM.

  18. Restoration of outer segments of foveal photoreceptors after resolution of central serous chorioretinopathy.

    Science.gov (United States)

    Ojima, Yumiko; Tsujikawa, Akitaka; Yamashiro, Kenji; Ooto, Sotaro; Tamura, Hiroshi; Yoshimura, Nagahisa

    2010-01-01

    To study morphologically and functionally the prognosis of damaged outer segments of the foveal photoreceptor layer in eyes with resolved central serous chorioretinopathy (CSC). We studied retrospectively the medical records of 70 patients (74 eyes) with resolved CSC. Optical coherence tomography was used to detect the junctions between inner and outer segments of the photoreceptors (IS/OS) as a hallmark of the integrity of the outer photoreceptor layer. In 53 eyes (71.6%), the IS/OS line was clearly detected beneath the fovea immediately after resolution of the retinal detachment, with good visual acuity (VA). In the remaining 21 eyes (28.4%), however, the foveal IS/OS line could not be detected shortly after resolution of CSC, and VA was variable, ranging from 0.1 to 1.5 (median, 0.9). Of these 21 eyes, 15 had a follow-up examination with OCT, and in four the foveal IS/OS line was not detected at the follow-up and vision in these eyes remained poor. However, nine eyes showed recovery of the foveal IS/OS line during follow-up, and these eyes had substantial visual recovery. Immediately after resolution of active CSC, although the IS/OS line cannot be detected beneath the fovea, it often shows restoration over time, with visual recovery, though in some eyes no restoration takes place and the prognosis remains poor.

  19. PTEN Sequence Analysis in Endometrial Hyperplasia and Endometrial Carcinoma in Slovak Women

    Directory of Open Access Journals (Sweden)

    H. Gbelcová

    2015-01-01

    Full Text Available Phosphatase and tensin homolog (PTEN is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa. ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3, complex hyperplasia (5, atypical complex hyperplasia (7, endometrioid carcinomas G1 (20 and G3 (5, and serous carcinoma (5 were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.

  20. Carcinoma gallbladder.

    Science.gov (United States)

    Biswas, P K

    2010-07-01

    Carcinoma gallbladder (CaGb) is a rare disease. The aetiology of CaGb is yet not known. However the risk of CaGb is increased in anomalous pancreaticobiliary duct junction (APBDJ), gall stones, xanthogranulomatus cholecystitis, calcified or porcelain gallbladder, cholelithiasis with typhoid carriers, gallbladder adenoma, red meat consumption and tobacco uses. There are protective effects of vegetables on CaGb. Most of the cases present with advanced disease. In early carcinoma of a gallbladder sign and symptoms mimic benign disease. The diagnosis is established by ultrasonography, computerized tomography and guided fine needle aspiration cytology (FNAC). Biochemical tests are of very little value in making a diagnosis. The treatment depends on the clinical stage at presentation. Surgery offers the best chance of cure. In stage T1a, laparoscopic or open cholecystectomy alone is curative, and in T1b, cholecystectomy with hepatoduodenal lymph node dissection without combined resection of an adjacent organ is required. Segment S4a+5 hepatectomy combined with extrahepatic bile duct resection (BDR) and D2 lymph node dissection is a highly recommended operation for the treatment of T2 and T3 CaGb. The dye injection method is useful in determining the appropriate extent of hepatic resection for advanced CaGb. Resurgery is required only in those cases where tumour has invaded the serosa and/ or adjacent structures when diagnosed postoperatively. Biliary bypass is required for palliation. Prognosis depends on early diagnosis and appropriate surgical excision.

  1. Irradiation of metastatic carcinoma parotid

    International Nuclear Information System (INIS)

    Jack, G.A.

    1981-01-01

    Acinic cell carcinomas of the parotid should be considered distinct malignancies despite descriptions of low-grade malignant potential and innocuous histologic patterns. Benign-appearing tumors frequently have a clinically malignant course. Blood-borne metastases may oocur early despite gross and microscopic innocence. Indolent growth may be a characteristic of local disease, which may then be approached with less than radical parotidectomy and sacrifice of the facial nerve. These tumors prove to be radiosensitive. More agressive postoperative irradiation and palliative irradiation is recommended. Two cases of successful palliation of spinal metastases are presented as examples of radiosensitivity of this tumor

  2. Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis.

