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Sample records for serous borderline tumor

  1. Sonographic findings of an ovarian serous surface papillary borderline tumor.

    PubMed

    Kwon, Yohan; Park, Sung Bin; Lee, Jong Beum; Park, Hyun Jeong

    2013-01-01

    Sonographic findings of a serous surface papillary borderline tumor of the ovary have rarely been reported in the English literature. Here, we describe a case of serous surface papillary borderline tumor, which was depicted on gray-scale and Doppler ultrasonography as smoothly lobulated and polypoid heterogeneous echoic bilateral adnexal masses encased or surrounded by what was presumed to be normal-appearing ovarian follicles with increased vascular flow. PMID:23938140

  2. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.

    PubMed

    Curry, Edward W J; Stronach, Euan A; Rama, Nona R; Wang, Yuepeng Y P; Gabra, Hani; El-Bahrawy, Mona A

    2014-03-01

    Borderline ovarian tumors show heterogeneity in clinical behavior. Most have excellent prognosis, although a small percentage show recurrence or progressive disease, usually to low-grade serous carcinoma. The aim of this study was to understand the molecular relationship between these entities and identify potential markers of tumor progression and therapeutic targets. We studied gene expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An independent data set of 18 serous borderline tumors and 3 low-grade serous carcinomas was used for validation. Unsupervised clustering revealed clear separation of benign and malignant tumors, whereas borderline tumors showed two distinct groups, one clustering with benign and the other with malignant tumors. The segregation into benign- and malignant-like borderline molecular subtypes was reproducible on applying the same analysis to an independent publicly available data set. We identified 50 genes that separate borderline tumors into their subgroups. Functional enrichment analysis of genes that separate borderline tumors to the two subgroups highlights a cell adhesion signature for the malignant-like subset, with Claudins particularly prominent. This is the first report of molecular subtypes of borderline tumors based on gene expression profiling. Our results provide the basis for identification of biomarkers for the malignant potential of borderline ovarian tumor and potential therapeutic targets for low-grade serous carcinoma. PMID:23948749

  3. Ultrasound diagnosis of serous surface papillary borderline ovarian tumor: A case series with a review of the literature.

    PubMed

    Ludovisi, Manuela; Foo, Xulin; Mainenti, Sara; Testa, Antonia Carla; Arora, Rupali; Jurkovic, Davor

    2015-01-01

    Serous surface papillary borderline ovarian tumors (SSPBOTs) are a rare morphologic variant of serous ovarian tumors that are typically confined to the ovarian surface, while the ovaries themselves tend to appear normal in size and shape. In this report, we describe the findings from five premenopausal women diagnosed with SSPBOTs, in whom ultrasound showed grossly normal ovaries that were partially or wholly covered with irregular solid tumors. In all five cases, histologic examination showed evidence of borderline serous tumors. These findings demonstrate that SSPBOTs can be diagnosed on a preoperative sonographic examination, which could facilitate conservative, fertility-sparing surgery in young women affected by this condition. PMID:25706035

  4. KRAS (but not BRAF) mutations in ovarian serous borderline tumor are associated with recurrent low-grade serous carcinoma

    PubMed Central

    Tsang, Yvonne T.; Deavers, Michael T.; Sun, Charlotte C.; Kwan, Suet-Yan; Kuo, Eric; Malpica, Anais; Mok, Samuel C.; Gershenson, David M.; Wong, Kwong-Kwok

    2014-01-01

    BRAF and KRAS mutations in ovarian serous borderline tumors (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumor samples from 23 recurrent LGSC patients with known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for 5 patients, and either OSBT or LGSC were available for another 18 patients. Tumor cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumors that appeared to have wild-type KRAS by conventional PCR–Sanger sequencing were further analyzed by full COLD (coamplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR–Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in 10 patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in 7 OSBT samples and 6 LGSC samples. To our surprise, patients with the KRAS G12V mutation appeared to have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumor cells with or without detectable KRAS mutations. PMID:24549645

  5. Fine needle aspiration cytology of cervical lymph node involvement by ovarian serous borderline tumor

    PubMed Central

    Chen, Longwen; Butler, Kristina A.; Bell, Debra A.

    2016-01-01

    Serous borderline tumor (SBT) involving a cervical lymph node is extremely rare. In addition, fine needle aspiration (FNA) cytology of the involved cervical lymph node shares tremendous morphologic similarity with other low-grade papillary carcinomas. Thus, it can be easily misdiagnosed as metastatic carcinoma. A 42-year-old female had a history of bilateral SBT and postbilateral salpingo-oophorectomy. She presented with left cervical lymphadenopathy 6 months later. FNA cytology showed a low-grade papillary neoplasm with psammoma bodies. Needle core biopsy along with immunostains was diagnostic of cervical lymph node involvement (LNI) of SBT. although extremely rare, cervical LNI can be found in patients with SBTs. FNA cytology, sometimes, is indistinguishable from metastatic papillary adenocarcinoma. Cell block or needle core biopsy is essential to make the correct diagnosis.

  6. Classification of Extraovarian Implants in Patients With Ovarian Serous Borderline Tumors (Tumors of Low Malignant Potential) Based on Clinical Outcome.

    PubMed

    McKenney, Jesse K; Gilks, C Blake; Kalloger, Steve; Longacre, Teri A

    2016-09-01

    The classification of extraovarian disease into invasive and noninvasive implants predicts patient outcome in patients with high-stage ovarian serous borderline tumors (tumors of low malignant potential). However, the morphologic criteria used to classify implants vary between studies. To date, there has been no large-scale study with follow-up data comparing the prognostic significance of competing criteria. Peritoneal and/or lymph node implants from 181 patients with high-stage serous borderline tumors were evaluated independently by 3 pathologists for the following 8 morphologic features: micropapillary architecture; glandular architecture; nests of epithelial cells with surrounding retraction artifact set in densely fibrotic stroma; low-power destructive tissue invasion; single eosinophilic epithelial cells within desmoplastic stroma; mitotic activity; nuclear pleomorphism; and nucleoli. Follow-up of 156 (86%) patients ranged from 11 to 264 months (mean, 89 mo; median, 94 mo). Implants with low-power destructive invasion into underlying tissue were the best predictor of adverse patient outcome with 69% overall and 59% disease-free survival (P<0.01). In the evaluation of individual morphologic features, the low-power destructive tissue invasion criterion also had excellent reproducibility between observers (κ=0.84). Extraovarian implants with micropapillary architecture or solid nests with clefts were often associated with tissue invasion but did not add significant prognostic value beyond destructive tissue invasion alone. Implants without attached normal tissue were not associated with adverse outcome and appear to be noninvasive. Because the presence of invasion in an extraovarian implant is associated with an overall survival analogous to that of low-grade serous carcinoma, the designation low-grade serous carcinoma is recommended. Even though the low-power destructive tissue invasion criterion has excellent interobserver reproducibility, it is further

  7. Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor

    2016-06-01

    Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays. PMID:27003157

  8. Ovarian serous cystadenofibromas associated with a low-grade serous carcinoma of the peritoneum.

    PubMed

    Hinson, Stacy A; Silva, Elvio G; Pinto, K

    2013-06-01

    Ovarian serous cystadenofibromas are benign neoplasms that sometimes have focal areas of borderline serous tumor and rarely have been associated with epithelial proliferations in the peritoneum, resembling implants. We are reporting 2 cases of ovarian serous cystadenofibromas with serous peritoneal lesions of higher grade than the ovarian tumor: 1 case had a serous carcinoma and another 1 a serous borderline tumor. PMID:22921726

  9. [A serous cystadenoma of the ovary of borderline malignancy with a fifteen-year history. A case report].

    PubMed

    Nagata, O; Aramaki, S; Iino, H; Ishikawa, S; Yoshida, H; Azekami, M; Yamaguchi, Y; Iwasa, T; Matsukuma, K; Iwata, Y

    1990-04-01

    A case of a serous cystadenoma of a ovary of borderline malignancy is reported. Sixteen years earlier, the patient had undergone an exploratory laparotomy because of ovarian tumor, and the histologic diagnosis had been a serous cystadenocarcinoma. Postoperative chemotherapy was not effective and drainage of the tumor fluid had been performed for 15 years, with the estimated drainage volume estimated to have reached, 1,000 1. Gradual malnutrition and marked tumor growth then become apparent. A reevaluation of the initial histologic slides and her clinical course strongly suggested a serous cystadenoma of borderline malignancy. Thus a tumor resection, a bilateral salpingo-oophorectomy, and a hysterectomy was performed. A histologic diagnosis of a resected specimen confirmed a serous cystadenoma of borderline malignancy and the histologic features were quite similar to those of the initial biopsy specimens. The patient is living well postoperatively for 8 months without postoperative chemotherapy. PMID:2325270

  10. Paired box gene 2 is associated with estrogen receptor α in ovarian serous tumors: Potential theory basis for targeted therapy

    PubMed Central

    Wang, Min; Ma, Haifen

    2016-01-01

    It has been suggested that Paired box gene (PAX)2 is activated by estradiol via estrogen receptor (ER)α in breast and endometrial cancer. The expression of PAX2 was restricted to ovarian serous tumors and only one case was positive in borderline mucinous tumor in our previous study. In the present study, immunohistochemistry was performed to assess the expression of ERα in 58 cases of ovarian serous tumors, including 30 serous cystadenomas, 16 borderline serous cystadenomas, 12 serous carcinomas and 67 cases of ovarian mucinous tumors, including 29 mucinous cystadenoma, 23 borderline mucinous cystadenoma and 15 mucinous carcinoma, which were the same specimens with detection of PAX2 expression. The results demonstrated that ERα was expressed in 10% (3/30) of serous cystadenomas, 62.5% (10/16) borderline serous cystadenomas and 66.7% (8/12) serous carcinomas. The expression of ERα in borderline serous cystadenomas and serous carcinomas were significantly higher compared with that in serous cystadenomas (P<0.01). ERα was detected in 3.4% (1/29) mucinous cystadenoma, 26.1% (6/23) borderline mucinous cystadenoma and only 6.7% (1/15) mucinous carcinoma. Furthermore, a scatter plot of the expression of PAX2 and ERα revealed a linear correlation between them in ovarian serous tumors (P<0.0001). With few positive results, no correlation was determined in ovarian mucinous tumors. It was demonstrated that PAX2 is associated with ERα in ovarian serous tumors, and this may become a potential theory basis for targeted therapy for ovarian serous tumors. Further research is required to determine how PAX2 and ERα work together, and the role of targeted therapy in ovarian serous tumors. PMID:27446571

  11. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes.

    PubMed

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David G; Hird, Vicky; Brown, Robert; Flanagan, James; Gabra, Hani; Mills, Gordon B; Agarwal, Roshan; El-Bahrawy, Mona

    2013-04-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study, we conducted an extensive analysis of mutations and single-nucleotide polymorphisms (SNPs) in borderline ovarian tumors. Using the Sequenom MassArray platform, we investigated 160 mutations/polymorphisms in 33 genes involved in cell signaling, apoptosis, angiogenesis, cell cycle regulation and cellular senescence. Of 52 tumors analyzed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in eight tumors (six serous and two mucinous), BRAF V600E mutations in two serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT, respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in vascular endothelial growth factor (VEGF), ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at four loci. PHLPP2 polymorphisms were more frequent in mucinous as compared with serous tumors (P=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional SNPs in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbor somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  12. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes

    PubMed Central

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David Gonzalez; Hird, Vicky; Brown, Robert; Flanagan, James; Hani Gabra, H; Mills, Gordon B.; Agarwal, R; El-Bahrawy, Mona

    2013-01-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study we conducted an extensive analysis of mutations and single nucleotide polymorphisms in borderline ovarian tumors. Using the Sequenom MassARRAY platform we investigated 160 mutations/polymorphisms in 33 genes involved in cell signalling, apoptosis, angiogenesis, cell cycle regulation, and cellular senescence. Of 52 tumors analysed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in 8 tumors (6 serous and 2 mucinous), BRAF V600E mutations in 2 serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in VEGF, ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at 4 loci. PHLPP2 polymorphisms were more frequent in mucinous as compared to serous tumors (p=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional single nucleotide polymorphisms in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbour somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  13. Mucinous borderline ovarian tumor with ascites.

    PubMed

    Batool, Tahira; Ullah, Nasreen Rehmat

    2014-11-01

    Borderline mucinous tumors are epithelial ovarian tumors with low rate of growth and low potential to invade or metastasize and associated with significantly better prognosis and excellent disease-free survival after surgical removal than other epithelial ovarian cancers. The accepted initial treatment is surgical removal of the tumor. Fertility-sparing surgery may suffice in young patients with tumors confined to the ovary. Radical surgery is recommended in patients with advanced disease and advanced age. Long-term surveillance is recommended to document and treat late recurrences. We report a case of a 59 years old postmenopausal patient with complex ovarian mucinous tumor and gross ascites; she had received three lines of chemotherapeutic agents pre-operatively, without any favorable outcome. Then, she went for staging laparotomy and histopathology showed borderline ovarian mucinous tumor required no further treatment and is fine till date. PMID:25518783

  14. Serous Ovarian Carcinoma Recurring as Malignant Mixed Mullerian Tumor

    PubMed Central

    Hale, Demir; Senem, Demiroz Ahu; Ovgu, Aydin; Hakan, Erenel; Sennur, Ilvan; Zerrin, Calay; Fuat, Demirkiran

    2015-01-01

    Only five cases of recurrence of malignant mixed Mullerian tumor (carcinosarcoma) from the ovarian carcinoma have been published in the literature to our knowledge. A 64-year-old woman first underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of pelvic mass. Histological diagnosis was serous papillary carcinoma of the left ovary. After six courses of chemotherapy, CA125 level returned to normal range. However, she had persistent multiple mediastinal and para-aortic lymphadenopathies in spite of additional six courses of chemotherapy. Then she underwent the second operation about 2 years after primary surgery. Multiple excisional biopsies were taken from subcutaneous tissue, over the bowels and the left external iliac artery. The histopathological diagnosis which was confirmed by immunohistochemical study was malignant mixed Mullerian tumor for all metastatic foci. A rare case of ovarian serous papillary carcinoma recurring as malignant mixed Mullerian tumor is reported. PMID:26713165

  15. A case-control study of borderline ovarian tumors: the influence of perineal exposure to talc.

    PubMed

    Harlow, B L; Weiss, N S

    1989-08-01

    The authors interviewed 116 female residents of western Washington State with serous and mucinous borderline ovarian tumors diagnosed between 1980 and 1985 and questioned them on their use of hygienic powders. A sample of 158 control women from the same counties were identified through random digit dialing and were interviewed as well. Neither the perineal application of baby powder nor the perineal application of cornstarch was associated with an appreciably altered risk of borderline ovarian tumors. However, women who used deodorizing powders alone or in combination with other talc-containing powders had 2.8 times the risk (95% confidence interval 1.1-11.7) of women who had not had perineal exposure to powder. These results suggest that future studies of ovarian tumors in relation to the application of talc-containing powders should consider ascertaining the specific type(s) of powder used. PMID:2750733

  16. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

    PubMed Central

    el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.

    2015-01-01

    BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284

  17. Borderline phylloides tumor in an 11-year-old girl.

    PubMed

    Selamzade, M; Gidener, C; Koyuncuoglu, M; Mevsim, A

    1999-07-01

    Phylloides tumor is an uncommon breast tumor in children. Only a few cases have been reported in the literature. A case of borderline phylloides tumor in an 11-year-old girl is described. PMID:10415310

  18. Principles of Treatment for Borderline, Micropapillary Serous, and Low-Grade Ovarian Cancer.

    PubMed

    Hacker, Kari E; Uppal, Shitanshu; Johnston, Carolyn

    2016-09-01

    Borderline ovarian tumors (BOTs) are less common than epithelial ovarian cancers (EOCs). Low-grade EOCs (LG-EOCs) occur even less frequently than BOTs. After primary therapy, recurrence rates of BOTs and LG-EOCs are significantly lower and the stage-adjusted survival is higher than for high-grade EOCs. Thus, determining the best management in terms of traditional ovarian cancer staging and debulking procedures is more challenging and has been recently brought to question. This article reviews the particulars of BOTs and LG-EOCs, their similarities and differences, and how they are best managed and treated, and emphasizes the major role of surgery and the controversial role of chemotherapy. Because these tumors disproportionately affect younger women, this review addresses ovarian preservation in circumstances when fertility or hormonal preservation is desired. PMID:27587627

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

    PubMed Central

    Vitiazeva, Varvara; Kattla, Jayesh J.; Flowers, Sarah A.; Lindén, Sara K.; Premaratne, Pushpa; Weijdegård, Birgitta; Sundfeldt, Karin; Karlsson, Niclas G.

    2015-01-01

    Background 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. Methods 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. Results 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). Conclusion Mucinous benign and LMPs along with mucinous low-grade carcinomas

  20. Detection of the BRAF V600E mutation in serous ovarian tumors: a comparative analysis of immunohistochemistry with a mutation-specific monoclonal antibody and allele-specific PCR.

    PubMed

    Bösmüller, Hans; Fischer, Anna; Pham, Deborah L; Fehm, Tanja; Capper, David; von Deimling, Andreas; Bonzheim, Irina; Staebler, Annette; Fend, Falko

    2013-03-01

    Mutations of components of the mitogen-activated protein kinase pathway, mainly BRAF, are common in serous ovarian borderline tumors, whereas high-grade serous ovarian carcinomas rarely show this feature. With the advent of specific kinase inhibitors active against BRAF-mutated cancers, rapid and sensitive detection of the BRAF V600E, by far the most common mutation of this gene, is of great practical relevance. Currently, BRAF mutations are detected by DNA-based techniques. Recently, a monoclonal antibody (VE1) specific for the BRAF V600E protein suitable for archival tissues has been described. In this study, we compared detection of the V600E mutation in serous ovarian tumors by VE1 immunostaining and by allele-specific polymerase chain reaction. All 141 cases of high-grade serous ovarian cancer showed negative or rarely weak, diffuse background VE1 immunostaining, and BRAF wild type was confirmed by molecular analysis in all tested cases. In contrast, 1 (14%) of 7 low-grade serous carcinomas and 22 (71%) of 31 serous borderline tumors revealed moderate to strong VE1 positivity. Immunostaining was clearly evaluable in all cases with sufficient tumor cells, and only rare cases with narrow cytoplasm were difficult to interpret. The V600E mutation was confirmed by allele-specific polymerase chain reaction and sequencing in all VE1-positive cases. Two VE1-positive cases with low epithelial cell content required repeat microdissection to confirm the presence of the mutation. Immunohistochemistry with the VE1 antibody is a specific and sensitive tool for detection of the BRAF V600E mutation in serous ovarian tumors and may provide a practical screening test, especially in tumor samples with low epithelial content. PMID:23089489

  1. Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study

    PubMed Central

    Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

    2015-01-01

    Background: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). Results: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Conclusion: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed. PMID:25562434

  2. Diagnosis, Treatment, and Follow-Up of Borderline Ovarian Tumors

    PubMed Central

    Zikan, Michal; Dundr, Pavel; Cibula, David

    2012-01-01

    Borderline ovarian tumors represent a heterogeneous group of noninvasive tumors of uncertain malignant potential with characteristic histology. They occur in younger women, are present at an early stage, and have a favorable prognosis, but symptomatic recurrence and death may be found as long as 20 years after therapy in some patients. The molecular changes in borderline ovarian tumors indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). The pathological stage of disease and subclassification of extraovarian disease into invasive and noninvasive implants, together with the presence of postoperative macroscopic residual disease, appear to be the major predictor of recurrence and survival. However, it should be emphasized that the most important negative prognostic factor for recurrence is just the use of conservative surgery, but without any impact on patient survival because most recurrent diseases are of the borderline type—easily curable and with an excellent prognosis. Borderline tumors are difficult masses to correctly preoperatively diagnose using imaging methods because their macroscopic features may overlap with invasive and benign ovarian tumors. Over the past several decades, surgical therapy has shifted from a radical approach to more conservative treatment; however, oncologic safety must always be balanced. Follow-up is essential using routine ultrasound imaging, with special attention paid to the remaining ovary in conservatively treated patients. Current literature on this topic leads to a number of controversies that will be discussed thoroughly in this article, with the aim to provide recommendations for the clinical management of these patients. PMID:23024155

  3. Ovarian-type epithelial tumours of the testis: immunohistochemical and molecular analysis of two serous borderline tumours of the testis.

    PubMed

    Bürger, Tobias; Schildhaus, Hans-Ulrich; Inniger, Reinhard; Hansen, Joachim; Mayer, Peter; Schweyer, Stefan; Radzun, Heinz Joachim; Ströbel, Philipp; Bremmer, Felix

    2015-01-01

    Tumours of ovarian-epithelial type of the testis, including serous borderline tumours, represent very rare entities. They are identical to the surface epithelial tumours of the ovary and have been reported in patients from 14 to 68 years of age. We describe two cases of a 46- and a 39-year old man with incidental findings of intratesticular masses of the left respectively right testis. Under the assumption of a malignant testicular tumour the patients were subjected to inguinal orchiectomy. Histologically, the tumours were identical to their ovarian counterparts: They showed a cystic configuration with a fibrous wall and irregular papillary structures lined by partially multistratified columnar cells and areas of hobnail cells. Furthermore, there was mild cytological atypia with a proliferative activity of below 5% as proved by Ki67 staining; mitoses could not be detected. Immunohistochemically, the tumour cells displayed expression of pan-cytokeratin AE3, progesterone receptor, Wilms' tumour protein (WT1), and PAX8 (Paired box gene 8). Estrogen receptor was expressed in one case. Octamer-binding transcription factor-4 (OCT4), calretinin, thrombomodulin, and D2-40 were not expressed. Mutation testing of BRAF revealed a BRAF V600E mutation in one case, while testing for KRAS mutations proved to be negative in both. The BRAF mutated tumour showed strong cytosolic and membranous positivity for B-Raf also on immunohistochemical analysis. Comparative genomic hybridization of one case could not reveal any chromosomal aberrations. PMID:26197800

  4. Extremely rare borderline phyllodes tumor in the male breast: a case report.

    PubMed

    Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun

    2015-01-01

    Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation. PMID:26316459

  5. Peritoneal tumor spread in serous ovarian cancer-epithelial mesenchymal status and outcome

    PubMed Central

    Auer, Katharina; Bachmayr-Heyda, Anna; Aust, Stefanie; Sukhbaatar, Nyamdelger; Reiner, Agnes Teresa; Grimm, Christoph; Horvat, Reinhard; Zeillinger, Robert; Pils, Dietmar

    2015-01-01

    In this study we aimed to analyze the biological mechanisms underlying apparently different modes of peritoneal tumor spread in serous ovarian cancer: miliary (widespread, millet-like lesions) versus non-miliary (bigger, exophytically growing implants). Tumor tissues and ascites from 23 chemotherapy naive patients were analyzed by RNA-sequencing and flow cytometry. On the basis of differential gene expression between miliary and non-miliary, gene signatures were developed. A calculated tumor spread factor revealed a significant independent negative impact of miliary spread on overall survival (HR 3.77; CI95 1.14–12.39; p = 0.029) in an independent cohort of 165 serous ovarian cancer patients. Comparing previously published epithelial-mesenchymal transition (EMT) gene signatures, non-miliary spread correlated significantly with a reduced epithelial status. We conclude that serous ovarian cancer is a heterogeneous disease with distinct modes of peritoneal tumor spread, differing not only in clinical appearance, but also in molecular characteristics and outcome.. EMT, peritoneal inflammation status, and therapeutic options are discussed. Significance More than half of serous epithelial ovarian cancer patients present with a newly described type of intraperitoneal tumor spread, associated with differences in the inflammation status, activated oncogenic pathways, lack of EMT, and thus reduced overall survival. Both, the diminished immune reaction and the enhanced epithelial and malignant characteristics of the tumor cells open new avenues for therapeutic options and strategies, like Catumaxomab, already in clinical use. PMID:25991672

  6. Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman

    PubMed Central

    Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep

    2015-01-01

    Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682

  7. Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer☆

    PubMed Central

    Makowski, Liza; Zhou, Chunxiao; Zhong, Yan; Kuan, Pei Fen; Fan, Cheng; Sampey, Brante P.; Difurio, Megan; Bae-Jump, Victoria L.