    Science.gov (United States)

    Rubio, Carlos A; DE Petris, Giovanni; Puppa, Giacomo

    2018-02-01

    In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours. The clinical history, age, gender, endoscopic descriptions, and the pathology (localization, gross and histological descriptions of the luminal surface) of the four UC-GALT carcinomas reported in the literature were reviewed. The luminal surface in three out of the four carcinomas revealed conventional (tubular/villous) adenomas or high-grade dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0). GALT carcinomas do occur, albeit infrequently, in patients with UC. The finding that three out of the four GALT carcinomas on record were covered by conventional adenomas or by high-grade dysplasia strongly suggests that non-invasive conventional neoplasias might often precede GALT carcinomas in UC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Vulvar carcinoma

    International Nuclear Information System (INIS)

    Anderson, John M.; Cassady, J. Robert; Shimm, David S.; Stea, Baldassarre

    1995-01-01

    Purpose: Controversies exist regarding the use of radiation therapy in the treatment of vulvar carcinoma. A retrospective review was performed to evaluate our institution's experience with surgery and radiation for this disease. Methods and Materials: The medical records of 47 patients treated for squamous cell carcinoma of the vulva at our institution (1974-1992) were reviewed for TNM stage (AJCC criteria), treatment modality, and associated 5-year local control and survival based on Kaplan-Meier analysis. Results: Twenty-eight patients (60%) presented with Stage I and II disease and their 5-year survival was 69%. Stage III patients accounted for 12 (25%) of the patients and their 5-year survival was 73%. Seven patients presented with Stage IV disease and five died within 13 months of diagnosis after predominantly palliative therapy. The 40 patients with Stages I, II, and III disease were treated aggressively and were further evaluated for treatment-modality-associated survival and local control. Radiation therapy was used as primary treatment in nine patients, of whom seven were treated with radiation alone and two were treated postoperatively after wide excision. Surgery alone was performed in 31 patients consisting of either radical vulvectomy (20 patients) or wide excision (11 patients). When comparing outcomes of radical vulvectomy vs. radiation therapy, we noted that the 5-year actuarial survivals were comparable (74% for either modality), despite the presence of more favorable prognostic factors in the group treated with radical vulvectomy. Patients treated with wide excision alone had a trend for a poorer 5-year actuarial survival (51%) and local control (50%). Conclusions: Radical vulvectomy offers good locoregional control and survival. This retrospective review further supports the use of radiation therapy with conservative surgery as an alternative treatment option for patients with vulvar carcinoma treated with curative intent. In contrast, the use of

  4. Teachers' Grading Decision Making

    Science.gov (United States)

    Isnawati, Ida; Saukah, Ali

    2017-01-01

    This study investigated teachers' grading decision making, focusing on their beliefs underlying their grading decision making, their grading practices and assessment types, and factors they considered in grading decision making. Two teachers from two junior high schools applying different curriculum policies in grade reporting in Indonesian…

  5. Oropharyngeal carcinoma

    International Nuclear Information System (INIS)

    Nose, Takayuki; Inoue, Takehiro; Inoue, Toshihiko

    1996-01-01

    From June 1993 through October 1996, nineteen oropharynx cancer patients (squamous cell carcinoma T1; 1, T2; 10, T3; 6, T4; 1, and adenocarcinoma T2; 1) were treated with high dose rate interstitial radiotherapy combined with moderate external radiotherapy. Fourteen patients (T1; 1, T2; 10 and T3; 3) were controlled locally and five patients (T3; 3, T4; 1 and adenocarcinoma; 1) were not. Temporary soft tissue necrosis were experienced among four patients. With short follow-up period xerostomia and dysgeusia were less than definitive external radiotherapy as clinical impression. In addition with markedly increased tumor dose the local control rate can be improved. This treatment method can be an alternative to definitive external radiotherapy to gain better QOL and higher control rate. (author)