    2014-01-01

    Objectives Obesity is associated with increased risk and worse outcomes for ovarian cancer. Thus, we examined the effects of obesity on ovarian cancer progression in a genetically engineered mouse model of serous ovarian cancer. Methods We utilized a unique serous ovarian cancer mouse model that specifically deletes the tumor suppressor genes, Brca1 and p53, and inactivates the retinoblastoma (Rb) proteins in adult ovarian surface epithelial cells, via injection of an adenoviral vector expressing Cre (AdCre) into the ovarian bursa cavity of adult female mice (KpB mouse model). KpB mice were subjected to a 60% calories-derived from fat in a high fat diet (HFD) versus 10% calories from fat in a low fat diet (LFD) to mimic diet-induced obesity. Tumors were isolated at 6 months after AdCre injection and evaluated histologically. Untargeted metabolomic and gene expression profiling was performed to assess differences in the ovarian tumors from obese versus non-obese KpB mice. Results At sacrifice, mice on the HFD (obese) were twice the weight of mice on the LFD (non-obese) (51 g versus 31 g, p = 0.0003). Ovarian tumors were significantly larger in the obese versus non-obese mice (3.7 cm2 versus 1.2 cm2, p = 0.0065). Gene expression and metabolomic profiling indicated statistically significant differences between the ovarian tumors from the obese versus non-obese mice, including metabolically relevant pathways. PMID:24680597

  8. Ovarian Yolk Sac Tumor With High-Grade Serous Carcinoma in a 62-Year-Old Woman.

    PubMed

    McCarthy, Whitney A; Masand, Ramya P

    2016-06-01

    Ovarian yolk sac tumors are germ cell tumors that usually present in children and young women. Rarely, these tumors can arise in older women, usually in conjunction with surface epithelial tumors, suggesting divergent differentiation from the latter. The combination of mixed ovarian yolk sac tumor and high-grade serous carcinoma is rare, with only one case documented in the literature. We present a case of mixed ovarian yolk sac tumor and high-grade serous carcinoma in a postmenopausal woman, including a brief discussion of the immunohistochemical findings and differential diagnosis. Despite the rarity of mixed ovarian yolk sac tumor and surface epithelial tumors, it is important to recognize the biphasic nature of the tumor, which should prompt a thorough immunohistochemical evaluation. The therapeutic and prognostic implications of proper diagnosis cannot be overemphasized. PMID:26782153

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

    PubMed Central

    Ohman, Anders W.; Hasan, Noor; Dinulescu, Daniela M.

    2014-01-01

    The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early-stages and improving the disease prognosis. PMID:25478323

  10. A case report of a young girl with mucinous borderline tumor of the ovary

    PubMed Central

    Lee, Hyun-Mi; So, Kyeong A; Kim, Mi Kyung; Lee, Yoo Kyung; Lee, In-Ho; Kim, Tae-Jin

    2016-01-01

    Ovarian tumors are relatively rare in children and adolescent. The incidence of malignancies in these groups is 1% to 1.5%. The common histologic type is non-epithelial type such as germ cell tumors or sex cord-stromal tumors and only 10% to 17% of those are epithelial tumors. It is important to accurately diagnose in the early these rare tumors for proper staging and treatment to save the patient's life and fertility. We present a case of a 13-year-old girl with a giant ovarian mucinous borderline tumor. PMID:27462604

  11. A case report of a young girl with mucinous borderline tumor of the ovary.

    PubMed

    Lee, Hyun-Mi; So, Kyeong A; Kim, Mi Kyung; Lee, Yoo Kyung; Lee, In-Ho; Kim, Tae-Jin; Lee, Ki Heon

    2016-07-01

    Ovarian tumors are relatively rare in children and adolescent. The incidence of malignancies in these groups is 1% to 1.5%. The common histologic type is non-epithelial type such as germ cell tumors or sex cord-stromal tumors and only 10% to 17% of those are epithelial tumors. It is important to accurately diagnose in the early these rare tumors for proper staging and treatment to save the patient's life and fertility. We present a case of a 13-year-old girl with a giant ovarian mucinous borderline tumor. PMID:27462604

  12. Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature.

    PubMed

    Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard

    2016-04-10

    Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651

  13. Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature

    PubMed Central

    Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard

    2016-01-01

    Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651

  14. Jejunal Metastasis Colliding With a Borderline Tumor in the Ovary: A Hitherto Unreported Eventuality.

    PubMed

    Piana, Simonetta; Giunta, Alessandro; Valli, Riccardo

    2015-10-01

    Metastatic adenocarcinomas to the ovary can show morphologically innocuous areas simulating primary benign lesions or borderline tumors. Ruling out a metastasis can be a difficult issue for pathologists, especially when facing with cystic tumors. Because of the important clinical implications of differentiating metastatic adenocarcinomas from primary ovarian tumors, the integration of clinical, pathological, and immunohistochemical features is warranted, primarily in case of mucinous adenocarcinomas. Vice versa, the synchronous presence of a metastasis and a primary in the same ovary is virtually excluded as a very unlikely eventuality. Here, we describe a case of metastatic adenocarcinoma from the jejunum colliding with a seromucinous borderline tumor in the same ovary, an unreported eventuality so far. PMID:25911566

  15. Sarcoma-like mural nodule in a borderline mucinous tumor of the ovary: A rare entity.

    PubMed

    Ghosh, Prithwijit; Saha, Kaushik; Bhowmik, Sourav

    2014-10-01

    Sarcoma-like mural nodule (SLMN) is a very uncommon and misleading benign entity which may be associated with benign, borderline or malignant mucinous neoplasm of the ovary. It should be distinguished from other malignant mural nodules with sarcoma, carcinosarcoma or anaplastic carcinoma for proper management. We report a rare case of SLMN in a borderline mucinous tumor of the ovary in a 30-year-old lady. In spite of having confusing histopathological features the final diagnosis was made depending on the younger age of the patient, well circumscription of the nodule, absence of vascular invasion and immunohistochemical profile. PMID:25540570

  16. Multiple direct and indirect mechanisms drive estrogen-induced tumor growth in high grade serous ovarian cancers

    PubMed Central

    Ciucci, Alessandra; Zannoni, Gian Franco; Buttarelli, Marianna; Lisi, Lucia; Travaglia, Daniele; Martinelli, Enrica; Scambia, Giovanni; Gallo, Daniela

    2016-01-01

    The notion that menopausal estrogen replacement therapy increases ovarian cancer risk, but only for the two more common types (i.e. serous and endometrioid), while possibly decreasing risk for clear cell tumors, is strongly suggestive of causality. However, whether estradiol (E2) is tumorigenic or promotes development of occult preexisting disease is unknown. The present study investigated molecular and cellular mechanisms by which E2 modulates the growth of high grade serous ovarian cancer (HGSOC). Results showed that ERα expression was necessary and sufficient to induce the growth of HGSOC cells in in vitro models. Conversely, in vivo experimental studies demonstrated that increasing the levels of circulating estrogens resulted in a significant growth acceleration of ERα-negative HGSOC xenografts, as well. Tumors from E2-treated mice had significantly higher proliferation rate, angiogenesis, and density of tumor-associated macrophage (TAM) compared to ovariectomized females. Accordingly, immunohistochemical analysis of ERα-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women. This study describes novel insights into the impact of E2 on tumor microenvironment, independently of its direct effect on tumor cell growth, thus supporting the idea that multiple direct and indirect mechanisms drive estrogen-induced tumor growth in HGSOC. PMID:26797759

  17. Endometrioid Paraovarian Borderline Cystic Tumor in an Infant with Proteus Syndrome

    PubMed Central

    Vasquez, Liliana; Tello, Mariela; Maza, Ivan; Oscanoa, Monica; Dueñas, Milagros; Castro, Haydee; Latorre, Alan

    2015-01-01

    Ovarian and paraovarian neoplasms are uncommon in children, mainly originating from germ cell tumors and, least frequently, epithelial tumors. There is an association between genital tract tumors and Proteus syndrome, a rare, sporadic, and progressive entity, characterized by a postnatal overgrowth in several tissues caused by a mosaic mutation in the AKT1 gene. We describe a 20-month-old asymptomatic infant with Proteus syndrome who developed an endometrioid paraovarian borderline cystic tumor. This is the youngest patient so far reported in the literature with this rare syndrome and an adnexal tumor of borderline malignancy. A total of nine patients have been described with female tract tumors and associated Proteus syndrome, which includes bilateral ovarian cystadenomas and other benign masses. A paraovarian neoplasm is extremely rare in children and could be considered a criterion for Proteus syndrome. Standardized staging and treatment of these tumors are not well established; however, most authors conclude that these neoplasms must be treated as their ovarian counterparts. PMID:26558123

  18. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  19. A Meta-Analysis on the Impact of Platinum-Based Adjuvant Treatment on the Outcome of Borderline Ovarian Tumors With Invasive Implants

    PubMed Central

    Olschewski, Jessica; Braicu, Ioana; Sehouli, Jalid

    2015-01-01

    Background. Treatment of borderline ovarian tumors (BOTs) remains contentious, and there is no consensus regarding therapy for BOTs with invasive implants (BOTi). The benefits of platinum-based adjuvant treatment were evaluated in patients with BOTi at primary diagnosis. Methods. The PubMed database was systematically searched for articles using the following terms: ((borderline) OR (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND (invasive implants) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR (adjuvant treatment) OR (surgery) OR (surgical treatment)). Results. We identified 27 articles including 3,124 patients, 181 with invasive implants. All studies provided information regarding mortality or recurrence rates. Central pathological examination was performed in 19 studies. Eight studies included more than 75% stage I patients; 7 included only advanced-stage patients, and 14 included only serous BOT. The pooled recurrence estimates for both treatment groups (adjuvant treatment: 44.0%, upfront surgery: 21.3%) did not differ significantly (p = .114). A meta-analysis of the 6 studies providing separate mortality data for both treatment groups favored surgical treatment only, but this difference did not reach statistical significance (.05 < p < .1; odds ratio: 0.33; 95% confidence interval: 0.09–1.71; p = .086). We were unable to pool the results of the included studies because not all studies registered events in both treatment groups. Egger’s regression indicated low asymmetry of the studies (p = .39), and no heterogeneity was found (I2 = 0%). Conclusion. We did not find evidence supporting platinum-based adjuvant therapy for BOT with invasive implants. PMID:25601963

  20. Surgical Management of Benign and Borderline Phyllodes Tumors of the Breast.

    PubMed

    Moutte, Amandine; Chopin, Nicolas; Faure, Christelle; Beurrier, Frédéric; Ho Quoc, Christophe; Guinaudeau, Florence; Treilleux, Isabelle; Carrabin, Nicolas

    2016-09-01

    Phyllodes tumors (PT) are uncommon fibroepithelial breast neoplasms and there is currently no clear consensual treatment for these tumors. The aim of our study was to evaluate the surgical management and outcome of benign and borderline PT. We retrospectively assessed 76 cases of benign or borderline PT managed at the Leon Berard comprehensive cancer center in Lyon, France between July 2003 and December 2013. The mean age at diagnosis was 37.9 years and the median follow-up was 58 months. Seventy-five patients (99%), with a mean tumor size of 27 mm, underwent a breast-conserving procedure. The tumor margins were considered positive (when the tumor was present at the inked surgical section) in seven of 76 cases (9%) and negative in 65 out of 76 cases (86%). We observed the presence of small negative surgical margins <10 mm in 89% and <1 mm in 71% of the patients. Although no re-excision was performed to increase these margins, we did not see any increase in the local recurrence rate (4%) when compared to recurrence rates reported in the literature. We thus suggest that systematic revision surgery for close or positive surgical margins for benign PT should not be systematically performed. However, as recurrences occur within 2 years of initial excision, we recommend a regular clinical and imaging follow-up especially during this period for which patient's compliance is essential. PMID:27265474

  1. Mucinous borderline ovarian tumors: Analysis of 75 patients from a single center

    PubMed Central

    Cömert, Duygu Kavak; Üreyen, Işın; Karalok, Alper; Taşçı, Tolga; Türkmen, Osman; Öcalan, Reyhan; Turan, Taner; Tulunay, Gökhan

    2016-01-01

    Objective To analyze the clinicopathologic features, recurrence and survival rates, reproductive history, and treatment of patients with mucinous borderline ovarian tumors (mBOTs). Material and Methods Patients with a diagnosis of mBOT were evaluated retrospectively. Patients with borderline ovarian tumors other than mucinous type and concomitant invasive cancer were excluded. Results A total of 75 patients were identified. Median age was 38 years. The most common symptom was pain (42.7%). Median CA-125 level was 23.5 IU/mL (range, 1–809 IU/mL). Median tumor size was 200 mm (range, 40–400 mm), and 6.7% of mBOTs were bilateral. Thirty-six (48%) patients underwent staging surgery. Two patients (5.9%) had nodal involvement. One patient received platinum-based adjuvant chemotherapy. One (1.3%) patient had recurrence. None of the patients died because of the ovarian tumor. A total of 43 patients had conservative surgery. Conclusion Prognosis of mBOTs is excellent, and fertility-sparing surgery should be considered in the reproductive age group. Furthermore, the necessity of staging surgery is controversial. PMID:27403076

  2. Granulosa cell tumor presenting with ovarian torsion and de novo borderline mucinous ovarian tumor in the contralateral ovary.

    PubMed

    Ates, S; Sevket, O; Sudolmus, S; Sonmez, F C; Dansuk, R

    2015-01-01

    The authors report a case of 25-year-old women with a rare acute presentation of granulosa cell tumor (GCT) as an ovarian torsion. Right salpingoo-ooferectomy was performed. The pathological diagnosis was GCT One month after the surgery there was a three-cm ovarian cyst in the contralateral ovary and the tumor size increased to six cm in diameter in the following month. Serum inhibin-B levels progressively increased. Cystectomy was performed to contralateral ovary as frozen-section examination indicated mucinous tumor. Final histopathological examination revealed borderline mucinous tumor. Regarding her request, the patient was reoperated again and unilateral oophorectomy and hysterectomy were performed. Clinicians must be aware of the possibility of an underlying malignancy associated with adnexal torsion even in young patients. Frozen section will be helpful in order to avoid incomplete surgeries. Cyst rapidly growing in the ovary in young women should raise the suspicion of a de novo malignancy. PMID:26189271

  3. Primary uterine müllerian mucinous borderline tumor (MMBT) associated with adenomyosis: a case report.

    PubMed

    Kawamura, Keiko; Kaneki, Eisuke; Ogawa, Shinji; Imamura, Hiroko; Ohishi, Yoshihiro; Kobayashi, Hiroaki; Kato, Kiyoko

    2014-03-01

    Müllerian mucinous borderline tumors (MMBTs) usually arise from the ovary. The present report is the first case of primary uterine MMBTs associated with adenomyosis. A 51-year-old woman was referred to our hospital for a complex cystic and solid 4×3 cm right adnexal mass. She had a history of a left ovarian endometriotic cyst and had undergone a left oophorectomy 2 yr prior. A laparotomy was performed, and the tumor was found to be originating in the posterior wall of the uterus. She underwent a total abdominal hysterectomy, right salpingo-oophorectomy, and left salpingectomy. Microscopically, the solid portion of the tumor contained papillary proliferations of glands, which were covered by a mucinous epithelium with mild to moderate nuclear atypia, accompanied by stromal infiltration of inflammatory cells. Islands of adenomyosis were also observed around the cyst. These pathologic findings were similar to the features of ovarian MMBT. We diagnosed this tumor as a uterine MMBT, probably arising from adenomyosis. PMID:24487469

  4. Recognition of serous ovarian tumors in human samples by multimodal nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Adur, Javier; Pelegati, Vitor B.; Costa, Leverson F. L.; Pietro, Luciana; de Thomaz, Andre A.; Almeida, Diogo B.; Bottcher-Luiz, Fatima; Andrade, Liliana A. L. A.; Cesar, Carlos L.

    2011-09-01

    We used a multimodal nonlinear optics microscopy, specifically two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG/THG) microscopies, to observe pathological conditions of ovarian tissues obtained from human samples. We show that strong TPEF + SHG + THG signals can be obtained in fixed samples stained with hematoxylin and eosin (H&E) stored for a very long time, and that H&E staining enhanced the THG signal. We then used the multimodal TPEF-SHG-THG microscopies in a stored file of H&E stained samples of human ovarian cancer to obtain complementary information about the epithelium/stromal interface, such as the transformation of epithelium surface (THG) and the overall fibrillary tissue architecture (SHG). This multicontrast nonlinear optics microscopy is able to not only differentiate between cancerous and healthy tissue, but can also distinguish between normal, benign, borderline, and malignant specimens according to their collagen disposition and compression levels within the extracellular matrix. The dimensions of the layers of epithelia can also be measured precisely and automatically. Our data demonstrate that optical techniques can detect pathological changes associated with ovarian cancer.

  5. Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

    PubMed Central

    Corvigno, Sara; Wisman, G. Bea A.; Mezheyeuski, Artur; van der Zee, Ate G.J.; Nijman, Hans W.; Åvall-Lundqvist, Elisabeth; Östman, Arne; Dahlstrand, Hanna

    2016-01-01

    Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers α-SMA, PDGFβR and desmin. Images were digitally analyzed to yield “metrics” related to vasculature and stroma features. Intra-case analyses showed that PDGFβR in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning α-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGFβR-positive stroma fraction and high PDGFβFR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGFβR- and α-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGFβR in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer. PMID:26918345

  6. Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis

    PubMed Central

    Andersson, Emilia; Poschke, Isabel; Villabona, Lisa; Carlson, Joseph W; Lundqvist, Andreas; Kiessling, Rolf; Seliger, Barbara; Masucci, Giuseppe V

    2016-01-01

    In our previous studies, we have shown that patients with serous ovarian carcinoma in advanced surgical stage disease have a particularly poor prognosis if they carry the HLA-A*02 genotype. This represent a stronger prognostic factor than loss or downregulation of the MHC class I heavy chain (HC) on tumor cells. In this study, we investigated the expression of the non-classical, immune tolerogenic HLA -G and -E on the tumor cells along with the infiltration of immune cells in the tumor microenvironment. FFPE primary tumors from 72 patients with advanced stages of serous adenocarcinoma and metastatic cells present in ascites fluid from 8 additional patients were included in this study. Both expression of HLA-G and aberrant expression of HLA-E were correlated to a significant worse prognosis in patients with HLA-A*02, but not with different HLA genotypes. Focal cell expression of HLA-G correlated to a site-specific downregulation of classical MHC class I HC products and aberrant HLA-E expression, showing a poor survival. HLA-G was more frequently expressed in metastatic cells than in primary tumor lesions and the expression of HLA-G inversely correlated with the frequency of tumor infiltrating immune cells. All these parameters can contribute together to identify and discriminate subpopulations of patients with extremely poor prognosis and can give them the opportunity to receive, and benefit of individually tailored treatments. PMID:26942060

  7. Uterine papillary serous carcinoma.

    PubMed

    Moore, Kathleen N; Fader, Amanda Nickles

    2011-06-01

    Uterine papillary serous carcinoma (UPSC) is a histologic variant of endometrial cancer that accounts for only 10% of new cases of uterine cancer but is responsible for 40% of deaths from the disease. UPSC is an aggressive tumor with a predilection for early spread beyond the uterus. Treatment for UPSC typically entails surgery and in most women is followed by multimodality adjuvant therapy. In this review, we describe the epidemiology, natural history, treatment, and outcome of UPSC. PMID:21508697

  8. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

    PubMed Central

    Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar

    2016-01-01

    Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484

  9. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer

    PubMed Central

    Chuong, Michael D.; Frakes, Jessica M.; Figura, Nicholas; Hoffe, Sarah E.; Shridhar, Ravi; Mellon, Eric A.; Hodul, Pamela J.; Malafa, Mokenge P.; Springett, Gregory M.

    2016-01-01

    Background While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. Methods This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. Results We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. Conclusions These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients. PMID:27034789

  10. Invasive ductal carcinoma within borderline phyllodes tumor with lymph node metastases: A case report and review of the literature

    PubMed Central

    WU, DI; ZHANG, HAIPENG; GUO, LIANG; YAN, XU; FAN, ZHIMIN

    2016-01-01

    Phyllodes tumor (PT) is a rare type of biphasic fibroepithelial neoplasm that may coexist with a breast tumor in rare cases. In the current study, a 52-year-old female presented with a left breast lump. Mammography and sonographic examination results suggested a diagnosis of malignant tumor. Histological analysis revealed a borderline PT with invasive ductal carcinoma (IDC) within the tumor. Due to the presence of a single micrometastasis in three of the sentinel lymph nodes, the patient underwent modified radical mastectomy. The excised tumor contained triple negative breast cancer; therefore, postoperative treatment included six cycles of chemotherapy and 25 cycles of radiotherapy. The patient exhibited no recurrence and no metastatic disease at the 23-month follow-up examination. Thus, the present study discussed the case of a female patient that presented with IDC within borderline PT and reviewed the literature on this rare type of neoplasm. Various types of breast carcinoma have been identified to coexist with PT in different masses; however, no standard therapeutic regimen has been established for the coexistence of PT and breast cancer in the same mass. The present study indicates that determination of an appropriate treatment strategy predominantly depends on the characteristics of the individual breast tumor. PMID:27073506

  11. Clinically occult tubal and ovarian high-grade serous carcinomas presenting in uterine samples: diagnostic pitfalls and clues to improve recognition of tumor origin.

    PubMed

    Bagby, Christina; Ronnett, Brigitte M; Yemelyanova, Anna; Maleki, Zahra; Kuhn, Elisabetta; Vang, Russell

    2013-09-01

    We report the clinicopathologic and immunohistochemical features in 8 patients with tubal or ovarian high-grade serous carcinoma that was present in uterine samples, in which there was the potential for clinical and morphologic misinterpretation as a primary uterine lesion before hysterectomy/bilateral salpingo-oophorectomy. Patients ranged in age from 45 to 70 yr (mean, 57 yr). The initial presentation was variable, ranging from incidental findings on routine Pap smears to pleural effusion. During the preoperative clinical investigation, 7 of 8 patients did not have evidence of an adnexal tumor based on physical examination and radiologic imaging, and serum CA-125 levels were normal to low in 4 of 5 patients. Six patients required multiple rounds of uterine samples, and the preoperative uterine specimens that contained lesional tissue and were available for rereview in all 8 patients included endometrial biopsies/curettages (n=6), endocervical curettages (n=3), Pap smears (n=2), and a hysteroscopic myomectomy specimen (n=1). The amount of carcinoma in these specimens was typically scanty. The lesions in most cases were characterized by detached and minute epithelial clusters, small papillae, and/or individual cells. The constituent glandular cells exhibited notable atypia. Psammoma bodies were identified in only 2 cases. Immunostains for WT-1 were positive in 3 of 4 preoperative specimens. All patients ultimately underwent a hysterectomy/bilateral salpingo-oophorectomy, which revealed an invasive high-grade serous carcinoma of tubal (n=6) or ovarian (n=2) origin. The mean/median tumor size was 3.2/1.7 cm. Transtubal spread was considered the most likely mechanism resulting in tubal/ovarian carcinoma being found in the preoperative uterine samples. These findings highlight the deceptive clinical features of some tubal/ovarian high-grade serous carcinomas, and demonstrate that small and clinically undetectable adnexal high-grade serous carcinomas can initially

  12. Recurrence of Brenner ovary borderline tumor in the abdominal wall postoperative scar--a case report and research of the literature.

    PubMed

    Klasa, Lukasz; Wydra, Dariusz; Biernat, Wojciech

    2014-11-01

    We report a case of a 74-year-old female, who underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy due to a solid-cystic tumor of the right ovary. The histopathological diagnosis revealed a borderline Brenner tumor (BBT). After 25 disease-free months the patient was admitted to a hospital because of a tumor in the postoperative scar of the abdominal wall, later diagnosed as infiltrating Brenner tumor consistent with ovarian borderline lesion. The tumor in the postoperative scar was therefore diagnosed as BBT. The article presents results of literature search on BBT in order to find characteristic features of this very rare ovarian tumor. To the best of our knowledge, this is the first report of subcutaneous recurrence of Brenner ovary tumor of low malignant potential. PMID:25675807

  13. Microfocus of Anaplastic Carcinoma Arising in Mural Nodule of Ovarian Mucinous Borderline Tumor With Very Rapid and Fatal Outcome.

    PubMed

    Mhawech-Fauceglia, Paulette; Ramzan, Amin; Walia, Saloni; Pham, Huyen Q; Yessaian, Annie

    2016-07-01

    A 36-yr-old woman presented with abdominal discomfort. A computed tomography scan revealed a large left cystic and solid pelvic mass without evidence of metastatic disease. Total hysterectomy with bilateral salpingo-oophorectomy and tumor staging was performed. Grossly, the ovarian mass measured 20×18 cm and the cut surface was multiloculated with 1 single mural nodule measuring 2×1.5 cm. The histologic diagnosis of ovarian mucinous borderline tumor with a microfocus of anaplastic carcinoma arising in sarcoma-like mural nodule, FIGO Stage IA was rendered. After 3 mo, the patient returned with symptomatic anemia. A computed tomography scan showed enlarged retroperitoneal and pelvic lymph nodes. Image-guided biopsy of the pelvic lymph node showed a metastatic anaplastic carcinoma from her primary ovarian carcinoma. Chemotherapy was initiated, but the patient developed fulminant disseminated intravascular coagulation within <1 wk of her presentation which was fatal. PMID:26598983

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

    PubMed

    Kurman, R J

    2013-12-01

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

  15. Label-Free LC-MSe in Tissue and Serum Reveals Protein Networks Underlying Differences between Benign and Malignant Serous Ovarian Tumors

    PubMed Central

    Wegdam, Wouter; Argmann, Carmen A.; Kramer, Gertjan; Vissers, Johannes P.; Buist, Marrije R.; Kenter, Gemma G.; Aerts, Johannes M. F. G.; Meijer, Danielle; Moerland, Perry D.

    2014-01-01

    Purpose To identify proteins and (molecular/biological) pathways associated with differences between benign and malignant epithelial ovarian tumors. Experimental Procedures Serum of six patients with a serous adenocarcinoma of the ovary was collected before treatment, with a control group consisting of six matched patients with a serous cystadenoma. In addition to the serum, homogeneous regions of cells exhibiting uniform histology were isolated from benign and cancerous tissue by laser microdissection. We subsequently employed label-free liquid chromatography tandem mass spectrometry (LC-MSe) to identify proteins in these serum and tissues samples. Analyses of differential expression between samples were performed using Bioconductor packages and in-house scripts in the statistical software package R. Hierarchical clustering and pathway enrichment analyses were performed, as well as network enrichment and interactome analysis using MetaCore. Results In total, we identified 20 and 71 proteins that were significantly differentially expressed between benign and malignant serum and tissue samples, respectively. The differentially expressed protein sets in serum and tissue largely differed with only 2 proteins in common. MetaCore network analysis, however inferred GCR-alpha and Sp1 as common transcriptional regulators. Interactome analysis highlighted 14-3-3 zeta/delta, 14-3-3 beta/alpha, Alpha-actinin 4, HSP60, and PCBP1 as critical proteins in the tumor proteome signature based on their relative overconnectivity. The data have been deposited to the ProteomeXchange with identifier PXD001084. Discussion Our analysis identified proteins with both novel and previously known associations to ovarian cancer biology. Despite the small overlap between differentially expressed protein sets in serum and tissue, APOA1 and Serotransferrin were significantly lower expressed in both serum and cancer tissue samples, suggesting a tissue-derived effect in serum. Pathway and subsequent

  16. Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor recurrence in high-grade serous ovarian cancer.

    PubMed

    Ganapathi, Mahrukh K; Jones, Wendell D; Sehouli, Jalid; Michener, Chad M; Braicu, Ioana E; Norris, Eric J; Biscotti, Charles V; Vaziri, Susan A J; Ganapathi, Ram N

    2016-02-01

    Tumor recurrence, following initial response to adjuvant chemotherapy, is a major problem in women with high-grade serous ovarian cancer (HGSOC). Microarray analysis of primary tumors has identified genes that may be useful in risk stratification/overall survival, but are of limited value in predicting the >70% rate for tumor recurrence. In this study, we performed RNA-Seq analysis of primary and recurrent HGSOC to first identify unique differentially expressed genes. From this dataset, we selected 21 archetypical coding genes and one noncoding RNA, based on statistically significant differences in their expression profile between tumors, for validation by qPCR in a larger cohort of 110 ovarian tumors (71 primary and 39 recurrent) and for testing association of specific genes with time-to-recurrence (TTR). Kaplan-Meier tests revealed that high expression of collagen type II, alpha 1 (COL2A1) was associated with delayed TTR (HR = 0.47, 95% CI: 0.27-0.82, p = 0.008), whereas low expression of the pseudogene, solute carrier family 6 member 10 (SLC6A10P), was associated with longer TTR (HR = 0.53, 95% CI: 0.30-0.93, p = 0.027). Notably, TTR was significantly delayed for tumors that simultaneously highly expressed COL2A1 and lowly expressed SLC6A10P (HR = 0.21, 95% CI: 0.082-0.54, p = 0.0011), an estimated median of 95 months as compared to an estimated median of 16 months for subjects expressing other levels of COL2A1 and SLC6A10P. Thus, evaluating expression levels of COL2A1 and SLC6A10P at primary surgery could be beneficial for clinically managing recurrence of HGSOC. PMID:26311224

  17. Borderline Ovarian Tumors and Diagnostic Dilemma of Intraoperative Diagnosis: Could Preoperative He4 Assay and ROMA Score Assessment Increase the Frozen Section Accuracy? A Multicenter Case-Control Study

    PubMed Central

    Gizzo, Salvatore; Berretta, Roberto; Di Gangi, Stefania; Guido, Maria; Zanni, Giuliano Carlo; Franceschetti, Ilaria; Quaranta, Michela; Plebani, Mario; Nardelli, Giovanni Battista; Patrelli, Tito Silvio

    2014-01-01

    The aim of our study was to assess the value of a preoperative He4-serum-assay and ROMA-score assessment in improving the accuracy of frozen section histology in the diagnosis of borderline ovarian tumors (BOT). 113 women presenting with a unilateral ovarian mass diagnosed as serous/mucinous BOT at frozen-section-histology (FS) and/or confirmed on final pathology were recruited. Pathologists were informed of the results of preoperative clinical/instrumental assessment of all patients. For Group_A patients, additional information regarding He4, CA125, and ROMA score was available (in Group_B only CA125 was known). The comparison between Group A and Group B in terms of FS accuracy, demonstrated a consensual diagnosis in 62.8% versus 58.6% (P: n.s.), underdiagnosis in 25.6% versus 41.4% (P < 0.05), and overdiagnosis in 11.6% versus 0% (P < 0.01). Low FS diagnostic accuracy was associated with menopausal status (OR: 2.13), laparoscopic approach (OR: 2.18), mucinous histotype (OR: 2.23), low grading (OR: 1.30), and FIGO stage I (OR: 2.53). Ultrasound detection of papillae (OR: 0.29), septa (OR: 0.39), atypical vascularization (OR: 0.34), serum He4 assay (OR: 0.39), and ROMA score assessment (OR: 0.44) decreased the probability of underdiagnosis. A combined preoperative assessment through serum markers and ultrasonographic features may potentially reduce the risk of underdiagnosis of BOTs on FS while likely increasing the concomitant incidence of false-positive events. PMID:25431767

  18. Cigarette smoking and risk of borderline and invasive epithelial ovarian cancer.

    PubMed

    Gram, Inger T; Braaten, Tonje; Adami, Hans-Olov; Lund, Eiliv; Weiderpass, Elisabete

    2008-02-01

    Studies regarding the association between smoking and risk of epithelial ovarian cancer (EOC) are inconsistent. The purpose of this study was to examine the association between smoking and EOC, overall and according to invasiveness and histological subtype in a cohort of women with a high proportion of smokers at enrollment. We followed 103,081 women, aged 30-50 years in 1991/1992, from the Norwegian-Swedish Women's Lifestyle and Health cohort. The women completed a questionnaire on personal characteristics and exposures at enrollment and were subsequently followed with linkages to national registers through December 31, 2004. We used Cox proportional hazard regression models to estimate hazard ratio (RR) of EOC with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 343 [241 (70%) invasive and 102(30%) borderline] incident EOC cases were identified. Former [HR = 2.2(95% CI 1.0-4.7)] and current [HR = 2.7(95% CI 1.2-5.7)] smokers had a more than doubling in risk for borderline tumors compared to never smokers. Women who had smoked for more than 20 years had 3 times [HR = 3.1(95% CI 1.5-6.7)] the risk of borderline tumors compared to never smokers. A test for trend according to smoking status was almost significant for mucinous tumors (p-trend = 0.05). A significant dose response relationship was found according to smoking intensity [pack-years; (0-9, 0-14, >or= 15)] and duration [number of years; (0-10, 11-20, >or= 20)] for borderline and serous tumors (p-trends < 0.05). In conclusion, smoking may increase the risk of borderline EOC. PMID:17918152

  19. Significance of apoptosis related proteins on malignant transformation of ovarian tumors: A comparison between Bcl-2/Bax ratio and p53 immunoreactivity.

    PubMed

    Zeren, Tamer; Inan, Sevinc; Vatansever, H Seda; Sayhan, Sevil

    2014-10-01

    In this study, we compared the immunoreactivities of Bcl-2, Bax and p53 proteins in ovarian tumors and related the immunohistochemical findings to the histological type of the tumors. Formalin-fixed, paraffin wax-embedded tissue sections from 40 patients who had serous-mucinous borderline tumors and serous-mucinous adenocarcinoma of the ovary (n=10 each) were stained with hematoxylin-eosin (H&E). After histopathological examination, serial sections were stained immunohistochemically with primary antibodies to Bcl-2, Bax and p53 using an avidin-biotin-peroxidase method. A semi-quantitative grading system was used to compare the immunohistochemical staining intensities. The nuclear DNA fragmentation of apoptosis was determined using TUNEL method. As a result of immunohistochemical staining, increased immunoreactivity of Bcl-2 was observed in adenocarcinomas when compared to borderline tumors (P<0.001). Strong immunoreactivity of Bcl-2 and mild immunoreactivities of Bax and p53 were detected in ovarian adenocarcinomas. There were no significant statistical differences in the immunoreactivity of Bax among the histological type of ovarian tumors. Whereas a balance was observed between the immunoreactivities of Bcl-2 and Bax in the borderline cases, and this balance was strongly changed toward the anti-apoptotic Bcl-2 protein in patients with adenocarcinoma. TUNEL staining of sections indicated apoptotic cells in the serous borderline tumors were about 8-fold higher than in the serous adenocarcinoma. The results of this study on apoptosis-related factors might help to develop novel protective and therapeutic approaches, such as isoflavonoids and isothiocyanates, which were associated with decreased Bcl-2/Bax ratio, against the malignant epithelial ovarian tumors. PMID:25108507

  20. Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination

    PubMed Central

    Miyoshi, Ai; Miyatake, Takashi; Hara, Takeya; Tanaka, Asuka; Komura, Naoko; Komiya, Shinnosuke; Kanao, Serika; Takeda, Masumi; Mimura, Mayuko; Nagamatsu, Masaaki; Yokoi, Takeshi

    2015-01-01

    Borderline ovarian tumors are benign but relatively large tumors that are often initially mistaken as ovarian cancers. We report three cases of stage I borderline ovarian tumors having massive ascites that we (preoperatively) suspected of being advanced ovarian cancer. The three patients (35, 47, and 73 years old) reported feeling fullness of the abdomen before consulting their gynecologist. By CT scan, they were diagnosed with a pelvic tumor accompanied by massive ascites, the diameters of which were 11, 20, and 11 cm, respectively. Postsurgical pathology showed all were stage I borderline ovarian tumors without dissemination; two were mucinous and one was serous. The amount of ascites was 6,300, 2,600, and 3,600 mL, respectively, and was serous in all. Cytodiagnosis of the ascites found that one was positive for tumor cells and two were negative. After resection of the mass, the ascites disappeared in all three cases. No pleural effusion was present at any time. The literature is reviewed concerning ascites and pleural effusions linked to ovarian tumors, and a supposition is forwarded of why pleural effusion presents sporadically in these cases. PMID:26858849

  1. Elevated CA125 in primary peritoneal serous psammocarcinoma: a case report and review of the literature

    PubMed Central

    Zhen-Zhong, Deng; Zheng, Ning; Liu, Heng; Liao, Dong-Ying; Ye, Xiao-Qin; Zhou, Qiu-Ming; Jie; Li, Huai-Hui; Liu, Qi; Lu, Kang-Min

    2009-01-01

    Psammocarcinoma is a rare form of serous carcinoma of the ovary or peritoneum, and it is characterised by extensive psammoma body formation and invasion of surrounding structures. This report describes the case of a 42-year-old woman who presented with large ascites and raised CA125 level. Following a full staging laparotomy, she was made stable in stage IIIC. Despite the limited number of cases reported, the clinical prognosis of carcinomas resembling the serous borderline lesions seems much more favourable than the common serous carcinomas. A summary of all the reported cases is provided to highlight the clinical and prognostic features of this scarce tumour. PMID:21686474

  2. Sox10 expression in ovarian epithelial tumors is associated with poor overall survival.

    PubMed

    Kwon, Ah-Young; Heo, Ilyeong; Lee, Hye Jin; Kim, Gwangil; Kang, Haeyoun; Heo, Jin-Hyung; Kim, Tae Hoen; An, Hee Jung

    2016-05-01

    Sox10 is a transcription factor regulating the development of several cell lineages and is involved in tumor development. However, the clinicopathological relevance of Sox10 expression in ovarian cancer has not been examined. We assessed expression of Sox10 in ovarian epithelial tumors by immunohistochemistry and assessed its prognostic value by analyzing the correlation between its expression and clinicopathological factors. We used tissue microarrays including 244 ovarian epithelial tumors. Sox10 staining was found in the cytoplasm or nucleus of tumor cells. Malignant serous, mucinous, and endometrioid tumors were significantly more likely to express Sox10 than benign and borderline tumors. Expression patterns in adenocarcinomas were different for histologic subtypes: nuclear Sox10 staining was common in clear-cell adenocarcinomas and serous adenocarcinomas, whereas all cases of mucinous and endometrioid tumors were negative for nuclear staining. Nuclear Sox10 staining was also associated with chemoresistance and shorter overall survival in ovarian adenocarcinomas, notably in high-grade serous adenocarcinoma. Sox10 is expressed in many ovarian carcinomas, suggesting that it might be involved in oncogenesis of ovarian carcinoma. Expression pattern of Sox10 differs between histological subtypes. Nuclear Sox10 expression is an independent indicator of poor prognosis in ovarian adenocarcinomas, notably in high-grade serous adenocarcinomas. PMID:26951260

  3. Malignant and borderline phyllodes tumor of breast treated with a multi-modality approach in a tertiary cancer care centre in North India

    PubMed Central

    Mallick, Supriya; Joshi, Nikhil P.; Roy, Soumyajit; Gandhi, Ajeet Kumar; Pandit, Subhash; Sharma, Dayanand; Julka, Pramod Kumar; Rath, Goura Kishore

    2016-01-01

    Background: Phyllodes tumor (PT) of the breast can be categorized into benign, borderline and malignant subgroups depending on various histopathological factors. Although malignant PTs may be indolent and controlled by local excision, they frequently show local and distant relapses. Literature reveals local recurrence to be the predominant pattern of failure and thus emphasizes the importance of adjuvant radiation in these tumors. The role of systemic chemotherapy has remained doubtful. Materials and Methods: We have analyzed details of all patients of PT (n = 33) treated with adjuvant multi-modality approach in our institute since 1994–2009. The demographic data, treatment details, recurrence patterns and salvage treatment options were documented. Results: All patients received adjuvant radiation. Seven patients received adjuvant chemotherapy. The mean survival of the entire cohort was 150.618 months. There was a trend for better overall survival with borderline grade (193.6 vs. 160.2 months; P = 0.08, log rank). The disease free survival (DFS) favored borderline grade (193.6 months vs. 82.9 months for high grade; P = 0.02, log rank). The DFS was significantly better in tumors having negative margins on postoperative histopathological examination (DFS rate at 5 years being 100% vs. 69.2% for positive or close margins; P = 0.015). The mode of surgery did not have any impact on survival. Conclusion: Adjuvant Radiation should be discussed taking into account surgical margins, size and various pathological factors of the primary. Adjuvant radiation may be utilized in high risk patients to enhance loco-regional control. Systemic chemotherapy is an option, worth exploring, in cases of systemic failure. PMID:27169106

  4. Recurrent intestinal mucinous borderline tumors of the ovary: a report of 5 cases causing problems in diagnosis, including distinction from mucinous carcinoma.

    PubMed

    Irving, Julie A; Clement, Philip B

    2014-03-01

    Intestinal mucinous borderline tumors (IMBTs) of the ovary are generally associated with a highly favorable outcome and rarely recur. We describe 5 cases of IMBT initially treated by cystectomy or by salpingo-oophorectomy that was likely incomplete, with subsequent recurrences. Three cases were received in consultation, and in each of these, the clinical and intraoperative findings were worrisome for mucinous carcinoma, and diagnostic difficulty was encountered by the referring pathologist. The patient age ranged from 28 to 69 (median 53) yrs. All tumors were clinically Stage I at presentation; in at least 3 cases, extensive adhesiolysis was required during their removal. A pathologic diagnosis of IMBT was made in 4 cases; the remaining tumor was inadequately sampled (3 blocks from a 7.5-cm tumor showed predominantly benign to focally borderline mucinous epithelium). A total of 8 recurrences, all as IMBT, developed at mean follow-up of 26 (range, 6-102) mo; 6 of these occurred within ≤2 yr. In 4 cases, removal of recurrent tumor required an extensive operation because of bowel and/or vaginal involvement. Residual ovarian stroma was identified in all recurrences. There was no evidence of invasive mucinous carcinoma, pseudomyxoma peritonei, or a primary tumor elsewhere (including appendix) in any of the cases. Our findings indicate that patients with IMBTs who undergo cystectomy or oophorectomy requiring adhesiolysis are at increased risk of recurrence, which may occur early, be multiple, and potentially require extensive resection if sites such as bowel or vagina are involved. Recurrences of IMBT that develop in this setting likely represent regrowth of incompletely resected IMBT, or arise within residual ovarian tissue. This is the first detailed clinicopathologic study of such cases. PMID:24487471

  5. [Preserving ovarian function in the treatment of epithelial and special (other) malignant ovarian tumors].

    PubMed

    Kolstad, P

    1987-10-01

    About 90% of malignant tumors of the ovary in Scandinavia develop from the germinal epithelium. There are great differences in the incidence rates between countries in the Western world and in Africa and Asia. The WHO classification of ovarian malignancies is generally used. The epithelial tumors comprise the serous, mucinous, endometrioid, clear cell, undifferentiated and mixed true carcinomas. In addition, borderline lesions of especially the serous and mucinous types are of interest when the question of preservation of ovarian function comes into notice. Conservative surgery, which means removal of only the afflicted ovary should be restricted to young women of the childbearing age who want to preserve the possibility of becoming pregnant. However, certain prerequisites must be fulfilled. The tumor must be located to one ovary only (Stage Ia) and must be either a borderline lesion or a Grade 1 true carcinoma of either the serous, mucinous or endometrioid type. There must be no ascites and peritoneal washings must be negative for cancer cells. Germ cell tumors are usually found in young women. Only the dysgerminomas are regularly bilateral in 10-15% of the cases. All other germ cell tumors are rarely bilateral. But both in borderline lesions, Grade 1 true carcinomas, and in germ cell tumors, a biopsy of the normal looking contralateral ovary should always be performed. Endodermal sinus tumors and immature teratomas may well be treated conservatively by surgery, but modern triple chemotherapy (VAC, PVB) must be added. Granulosa theca cell tumors are bilateral in only about 5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2824278

  6. Expression of LATS family proteins in ovarian tumors and its significance.

    PubMed

    Xu, Bing; Sun, Duoxiang; Wang, Zhihua; Weng, Haiyan; Wu, Dabao; Zhang, Xuefen; Zhou, Ying; Hu, Weiping

    2015-06-01

    Epithelial ovarian cancer is composed of a diverse group of tumors that can be derived from the fallopian tube, endometrium, or ovary. In this study, we explored the expression levels of LATS family members in ovarian tumors using normal ovaries, fallopian tubes, and endometrium as controls. Immunohistochemistry studies of LATS1, LATS2, Pax8, and calretinin were performed on normal ovary, fallopian tube, normal endometrium, and ovarian tumor sections. Statistical analyses were conducted using the χ(2) test, Fisher exact test, or Kruskal-Wallis H test. Patient survival was analyzed using the Kaplan-Meier method. LATS1 was expressed in normal ovarian epithelia, endometrium, and fallopian tubes, whereas LATS2 expression was observed in the normal fallopian tubes and endometrium. High expressions of LATS1 and LATS2 in serous cystadenomas gradually decreased in borderline cystadenomas and carcinomas, respectively. However, an opposite expression pattern was observed in mucinous tumors. Low expressions of LATS1 and LATS2 were also detected in clear cell carcinoma. Both LATS1 and LATS2 expression levels significantly correlated with recurrence and stage; LATS1 levels were also related with tumor grades in serous carcinoma. However, univariate and multivariate Cox regression analyses revealed that high expression of LATS1 was associated with better prognosis in patients with serous carcinoma. Both LATS1 and LATS2 were not related with the clinical variables in mucinous and clear cell carcinoma. LATS1 expression levels might be a valuable survival indicator in ovarian serous carcinoma. PMID:25841306

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

    PubMed Central

    Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna

    2016-01-01

    Aims Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. Results PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively). Conclusions Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity. PMID:26625204

  8. 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.