  6. High-grade acute organ toxicity and p16INK4A expression as positive prognostic factors in primary radio(chemo)therapy for patients with head and neck squamous cell carcinoma

    International Nuclear Information System (INIS)

    Tehrany, Narges; Rave-Fraenk, Margret; Hess, Clemens F.; Wolff, Hendrik A.; Kitz, Julia; Li, Li; Kueffer, Stefan; Lorenzen, Stephan; Beissbarth, Tim; Burfeind, Peter; Reichardt, Holger M.; Canis, Martin

    2015-01-01

    Superior treatment response and survival for patients with human papilloma virus (HPV)-positive head and neck cancer (HNSCC) are documented in clinical studies. However, the relevance of high-grade acute organ toxicity (HGAOT), which has also been correlated with improved prognosis, has attracted scant attention in HPV-positive HNSCC patients. Hence we tested the hypothesis that both parameters, HPV and HGAOT, are positive prognostic factors in patients with HNSCC treated with definite radiotherapy (RT) or radiochemotherapy (RCT). Pretreatment tumor tissue and clinical records were available from 233 patients receiving definite RT (62 patients) or RCT (171 patients). HPV infection was analysed by means of HPV DNA detection or p16 INK4A expression; HGAOT was defined as the occurrence of acute organ toxicity >grade 2 according to the Common Toxicity Criteria. Both variables were correlated with overall survival (OS) using Cox proportional hazards regression. Positivity for HPV DNA (44 samples, 18.9 %) and p16 INK4A expression (102 samples, 43.8 %) were significantly correlated (p < 0.01), and HGAOT occurred in 77 (33 %) patients. Overall, the 5-year OS was 23 %; stratified for p16 INK4A expression and HGAOT, OS rates were 47 %, 42 %, 20 % and 10 % for patients with p16 INK4A expression and HGAOT, patients with HGAOT only, patients with p16 INK4A expression only, and patients without p16 INK4A expression or HGAOT, respectively. After multivariate testing p16 INK4A expression (p = 0.003) and HGAOT (p < 0.001) were significantly associated with OS. P16 INK4A expression and HGAOT are independent prognostic factors for OS of patients with HNSCC, whereas p16 INK4A expression is particularly important for patients without HGAOT. (orig.) [de

  7. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  8. Student Attitudes Toward Grades and Grading Practices.

    Science.gov (United States)

    Stallings, William M.; Leslie, Elwood K.

    The result of a study designed to assess student attitudes toward grading practices are discussed. Questionnaire responses of 3439 students in three institutions were tabulated. Responses were generally negative toward conventional grading systems. (MS)

  9. Mucoepidermoid carcinoma of lung masquerading as urothelial carcinoma of bladder

    Science.gov (United States)

    Graham, Donna M.; O’Connor, Kate M.; Hinchion, John; Coate, Linda E.; Burke, Louise; Power, Derek G.

    2013-01-01

    Background Mucoepidermoid carcinoma (MEC) of the lung is a rare subtype of non-small cell lung cancer. There is no consensus regarding optimal management for this disease. Case report We present a case of MEC of the lung in a 75 year-old female with a history of superficial urothelial carcinoma of the bladder. The patient was found to have an asymptomatic lung mass. Initial biopsy suggested metastatic recurrence of urothelial carcinoma and therefore, cisplatin and gemcitabine chemotherapy was administered prior to surgical resection. Pathological analysis of the resected specimen confirmed a diagnosis of stage IIIA MEC with focal high-grade features including transitional cell-like areas. Adjuvant radiotherapy was administered due to a positive microscopic resection margin. No chemotherapy was given due to lack of supporting data. The patient developed widespread metastatic disease 3 months following completion of radiotherapy and died 1 month later. Conclusion This case demonstrates the possibility of dual pathology in cases where metastatic disease is suspected. The use of small tissue samples may complicate diagnosis due to the heterogeneity of malignant tumours. PMID:24936321

  10. RhoB mediates antitumor synergy of combined ixabepilone and sunitinib in human ovarian serous cancer.

    Science.gov (United States)

    Vishnu, Prakash; Colon-Otero, Gerardo; Kennedy, Gregory T; Marlow, Laura A; Kennedy, William P; Wu, Kevin J; Santoso, Joseph T; Copland, John A

    2012-03-01

    The aim was to evaluate antitumor activity of the combination of ixabepilone and sunitinib in pre-clinical models of chemotherapy naïve and refractory epithelial ovarian tumors, and to investigate the mechanism of synergy of such drug combination. HOVTAX2 cell line was derived from a metastatic serous papillary epithelial ovarian tumor (EOC) and a paclitaxel-resistant derivative was established. Dose response curves for ixabepilone and sunitinib were generated and synergy was determined using combination indexes. The molecular mechanism of antitumor synergy was examined using shRNA silencing. The combination of ixabepilone and sunitinib demonstrated robust antitumor synergy in naïve and paclitaxel-resistant HOVTAX2 cell lines due to increased apoptosis. The GTPase, RhoB, was synergistically upregulated in cells treated with ixabepilone and sunitinib. Using shRNA, RhoB was demonstrated to mediate antitumor synergy. These results were validated in two other EOC cell lines. Ixabepilone plus sunitinib demonstrated antitumor synergy via RhoB in naïve and paclitaxel-resistant cells resulting in apoptosis. This study demonstrates a novel mechanism of action leading to antitumor synergy and provides 'proof-of-principle' for combining molecular targeted agents with cytotoxic chemotherapy to improve antitumor efficacy. RhoB could be envisioned as an early biomarker of response to therapy in a planned Phase II clinical trial to assess the efficacy of ixabepilone combined with a receptor tyrosine kinase inhibitor such as sunitinib. To the best of our knowledge, this is the first demonstration of antitumor synergy between these two classes of drugs in EOC and the pivotal role of RhoB in this synergy. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Central serous chorioretinopathy fundus autofluorescence comparison with two different confocal scanning laser ophthalmoscopes.

    Science.gov (United States)

    Nam, Ki Tae; Yun, Cheol Min; Kim, Jee Taek; Yang, Kyung-Sook; Kim, Hyun Joo; Kim, Seong-Woo; Oh, Jaeryung; Huh, Kuhl

    2015-12-01

    To compare the lesion characteristics of two different types of confocal scanning laser ophthalmoscopy (cSLO) autofluorescence (AF) images in central serous chorioretinopathy (CSC). The study included 63 eyes of 61 patients; 63 pairs of fundus autofluorescence (FAF) images were compared before CSC resolution in 63 eyes, FAF images of 31 eyes were also compared after CSC resolution. The lesion characteristics (brightness and composite pattern) were compared between Heidelberg Retina Angiograph 2 (HRA2; Heidelberg Engineering, Germany) and Optomap Tx (Optomap; Optos, Scotland) FAF images. The lesion composite pattern was categorized as diffuse or granular. Diffuse AF was defined as homogenously increased or decreased AF, and granular AF was defined as dot-like, coarse changes in AF. The mean disease duration and subretinal fluid (SRF) height in the spectral domain optical coherence tomography were compared according to the FAF image characteristics. Lesion brightness before CSC resolution was hypo-AF in 48 eyes (76.2 %), hyper-AF in three (4.8 %), and mixed-AF in 12 (19.0 %) in HRA2 FAF images. In comparison, nine (14.3 %) images were hypo-AF, 44 (69.8 %) were hyper-AF, and 10 (15.9 %) were mixed-AF in Optomap FAF images (P < 0.0001). There was no significant difference in lesion composite pattern between the two FAF image wavelengths. Patients with lesions that were hyper-AF in Optomap FAF and hypo-AF in HRA2 FAF had a shorter disease duration and greater SRF height (1 month, 281 um) than those who were hyper-AF in both Optomap and HRA2 images (26 months, 153 um; P = 0.004, 0.001). The two types of FAF images of CSC showed different lesion brightness before and after CSC resolution but demonstrated similar lesion composite patterns.