    PubMed

    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. PMID:26980026

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

    PubMed Central

    Nakamura, Kohei; Nakayama, Kentaro; Ishibashi, Tomoka; Ishikawa, Noriyoshi; Ishikawa, Masako; Katagiri, Hiroshi; Minamoto, Toshiko; Sato, Emi; Sanuki, Kaori; Yamashita, Hitomi; Iida, Kouji; Sultana, Razia; Kyo, Satoru

    2016-01-01

    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. PMID:27128903

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

    PubMed

    Koncoro, Hendra; Putra, I Komang W D; Wibawa, I Dewa N

    2016-04-01

    Macrocystic serous cystadenoma is an unusual and essentially benign pancreatic tumor. Herein, we report on a 40-year-old woman diagnosed with macrocystic serous cystadenoma who presented with obstructive jaundice. A cystic lesion in the head and body of the pancreas was revealed by abdominal computed tomography. Intraoperative pancreatic cyst aspiration ruled out mucinous cystic neoplasm which has a malignant potential. The pancreatic cyst fluid cytology was basophilic amorph materials concluded as benign cystic lesion. Internal drainage was performed instead of pancreatic resection which showed good outcome. Biliary obstruction is a rare complication of serous cystadenoma. This case describes an unusual clinical presentation of macrocystic serous cystadenoma. PMID:27550882

  11. Borderline personality disorder

    MedlinePlus

    Personality disorder - borderline ... Cause of borderline personality disorder (BPD) is unknown. Genetic, family, and social factors are thought to play roles. Risk factors for BPD include: Abandonment ...

  12. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer

    PubMed Central

    Strickland, Kyle C.; Howitt, Brooke E.; Shukla, Sachet A.; Rodig, Scott; Ritterhouse, Lauren L.; Liu, Joyce F.; Garber, Judy E.; Chowdhury, Dipanjan; Wu, Catherine J.; D'Andrea, Alan D.; Matulonis, Ursula A.; Konstantinopoulos, Panagiotis A.

    2016-01-01

    Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas and lung carcinomas. One explanation for this effect is that hypermutated lesions harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes (TILs), which is counterbalanced by overexpression of immune checkpoints such as PD-1 or PD-L1. Given that BRCA1/2-mutated high grade serous ovarian cancers (HGSOCs) exhibit a higher mutational load and a unique mutational signature with an elevated number of larger indels up to 50 bp, we hypothesized that they may also harbor more tumor-specific neoantigens, and, therefore, exhibit increased TILs and PD-1/PD-L1 expression. Here, we report significantly higher predicted neoantigens in BRCA1/2-mutated tumors compared to tumors without alterations in homologous recombination (HR) genes (HR-proficient tumors). Tumors with higher neoantigen load were associated with improved overall survival and higher expression of immune genes associated with tumor cytotoxicity such as genes of the TCR, the IFN-gamma and the TNFR pathways. Furthermore, immunohistochemistry studies demonstrated that BRCA1/2-mutated tumors exhibited significantly increased CD3+ and CD8+ TILs, as well as elevated expression of PD-1 and PD-L1 in tumor-associated immune cells compared to HR-proficient tumors. Survival analysis showed that both BRCA1/2-mutation status and number of TILs were independently associated with outcome. Of note, two distinct groups of HGSOCs, one with very poor prognosis (HR proficient with low number of TILs) and one with very good prognosis (BRCA1/2-mutated tumors with high number of TILs) were defined. These findings support a link between BRCA1/2-mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs. PMID

  13. Borderline Personality

    PubMed Central

    Sansone, Randy A.; Sansone, Lori A.

    2004-01-01

    BORDERLINE PERSONALITY DISORDER (BPD) IS A COMPLEX AXIS II Phenomenon that is typically described in a psychological or psychiatric context. In this article, we translate the various aspects of BPD to the primary care setting. Previous work in this area has explored specific relationships between BPD and individual medical disorders or between BPD and general somatic symptoms, but the synthesis of these findings and their augmentation with cogent psychological theory is new to the field. Specifically, we highlight the prevalence rate of BPD in the primary care setting, the effects on healthcare utilization, the themes of somatic preoccupation and somatization disorder, several medical syndromes that illustrate the dynamics of the disorder in the medical setting, and the relationship of BPD to disability. We believe that the BPD concept needs to extend beyond its traditional psychological/psychiatric borders to include the subset of BPD patients with somatic symptoms who are seen in primary care settings. PMID:21197375

  14. Immunocytochemical identification of carcinomas of unknown primary in serous effusions.

    PubMed

    Pomjanski, Natalia; Grote, Hans Juergen; Doganay, Peyrüze; Schmiemann, Viola; Buckstegge, Birgit; Böcking, Alfred

    2005-11-01

    Metastases from carcinomas of unknown primary site (CUP) in serous effusion are a common clinical problem. Immunocytochemistry was applied as an adjunct to the cytological diagnosis of metastatic carcinomas in serous effusions. Subjects of this study were 118 pleural, 53 peritoneal, and 9 pericardial effusions from 180 patients routinely investigated in the Institute of Cytopathology. Specimens were primarily stained according to Papanicolaou (Pap). The avidin-biotin-complex method (ABC) was secondarily applied for the visualization of immunologic reactions. We have used a panel of six monoclonal antibodies (CK 5/6, CK 7, CK 20, CA 125, TTF-1, and cdx 2) so as to identify the primary tumor site of metastatic carcinoma cells in serous effusions. Applying an algorithm of immunocytochemical marker constellations, we were able to correctly diagnose primary tumor sites in 86 of 101 (85.1%) patients with CUP syndromes. The best result was achieved for the identification of metastatic carcinomas of the ovaries (94.7%) and the lungs (88.1%). We established an algorithm comprising six immunocytochemical markers that enabled a correct diagnosis of primary tumor sites in 85.1%. The panel studied could be useful in diagnostic routine for the identification of primary tumors of unknown origin metastatic to the serous membranes. PMID:16240395

  15. PIMASERTIB AND SEROUS RETINAL DETACHMENTS

    PubMed Central

    AlAli, Alaa; Bushehri, Ahmad; Park, Jonathan C.; Krema, Hatem

    2016-01-01

    Purpose: To report a case of multifocal serous retinal detachments associated with pimasertib. Methods: The authors report a 26-year-old patient who developed bilateral multifocal serous retinal detachments appearing 2 days after starting pimasertib (as part of a clinical trial investigating its use in low-grade metastatic ovarian cancer) and rapidly resolving 3 days after stopping it. Conclusion: The mechanism of MEK inhibitor induced visual toxicity remains unclear. The pathophysiology of multifocal serous retinal detachments as a complication of pimasertib is still poorly understood. PMID:26444523

  16. NOTCH2 expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype

    PubMed Central

    Galic, Vijaya; Shawber, Carrie J.; Reeves, Claire; Shah, Monjri; Murtomaki, Aino; Wright, Jason; Herzog, Thomas; Tong, Guo Xia; Kitajewski, Jan

    2014-01-01

    Background: Notch family members function as both oncogenes and tumor suppressors. NOTCH2 is down-regulated in colon cancer, and reduced expression is associated with a less differentiated, more aggressive phenotype, and reduced overall survival. NOTCH2 has also been shown to have pro-apoptotic and growth suppressive effects in thyroid carcinoma, and carcinoid tumors. The expression pattern of NOTCH2 in ovarian cancer is unknown. Methods: An immunohistochemical analysis using a polyclonal antibody to the NOTCH2 intracellular domain was performed on a total of 119 ovarian carcinomas, and 7 serous borderline tumors, arranged onto tissue arrays. Normal ovarian and fallopian tube epithelium were used as controls. Specimens were scored as low or high NOTCH2 expression. The score distributions for the subtypes were analyzed with the chi square test. Results: Fifty two of 61 (85.2%) papillary serous, eight of 13 (61.5%) clear cell, and 23 of 30 (76.7%) endometrioid, demonstrated negative or lower NOTCH2 expression than normal fallopian tubal epithelium or ovarian surface epithelium. In contrast, 10 of 15 (66.7%) mucinous carcinomas had a high level of NOTCH2 expression and consistently demonstrated intense polarized staining (P<.001). The apical expression of NOTCH2 protein present in the normal fallopian tube epithelium and many borderline tumors was absent in the high grade carcinomas, most notably in papillary serous. Conclusion: Decreased NOTCH2 expression is associated with the poorly differentiated serous epithelial ovarian carcinoma histology. Further studies are needed to assess the functional role of NOTCH2 in ovarian cancer and its effect on prognosis. PMID:24707357

  17. Pancreatic mixed serous neuroendocrine neoplasm with clear cells leading to diagnosis of von Hippel Lindau disease.

    PubMed

    Kakkar, Aanchal; Sharma, Mehar C; Yadav, Rajni; Panwar, Rajesh; Mathur, Sandeep R; Iyer, Venkateswaran K; Sahni, Peush

    2016-08-01

    Mixed serous neuroendocrine neoplasms are extremely rare tumors that are usually seen in female patients and are often associated with von Hippel Lindau (VHL) disease. We describe the case of a 38-year-old male who presented with complaints of anorexia, weight loss, and abdominal pain. CT abdomen showed a mass in the head of the pancreas, multiple small nodules in the body of pancreas, and bilateral adrenal masses. Fine needle aspiration cytology (FNAC) from the mass showed features of a neuroendocrine tumor, with many of the cells demonstrating abundant clear cytoplasm. Histopathological examination of the pancreaticoduodenectomy specimen showed a mixed serous neuroendocrine neoplasm with two components viz. serous cystadenoma and neuroendocrine tumor (NET) World Health Organization (WHO) grade 2. In addition, he was diagnosed to have bilateral pheochromocytomas and a paraganglioma. The synchronicity of these tumors suggested the possibility of VHL disease. Thus, identification of a NET with clear cells or of a mixed serous neuroendocrine neoplasm should raise suspicion of VHL disease. In a mixed tumor, FNAC may identify only one of the two components. Thorough processing of all pancreatic serous tumors for pathological examination is recommended, as NET may occur as a small nodule within the serous cystadenoma. PMID:27161305

  18. Borderline resectable pancreatic cancer.

    PubMed

    Hackert, Thilo; Ulrich, Alexis; Büchler, Markus W

    2016-06-01

    Surgery followed by adjuvant chemotherapy remains the only treatment option for pancreatic ductal adenocarcinoma (PDAC) with the chance of long-term survival. If a radical tumor resection is possible, 5-year survival rates of 20-25% can be achieved. Pancreatic surgery has significantly changed during the past years and resection approaches have been extended beyond standard procedures, including vascular and multivisceral resections. Consequently, borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC), which has recently been defined by the International Study Group for Pancreatic Surgery (ISGPS), has become a controversial issue with regard to its management in terms of upfront resection vs. neoadjuvant treatment and sequential resection. Preoperative diagnostic accuracy to define resectability of PDAC is a keypoint in this context as well as the surgical and interdisciplinary expertise to perform advanced pancreatic surgery and manage complications. The present mini-review summarizes the current state of definition, management and outcome of BR-PDAC. Furthermore, the topic of ongoing and future studies on neoadjuvant treatment which is closely related to borderline resectability in PDAC is discussed. PMID:26970276

  19. Papillary serous carcinoma of the peritoneal surface: matched-case comparison with papillary serous ovarian carcinoma.

    PubMed

    Killackey, M A; Davis, A R

    1993-11-01

    Between 1984 and 1991, 199 patients underwent laparotomy for epithelial "ovarian" malignancy. In 29 cases (15%) normal-sized ovaries (< 4 cm in diameter) with minimal invasion by papillary serous carcinoma were found. This entity in the setting of peritoneal carcinomatosis has been previously described and is reported here as papillary serous cancer of the peritoneal surface (PSPS). The clinical, surgical, and pathologic features of PSPS are compared with a group of age-, grade-, and stage-matched cases with papillary serous ovarian carcinomas (PSOC). PSPS was also characterized by ascites (mean = 3036 cc), malignant washings (91%), and omental involvement with bulky infiltration and/or multiple tumor nodules (96%). Mean cytoreduction in the PSPS group was 65.5% compared to 79% in the PSOC group (P = 0.049). Patients received combination chemotherapy with platinum-based regimens. In general, there was a poor response to treatment with a disease-free interval of 3.4 and median survival time of 19 months in PSPS compared to 11.7 and 31 months in the PSOC patients. Patients with PSPS have more limited cytoreduction, shorter disease-free interval, and shorter overall survival time. Such differences prompt re-evaluation of treatment modalities for PSPS and recognition that this is a condition distinct from PSOC. PMID:8276289

  20. Low-grade serous carcinoma of the ovary or peritoneum.

    PubMed

    Gershenson, D M

    2016-04-01

    Over the past decade, the strategy for clinical trial design in making progress against epithelial cancers of the ovary/peritoneum/fallopian tube has changed dramatically. The NRG (GOG) Rare Tumor Committee has been a leader in this transformation. No longer does 'one size fit all'. Rather, separate clinical trials for rare subtypes have been developed and, in some cases, completed. An enhanced understanding of their pathologic diagnosis, molecular biology, and clinical behavior has galvanized this change. Low-grade serous carcinoma may occur de novo or following an initial diagnosis of serous tumor of low malignant potential. It is characterized by young age at diagnosis, relative chemoresistance, and prolonged survival compared with high-grade serous carcinoma. Historically, conventional chemotherapy has demonstrated very limited activity in this subtype. Hormonal therapy may provide benefit in this subtype. Preclinical studies have identified and elucidated genes and pathways-MAP kinase pathway, IGF1-R, the angiogenesis pathway, and possibly, the PI3K/AKT/mTOR pathway in low-grade serous carcinoma. To date, clinical evidence supports the activity of MEK and BRAF inhibitors and bevacizumab. Further pursuit of targeted therapy trials is clearly warranted. PMID:27141071

  1. Biological role and clinical implications of homeobox genes in serous epithelial ovarian cancer.

    PubMed

    Miller, Katherine R; Patel, Jai N; Ganapathi, Mahrukh K; Tait, David L; Ganapathi, Ram N

    2016-06-01

    Homeobox (HOX) genes are a family of transcription factors that are essential regulators of development. HOX genes play important roles in normal reproductive physiology, as well as in the development and progression of serous carcinomas, the predominant and most aggressive subtype of epithelial ovarian cancer (EOC). This review discusses aberrant HOX gene expression in serous EOC and its impact on tumor development and progression. Further identification of HOX target genes may facilitate the development of novel diagnostic and therapeutic strategies to improve the prognosis of patients with serous EOC. PMID:26957480

  2. Solid Serous Adenoma of the Pancreas: A Case Report and Review of the Literature.

    PubMed

    Katsourakis, Anastasios; Dimitriou, Ioannis; Noussios, Georgios; Chatzis, Iosiph; Chatzitheoclitos, Efthimios

    2016-01-01

    Herein, we report a case of a solid-type serous cystadenoma of the pancreas which is the 16th case reported worldwide and the first ever reported in Greece. Magnetic resonance imaging showed a hypervascular mass in the tail of the pancreas of a 72-year-old female who presented with mild abdominal pain. Distal pancreatectomy was performed by laparotomy and histological and immunohistochemical examination revealed a solid-type serous cystadenoma of the pancreas. Preoperative diagnosis of a solid-type serous cystadenoma of the pancreas is difficult, and, due to its benign nature, simple excision of the tumor is the recommended treatment. PMID:27525151

  3. Solid Serous Adenoma of the Pancreas: A Case Report and Review of the Literature

    PubMed Central

    Noussios, Georgios

    2016-01-01

    Herein, we report a case of a solid-type serous cystadenoma of the pancreas which is the 16th case reported worldwide and the first ever reported in Greece. Magnetic resonance imaging showed a hypervascular mass in the tail of the pancreas of a 72-year-old female who presented with mild abdominal pain. Distal pancreatectomy was performed by laparotomy and histological and immunohistochemical examination revealed a solid-type serous cystadenoma of the pancreas. Preoperative diagnosis of a solid-type serous cystadenoma of the pancreas is difficult, and, due to its benign nature, simple excision of the tumor is the recommended treatment. PMID:27525151

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

    PubMed Central

    2010-01-01

    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 < 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). 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. PMID:20846453

  5. [Extraovarian peritoneal serous papillary carcinoma: an unusual surgical case].

    PubMed

    Meier, C; Seifert, M; Wehrli, H

    1999-01-01

    The extraovarian peritoneal serous papillary carcinoma (EPSPC) is a multicentric peritoneal tumor with minimal or absent involvement of the ovaries. The actual treatment regimen consists of a cytoreductive surgery followed by a combination chemotherapy. Few studies have compared outcome of EPSPC to papillary serous ovarian cancer (PSOC). Several authors have documented similar clinical behavior between EPSPC and PSOC, but this finding has not been universal. A 64-year-old female patient with symptomatic gall stone disease underwent elective laparoscopic cholecystectomy. Unexpectedly we found some uncommon small nodular structures on the serosa of the right colon. The histological findings suggested a poorly differentiated peritoneal serous papillary carcinoma. Biopsies of both ovaries showed no signs of tumor infiltration and the diagnosis of EPSPC was established. After surgery, a combination chemotherapeutic regimen with carboplatin and cyclophosphamid was given. Laparoscopic reassessment 7 months after the first procedure showed no tumor. 3 identical cycles completed chemotherapy. Normal ovaries and no other tumor sites were found in a final laparoscopic look after 11 months. PMID:10073126

  6. A novel truncated form of HMGA2 in tumors of the ovaries

    PubMed Central

    Agostini, Antonio; Panagopoulos, Ioannis; Davidson, Ben; Trope, Claes Goran; Heim, Sverre; Micci, Francesca

    2016-01-01

    Neoplasms of the ovary are the second most common tumor of the female reproductive system, and the most lethal of the gynecological malignancies. Ovarian tumors are divided into a copious number of different groups reflecting their different features. The present study analyzed 187 ovarian tumors (39 sex-cord stromal tumors, 22 borderline tumors and 126 carcinomas) for the expression of the high-mobility group AT-hook 2 (HMGA2) gene, for mutations in the isocitrate dehydrogenase (NADP(+)) 1, cytosolic (IDH1), isocitrate dehydrogenase (NADP(+)) 2, mitochondrial (IDH2) and telomerase reverse transcriptase (TERT) genes, and for methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter. Reverse transcription-polymerase chain reaction analysis showed that HMGA2 was expressed in 74.5% of the samples (120/161). A truncated transcript of HMGA2 was identified in 11 cases. A novel truncated form of HMGA2 was found in 4 serous high-grade carcinomas. Only 4 tumors (4/185) showed the TERT C228T mutation. No IDH1 or IDH2 mutations were found. Methylation of the promoter of MGMT was found in 2 borderline tumors (2/185). HMGA2 was expressed, in its truncated and native form, in different ovarian tumors, even the less aggressive types, underscoring the general importance of this gene in ovarian tumorigenesis. Mutations involving TERT, as well as MGMT promoter methylation, are rare events in ovarian tumors. PMID:27446471

  7. Borderline personality disorder

    MedlinePlus

    ... Names Personality disorder - borderline References American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. ...

  8. Uterine Serous Adenocarcinoma in an Elderly Postmenopausal Woman: Clinically Misdiagnosed as Uterine Cervix Cancer

    PubMed Central

    Hong, Jeong-A; Lee, Hae-Hyeog; Chung, Soo-Ho; Heo, Gyeong-Eun; Jeon, Dong-Su; Kwak, Jeong Ja; Choi, Seung Do; Han, Eunkyung

    2015-01-01

    Uterine serous adenocarcinoma (USC) is rare and invasive cancer. This cancer is more often reported in the ovary, the fallopian tube, and the endometrium than uterine cervix. No matter where the tumor is located, the tumor exhibits similar histological characteristics. So when uterine cancer is proven to be serous adenocarcinoma, it is necessary to see if the tumor originated from ovary or endometrium and invaded the cervix. We report a case of a 73-year-old postmenopausal woman with USC arising near the internal os of endocervical canal, clinically misdiagnosed as uterine cervix cancer. PMID:26793684

  9. Borderline Space for Voice

    ERIC Educational Resources Information Center

    Batchelor, Denise

    2012-01-01

    Being on the borderline as a student in higher education is not always negative, to do with marginalisation, exclusion and having a voice that is vulnerable. Paradoxically, being on the edge also has positive connections with integration, inclusion and having a voice that is strong. Alternative understandings of the concept of borderline space can…

  10. Borderline Personality and Criminality

    PubMed Central

    Sansone, Lori A.

    2009-01-01

    Borderline personality disorder is characteristically associated with a broad variety of psychiatric symptoms and aberrant behaviors. In this edition of The Interface, we discuss the infrequently examined association between borderline personality disorder and criminality. According to our review of the literature, in comparison with the rates of borderline personality disorder encountered in the general population, borderline personality disorder is over-represented in most studies of inmates. At the same time, there is considerable variation in the reported rates of this Axis II disorder in prison populations, which may be attributed to the methodologies of and populations in the various studies. Overall, female criminals appear to exhibit higher rates of borderline personality disorder, and it is oftentimes associated with a history of childhood sexual abuse, perpetration of impulsive and violent crimes, comorbid antisocial traits, and incarceration for domestic violence. PMID:20011575

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

    PubMed

    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. PMID:26575166

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26575166

  13. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  14. Precursors of ovarian cancer in the fallopian tube: Serous tubal intraepithelial carcinoma – an update

    PubMed Central

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

    2015-01-01

    Ovarian tumors comprise a wide variety of entities. The largest group, epithelial ovarian carcinoma, can be classified into two main groups, type I and type II tumors. Recent advances in the understanding of ovarian cancer development have resulted in the finding of ‘serous tubal intraepithelial carcinoma’, which is believed to represent the precursor lesion in high-grade serous ovarian carcinoma. In this review, lines of evidence for this are discussed and possible future implications for clinical and research settings are outlined. PMID:25330822

  15. The significance of the alteration of 8-OHdG in serous ovarian carcinoma

    PubMed Central

    2013-01-01

    Background Oxidative damage and DNA repair dysfunction are associated with carcinogenesis. 8-OHdG is one of the major oxidative DNA adducts. Present work aims to investigate whether the expression of 8-OHdG and its key repair gene hOGG1 play distinctive role in two types of serous ovarian cancer. Materials and methods 8-OHdG level in DNA from tumor and matched tumor-adjacent normal tissue in 48 high-grade papillary serous carcinomas (HG-SOC), 24 low-grade papillary serous carcinomas (LG-SOC), 20 serous cystadenomas, and 16 non-tumor control ovaries was tested. The Cox proportional hazards model and the log-rank test were used to assess the associations between the 8-OHdG level in two types of serous cancer and patients’ survival. Real-time polymerase chain reaction and protein immunoblot were employed to detect hOGG1 mRNA and protein levels in tumor and adjacent normal tissues. Immunohistochemistry was used to determine the expression of hOGG1 and p53. Results There was no difference of average 8-OHdG/106dG DNA level either between HG-SOC (27.8 ± 8.9), LG-SOC (25.2 ± 7.4) and benign serous cystadenoma (26.5 ± 7.7, p = 0.35); or between the tumor-adjacent normal tissue of HG-SOC (18.8 ± 5.2), LG-SOC (21.4 ± 6.5), benign serous cystadenoma (20.5 ± 9.1) and non-tumor ovary (21.6 ± 4.9, p = 0.62). The 8-OHdG/106dG level was significantly higher in tumor comparing to that in matched normal tissue adjacent to carcinoma in HG-SOC (1.52 ± 0.52, p = 0.02), but not in LG-SOC or benign serous cystadenoma. Increased level of 8-OHdG in tumor DNA was an independent factor of overall survival in serous ovarian carcinoma upon multivariate analysis (p < 0.01). Increased level of 8-OHdG in tumor DNA indicates poorer overall and progression-free survival durations than counterparts (47.3 vs 105.7 months and 13.5 vs 45.3 months, respectively). Protein levels of hOGG1 were remarkably decreased in HG-SOC (p < 0.01), but not in LG

  16. [A solid variant of a serous cystadenocarcinoma of the pancreas].

    PubMed

    Brandone, Nicolas; Poizat, Flora; Thomassin-Piana, Jeanne; Turrini, Olivier; Popovici, Cornel; Terris, Benoît

    2016-04-01

    Cystic pancreatic neoplasms concern 1 to 2 % of the pancreatic tumours. The serous ones are considered benign tumours but since 1989, several pancreatic serous cystadenocarcinomas (SCAC) cases have been reported. We report the case of a SCAC with a particular pattern. An 80-year-old female patient presented a 4-cm tumour in the neck of the pancreas associated with liver lesions evoking, on imagery exams, focal nodular hyperplasia nests. A cephalic duodenopancreatectomy and a resection of the liver lesions were carried out. The gross exam showed a tumour with a pattern mostly solid and an area made of cysts. The microscopic exam displayed two patterns: the solid one, predominant, made of mild atypical clear cells, and the cystic one. The liver lesions revealed solid pattern similar to the pancreatic tumour one. The tumoral cells were cytokeratin 7, AE1/AE3 and inhibin positives. The Periodic-acid Schiff showed cytoplasmic granulations, which were digested after diasatasis. Only the presence of metastases allows distinguishing a pancreatic serous cystadenoma from a SCAC. To date, thirty cases of pancreatic SCAC have been reported. Immunohistochemistry cannot confirm the malignancy nature of the lesion but it needs to be done in order to cross out the differential diagnosis, that is pancreatic metastatic clear cell renal carcinoma. Nevertheless, it remains a pathology with good prognosis. Only two cases have been reported but ours case a predominant solid pattern. PMID:26995101

  17. The life and times of low-grade serous carcinoma of the ovary.

    PubMed

    Gershenson, David M

    2013-01-01

    For the past several years, all women with epithelial ovarian cancer have been treated identically, whether in a clinical trial or off protocol. Over the past decade, we have come to appreciate the magnitude of the heterogeneity of ovarian cancer. The development of the binary grading system for serous carcinoma was a major advance, leading to separate clinical trials for patients with this subtype, originating from the Gynecologic Oncology Group's Rare Tumor Committee. The mitogen-activated protein kinase (MAPK) pathway appears to play a prominent role in the pathogenesis of this subtype. Approximately 20% to 40% of low-grade serous carcinomas have a KRAS mutation, while BRAF mutations are rare-approximately 5%. In genomic profiling studies, these tumors appear to cluster with serous tumors of low malignant potential. Compared with high-grade serous carcinomas, low-grade serous carcinomas are also characterized by a low frequency of p53 mutations, greater expression of ER and PR, and greater expression of PAX2 and IGF-1. Primary treatment of low-grade serous carcinoma includes surgery plus platinum-based chemotherapy (either adjuvant or neoadjuvant). Clinical behavior is characterized by young age at diagnosis, relative chemoresistance, and prolonged overall survival. Current options for treatment of relapsed disease include secondary cytoreduction in selected patients, salvage chemotherapy, or hormone therapy. A recently completed trial of a MEK inhibitor for women with recurrent disease demonstrated promising activity. Future directions will include further investigations of the molecular biology and biomarker-driven clinical trials with targeted agent monotherapy and combinations. PMID:23714500

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

    PubMed Central

    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. PMID:25535569

  19. Insights into endometrial serous carcinogenesis and progression.

    PubMed

    Fadare, Oluwole; Zheng, Wenxin

    2009-01-01

    Endometrial serous carcinomas (ESC) constitute only approximately 10% of endometrial cancers, but have a substantially higher case-fatality rate than their more common endometrioid counterparts. The precise composite of factors driving endometrial serous carcinogenesis and progression remain largely unknown, but we attempt to review the current state of knowledge in this report. ESC probably do not evolve through a single pathway, and their underlying molecular events probably occur early in their evolution. TP53 gene mutations occur in 22.7 to 96% of cases, and p53 protein overexpression is seen in approximately 76%. By gene expression profiling, p16 is upregulated in ESC significantly above both normal endometrial cells and endometrioid carcinomas, and 92-100% of cases display diffuse expression of the p16 protein by immunohistochemistry (IHC). Together, these findings suggest dysregulation of both the p16(INKA)/Cyclin D-CDK/pRb-E2F and the ARF-MDM2-p53 cell cycle pathways in ESC. By IHC, HER2/neu is overexpressed (2+ or 3+) in approximately 32.1% of ESC, and approximately 54.5% of cases scored as 2+ or 3+ by IHC display c-erbB2 gene amplification as assessed by fluorescent in situ hybridization. Genetic instability, typically manifested as loss of heterozygosity in multiple chromosomes, is a common feature of ESC, and one study found loss of heterozygosity at 1p32-33 in 63% of cases. A subset of ESC display protein expression patterns that are characteristic of high grade endometrial carcinomas, including loss of the metastasis suppressor CD82 (KAI-1) and epithelial-to-mesenchymal transformation, the latter manifested as E-cadherin downregulation, P-cadherin upregulation, and expression of epithelial-to-mesenchymal transformation-related molecules such as zinc-finger E-box-binding homeobox 1 (ZEB1) and focal adhesion kinase. Preliminary data suggests differential patterns of expression in ESC of some isoforms of claudins, proteases, the tumor invasiveness and

  20. A Five-Gene Expression Signature Predicts Clinical Outcome of Ovarian Serous Cystadenocarcinoma

    PubMed Central

    Guo, Wenna

    2016-01-01

    Ovarian serous cystadenocarcinoma is a common malignant tumor of female genital organs. Treatment is generally less effective as patients are usually diagnosed in the late stage. Therefore, a well-designed prognostic marker provides valuable data for optimizing therapy. In this study, we analyzed 303 samples of ovarian serous cystadenocarcinoma and the corresponding RNA-seq data. We observed the correlation between gene expression and patients' survival and eventually established a risk assessment model of five factors using Cox proportional hazards regression analysis. We found that the survival time in high-risk patients was significantly shorter than in low-risk patients in both training and testing sets after Kaplan-Meier analysis. The AUROC value was 0.67 when predicting the survival time in testing set, which indicates a relatively high specificity and sensitivity. The results suggest diagnostic and therapeutic applications of our five-gene model for ovarian serous cystadenocarcinoma. PMID:27478834

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

    PubMed

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

    2015-04-01

    Serous adenocarcinoma of the cervix (SACC) is a very rare tumor. Our study aimed to characterize the immune profile and human papillomavirus (HPV) status of SACC, in comparison with other serous adenocarcinomas arising in the female genital tract. The pathological specimens obtained from 81 patients with serous carcinoma of the uterine cervix (n = 12), 29 endometrium, 20 ovary and 20 patients with mucinous carcinoma of the uterine cervix were reviewed. We assessed the expression of WT-1, p53, p16, HER2, CEA, and CA125 by immunohistochemistry and HPV DNA by PCR in 12 SACC samples. Their immune profile was compared with that of uterine papillary serous carcinoma (UPSC), ovarian serous adenocarcinoma (OSA), and mucinous endocervical adenocarcinoma (MEA). WT-1 and HER2 were expressed in very few SACC samples (0 and 0%, respectively), but p16, CA125, CEA and p53 were present in 100, 92, 58 and 50%, respectively. The difference in WT-1 expression between SACC and UPSC, MEA is not significant, but SACC differ significantly from OSA (p < 0.01). HPV DNA (type 16 or 18) was detected in 4 of the 12 SACC. The immunophenotype of SACC was similar to UPSC, whereas the frequency of expression of WT-1 was significantly lower in SACC than OSA. It appeared that p53 expression was associated with worse clinical outcome in patients with SACC, and that HPV infection was related to its occurrence. PMID:25370301

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

    PubMed

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

    2016-05-01

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

  3. Marked heterogeneity of HER2/NEU gene amplification in endometrial serous carcinoma.

    PubMed

    Buza, Natalia; Hui, Pei

    2013-12-01

    Significant heterogeneity of HER2 protein expression has been recently observed in HER2 positive endometrial serous carcinomas. Tumor cells with HER2 overexpression and/or gene amplification in a heterogeneous tumor may represent a biologically more aggressive subclone that is clinically relevant to prognosis and potential targeted therapy. To correlate with HER2 protein heterogeneity, we investigated the heterogeneity of HER2/NEU gene amplification in endometrial serous carcinoma. A total of 17 endometrial serous carcinomas with heterogeneous HER2 protein expression were selected for the study, including nine cases with a 3+ and eight cases with a 2+ immunohistochemical score. Initial reflex HER2 FISH was available for seven of the eight 2+ cases, five of which showed HER2/NEU gene amplification. All 17 cases underwent repeat FISH targeting larger tumor tissue areas. Ten cases (72%) displayed striking heterogeneity of HER2/NEU gene copy number in the form of cluster amplification. Diffuse HER2 amplification was observed in four cases, no amplification was seen in three tumors. In cases with cluster amplification, HER2 protein overexpression by immunohistochemistry closely correlated at the cellular level with HER2/NEU gene amplification. In conclusion, the significant percentage of cases with heterogeneous HER2/NEU gene amplification indicates that the existing HER2 testing guidelines designed for breast cancer may not be applicable to endometrial serous carcinoma. Clinical testing on multiple different tumor samples or large tumor tissue sections is recommended for both immunohistochemistry and FISH assessment of HER2 status. Direct comparison with the HER2 immunostaining pattern may be helpful in detecting HER2 amplified areas in a heterogeneous tumor. PMID:24123408

  4. Overexpression and oncogenic function of HMGA2 in endometrial serous carcinogenesis

    PubMed Central

    Wei, Linxuan; Liu, Xiaolin; Zhang, Wenjing; Wei, Yuyan; Li, Yingwei; Zhang, Qing; Dong, Ruifen; Kwon, Jungeun Sarah; Liu, Zhaojian; Zheng, Wenxin; Kong, Beihua

    2016-01-01

    The high-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor highly expressed in fetal tissue and malignant tumors but rarely detected within normal adult tissues. The clinical implications and biological functions of HMGA2 in endometrial carcinoma are largely unknown. Here we report that HMGA2 expression was barely detected in benign endometrium samples (2 of 28 samples). However, HMGA2 expression increased significantly from precancerous lesion endometrial glandular dysplasia (7 of 17, 41.2%), to serous endometrial intraepithelial carcinoma (5 of 8, 62.5%) and to full blown endometrial serous carcinoma (39 of 59, 66.1%). Functional characterization of HMGA2 revealed that the gene has both tumor growth promotion and metastasis. In addition, HMGA2 induced epithelial-mesenchymal transition (EMT) through modulation vimentin and β-catenin. Furthermore, HMGA2 overexpression started from endometrial serous precancers, non-invasive cancers, as well as in full blown carcinomas in a p53 knockout mouse model we recently established in our laboratory. Our findings suggest that HMGA2 may serve as a useful diagnostic marker in the assessment of endometrial serous cancer and its precursor lesions. PMID:27186400

  5. Borderline ovarian tumours.

    PubMed

    Tropé, Claes Göran; Kaern, Janne; Davidson, Ben

    2012-06-01

    Borderline ovarian tumours account for 10-20% of all epithelial ovarian cancer. Historically, standard primary surgery has included borderline ovarian tumours, omentectomy, peritoneal washing and multiple biopsies. As one-third of borderline ovarian tumours are diagnosed in women under the age of 40 years, fertility-sparing treatment has been more frequently used in the past 10 years. Fertility drugs are well tolerated in women with infertility after fertility-sparing surgery. Careful selection of candidates is necessary. Laparoscopic techniques can be used, but should be reserved for oncologic surgeons. This conservative treatment increases the rate of recurrence, albeit with no effect on survival. The pregnancy rate is nearly 50%, and most are achieved spontaneously. These women should be closely followed up. The question is whether this is acceptable from a gynaecologic oncologic point of view. For this reason, we will discuss recently published studies and gynaecologic oncologic concerns about the mode of fertility-sparing surgery and its consequences. PMID:22321906

  6. SPIRONOLACTONE FOR NONRESOLVING CENTRAL SEROUS CHORIORETINOPATHY

    PubMed Central

    Bousquet, Elodie; Beydoun, Talal; Rothschild, Pierre-Raphaël; Bergin, Ciara; Zhao, Min; Batista, Rui; Brandely, Marie-Laure; Couraud, Benedicte; Farman, Nicolette; Gaudric, Alain; Chast, François

    2015-01-01

    Purpose: To evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, for nonresolving central serous chorioretinopathy. Methods: This is a prospective, randomized, double-blinded, placebo-controlled crossover study. Sixteen eyes of 16 patients with central serous chorioretinopathy and persistent subretinal fluid (SRF) for at least 3 months were enrolled. Patients were randomized to receive either spironolactone 50 mg or placebo once a day for 30 days, followed by a washout period of 1 week and then crossed over to either placebo or spironolactone for another 30 days. The primary outcome measure was the changes from baseline in SRF thickness at the apex of the serous retinal detachment. Secondary outcomes included subfoveal choroidal thickness and the ETDRS best-corrected visual acuity. Results: The mean duration of central serous chorioretinopathy before enrollment in study eyes was 10 ± 16.9 months. Crossover data analysis showed a statistically significant reduction in SRF in spironolactone treated eyes as compared with the same eyes under placebo (P = 0.04). Secondary analysis on the first period (Day 0–Day 30) showed a significant reduction in subfoveal choroidal thickness in treated eyes as compared with placebo (P = 0.02). No significant changes were observed in the best-corrected visual acuity. There were no complications related to treatment observed. Conclusion: In eyes with persistent SRF due to central serous chorioretinopathy, spironolactone significantly reduced both the SRF and the subfoveal choroidal thickness as compared with placebo. PMID:26017871

  7. Low-grade Serous Carcinoma of the Ovary: Clinicopathologic Analysis of 52 Invasive Cases and Identification of a Possible Noninvasive Intermediate Lesion.

    PubMed

    Ahn, Geunghwan; Folkins, Ann K; McKenney, Jesse K; Longacre, Teri A

    2016-09-01

    Low-grade serous carcinoma (LGSC) is an uncommon but distinct histologic subtype of ovarian carcinoma. Although the histologic features and natural history of LGSC have been described in the literature, there is no robust correlative study that has specifically addressed histologic features in correlation with clinical follow-up. To refine the criteria for invasion patterns of LGSC and determine additional clinically pertinent morphologic features of LGSC predisposing to a more aggressive clinical course, the clinicopathologic features of 52 LGSCs were evaluated and compared with those of a large series of serous borderline tumors (SBT), with and without invasive implants. To qualify for LGSC, the tumor needed to demonstrate destructive invasion, nuclear atypia that was mild to moderate at most (grade 1 or 2), and a mitotic index that did not exceed 12 mitoses per 10 high-power fields. On the basis of histologic evaluation, destructive invasion was classified into 7 primary architectural patterns: (1) micropapillary and/or complex papillary; (2) compact cell nests; (3) inverted macropapillae; (4) cribriform; (5) glandular and/or cystic; (6) solid sheets with slit-like spaces; and (7) single cells. Five-year overall survival and disease-free survival for LGSC were 82% (median, 72 mo) and 47% (median, 54 mo), respectively. All the patients with fatal outcome demonstrated tumors showing invasion with predominant patterns of cribriform glands, micropapillae and/or complex papillae, or compact cell nests. Notably, 2 of 9 patients with fatal outcome had only small foci of destructive invasion (2 and 3 mm, respectively) with compact cell nests and cribriform glands as the predominant patterns. There was no statistically significant association between pattern of invasion and disease-free survival. Classic stromal microinvasion, as defined by nondestructive stromal invasion <5 mm was identified in 52% of LGSC and was statistically more frequent in LGSC than in SBT (P<0

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

    PubMed Central

    Pathiraja, P; Dhar, S; Haldar, K

    2013-01-01

    Background 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. Patients and methods 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. Conclusion 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. PMID:23861597

  9. FOXO3a loss is a frequent early event in high-grade pelvic serous carcinogenesis.

    PubMed

    Levanon, K; Sapoznik, S; Bahar-Shany, K; Brand, H; Shapira-Frommer, R; Korach, J; Hirsch, M S; Roh, M H; Miron, A; Liu, J F; Vena, N; Ligon, A H; Fotheringham, S; Bailey, D; Flavin, R J; Birrer, M J; Drapkin, R I

    2014-08-28

    Serous ovarian carcinoma is the most lethal gynecological malignancy in Western countries. The molecular events that underlie the development of the disease have been elusive for many years. The recent identification of the fallopian tube secretory epithelial cells (FTSECs) as the cell-of-origin for most cases of this disease has led to studies aimed at elucidating new candidate therapeutic pathways through profiling of normal FTSECs and serous carcinomas. Here we describe the results of transcriptional profiles that identify the loss of the tumor suppressive transcription factor FOXO3a in a vast majority of high-grade serous ovarian carcinomas. We show that FOXO3a loss is a hallmark of the earliest stages of serous carcinogenesis and occurs both at the DNA, RNA and protein levels. We describe several mechanisms responsible for FOXO3a inactivity, including chromosomal deletion (chromosome 6q21), upregulation of miRNA-182 and destabilization by activated PI3K and MEK. The identification of pathways involved in the pathogenesis of ovarian cancer can advance the management of this disease from being dependant on surgery and cytotoxic chemotherapy alone to the era of targeted therapy. Our data strongly suggest FOXO3a as a possible target for clinical intervention. PMID:24077281

  10. Bullous variant of idiopathic central serous chorioretinopathy

    PubMed Central

    Sahu, D.; Namperumalsamy, P; Hilton, G.; de Sousa, N. F

    2000-01-01

    BACKGROUND—Spontaneous bullous serous retinal detachment (RD) with subretinal exudation complicating idiopathic central serous chorioretinopathy (ICSC) is a rare and infrequently described clinical entity. Clinical observations are described on this variant form in 11 patients, the largest series reported to date.
METHODS—13 eyes of 11 Indian patients having this entity were followed up clinically and angiographically for 12-24 months (retrospective, longitudinal). None of the patients had any previous history of other diseases nor were they on any medications. Four eyes received laser treatment (group A); nine eyes were not treated (group B).
RESULTS—All 11 patients were male, aged 23-49 years (median 37 years). The clinical and photographic records revealed subretinal exudation and inferior bullous serous RD complicating ICSC with evidence of large, single or multiple, leaking retinal pigment epithelial detachments (PEDs) in all the cases. In group A, resolution of serous RD occurred in 12 weeks (median) with a visual recovery of ⩾20/30 in three out of four eyes while in group B resolution of serous retinal detachment was observed in 14 weeks (median) with eight out of nine eyes achieving a visual acuity of ⩾20/30. Subretinal fibrosis developed in two eyes in group A and none of the eyes in group B.
CONCLUSION—The disease is an exaggerated form of ICSC and can occur spontaneously without any history of corticosteroid therapy. Recognition of this atypical presentation is important to avoid inappropriate treatment. These observations suggest that with respect to the duration of the disease and the final visual outcome laser therapy offers no additional benefit over the natural course of this variant form of ICSC.

 PMID:10781512

  11. Prescribing and borderline personality disorder

    PubMed Central

    Chanen, Andrew M; Thompson, Katherine N

    2016-01-01

    Summary Accurate diagnosis is fundamental to effective management of borderline personality disorder, but many patients remain undetected. The first-line management for borderline personality disorder is psychosocial treatment, not drugs. There are major prescribing hazards including polypharmacy, overdose and misuse. Drug treatment might be warranted for patients who have a co-occurring mental disorder such as major depression. If a drug is prescribed for borderline personality disorder, it should only be as an adjunct to psychosocial treatment. There should be clear and collaborative goals that are regularly reviewed with the patient. Use single drugs prescribed in limited quantities for a limited time. Stop drugs that are ineffective. PMID:27340322

  12. Serous carcinoma of endometrium in combination with neuroendocrine small-cell: A case report and literature review.

    PubMed

    Brudie, Lorna A; Khan, Faizan; Radi, Michael J; Ahmad, Sarfraz

    2016-08-01

    Endometrial serous carcinomas are very clinically aggressive, which constitutes 40% of all deaths and recurrences associated with endometrial cancer. Small-cell carcinoma of the endometrium is relatively rare but aggressive, and often presents a component of endometrioid carcinoma, and is not generally associated with serous carcinoma. Herein, we report a case of 74-year-old African-American female, who presented with intermittent post-menopausal bleeding for > 1-month. She underwent robotic-assisted laparoscopic hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node mapping, and pelvic-and-aortic lymphadenectomy. Final pathology was consistent with serous carcinoma of the endometrium in combination with neuroendocrine small-cell carcinoma. This extremely rare combination of tumors presents a challenge for treatment. The mainstay of treatment seems to be surgery followed by chemotherapy ± radiation therapy. To our knowledge, it represents an under-reported area of gynecological medicine. PMID:27508271

  13. [CLINICAL APPROACH TO PEDIATRIC SEROUS OTITIS MEDIA].

    PubMed

    Gruber, Maayan; Honigman, Tal; Cohen-Kerem, Raanan

    2015-06-01

    Serous otitis media (also known as otitis media with effusion) is one of the most prevalent pediatric diagnoses. However, the recommended clinical approach and significance of this entity are controversial. Pathogenesis is usually based upon a combination of factors as overviewed in the body of the article. The cognitive and behavioral effects amongst children suffering serous otitis media were extensively studied and data points to little if any effects during long term follow-ups in otherwise healthy children. The therapeutic approach can be divided into watchful waiting, systemic drugs, topical drugs, mechanical therapies and surgical therapy (i.e. ventilation tube insertion). The reviewed literature mainly supports the effectiveness of the surgical approach in carefully selected cohorts of patients. PMID:26281082

  14. [A case of peritoneal serous papillary carcinoma].

    PubMed

    Takeuchi, Nobuhiro; Sakata, Yoshio; Nishida, Yu; Nomura, Yusuke; Makino, Tetsuya; Maeda, Tetsuo; Tada, Hidetoshi; Kimoto, Takeo; Ueno, Sayaka; Fujiwara, Kiyoshi

    2011-08-01

    A 65-year-old female was admitted to our hospital with abdominal distension. Abdominal CT and MRI revealed massive ascites and an omental cake, but the ovaries were of normal size. After an omentum biopsy was performed during open abdominal surgery, she was diagnosed as peritoneal serous papillary adenocarcinoma. After 6 courses of chemotherapy with paclitaxel and carboplatin, the massive ascites totally disappeared, and a second look operation could be performed. She is still alive with no sign of recurrence. PMID:21829076

  15. Mammary serine protease inhibitor and CD138 immunohistochemical expression in ovarian serous and clear cell carcinomas.

    PubMed

    Hasby, Eiman Adel

    2016-04-01

    This study aims to investigate the immunohistochemical expression of mammary serine protease inhibitor (maspin) and CD138 in primary ovarian high-grade serous carcinomas (HGSC) as compared to low-grade serous carcinomas (LGSC) and clear cell carcinomas and investigate if the studied markers have a correlation to International Federation of Gynaecology and Obstetrics (FIGO) stage, Ki67 proliferation index, and to each other. Maspin cellular location varied significantly between studied groups with only nuclear expression seen in 46.7 % of LGSC group, mixed nuclear and cytoplasmic in 13.3, 28.6, and 20 % of LGSC, HGSC, and clear cell carcinoma, respectively, and was only cytoplasmic in 26.7, 71.4, and 80 % of LGSC, HGSC, and clear cell carcinoma, respectively. Mean maspin and CD138 counts were significantly higher in HGSC and clear cell carcinoma compared to LGSC. Both maspin and CD138 scores varied significantly between studied groups and were positively correlated with adverse prognostic factors in studied carcinomas including FIGO stage and Ki67 proliferation index. Besides, both maspin and CD138 had significant correlation to each other. These findings suggest that epithelial cytoplasmic expression of maspin and CD138 may have a significant role in tumorigenesis in ovarian high-grade serous carcinomas and clear cell carcinomas; these markers may regulate tumor cell proliferation, and their significant correlation to each other may suggest that CD138 probably induces maspin expression to protect tumor growth factors from being lysed by proteolytic enzymes. PMID:26526579

  16. Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer

    PubMed Central

    El-Sahwi, Karim S; Schwartz, Peter E; Santin, Alessandro D

    2012-01-01

    Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis. By contrast, type II ECs develop in older patients, are not hormone dependent and are responsible for most recurrences and deaths from EC. Uterine serous cancer constitutes up to 10% of all endometrial tumors, and represents the most biologically aggressive variant of type II EC. This article will describe the most salient molecular markers that have been identified in uterine serous cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a series of therapeutic markers for the treatment of this highly-aggressive subset of ECs. PMID:22149431

  17. Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer.