  12. Cushing’s Syndrome and Hypothalamic–Pituitary–Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy

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    Femke M. van Haalen

    2018-02-01

    Full Text Available ObjectiveCentral serous chorioretinopathy (CSC, a specific form of macular degeneration, has been reported as presenting manifestation of Cushing’s syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing’s syndrome. It is important to know whether CSC patients should be screened for Cushing’s syndrome. Although hypothalamic-pituitary-adrenal (HPA axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing’s syndrome prevalence is increased among chronic CSC (cCSC patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis.DesignCross-sectional study.Patients86 cCSC patients and 24 controls.MeasurementsPrevalence of Cushing’s syndrome, HPA axis activity.ResultsNone of the cCSC patients met the clinical or biochemical criteria of Cushing’s syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires.ConclusionNo case of Cushing’s syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing’s syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

  13. Macular Retinal Vessel Oxygen Saturation Elevation in Chinese Central Serous Chorioretinopathy

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    Cheng Li

    2017-01-01

    Full Text Available Purpose. To evaluate the retinal vessel oxygen saturation in central serous chorioretinopathy (CSC cases among the Chinese. Methods. Relative oxygen saturation of retinal blood vessels was measured in 33 Chinese patients with single-eye CSC using the Oxymap T1 retinal oximeter. The contralateral eyes were the control. The mean saturation of the retinal arteriole (AS and venule (VS, arteriovenous difference (AVS, and arteriole and venule diameters (AD, VD was analyzed in the optic disc area and macular region. Results. In the optic disc area, the inferotemporal quadrant (TI AS (93.2 ± 10.2% and inferonasal quadrant (NI VS (61.3 ± 7.3% were higher in the affected eyes than in the contralateral eyes (88.7 ± 7.7% and 56.9 ± 6.5% and AVS in NI (36.7 ± 10.4% decreased compared to the contralateral eyes (41.5 ± 11.2%. The VD in TI was expanded (19.9 ± 2.5 pixels versus 18.1 ± 3.4 pixels. Around the macular region, AS was 93.6 ± 7.6%, higher than in the contralateral eyes (89.5 ± 6.3%. No other significant changes were found. Conclusions. AS increased in the TI, and VS decreased in the NI in the eyes with CSC. In addition, AS also increased around the macular region, suggesting that these are contributors to CSC pathophysiology.

  14. Cigarette smoking and the association with serous ovarian cancer in African American women: African American Cancer Epidemiology Study (AACES).

    Science.gov (United States)

    Kelemen, Linda E; Abbott, Sarah; Qin, Bo; Peres, Lauren Cole; Moorman, Patricia G; Wallace, Kristin; Bandera, Elisa V; Barnholtz-Sloan, Jill S; Bondy, Melissa; Cartmell, Kathleen; Cote, Michele L; Funkhouser, Ellen; Paddock, Lisa E; Peters, Edward S; Schwartz, Ann G; Terry, Paul; Alberg, Anthony J; Schildkraut, Joellen M

    2017-07-01

    Smoking is a risk factor for mucinous ovarian cancer (OvCa) in Caucasians. Whether a similar association exists in African Americans (AA) is unknown. We conducted a population-based case-control study of incident OvCa in AA women across 11 geographic locations in the US. A structured telephone interview asked about smoking, demographic, health, and lifestyle factors. Odds ratios and 95% confidence intervals (OR, 95% CI) were estimated from 613 cases and 752 controls using unconditional logistic regression in multivariable adjusted models. Associations were greater in magnitude for serous OvCa than for all OvCa combined. Compared to never smokers, increased risk for serous OvCa was observed for lifetime ever smokers (1.46, 1.11-1.92), former smokers who quit within 0-2 years of diagnosis (5.48, 3.04-9.86), and for total pack-years smoked among lifetime ever smokers (0-5 pack-years: 1.79, 1.23-2.59; >5-20 pack-years: 1.52, 1.05-2.18; >20 pack-years: 0.98, 0.61-1.56); however, we observed no dose-response relationship with increasing duration or consumption and no significant associations among current smokers. Smoking was not significantly associated with mucinous OvCa. Associations for all OvCa combined were consistently elevated among former smokers. The proportion of ever smokers who quit within 0-2 years was greater among cases (23%) than controls (7%). Cigarette smoking may be associated with serous OvCa among AA, which differs from associations reported among Caucasians. Exposure misclassification or reverse causality may partially explain the absence of increased risk among current smokers and lack of dose-response associations. Better characterization of smoking patterns is needed in this understudied population.