    PubMed

    McPherson, Andrew; Roth, Andrew; Laks, Emma; Masud, Tehmina; Bashashati, Ali; Zhang, Allen W; Ha, Gavin; Biele, Justina; Yap, Damian; Wan, Adrian; Prentice, Leah M; Khattra, Jaswinder; Smith, Maia A; Nielsen, Cydney B; Mullaly, Sarah C; Kalloger, Steve; Karnezis, Anthony; Shumansky, Karey; Siu, Celia; Rosner, Jamie; Chan, Hector Li; Ho, Julie; Melnyk, Nataliya; Senz, Janine; Yang, Winnie; Moore, Richard; Mungall, Andrew J; Marra, Marco A; Bouchard-Côté, Alexandre; Gilks, C Blake; Huntsman, David G; McAlpine, Jessica N; Aparicio, Samuel; Shah, Sohrab P

    2016-07-01

    We performed phylogenetic analysis of high-grade serous ovarian cancers (68 samples from seven patients), identifying constituent clones and quantifying their relative abundances at multiple intraperitoneal sites. Through whole-genome and single-nucleus sequencing, we identified evolutionary features including mutation loss, convergence of the structural genome and temporal activation of mutational processes that patterned clonal progression. We then determined the precise clonal mixtures comprising each tumor sample. The majority of sites were clonally pure or composed of clones from a single phylogenetic clade. However, each patient contained at least one site composed of polyphyletic clones. Five patients exhibited monoclonal and unidirectional seeding from the ovary to intraperitoneal sites, and two patients demonstrated polyclonal spread and reseeding. Our findings indicate that at least two distinct modes of intraperitoneal spread operate in clonal dissemination and highlight the distribution of migratory potential over clonal populations comprising high-grade serous ovarian cancers. PMID:27182968

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

    PubMed

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

    2016-03-01

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

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

    PubMed

    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 < 0.001). No differences in tubal injury or inflammation were seen when comparing the sporadic serous cancer group and the control group or within the hereditary group. 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. PMID:27003156

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

    PubMed Central

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

    2014-01-01

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

  1. Borderline Personality Disorder

    PubMed Central

    Brüne, Martin

    2016-01-01

    The term ‘Borderline Personality Disorder’ (BPD) refers to a psychiatric syndrome that is characterized by emotion dysregulation, impulsivity, risk-taking behavior, irritability, feelings of emptiness, self-injury and fear of abandonment, as well as unstable interpersonal relationships. BPD is not only common in psychiatric populations but also more prevalent in the general community than previously thought, and thus represents an important public health issue. In contrast to most psychiatric disorders, some symptoms associated with BPD may improve over time, even without therapy, though impaired social functioning and interpersonal disturbances in close relationships often persist. Another counterintuitive and insufficiently resolved question is why depressive symptoms and risk-taking behaviors can occur simultaneously in the same individual. Moreover, there is an ongoing debate about the nosological position of BPD, which impacts on research regarding sex differences in clinical presentation and patterns of comorbidity. In this review, it is argued that many features of BPD may be conceptualized within an evolutionary framework, namely behavioral ecology. According to Life History Theory, BPD reflects a pathological extreme or distortion of a behavioral ‘strategy’ which unconsciously aims at immediate exploitation of resources, both interpersonal and material, based on predictions shaped by early developmental experiences. Such a view is consistent with standard medical conceptualizations of BPD, but goes beyond classic ‘deficit’-oriented models, which may have profound implications for therapeutic approaches. PMID:26929090

  2. Interventions for the treatment of borderline ovarian tumours

    PubMed Central

    Faluyi, Olusola; Mackean, Melanie; Gourley, Charlie; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown. Objectives To evaluate the benefits and harm of different treatment modalities offered for borderline ovarian tumours. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and EMBASE to 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) that compared different interventions in adult women diagnosed with borderline ovarian tumours of any histological variant. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed. Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intraperitoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias. One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral

  3. Ovarian low-grade serous carcinoma involving the cervix mimicking a cervical primary.

    PubMed

    Malpica, Anais; Deavers, Michael T

    2011-11-01

    We describe the clinicopathologic and immunohistochemical features of the first reported case of an ovarian low-grade serous carcinoma metastatic to the cervix mimicking a cervical primary. The patient, a 55-year-old woman, was found to have an abnormal cervix and an abnormal Pap smear during a preoperative workup for a rectocele repair. A subsequent cervical biopsy contained moderately differentiated adenocarcinoma and the patient underwent a cold knife conization. An infiltrating adenocarcinoma was found in the anterior cervical lip, the neoplasm reached the surface of the endocervical canal and was composed of mildly to moderately atypical, eosinophilic or amphophilic columnar cells arranged in glands and papillae. Mitotic figures were rare and no apoptotic bodies were seen. Psammoma bodies and intraglandular mucinous material were also noted. There was extensive vascular/lymphatic invasion. The tumor extended to all margins and was interpreted as a moderately differentiated (grade 2) adenocarcinoma of the uterine cervix with a linear spread of at least 1.4 cm and a depth of at least 0.6 cm (FIGO stage 1B1). The patient was treated with radiotherapy and cisplatin. Six months later, surveillance imaging studies showed that the patient's ovaries seemed to be enlarging. The patient underwent exploratory laparotomy, bilateral salpingo-oophorectomy, right pelvic lymph node sampling, omentectomy, peritoneal biopsies, and pelvic washings. The ovaries contained bilateral cystic tumors. There was gross tumor involving multiple peritoneal sites. Microscopic examination of the ovaries showed the typical features of low-grade serous carcinoma associated with a serous neoplasm of low malignant potential with a cribriform pattern. Metastatic low-grade serous carcinoma was detected in multiple peritoneal sites and in the pelvic washings. A consultation was obtained, with the consultant concurring that the tumors represented independent primaries. The patient received

  4. Treatment histories of borderline inpatients.

    PubMed

    Zanarini, M C; Frankenburg, F R; Khera, G S; Bleichmar, J

    2001-01-01

    In this study, we describe the types and amounts of psychiatric treatment received by a well-defined sample of borderline personality disorder (BPD) inpatients, and compare these parameters with those of a group of carefully diagnosed personality-disordered controls. Finally, we assess the risk factors associated with a history of intensive, high-cost treatment, which we defined as having had two or more prior psychiatric hospitalizations. The treatment histories of 290 borderline inpatients and 72 axis II controls were assessed using a reliable semistructured interview. All nine forms of treatment studied except electroconvulsive therapy (ECT) were common among borderline patients (36% to 96%). In addition, a significantly higher percentage of borderline patients than axis II controls reported a history of individual and group therapy, day and residential treatment, psychiatric hospitalization, participating in self-help groups, and taking standing medications. They were also significantly younger when they first entered individual therapy and began to take standing medications. In addition, borderline patients spent more time than axis II controls in individual therapy and psychiatric hospitals, and were on standing medications for a significantly longer period of time. They also reported a significantly higher number of psychiatric hospitalizations, lifetime number of standing medications, and number of psychotropic medications taken at the same time. In addition, we found a highly significant multivariate predictive model for multiple prior hospitalizations. The six significant predictors were age 26 or older, a history of quasi psychotic thought, lifetime number of self-mutilative efforts and suicide attempts, a childhood history of reported sexual abuse, and an adult history of being physically and/or sexually assaulted. Taken together, these results confirm clinical impressions concerning the high rates of mental health services used by borderline patients

  5. Lysophosphatidic Acid-Induced Transcriptional Profile Represents Serous Epithelial Ovarian Carcinoma and Worsened Prognosis

    PubMed Central

    Murph, Mandi M.; Liu, Wenbin; Yu, Shuangxing; Lu, Yiling; Hall, Hassan; Hennessy, Bryan T.; Lahad, John; Schaner, Marci; Helland, Åslaug; Kristensen, Gunnar; Børresen-Dale, Anne-Lise; Mills, Gordon B.

    2009-01-01

    Background Lysophosphatidic acid (LPA) governs a number of physiologic and pathophysiological processes. Malignant ascites fluid is rich in LPA, and LPA receptors are aberrantly expressed by ovarian cancer cells, implicating LPA in the initiation and progression of ovarian cancer. However, there is an absence of systematic data critically analyzing the transcriptional changes induced by LPA in ovarian cancer. Methodology and Principal Findings In this study, gene expression profiling was used to examine LPA-mediated transcription by exogenously adding LPA to human epithelial ovarian cancer cells for 24 h to mimic long-term stimulation in the tumor microenvironment. The resultant transcriptional profile comprised a 39-gene signature that closely correlated to serous epithelial ovarian carcinoma. Hierarchical clustering of ovarian cancer patient specimens demonstrated that the signature is associated with worsened prognosis. Patients with LPA-signature-positive ovarian tumors have reduced disease-specific and progression-free survival times. They have a higher frequency of stage IIIc serous carcinoma and a greater proportion is deceased. Among the 39-gene signature, a group of seven genes associated with cell adhesion recapitulated the results. Out of those seven, claudin-1, an adhesion molecule and phenotypic epithelial marker, is the only independent biomarker of serous epithelial ovarian carcinoma. Knockdown of claudin-1 expression in ovarian cancer cells reduces LPA-mediated cellular adhesion, enhances suspended cells and reduces LPA-mediated migration. Conclusions The data suggest that transcriptional events mediated by LPA in the tumor microenvironment influence tumor progression through modulation of cell adhesion molecules like claudin-1 and, for the first time, report an LPA-mediated expression signature in ovarian cancer that predicts a worse prognosis. PMID:19440550

  6. Clinical management of uterine papillary serous carcinoma.

    PubMed

    Roelofsen, Thijs; van Ham, Maaike A; de Hullu, Joanne A; Massuger, Leon F

    2011-01-01

    Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial cancer. Owing to its rarity, most clinicians are unfamiliar with the clinical aspects and management of UPSC. Furthermore, little prospective evidence exists regarding how best to treat this subset of patients. In anticipation of prospective clinical trials, this article summarizes the latest results of various clinical management options in the different substages of UPSC, with a special focus on the effects of cytoreductive surgery, comprehensive surgical staging and different adjuvant treatment options in relation to recurrence rate and survival outcome. PMID:21166512

  7. Hepatoid carcinoma of the pancreas combined with serous cystadenoma: a case report and review of the literature.

    PubMed

    Veerankutty, Fadl H; Yeldho, Varghese; Tu, Shabeer Ali; Venugopal, B; Manoj, Krishnan Sarojam; Vidhya, C

    2015-10-01

    Pancreatic hepatoid carcinoma (HC) is an extremely uncommon neoplasm of pancreas that resembles hepatocellular carcinoma (HCC). We report a case of incidentally detected pancreatic HC combined with a serous microcystic cystadenoma, in a 47-year-old man, while he was being evaluated for renal calculi. Contrast enhanced computed tomography (CECT) of abdomen revealed a lesion with mild heterogeneous enhancement in the tail of pancreas and another proximal lesion having moderate enhancement, and a calculus in the neck of gallbladder. Serum chromogranin, carcinoembryonic antigen (CEA) and CA 19-9 levels were within normal limits. He underwent laparoscopic distal pancreatectomy with splenectomy and cholecystectomy. Pathologically the distal tumor was encapsulated and characterized by eosinophilic cytoplasm, vesicular nucleus with prominent nucleolus and intranuclear eosinophilic inclusions. The cells were arranged in trabecular pattern separated by sinusoids. Canalicular and intercellular bile plugs were seen. On immunohistochemistry tumor cells were positive for hepatocyte specific antigen and weakly positive for alpha fetoprotein (AFP). The proximal tumor showed features of serous microcystic adenoma. Based on these findings, the case was diagnosed as hepatoid tumor of pancreas combined with serous microcystic cystadenoma. Post operative AFP was 1.75 IU/mL. The patient is on follow up for the last eight months and there is no evidence of recurrence. PMID:26605284

  8. Hepatoid carcinoma of the pancreas combined with serous cystadenoma: a case report and review of the literature

    PubMed Central

    Yeldho, Varghese; TU, Shabeer Ali; Venugopal, B.; Manoj, Krishnan Sarojam; Vidhya, C.

    2015-01-01

    Pancreatic hepatoid carcinoma (HC) is an extremely uncommon neoplasm of pancreas that resembles hepatocellular carcinoma (HCC). We report a case of incidentally detected pancreatic HC combined with a serous microcystic cystadenoma, in a 47-year-old man, while he was being evaluated for renal calculi. Contrast enhanced computed tomography (CECT) of abdomen revealed a lesion with mild heterogeneous enhancement in the tail of pancreas and another proximal lesion having moderate enhancement, and a calculus in the neck of gallbladder. Serum chromogranin, carcinoembryonic antigen (CEA) and CA 19-9 levels were within normal limits. He underwent laparoscopic distal pancreatectomy with splenectomy and cholecystectomy. Pathologically the distal tumor was encapsulated and characterized by eosinophilic cytoplasm, vesicular nucleus with prominent nucleolus and intranuclear eosinophilic inclusions. The cells were arranged in trabecular pattern separated by sinusoids. Canalicular and intercellular bile plugs were seen. On immunohistochemistry tumor cells were positive for hepatocyte specific antigen and weakly positive for alpha fetoprotein (AFP). The proximal tumor showed features of serous microcystic adenoma. Based on these findings, the case was diagnosed as hepatoid tumor of pancreas combined with serous microcystic cystadenoma. Post operative AFP was 1.75 IU/mL. The patient is on follow up for the last eight months and there is no evidence of recurrence. PMID:26605284

  9. Central Serous Chorioretinopathy Treatments: A Mini Review.

    PubMed

    Iacono, Pierluigi; Battaglia Parodi, Maurizio; Falcomatà, Bruno; Bandello, Francesco

    2015-01-01

    Central serous chorioretinopathy (CSC) is a retinal disorder that primarily affects young (20- to 50-year-old) white men, although it is seen occasionally in older patients and females. CSC is characterized by avascular focal leakage through the retinal pigment epithelium (RPE), resulting in serous detachment of the neurosensory retina. The course is usually self-limiting and in most cases resolves spontaneously within a 3-month period, with visual acuity usually recovering to 20/30 or better. However, chronic CSC may develop as a consequence of recurrences or persistent neurosensory detachment, and can result in progressive RPE atrophy and permanent visual loss. A primary involvement of the RPE and choroidal vascularization play a significant role in the pathogenesis of CSC and the current treatment options attempt to restore the functions of the RPE and the normal choroidal vasculature. The aim of the current review is to provide an overview of the current therapeutical approaches to CSC, including observation, laser treatment, photodynamic therapy with verteporfin, intravitreal anti-vascular endothelial growth factor therapy and the mineralocorticoid receptor antagonists. PMID:26619293

  10. Primary peritoneal serous papillary carcinoma: a study of 25 cases and comparison with stage III-IV ovarian papillary serous carcinoma.

    PubMed

    Ben-Baruch, G; Sivan, E; Moran, O; Rizel, S; Menczer, J; Seidman, D S

    1996-03-01

    The clinical characteristics and treatment outcome of patients with primary peritoneal serous papillary carcinoma (PPSC) (n = 22) was compared with stage III-IV papillary serous ovarian carcinoma (PSOC) patients (n = 63). There were no statistically significant differences between the PPSC and PSOC patients with regard to the mean age, menopausal status, parity, ascites fluid volume, proportion of stage IV disease, and the rate of optimal debulking achieved. The median disease-free interval was 15 and 18 months; the median survival was 21 and 26 months; and the 5-year survival was 18 and 24% for the PPSC and PSOC groups, respectively. The median survival time for patients with a residual tumor > or = 2 cm was 20.5 and 24 months, and for residual tumor > or = 2 cm was 46 and 41 months, in PPSC and PSOC patients, respectively. Survival was thus better, in both groups, when residual disease at the end of the operation was < 2 cm, though this was statistically significant only for PSOC (P < 0.02). We conclude that patients with PPSC should be treated as other stage II-IV PSOC patients. Combining optimal debulking with a platinum-based chemotherapy may offer the patient the most effective treatment. PMID:8774644

  11. Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

    ClinicalTrials.gov

    2013-04-11

    Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Ovarian Epithelial Cancer; Stage III Borderline Ovarian Surface Epithelial-stromal Tumor; Stage III Ovarian Epithelial Cancer; Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor; Stage IV Ovarian Epithelial Cancer

  12. Extraovarian peritoneal serous papillary carcinoma: a case-control retrospective comparison to papillary adenocarcinoma of the ovary.

    PubMed

    Bloss, J D; Liao, S Y; Buller, R E; Manetta, A; Berman, M L; McMeekin, S; Bloss, L P; DiSaia, P J

    1993-09-01

    Since the establishment of extraovarian peritoneal serous papillary carcinoma (EPSPC) as a clinical entity in 1959, less than 250 cases have been described and its clinicopathologic features remain obscure. The present series is a retrospective, case-controlled study comparing the response and survival to cytoreductive surgery followed by cisplatin-based multiagent chemotherapy of 33 women with confirmed EPSPC versus 33 cases with papillary serous ovarian cancer (PSOC). Each EPSPC case was matched to a PSOC control for extent and distribution of disease prior to and following cytoreductive surgery, tumor grade, patient age, and treatment. Additionally, the new Gynecologic Oncology Group criteria for the diagnosis for EPSPC are discussed. There were no significant differences in tumor response to therapy, disease-free interval, and actuarial survival between cases and controls. These data suggest that EPSPC is clinically similar to PSOC and support the need for a prospective clinical trial to compare these two entities further. PMID:8406199

  13. Up-regulation of stromal versican expression in advanced stage serous ovarian cancer

    PubMed Central

    Ghosh, Sue; Albitar, Lina; LeBaron, Richard; Welch, William R.; Samimi, Goli; Birrer, Michael J.; Berkowitz, Ross S.; Mok, Samuel C.

    2010-01-01

    Objective The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes. Methods Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RT-PCR) was performed on one of the up-regulated genes, VCAN. Immunolocalization of VCAN (n=111) and CD31 (n= 56) were done on serous ovarian tumors. CD31 staining was performed to examine microvessel density (MVD). Q-RT-PCR was performed on 65 samples to evaluate the differential expression of VCAN isoforms. Cell proliferation and invasion assays were performed to examine how V1-treated ovarian cancer cell lines and an endothelial cell line would differ from controls. Univariate survival analyses were done with VCAN expression. Correlation analysis was done with CD31, platinum resistance, and clinical data. Results Validation studies using Q-RT-PCR and immunohistochemistry showed significantly higher VCAN V1 isoform expression in ovarian cancer stroma compared with normal ovarian stroma and ovarian cancer cells. Correlation studies showed stromal VCAN expression was associated with poorer overall and progression free survival, platinum resistance, and increased MVD. VCAN-treated ovarian cancer and endothelial cells showed increased invasion potential. Conclusions VCAN overexpression is associated with increased MVD and invasion potential, which may lead to poorer overall and progression free survival and platinum resistance. PMID:20619446

  14. Genetic imbalance on chromosome 17 in papillary serous carcinoma of the peritoneum.

    PubMed

    Bandera, C A; Muto, M G; Welch, W R; Berkowitz, R S; Mok, S C

    1998-07-01

    We extend the evaluation of allelic loss patterns on chromosome 17 to papillary serous carcinoma of the peritoneum (PSCP) which is histologically identical to papillary serous ovarian carcinoma (PSOC). DNA was obtained from 11 archival cases of PSCP, with 1-11 tumor sites per case. Using ten loci spanning chromosome 17, loss of heterozygosity (LOH) was identified in all 11 cases (100%). Furthermore, 75-100% of informative cases exhibited LOH at the loci p53, D17S1322 (intragenic to the tumor suppressor gene BRCA1), D17S1327 and MPO. PSCP cases exhibit a higher rate of LOH at most loci when compared with PSOC. Alternating allelic loss at different tumor sites was identified in three cases supporting a multifocal origin of PSCP. Microsatellite instability (MI) is an uncommon event which was identified in four cases. These data implicate chromosome 17 as a potential location of genetic events important in the pathogenesis of PSCP as well as ovarian cancer. PMID:9692553

  15. Adrenal Metastasis from Uterine Papillary Serous Carcinoma

    PubMed Central

    Lubana, Sandeep Singh; Singh, Navdeep; Tuli, Sandeep S.; Seligman, Barbara

    2016-01-01

    Patient: Female, 60 Final Diagnosis: UPSC with adrenal metastasis Symptoms: Post menopausal bleeding Medication: — Clinical Procedure: Adrenalectomy Specialty: Oncology Objective: Rare disease Background: Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. Case Report: A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. Conclusions: UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case. PMID:27117594

  16. Adrenal Metastasis from Uterine Papillary Serous Carcinoma.

    PubMed

    Singh Lubana, Sandeep; Singh, Navdeep; Tuli, Sandeep S; Seligman, Barbara

    2016-01-01

    BACKGROUND Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. CASE REPORT A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. CONCLUSIONS UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case. PMID:27117594

  17. Chronic suicidality and borderline personality.

    PubMed

    Sansone, Randy A

    2004-06-01

    Suicidal ideation is a complex clinical event. In this article, acute suicidal ideation is compared with chronic suicidal ideation, specifically their different meanings, relationships with Axis I and Axis II disorders, intrapsychic functions, approaches to assessment, and interventions. The potential risks of acute hospitalization of the chronically suicidal borderline personality disorder patient are discussed as well as a longitudinal, multidimensional treatment strategy for the chronically suicidal individual. PMID:15237042

  18. [A psychoanalytical approach of the borderline personality].

    PubMed

    Slucki, Daniel; Wikinski, Mariana

    A bibliographic review of the last year's psychoanalytic literature on borderline personality is presented. We expose diagnostic considerations, with special emphasis on those which refer to the boundaries between borderline personality, neurosis and psychosis on one hand, and those which distinguish between borderline personality and narcissistic disorders on the other. Vicissitudes of these patient's object relationships, their bond with other significant persons, their main psychic mechanisms, clinical traits and technical difficulties in the treatment are also described. PMID:15597123

  19. Giant Serous Cystadenoma of the Pancreas (⩾10 cm): The Clinical Features and CT Findings

    PubMed Central

    Zhou, Jun; Zeng, Yu-Rong; Lin, Xiao-Feng; Min, Jun

    2016-01-01

    Purpose. To report the clinical features and CT manifestations of giant pancreatic serous cystadenoma (≥10 cm). Methods. We retrospectively reviewed the clinical features and CT findings of 6 cases of this entity. Results. All 6 patients were symptomatic. The tumors were 10.2 cm–16.5 cm (median value, 13.0 cm). CT imaging revealed that all 6 cases showed microcystic appearances (n = 5) or mixed microcystic and macrocystic appearances (n = 1). Five patients with tumors at the distal end of the pancreas received distal pancreatectomy. Among these 5 patients, 2 patients underwent partial transverse colon resection or omentum resection due to close adhesion. One patient whose tumor was located in the pancreatic head underwent pancreaticoduodenectomy; however, due to encasement of the portal and superior mesenteric veins, the tumor was incompletely resected. One patient had abundant draining veins on the tumor surface and suffered large blood loss (700 mL). After 6–49 months of follow-up the 6 patients showed no tumor recurrence or signs of malignant transformation. Conclusions. Giant pancreatic serous cystadenoma necessitates surgical resection due to large size, symptoms, uncertain diagnosis, and adjacent organ compression. The relationship between the tumors and the neighboring organs needs to be carefully assessed before operation on CT image. PMID:27610132

  20. Giant Serous Cystadenoma of the Pancreas (⩾10 cm): The Clinical Features and CT Findings.

    PubMed

    Liu, Qing-Yu; Zhou, Jun; Zeng, Yu-Rong; Lin, Xiao-Feng; Min, Jun

    2016-01-01

    Purpose. To report the clinical features and CT manifestations of giant pancreatic serous cystadenoma (≥10 cm). Methods. We retrospectively reviewed the clinical features and CT findings of 6 cases of this entity. Results. All 6 patients were symptomatic. The tumors were 10.2 cm-16.5 cm (median value, 13.0 cm). CT imaging revealed that all 6 cases showed microcystic appearances (n = 5) or mixed microcystic and macrocystic appearances (n = 1). Five patients with tumors at the distal end of the pancreas received distal pancreatectomy. Among these 5 patients, 2 patients underwent partial transverse colon resection or omentum resection due to close adhesion. One patient whose tumor was located in the pancreatic head underwent pancreaticoduodenectomy; however, due to encasement of the portal and superior mesenteric veins, the tumor was incompletely resected. One patient had abundant draining veins on the tumor surface and suffered large blood loss (700 mL). After 6-49 months of follow-up the 6 patients showed no tumor recurrence or signs of malignant transformation. Conclusions. Giant pancreatic serous cystadenoma necessitates surgical resection due to large size, symptoms, uncertain diagnosis, and adjacent organ compression. The relationship between the tumors and the neighboring organs needs to be carefully assessed before operation on CT image. PMID:27610132

  1. [A case of serous surface papillary carcinoma of the peritoneum metastatic to the brain].

    PubMed

    Sakakibara, Yohtaro; Endo, Shu; Yoshida, Yasuyuki; Tanaka, Yuichiro; Hashimoto, Takuo; Ohara, Tatsuru

    2011-06-01

    A case of brain metastasis from peritoneal serous surface papillary carcinoma (SSPC) was reported. This 68-year-old woman was admitted to our department because of decreased consciousness level for the last few days. Her medical past history revealed breast cancer and SSPC of the peritoneum at the age of 64. On admission she was comatose and irritable. Serum and urine examination revealed the syndrome of inappropriate secretion of antidiuretic hormone that was treated with strict restriction of water intake. MRI of the brain demonstrated a nonspecific mass in the subcortical area of the right superior parietal lobule. The mass was successfully removed in en bloc fashion. Pathological diagnosis was SSPC that was compatible with the previous diagnosis obtained from the peritoneum four years previously. Although the patient received whole brain radiation therapy postoperatively, her condition deteriorated rapidly. She died four months after brain surgery. SSPC of the peritoneum is a rare malignant tumor that is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. Because of the prolongation of survival resulting from advanced chemotherapy for SSPC of the peritoneum, more patients live long enough to develop brain metastasis. Therefore, SSPC of the peritoneum should be kept in mind in the differential diagnosis of a primary site for brain metastasis. PMID:21628741

  2. Establishment of human ovarian serous carcinomas cell lines in serum free media.

    PubMed

    Pan, Zhuangyu; Hooley, Jeffrey; Smith, Douglas H; Young, Peter; Roberts, Penelope E; Mather, Jennie P

    2012-03-01

    Ovarian cancers are the fifth leading cause of cancer death among US woman. The majority of ovarian cancers belong to a category of serous adenocarcinomas. This type of cancer is often diagnosed at a late stage of the disease. Surgical debulking, followed by chemotherapy is the current treatment. Half of all patients will die within 5 years of diagnosis of the disease. Poor survival may be due to disease progression as a consequence of development of drug resistance, cancer cell heterogeneity within the tumor, or the persistence of cancer stem cells. Cancer stem cells (CSC) are defined as a minority cell type in the tumor, which retains the capacity, through asymmetric division, for self-renewal as well as differentiation into multiple cell types. Through this process, CSC can regenerate the entire tumor phenotype and subsequent metastases. Initial in vitro work in the area of solid tumor CSC biology has focused on the isolation and propagation of cells with CSC-like properties from breast and colon tumors. Breast and colon cell lines with CSC-like properties have been isolated and maintained in vitro for extended periods of time. The in vitro maintenance of these CSC requires growth in hormone-supplemented serum-free media and the use of matrix or growth as tumor spheres (Roberts, Ricci-Vitiani et al., Cammareri et al.). Based on the pioneering work generating breast and colon CSC, our lab has begun to develop methods for the establishment cell lines with CSC-like properties from additional solid tumors. In this article, we describe methods, using defined medium, which allow for the successful establishment of continuous cell cultures from a minority cell type within serous ovarian cancers. The cell lines established using these methods grow in serum-free hormone-supplemented medium either as a monolayer on a matrix, or as tumor spheres in suspension. These cells express markers previously reported for tumor stem cells, including CD44 and CD133, and form tumors

  3. The Borderline Personality--An Adlerian Overview.

    ERIC Educational Resources Information Center

    Rattner, Leo

    The person with a borderline personality is considered to be neither neurotic nor psychotic, but to exist somewhere in between these two diagnostic categories. Psychoanalytic theorists who have researched the phenomenon of the borderline personality have shifted their emphasis away from Freud's instinct psychology and toward an ego psychology…

  4. Borderline Clients: Practice Implications of Recent Research.

    ERIC Educational Resources Information Center

    Johnson, Harriette C.

    1991-01-01

    Reviews current research on treatment of borderline clients with medication, individual counseling, and family interventions. Notes that recent studies indicate that borderline personality is heterogeneous condition in which different underlying disorders (affective, schizotypal, and neurological) may be present. Reviews effectiveness of various…

  5. Microperimetry in patients with central serous retinopathy.

    PubMed

    Toonen, F; Remky, A; Janssen, V; Wolf, S; Reim, M

    1995-09-01

    In patients with acute central serous retinopathy (CSR), evaluation of visual acuity alone may not represent visual function. In patients with acute CSR, visual function may be disturbed by localized scotomas, distortion, and waviness. For the assessment of localized light sensitivity and stability of fixation, patients with CSR were evaluated by fundus perimetry with a scanning laser ophthalmoscope (SLO 101, Rodenstock Instruments). In all, 21 patients with acute CSR and 19 healthy volunteers were included in the study. Diagnosis of CSR was established by ophthalmoscopy and digital video fluorescein angiography. All patients and volunteers underwent static suprathreshold perimetry with the SLO. Light sensitivity was quantified by presenting stimuli with different light intensities (intensity, 0-27.9 dB above background; size, Goldmann III; wavelength, 633 nm) using an automatic staircase strategy. Stimuli were presented with simultaneous real-time monitoring of the retina. Fixation stability was quantified by measuring the area encompassing 75% of all points of fixation. Light sensitivity was 18-20 dB in affected areas, whereas in healthy eyes and outside the affected area, values of 22-24 dB were obtained. Fixation stability was significantly decreased in the affected eye as compared with normal eyes (33 +/- 12 versus 21 +/- 4 min of arc; P < 0.01). Static perimetry with an SLO is a useful technique for the assessment of localized light sensitivity and fixation stability in patients with macular disease. This technique could provide helpful information in the management of CSR. PMID:7496344

  6. Central Serous Chorioretinopathy Mistaken for Tuberculous Choroiditis

    PubMed Central

    Papadia, Marina; Herbort, Carl P.

    2011-01-01

    Purpose To report a patient erroneously diagnosed with tuberculous choroiditis who was accordingly treated with long term steroids which in turn, worsened the actual disease process that turned out to be central serous chorioretinopathy (CSC). Case Report A 59-year-old Caucasian man developed a chorioretinal disease in his right eye in 1997. Having a positive tuberculin skin test, tuberculous chorioretinitis was suspected and antituberculous therapy was administered for 4 months. In 2005, visual symptoms in the same eye recurred and despite negative interferon gamma release assay, tuberculous choroiditis was considered as the diagnosis and the patient further received massive corticosteroid therapy along with antituberculous agents. Despite a deteriorating clinical picture, therapy was continued. Upon initial examination at our center, no sign of inflammation was observed and a diagnosis of CSC was made, consequently steroid therapy was terminated. Conclusion In some chorioretinopathies, it is difficult to differentiate inflammatory from non-inflammatory causes. One should observe the course of the disease and question the initial diagnosis when no improvement or deterioration occurs despite therapy. PMID:22454755

  7. Borderline personality disorder: study in adolescence.

    PubMed

    James, A; Berelowitz, M; Vereker, M

    1996-04-01

    The study of the presentation, symptomatology and family characteristics of an exclusively adolescent sample of patients with borderline personality disorder (BPD) was undertaken. Twenty-four cases of borderline personality disorder, 20 females, 4 males, identified using chart review and meeting the criteria of the Diagnostic Interview for Borderlines (DIB) and DSM III-R, were matched with psychiatric controls. Adolescents with borderline personality disorder were found to have high rates of affective symptomatology with Axis I diagnosis of major depressive disorder MDD (DSM-III-R), and high rates of interpersonal psychopathology, i.e., manipulation, devaluation, and a pervasive sense of boredom. The latter seem to be characteristic as for adults with borderline personality disorder. The families were particularly angry and volatile. PMID:9117533

  8. Serous retinal detachment after trabeculectomy in angle recession glaucoma

    PubMed Central

    Roy, Avik Kumar; Padhy, Debananda

    2015-01-01

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

  9. An IL6-correlated signature in serous epithelial ovarian cancer associates with growth factor response

    PubMed Central

    2013-01-01

    Background Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers; the majority of EOC is the serous histotype and diagnosed at advanced stage. IL6 is the cytokine that has been found most frequently associated with carcinogenesis and progression of serous EOCs. IL6 is a growth-promoting and anti-apoptotic factor, and high plasma levels of IL6 in advanced stage EOCs correlate with poor prognosis. The objective of the present study was to identify IL6 co-regulated genes and gene network/s in EOCs. Results We applied bioinformatics tools on 7 publicly available data sets containing the gene expression profiles of 1262 EOC samples. By Pearson's correlation analysis we identified, in EOCs, an IL6-correlated gene signature containing 40 genes mainly associated with proliferation. 33 of 40 genes were also significantly correlated in low malignant potential (LMP) EOCs, while 7 genes, named C5AR1, FPR1, G0S2, IL8, KLF2, MMP19, and THBD were IL6-correlated only in advanced stage EOCs. Among the 40-gene signature EGFR ligand HBEGF, genes of the EGR family members and genes encoding for negative feedback regulators of growth factor signaling were included. The results obtained by Gene Set Enrichment and Ingenuity Pathway Analyses enabled the identification, respectively, of gene sets associated with ‘early growth factor response’ for the 40-gene signature, and a biological network related to ‘thrombosis and cardiovascular disease’ for the 7-gene signature. In agreement with these results, selected genes from the identified signatures were validated in vitro by real time RT-PCR in serous EOC cell lines upon stimulation with EGF. Conclusions Serous EOCs, independently of their aggressiveness, co-regulate IL6 expression together with that of genes associated to growth factor signaling, arguing for the hypothesis that common mechanism/s driven by EGFR ligands characterize both advanced-stage and LMP EOCs. Only advanced-stage EOCs appeared to be

  10. OBSTRUCTIVE SLEEP APNEA AND CENTRAL SEROUS CHORIORETINOPATHY

    PubMed Central

    BRODIE, FRANK L.; CHARLSON, EMILY S.; ALEMAN, TOMAS S.; SALVO, REBECCA T.; GEWAILY, DINA Y.; LAU, MARISA K.; FARREN, NEIL D.; ENGELHARD, STEPHANIE B.; PISTILLI, MAXWELL; BRUCKER, ALEXANDER J.

    2016-01-01

    Purpose The purpose of this study was to determine if there is an association between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSCR). Methods Patients with CSCR without a history of steroid use or secondary retinal disease were matched based on age/gender/body mass index with control patients and administered the Berlin Questionnaire to assess for OSA risk. Patients were scored “OSA+” if they were at “high risk” on the Berlin Questionnaire or reported a previous OSA diagnosis. Rates of OSA+ were compared between the 2 groups, odds ratio and its 95% confidence interval was calculated using exact conditional logistic regression. Results Forty-eight qualifying patients with CSCR were identified. There were no statistically significant differences between the CSCR and control groups by age (mean = 55 years), gender (79% male), body mass index (mean = 28.2), history of diabetes, or hypertension. Within the CSCR group, 22 patients (45.8%) were OSA+ versus 21 control patients (43.8%) (difference = 2.1%; 95% confidence interval, −18.2% to 22.2%; exact odds ratio = 1.08, 95% confidence interval, 0.47–2.49; P = 1.00). Conclusion When compared with matched controls, patients with CSCR did not have statistically significant higher rates of OSA risk or previous diagnosis. This finding contrasts with previous work showing a strong association between the diseases. The divergence is likely due to our matching controls for body mass index, a significant risk factor for OSA. PMID:25127049

  11. Estimation of Prognostic Marker Genes by Public Microarray Data in Patients with Ovarian Serous Cystadenocarcinoma

    PubMed Central

    Yang, San-Duk; Jang, Se-Song; Han, Jeong A.; Park, Hyun-Seok

    2016-01-01

    Purpose Lymphatic invasion (LI) is regarded as a predictor of the aggressiveness of ovarian cancer (OC). However, LI is not always the major determinant of long-term patient survival. To establish proper diagnosis and treatment for OC, we analyzed differentially expressed genes (DEGs) for patients with serous epithelial OC, with or without LI, who did or did not survive for 5 years. Materials and Methods Gene expression data from 63 patients with OC and LI, and 35 patients with OC but without LI, were investigated using an Affymetrix Human Genome U133 Array and analyzed using The Cancer Genome Atlas (TCGA) database. Among these 98 patients, 16 survived for 5 years or more. DEGs were identified using the Bioconductor R package, and their functions were analyzed using the DAVID web tool. Results We found 55 significant DEGs (p<0.01) from the patients with LI and 20 highly significant DEGs (p<0.001) from those without it. Pathway analysis showed that DEGs associated with carbohydrate metabolism or with renal cell carcinoma pathways were enriched in the patients with and without LI, respectively. Using the top five prognostic marker genes, we generated survival scores that could be used to predict the 5-year survival of patients with OC without LI. Conclusion The DEGs identified in this study could be used to elucidate the mechanism of tumor progression and to guide the prognosis and treatment of patients with serous OC but without LI. PMID:27189279

  12. Borderline Personality in the Medical Setting

    PubMed Central

    Sansone, Lori A.

    2015-01-01

    Objective: Individuals with borderline personality disorder in mental health settings tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior. In contrast, it appears that individuals with borderline personality disorder in medical settings manifest physical symptoms that are medically difficult to substantiate. Through a review of the literature, we examine 2 symptom manifestations among patients with borderline personality in primary care and general medical settings—namely pain sensitivity and multiple somatic complaints. In addition to reviewing the research of others, we also highlight our own investigations into these 2 areas. Data Sources: We conducted a literature search of the PubMed database and a previous version of the PsycINFO search engine (no restrictions). Search terms included borderline personality, borderline personality disorder, personality disorders; chronic pain, pain, pain syndromes; and somatization disorder, Briquet’s syndrome, somatic preoccupation, somatic. Study Selection: Published articles related to borderline personality, pain and somatic symptoms (ie, somatization disorder, somatic preoccupation) were examined. Results: According to our review, the literature indicates higher-than-expected rates of borderline personality disorder among patients in primary care and general medical settings who present with chronic pain conditions and/or somatic preoccupation. Conclusions: Unlike patients with borderline personality disorder in mental health settings, who tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior, patients with borderline personality disorder in primary care settings tend to present with unsubstantiated chronic pain of various types as well as somatic preoccupation. PMID:26644960

  13. Aggression in borderline personality disorder.

    PubMed

    Látalová, K; Prasko, J

    2010-09-01

    This review examined aggressive behavior in Borderline Personality Disorder (BPD) and its management in adults. Aggression against self or against others is a core component of BPD. Impulsiveness is a clinical hallmark (as well as a DSM-IV-TR diagnostic criterion) of BPD, and aggressive acts by BPD patients are largely of the impulsive type. BPD has high comorbidity rates with substance use disorders, Bipolar Disorder, and Antisocial Personality Disorder; these conditions further elevate the risk for violence. Treatment of BDP includes psychodynamic, cognitive behavioral, schema therapy, dialectic behavioral, group and pharmacological interventions. Recent studies indicate that many medications, particularly atypical antipsychotics and anticonvulsants, may reduce impulsivity, affective lability as well as irritability and aggressive behavior. But there is still a lack of large, double blind, placebo controlled studies in this area. PMID:20390357

  14. Phenomenology of Borderline Personality Disorder

    PubMed Central

    De Genna, Natacha M.; Feske, Ulrike

    2015-01-01

    Little is known about racial differences in borderline personality disorder (BPD) that may influence etiology, phenomenology, and treatment of women with BPD. A total of 83 women with BPD participated in this cross-sectional study: n = 41 white and n = 42 African-American women. Structured interviews were used to assess Axis I and II disorders, and a series of interviews and questionnaires captured internalizing and externalizing symptoms. The white women with BPD reported more severe internalizing symptoms, whereas the African-American women reported more severe externalizing symptoms. Except for the association between race and number of suicide attempts, the relationship between race and internalizing/externalizing symptoms was mediated by socioeconomic status. In conclusion, African-American women with BPD may present with more severe symptoms of lack of anger control and fewer suicidal behaviors than those of white women with BPD, raising the possibility that they are misdiagnosed and receive treatments that are not optimal for BPD. PMID:24284636

  15. Borderline personality disorder in adolescence.

    PubMed

    Kaess, Michael; Brunner, Romuald; Chanen, Andrew

    2014-10-01

    Borderline personality disorder (BPD) is a common and severe mental disorder that is associated with severe functional impairment and a high suicide rate. BPD is usually associated with other psychiatric and personality disorders, high burden on families and carers, continuing resource utilization, and high treatment costs. BPD has been a controversial diagnosis in adolescents, but this is no longer justified. Recent evidence demonstrates that BPD is as reliable and valid among adolescents as it is in adults and that adolescents with BPD can benefit from early intervention. Consequently, adolescent BPD is now recognized in psychiatric classification systems and in national treatment guidelines. This review aims to inform practitioners in the field of adolescent health about the nature of BPD in adolescence and the benefits of early detection and intervention. BPD diagnosis and treatment should be considered part of routine practice in adolescent mental health to improve these individuals' well-being and long-term prognosis. PMID:25246626

  16. Systematic Analysis of Immune Infiltrates in High-Grade Serous Ovarian Cancer Reveals CD20, FoxP3 and TIA-1 as Positive Prognostic Factors

    PubMed Central

    Milne, Katy; Köbel, Martin; Kalloger, Steven E.; Barnes, Rebecca O.; Gao, Dongxia; Gilks, C. Blake; Watson, Peter H.; Nelson, Brad H.

    2009-01-01

    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. PMID:19641607

  17. Tumor

    MedlinePlus

    ... be removed because of their location or harmful effect on the surrounding normal brain tissue. If a tumor is cancer , possible treatments may include: Chemotherapy Radiation Surgery Targeted cancer therapy Biologic therapy Other treatment options

  18. Utility of ovarian biopsy in pancreatic metastasis of high-grade serous ovarian carcinoma: A case report

    PubMed Central

    NAKAMURA, KOHEI; NAKAYAMA, KENTARO; ISHIKAWA, MASAKO; ISHIKAWA, NORIYOSHI; NAGASE, MAMIKO; KATAGIRI, HIROSHI; ISHIBASHI, TOMOKA; SATO, EMI; IIDA, KOHJI; SULTANA, RAZIA; KYO, SATORU

    2016-01-01

    It is very rare that ovarian carcinoma metastasizes to the pancreas, and pathological diagnosis is required to confirm the primary site. The present study reported a 73-year-old woman with serous carcinoma of the ovary that metastasized to the tail of the pancreas. Metastasis was confirmed by pathological and immunohistochemical examination of a biopsy of the ovarian tumor, an endoscopic ultrasound-guided fine-needle aspiration biopsy of the pancreatic tumor and computerized tomography-guided paraaortic lymph node biopsy. A biopsy of the ovarian tumor is useful to make a precise diagnosis and to determine proper treatment when ovarian and pancreatic tumors are identified at the same time and the primary neoplasm is uncertain. PMID:27330762

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

    PubMed

    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. PMID:27059324

  20. [Concepts of the borderline personality disorders].

    PubMed

    Ogłodek, Ewa; Araszkiewicz, Aleksander

    2011-08-01

    For many years, the borderline personality disorders have mainly been researched in terms of psychoanalytical theories, such as theories on relations with the object. Nowadays, there are three kinds of concepts that are distinguishable. The first ones are those which are group models, serving attempts to made characteristic sets of qualities, represented by individuals suffering from the borderline personality disorders, more precise. The remaining concepts are models of conflict and deficit, which explain complicated mechanisms of interactions of social, psychological and biological factors, and therefore, contribute to better understanding of the genesis of the symptoms of this disorder. Upon the basis of the attempts made so far in the field of describing the borderline personality disorders, one may indicate certain criteria, representative for the entire group of individuals with this diagnosis, regardless of the assumptions applicable to the genesis of the disorder and its symptoms, even though the population of the infirm suffering from the borderline personality disorders is not internally homogenous. The interest of psychologists, attempting to describe the borderline personality disorders, is focused upon certain sets of qualities, presented as the examples of descriptive models. Among the researchers, working on the issues of the borderline personality disorders in this manner, there are: Gunderson, Kernberg, Kohut, Winnicot, Guntrip, Fairbaim, Adler and Buie. PMID:21936354

  1. E2Fs mediate a fundamental cell-cycle deregulation in high-grade serous ovarian carcinomas.

    PubMed

    De Meyer, T; Bijsmans, I T G W; Van de Vijver, K K; Bekaert, S; Oosting, J; Van Criekinge, W; van Engeland, M; Sieben, N L G

    2009-01-01

    Several studies described a role for the E2F/Rb pathway in ovarian serous carcinomas (SCAs). Since E2F/Rb pathway deregulation is a general hallmark of human cancer, it remains unclear whether this deregulation is of particular importance in SCAs or whether it reflects a common oncological feature. Here, we have clarified this issue by the examination of microarray expression profiles of SCAs and particularly by the comparison with another, less malignant, ovarian cancer type, serous borderline tumours (SBTs). Results were validated by quantitative RT-PCR, both on the microarray samples and on an independent panel, and TP53 mutation analysis was performed. This integrated analysis revealed a significant increase in the expression of the transcription factors E2F1 and E2F3 in SCAs, when compared to SBTs. This was associated with vast overexpression of E2F target genes in SCAs compared to SBTs. High-grade SCAs in particular exhibited a major deregulated E2F target expression pattern. Generally, overexpression of E2F targets in SCAs appeared to be well structured since those targets considered negative regulators of the cell cycle or promoters of apoptosis were usually not overexpressed in SCAs. Similar to E2F target deregulation, TP53 mutations were identified in SCA3s, to a lesser extent in SCA1s, and not in SBTs. These results suggest that a structured, generally up-regulated E2F transcription factor activity is associated with a global cell-cycle disturbance in high-grade SCAs and exceeds typical E2F/Rb pathway disruption in tumours, at least compared with SBTs. PMID:18991331

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

    PubMed

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

    2016-07-28

    To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC. VIDEO ABSTRACT. PMID:27372738

  3. Pathway-Specific Engineered Mouse Allograft Models Functionally Recapitulate Human Serous Epithelial Ovarian Cancer

    PubMed Central

    Szabova, Ludmila; Bupp, Sujata; Kamal, Muhaymin; Householder, Deborah B.; Hernandez, Lidia; Schlomer, Jerome J.; Baran, Maureen L.; Yi, Ming; Stephens, Robert M.; Annunziata, Christina M.; Martin, Philip L.; Van Dyke, Terry A.