  15. Loss-of-heterozygosity on chromosome 19q in early-stage serous ovarian cancer is associated with recurrent disease

    International Nuclear Information System (INIS)

    Skirnisdottir, Ingiridur; Mayrhofer, Markus; Rydåker, Maria; Åkerud, Helena; Isaksson, Anders

    2012-01-01

    Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function. The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome

  16. Effect of ranibizumab on serous and vascular pigment epithelial detachments associated with exudative age-related macular degeneration

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    Panos GD

    2013-07-01

    Full Text Available Georgios D Panos,1 Zisis Gatzioufas,1 Ioannis K Petropoulos,1 Doukas Dardabounis,2 Gabriele Thumann,1 Farhad Hafezi11Department of Ophthalmology, Geneva University Hospitals and Faculty of Medicine of the University of Geneva, Switzerland; 2Department of Ophthalmology, University Hospital of Alexandroupolis, GreecePurpose: To report the effect of intravitreal ranibizumab therapy for serous and vascular pigment epithelial detachments (PED associated with choroidal neovascularisation (CNV secondary to age-related macular degeneration (AMD.Methods: In a prospective study, best-corrected visual acuity (BCVA and optical coherence tomography (OCT data were collected for 62 eyes of 62 patients, with serous or vascular PED associated with CNV secondary to AMD. Intravitreal ranibizumab 0.5 mg was administered with a loading phase of three consecutive monthly injections, followed by monthly review with further treatment, as indicated according to the retreatment criteria of the PrONTO study. The change in visual acuity and PED height from baseline to month 12 after the first injection was determined.Results: Sixty-one eyes of 61 patients (one of the patients developed retinal pigment epithelial tear and was excluded from the study were assessed at the 12-month follow-up examination. There were two types of PED, including vascular PED in 32 patients (Group A and serous PED (Group B in 29 patients. The mean improvement of mean BCVA from baseline to 12 months was 0.09 logMAR (Logarithm of the Minimum Angle of Resolution in Group A and 0.13 logMAR in Group B. Both groups showed significant improvement of the mean BCVA 12 months after the first injection compared with the baseline value (P < 0.05. In relation to the PED height, the mean decrease of mean PED height from baseline to 12 months was 135 µm in Group A and 180 µm in Group B. Both groups showed significant reduction of the PED height during the follow-up period (P < 0.01. The PED anatomical response

  17. Giant serous cystadenoma arising from an accessory ovary in a morbidly obese 11-year-old girl: a case report.

    Science.gov (United States)

    Sharatz, Steven M; Treviño, Taína A; Rodriguez, Luís; West, Jared H

    2008-01-18

    Ectopic ovarian tissue is an unusual entity, especially if it is an isolated finding thought to be of embryological origin. An 11-year-old, morbidly obese female presented with left flank pain, nausea, and irregular menses. Various diagnostic procedures suggested a large ovarian cyst, and surgical resection was performed. Histologically, the resected mass was not of tubal origin as suspected, but a serous cystadenoma arising from ovarian tissue. The patient's two normal, eutopic ovaries were completely uninvolved and unaffected. A tumor arising from ectopic ovarian tissue of embryological origin seems the most likely explanation. We suggest refining the descriptive nomenclature so as to more precisely characterize the various presentations of ovarian ectopia.

  18. Microcystic Variant of Urothelial Carcinoma

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    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  19. Primary Fallopian Tube Carcinoma: A Case Report and Literature Review.

    Science.gov (United States)

    Rexhepi, Meral; Trajkovska, Elizabeta; Ismaili, Hysni; Besimi, Florin; Rufati, Nagip

    2017-06-15

    Primary fallopian tube carcinoma (PFTC) is a rare tumour of the female genital tract with an incidence of 0.1-1.8% of all genital malignancies, and it is very difficult to diagnose preoperatively, because of its non-specific symptomatology. In most cases, it is an intraoperative finding or a histopathological diagnosis. It is a tumour that histologically and clinically resembles epithelial ovarian cancer. We are reporting a case of a 62-year-old, postmenopausal women with primary fallopian tube carcinoma of the right fallopian tube in stage IA. The patient has lower abdominal pain, watery vaginal discharge and repeated episodes of bleeding from the vagina. The clinical and radiological findings suggested a right adnexal tumour with elevated CA-125 levels. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and peritoneal washing were performed. Pathologic confirmation of primary serous cystadenocarcinoma of the right fallopian tube was made. Peritoneal washings were negative for malignancy. FIGO stage was considered as IA, and the patient received no courses of chemotherapy and postoperative radiation because she refused it. Ten months after initial surgery, the patient is alive and in good condition. Cytoreduction surgery followed by adequate cycles of chemotherapy is an important strategy to improve patients' prognosis.

  20. Choanal stenosis: a rare complication of radiotherapy for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Bonfils, P.; Preobrajenski, N. de; Florent, A.; Bensimon, J.L.

    2007-01-01

    Choanal stenosis is usually a congenital anomaly in children. Acquired choanal stenosis after radiotherapy for nasopharyngeal carcinoma is a very rare pathology; only two publications report seven cases in the literature. We describe the clinical history, preoperative evaluation, surgical treatment and outcome of a case of acquired choanal stenosis after radiotherapy. The patient, a 56-year-old woman, presented with a history of nasopharyngeal carcinoma (T2- NO-MO) one year before that had been successful treated with radiotherapy (68 Gy). At the end of radiotherapy, she complained of complete nasal obstruction, anosmia and hearing loss due to a bilateral serous otitis media. Bilateral complete choanal stenosis was confirmed by endoscopy and CT scan. Functional endoscopic surgery was performed, and nasal stents were left in place for 3 weeks. One year after, the patient have good airflow, and a patent nasopharynx without choanal stenosis. In conclusion, choanal stenosis is an unusual complication of radiotherapy that can be successfully treated with trans-nasal endoscopic resection. (authors)

  1. VEGF immunoexpression in penile carcinoma

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    Antonio Carlos Pereira Martins

    2002-01-01

    Full Text Available OBJECTIVE: To investigate the vessel endothelial growth factor (VEGF as a risk factor in squamous cell carcinoma of the penis (SCCP. METHODS: Forty-seven patients with penile carcinoma were evaluated retrospectively. The mean age and standard deviation were 61.1±11.7 years. All of them were treated by penectomy and those with positive nodes underwent groin lymphadenectomy. Tumor grading was 35 G1 and 12 G2/3. Primary lesion stage was 24 pT1 and 23 pT2-4. Positive inguinal nodes were observed in 15 patients. Selected paraffin embedded sections were submitted to VEGF immunohistochemical analysis by the avidin-biotin-immunoperoxidase method with antigen retrieval. All slides were examined using an automatic analyzer system and the proportion of labeled cells in 10 high magnification power fields (400X were recorded in a blind analysis. RESULTS: Median (% labeling index was 2.3 in G1 versus 2.2 in G2/3 tumors (p=0.60, and 4.0 in pT1 versus 1.8 pT2-4 tumors (p=0.10. The respective data for pN0 patients was 2.8 and for pN+ was 2.1 (p=0.20. Survival curves showed no association with patients survival. CONCLUSION: In squamous cell carcinoma of the penis the VEGF immunoexpression has no association with tumor grade or stage, as well as with patient survival.

  2. Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

    Science.gov (United States)

    2018-05-14

    Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma

  3. Thyroid cancer - medullary carcinoma

    Science.gov (United States)

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

  4. High-grade acute organ toxicity and p16{sup INK4A} expression as positive prognostic factors in primary radio(chemo)therapy for patients with head and neck squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tehrany, Narges; Rave-F