    2014-01-01

    The high mortality rate from ovarian cancers can be attributed to late-stage diagnosis and lack of effective treatment. Despite enormous effort to develop better targeted therapies, platinum-based chemotherapy still remains the standard of care for ovarian cancer patients, and resistance occurs at a high rate. One of the rate limiting factors for translation of new drug discoveries into clinical treatments has been the lack of suitable preclinical cancer models with high predictive value. We previously generated genetically engineered mouse (GEM) models based on perturbation of Tp53 and Rb with or without Brca1 or Brca2 that develop serous epithelial ovarian cancer (SEOC) closely resembling the human disease on histologic and molecular levels. Here, we describe an adaptation of these GEM models to orthotopic allografts that uniformly develop tumors with short latency and are ideally suited for routine preclinical studies. Ovarian tumors deficient in Brca1 respond to treatment with cisplatin and olaparib, a PARP inhibitor, whereas Brca1-wild type tumors are non-responsive to treatment, recapitulating the relative sensitivities observed in patients. These mouse models provide the opportunity for evaluation of effective therapeutics, including prediction of differential responses in Brca1-wild type and Brca1–deficient tumors and development of relevant biomarkers. PMID:24748377

  4. Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma

    PubMed Central

    Kannan, Kalpana; Kordestani, Gona Karimi; Galagoda, Anika; Coarfa, Cristian; Yen, Laising

    2015-01-01

    High-grade serous ovarian cancer (HGSC) is among the most lethal forms of cancer in women. By analyzing the mRNA-seq reads from The Cancer Genome Atlas (TCGA), we uncovered a novel cancer-enriched chimeric RNA as the result of splicing between MUC1, a highly glycosylated transmembrane mucin, TRIM46, a tripartite motif containing protein, and KRTCAP2, a keratinocyte associated protein. Experimental analyses by RT-PCR (reverse transcription PCR) and Sanger sequencing using an in-house cohort of 59 HGSC patient tumors revealed a total of six MUC1-TRIM46-KRTCAP2 isoforms joined by different annotated splice sites between these genes. These chimeric isoforms are not detected in non-cancerous ovaries, yet are present in three out of every four HGSC patient tumors, a significant frequency given the exceedingly heterogeneous nature of this disease. Transfection of the cDNA of MUC1-TRIM46-KRTCAP2 isoforms in mammalian cells led to the translation of mutant MUC1 fusion proteins that are unglycosylated and cytoplasmically localized as opposed to the cell membrane, a feature resembling the tumor-associated MUC1. Because the parental MUC1 is overexpressed in 90% of HGSC tumors and has been proposed as a clinical biomarker and therapeutic target, the chimeric MUC1-TRIM46-KRTCAP2 isoforms identified in this report could represent significantly better MUC1 variants for the same clinical utilities. PMID:26492273

  5. Extrauterine Pelvic Serous Carcinomas: Current Update on Pathology and Cross-sectional Imaging Findings.

    PubMed

    Katabathina, Venkata S; Amanullah, Farhan S; Menias, Christine O; Chen, Melissa M; Valente, Philip T; Chintapalli, Kedar N; Prasad, Srinivasa R

    2016-01-01

    The spectrum of extrauterine pelvic serous carcinomas includes ovarian serous carcinoma, primary peritoneal serous carcinoma, and primary fallopian tube carcinoma. Ovarian serous carcinoma, the most common ovarian malignant epithelial neoplasm, consists of two distinct entities: high-grade and low-grade serous carcinomas. Primary peritoneal serous carcinoma and primary fallopian tube carcinoma are rare malignancies that share many characteristics of high-grade serous carcinomas. Recent advances in the genetics and molecular biology of gynecologic cancers have suggested a common origin of many extrauterine pelvic serous carcinomas from fallopian tube epithelium. With the exception of low-grade serous carcinomas, which arise from cortical inclusion cysts lined by tubal epithelium, most extrauterine pelvic serous carcinomas are believed to originate from serous tubal intraepithelial carcinomas and show similar clinical-biologic behaviors and natural histories. Indeed, the International Federation of Gynecology and Obstetrics Committee on Gynecologic Oncology recently recognized that these cancers should be considered collectively, with a common system of staging and management strategies for ovarian, primary peritoneal, and fallopian tube cancers. A paradigm shift has occurred in our understanding of the pathogenesis of extrauterine pelvic serous carcinomas that has the potential to change current strategies for screening, prevention, diagnosis, and management. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging, and combined positron emission tomography and CT are pivotal in screening, initial diagnosis, and treatment follow-up; however, because of this paradigm shift, new radiologic techniques, such as contrast material-enhanced US and molecular US imaging, and various optical imaging techniques are being investigated as important screening and diagnostic tools. Because of evolving knowledge of genetic and molecular changes underlying the

  6. Network-based integration of GWAS and gene expression identifies a HOX-centric network associated with serous ovarian cancer risk

    PubMed Central

    Kar, Siddhartha P.; Tyrer, Jonathan P.; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel; 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 F.; Edwards, Robert P.; 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; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K.; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K.; Kelemen, Linda E.; Kellar, Melissa; Kelley, Joseph; 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; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain A.; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; 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; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston-Campbell, Lara E.; 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; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Monteiro, Alvaro N. A.; Freedman, Matthew L.; Gayther, Simon A.; Pharoah, Paul D. P.

    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 by co-expression may also be enriched for additional EOC risk associations. Methods We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly co-expressed with each selected TF gene in the unified microarray data set of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this data set 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 identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P<0.05 and FDR<0.05). These results were replicated (P<0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. Conclusion We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Impact Network analysis integrating large, context-specific data sets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. PMID:26209509

  7. Developmental aspects of borderline personality disorder.

    PubMed

    Reich, D B; Zanarini, M C

    2001-01-01

    This study examined whether patients with borderline personality disorder and controls with other personality disorders remember their childhoods differently with respect to separation difficulties, evocative memory, temperamental factors such as frustration tolerance and mood reactivity, and onset of symptoms. Two hundred and ninety patients with borderline personality disorder and 72 with other personality disorders were assessed using an instrument to rate memories of separation difficulties, temperamental problems, and onset of symptoms before age 18. Patients with borderline personality disorder remembered more difficulties with separation between ages 6 and 17 years, more mood reactivity and poorer frustration tolerance between ages 6 and 17, and the onset of more symptoms (most prominently sadness, depression, anxiety, and suicidality) before age 18 than did patients with other personality disorders. The groups did not differ in reports of evocative memory before age 18. These results indicate that many of the features of adult patients with borderline personality disorder may initially appear during childhood and adolescence and that these features may be used to differentiate borderline from other personality disorders. PMID:11600488

  8. Recognizing borderline personality disorder in the family practice setting.

    PubMed

    Hubbard, J R; Saathoff, G B; Bernardo, M J; Barnett, B L

    1995-09-01

    The first step in the management of borderline personality disorder is making the correct diagnosis. A clinical example illustrates symptoms of a patient with borderline personality disorder in a family practice setting. Major characteristics of borderline personality disorder include severe mood instability, fear of abandonment, chronic boredom, self-injury, unstable interpersonal relationships, "splitting," identity instability and borderline rage. Early diagnosis may help prevent potential management problems and possible doctor-patient conflicts. PMID:7653428

  9. [Treatment of serous macular retinal detachment with antihistamines].

    PubMed

    Kirschfeld, K

    2015-01-01

    The etiology of retinal detachment in central serous retinopathy (CSR) is unknown; however, three facts are generally accepted: (1) the serous exudate which raises the layers of the receptors/pigment epithelium is formed due to hyperpermeability in the choriocapillaries, (2) patients frequently suffer from headaches and (3) stress promotes the incidence of CSR. A high blood plasma histamine concentration can cause the abovementioned symptoms which suggests that histamine might provoke CSR. Within 1 week after administration of the antihistamine loratadin a considerable reduction in the retinal exudate and restoration of vision were observed. This supports the hypothesis that histamine could be involved in the process of retinal detachment. Further investigations and large scale clinical trials should clarify if this hypothesis can be proved or disproved and whether antihistamines can be used for age-related macular degeneration (AMD). PMID:25278347

  10. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 and Temsirolimus in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2014-05-29

    Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Recurrent Renal Cell Cancer; Stage III Endometrial Carcinoma; Stage III Renal Cell Cancer; Stage IV Endometrial Carcinoma; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  11. Fertility sparing treatment in borderline ovarian tumours

    PubMed Central

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  12. Fertility sparing treatment in borderline ovarian tumours.

    PubMed

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10-15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  13. Management of borderline resectable pancreatic cancer.

    PubMed

    Lal, Alysandra; Christians, Kathleen; Evans, Douglas B

    2010-04-01

    Borderline resectable pancreatic cancer is an emerging stage of disease defined by computed tomogrpahy criteria, patient (Katz type B), or disease characteristics (Katz type C). These patients are particularly well suited to a surgery-last strategy with induction therapy consisting of chemotherapy (gemcitabine alone or in combination) followed by chemoradiation. With appropriate selection and preoperative planning, many patients with borderline resectable disease derive clinical benefit from multimodality therapy. The use of a standardized system for the staging of localized pancreatic cancer avoids indecision and allows for the optimal treatment of all patients guided by the extent of their disease. In this article, 2 case reports are presented, and the term borderline resectable pancreatic cancer is discussed. The advantages of neoadjuvant therapy and surgery are also discussed. PMID:20159519

  14. Serous Macular Detachment Secondary to Optic Pit: Surgical Treatment and Long Time Results

    PubMed Central

    Cevher, Selim; Sahinoglu-Keskek, Nedime; Unal, Fikret; Demirduzen, Selahaddin; Oksuz, Huseyin

    2016-01-01

    32-year-old Turkish male patient presented with an optic disk pit and serous macular detachment in the left eye. Spectral domain optical coherence tomography revealed serous macular detachment and retinoschisis. After vitrectomy the retina gradually flattened and vision was gradually improved. We aimed to report a case of serous macula detachment secondary to optic pit and long term result of surgical treatment. PMID:26881159

  15. Central serous chorioretinopathy after dacryocystorhinostomy operation on the same side.

    PubMed

    Mondal, Lakshmikanta; Basu, Sayan; Baidya, Krishnapada; Bhaduri, Gautam

    2009-01-01

    A 43-year-old man developed central serous choroidoretinopathy in his left eye following dacryocystorhinostomy operation on the same side. He was using xylometazoline nasal drops in his left nostril. Action of xylometazoline or the stress related to the operation or the effect of both factors played the role in the causation of this ocular condition. Omission of nasal drops or relief from stress resulted in full recovery of vision and complete resolution of symptoms within one month. PMID:19075414

  16. An Overview of Countertransference With Borderline Patients

    PubMed Central

    GABBARD, GLEN O.

    1993-01-01

    Successful management of countertransference is critical to the psychotherapy of borderline patients. The author discusses the most common countertransference reactions encountered in such treatments. A theoretical framework is also proposed that conceptualizes countertransference as a joint creation between therapist and patient. It follows from this conceptual framework that therapists must constantly monitor their own contributions from past relationships as well as the aspects of countertransference evoked by the patient’s behavior. Countertransference in the psychotherapy of borderline patients must be viewed as a source of valuable diagnostic and therapeutic information and not simply as interference with the therapeutic process. PMID:22700123

  17. Serous Microcystic Adenocarcinoma of Pancreas Infiltrating Into Spleen: A Case Report

    PubMed Central

    Ramu, Sathyalakshmi; Mishra, Nidhi; Adaikalam, Mary Lilly Susai; Venkatesan, Ramya

    2015-01-01

    Cystic tumours of pancreas account for 5-10% of all pancreatic neoplasms and serous tumours represent 1% among those tumours. Most of the serous tumours are benign and very rarely they infiltrate adjacent organs like liver and spleen. Herewith we present a rare case report of serous cystadenocarcinoma of pancreas in a 65-year-old woman. The tumour involved the body and tail of pancreas and contiguously invaded the spleen. The histopathology of tumour was similar to serous cystadenoma with mild nuclear hyperchromasia and atypia. The spleen showed tumour infiltration as microcysts diffusely infitrating the red pulp. PMID:26500911

  18. Automatic differential diagnosis of pancreatic serous and mucinous cystadenomas based on morphological features.

    PubMed

    Song, Jae-Won; Lee, Ju-Hong; Choi, Joon-Hyuk; Chun, Seok-Ju

    2013-01-01

    Generally, pathological diagnosis using an electron microscope is time-consuming and likely to result in a subjective judgment, because pathologists perform manual screening of tissue slides at high magnifications. Recently, the advent of digital pathology technology has provided the basis for convenient screening and quantitative analysis by digitizing tissue slides through a computer system. However, a screening process with high magnification still takes quite a long time. To solve these problems, recently the use of computer-aided design techniques for performing pathologic diagnosis has been increasing in digital pathology. For pathological diagnosis, we need different diagnostic methods for different regions with different characteristics. Therefore, in order to effectively diagnose different lesions and types of diseases, a quantitative method for extracting specific features is required in computerized pathologic diagnosis. This study is about an automated differential diagnosis system to differentiate between benign serous cystadenoma and possibly-malignant mucinous cystadenoma. In order to diagnose cystic tumors, the first step is identifying a cystic region and inspecting its epithelial cells. First, we identify the lumen boundary of a cyst using the Direction Cumulative Map considering 8-ways. Then, the Epithelial Nuclei Identification algorithm is used to discern epithelial nuclei. After that, three morphological features for the differential diagnosis of mucinous and serous cystadenomas are extracted. To demonstrate the superiority of the proposed features, the experiments compared performance of the classifiers learned by using the proposed morphological features and the classical morphological features based on nuclei. The classifiers in the simulations are as follows; Bayesian Classifier, k-Nearest Neighbors, Support Vector Machine, and Artificial Neural Network. The results show that all classifiers using the proposed features have the best

  19. Clinical outcomes in patients with isolated serous tubal intraepithelial carcinoma (STIC): A comprehensive review.

    PubMed

    Patrono, Maria Guadalupe; Iniesta, Maria D; Malpica, Anais; Lu, Karen H; Fernandez, Rodrigo Orozco; Salvo, Gloria; Ramirez, Pedro T

    2015-12-01

    OBJECTIVE. Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic (i.e., ovarian or peritoneal) high-grade serous carcinoma. The incidence of STIC has been reported to range from 0.6% to 7% in BRCA mutations carriers. However, the clinical outcome of patients with 'isolated' STIC remains elusive. The aim of this study is to review the published literature on isolated STIC to determine outcomes of these ients and present a summary of management strategies. METHODS. A systematic English-language literature search was conducted in PubMed, MEDLINE-Ovid, Scopus, EBSCO host, Cochrane Library of articles published from February 2006 to April 2015. Study inclusion criteria for review were the following: risk-reducing salpingo-oophorectomy (RRSO), BRCA mutation carriers, non-BRCA mutation carriers, and benign surgical indication. Exclusion criteria were as follows: the presence of synchronous gynecological cancers, concurrent non-gynecological malignancies, the presence of ovarian intraepithelial lesions, and articles that did not include any clinical information and were restricted to pathology information only. RESULTS. A total of 78 patients with isolated STIC were included in our analysis. The median age for all patients was 53.7 years (range; 37-83). Surgical indication was RRSO in 67 patients with BRCA mutations or high-risk personal or family history. In the other 11 patients, an incidental STIC was detected after surgery for non-cancerous indications. Eleven (16.4%) patients received chemotherapy after the diagnosis of STIC. The follow-up time ranged from 2 to 150 months. Three (4.5%) patients with BRCA mutations were diagnosed with primary peritoneal carcinoma (PPC) during the follow-up at 43, 48 and 72 months after RRSO. CONCLUSIONS. The rate of primary peritoneal carcinoma in patients with BRCA mutations and isolated STIC is 4.5%. The role of adjuvant therapy remains elusive and routine surveillance with tumor markers

  20. Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients With Primary Ovarian Serous Carcinoma

    PubMed Central

    Gillet, Jean-Pierre; Calcagno, Anna Maria; Varma, Sudhir; Davidson, Ben; Bunkholt Elstrand, Mari; Ganapathi, Ram; Kamat, Aparna A.; Sood, Anil K.; Ambudkar, Suresh V.; Seiden, Michael V.; Rueda, Bo R.; Gottesman, Michael M.

    2012-01-01

    Purpose This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. Experimental Design We applied a customized TaqMan Low Density Array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes. Results Leave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (P=0.06), four covariates (age, stage, CA125 level and surgical debulking) do (P=0.03). When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in overall survival prediction (log-rank statistic P<0.003). The predictive power of this 11-gene signature was confirmed by dividing high and low risk patient groups, as defined by their clinical covariates, into four specific risk groups based on expression levels. Conclusion This study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin- and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer. PMID:22492981

  1. Markers of T Cell Infiltration and Function Associate with Favorable Outcome in Vascularized High-Grade Serous Ovarian Carcinoma

    PubMed Central

    Townsend, Katelin N.; Spowart, Jaeline E.; Huwait, Hassan; Eshragh, Sima; West, Nathan R.; Elrick, Mary A.; Kalloger, Steve E.; Anglesio, Michael; Watson, Peter H.; Huntsman, David G.; Lum, Julian J.

    2013-01-01

    Background When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL) could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. Methodology and Principal Findings In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3)) and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1)) correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049–5.106); p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF) expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097–5.799); p = 0.0294]. Significance Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions. PMID:24376535

  2. Borderline Intellectual Functioning: A Systematic Literature Review

    ERIC Educational Resources Information Center

    Peltopuro, Minna; Ahonen, Timo; Kaartinen, Jukka; Seppälä, Heikki; Närhi, Vesa

    2014-01-01

    The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health…

  3. The psychotherapy of core borderline psychopathology.

    PubMed

    Adler, G

    1993-01-01

    A psychodynamic formulation of borderline psychopathology includes the understanding of the borderline patient's aloneness problems, need-fear dilemma issues, and difficulties with primitive guilt. The aloneness problems are at the core of the disorder, and involve an inability to maintain an evocative memory, and holding and soothing introjects of significant people when under stress of separation. The possible childhood origins of these difficulties are explored and related to the ways these issues emerge in psychotherapy. The psychodynamic formulation is crucial in the psychotherapeutic approach to the aloneness problems. It helps the therapist work with the aloneness difficulties and understand the options as the therapy continues. Since rapid therapeutic decisions are often necessary with borderline patients, the formulation provides the necessary framework, and helps the therapist process and utilize countertransference feelings. Projective identification is an important concept that helps explain the complex transference/countertransference experiences, and is used in defining the resolution of the aloneness problems of borderline patients. Finally, limit-setting and the use of transitional objects are explored, utilizing the psychodynamic framework that has been defined. PMID:8517469

  4. Dysphoria and aloneness in borderline personality disorder.

    PubMed

    Pazzagli, A; Monti, M R

    2000-01-01

    A close examination of dysphoria, anger and aloneness (three main characteristics of the borderline syndrome) provides a theoretical model of reference for the therapist. Dysphoria results from the cyclical emotional oscillation between hope for stability and disappointment in its inattainability; a dependent-anaclitic depression arises from the mixture of anger, aloneness and inner emptiness which is so characteristic of the borderline syndrome. The tendency to be immersed in the here-and-now, an intra-festum mentality, exacerbates the sense of isolation, causing more irritation, mute frustration and, consequently, anger. The effects and ramifications of anger, and the resultant precarious cohesion of the self, are explored in the borderline syndrome; they are especially illuminated by the application of Kernberg's pain-anger-hate-vengefulness cycle concept. Meanings of solitude, in its forms of aloneness and loneliness, are explored in their pertinence. Aloneness - the constant needy search for, but condemnation to never finding, objects to fill an inner sense of emptiness - is especially germane. Suggestions for assisting subjects with borderline personality disorder to overcome aloneness and the lack of historical progression are made. PMID:10867581

  5. CDKN2D-WDFY2 Is a Cancer-Specific Fusion Gene Recurrent in High-Grade Serous Ovarian Carcinoma

    PubMed Central

    Rajapakshe, Kimal; Hawkins, Shannon M.; Matzuk, Martin M.; Milosavljevic, Aleksandar; Yen, Laising

    2014-01-01

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

  6. S100P is a useful marker for differentiation of ovarian mucinous tumors.

    PubMed

    Umezaki, Y; Ito, M; Nakashima, M; Mihara, Y; Naruke, Y; Kurohama, H; Yatsunami, N; Yasuhi, I

    2015-01-01

    The S100P protein stimulates cell proliferation and survival, thereby contributing to tumor progression. The purpose of this study was to evaluate S100P expression in the three subtypes of mucinous cystic tumors, cystadenomas, borderline tumors, and adenocarcinomas. The authors examined nuclear S100P expression in 60 mucinous ovarian tumor specimens, including 24 specimens of mucinous cystadenoma, 15 of borderline tumors, and 21 of adenocarcinomas. Immunohistochemistry revealed S100P expression followed one of three patterns: (1) Expressed in most nuclei of mucinous epithelial cells, (2) sporadic (spotted or patchy) expression, or (3) absent or rarely expressed in the nuclei of mucinous epithelial cells. Most adenomas showed the first expression pattern, and borderline tumors often showed a patchy expression pattern. Adenocarcinomas generally demonstrated absence of S100P expression. These data suggest that S100P is a useful histological marker to differentiate between benign, borderline, and malignant mucinous tumors of the ovary. PMID:26050349

  7. Femoral metastases from ovarian serous/endometroid adenocarcinoma

    PubMed Central

    Beresford–Cleary, NJA; Mehdi, SA; Magowan, B

    2012-01-01

    Bony metastases from ovarian cancer are rare, tend to affect the axial skeleton and are associated with abdomino-pelvic disease. The median time interval between diagnosis of ovarian carcinoma and presentation of bony metastases is 44 months (1). We describe a rare case of high grade left ovarian serous / endometrioid adenocarcinoma presenting with a pathological right femoral fracture 4 weeks following diagnosis and optimal debulking of the ovarian tumour. Orthopaedic surgeons must be vigilant when planning treatment of fractures presenting in patients with a history of ovarian cancer. PMID:24960734

  8. Central serous chorioretinopathy: from glucocorticoids to light intensity

    PubMed Central

    Norouzpour, Amir; Abrishami, Majid

    2016-01-01

    Central serous chorioretinopathy (CSC) is characterized by a localized accumulation of subretinal fluid and an idiopathic focal leakage from choroidal vessels. The exact pathogenesis of CSC, however, still remains obscure. In this paper, we hypothesized that CSC may result from a response of choroidal vessels to an acute increase in the environmental light intensity leading to a focal leakage from the choroidal vessels. High levels of glucocorticoids, in our proposed model, may cause persistence rather than initiation of the focal leakage, probably by suppressing the synthesis of collagen and extracellular matrix components and inhibiting fibroblastic activity. PMID:26949657

  9. Expression of Vascular Endothelial Growth Factor (VEGF) and Epidermal Growth Factor Receptor (EGFR) in Patients With Serous Ovarian Carcinoma and Their Clinical Significance

    PubMed Central

    Ranjbar, Reza; Nejatollahi, Foroogh; Nedaei Ahmadi, Ahmad Sina; Hafezi, Hossein; Safaie, Akbar

    2015-01-01

    Background: Vascular endothelial growth factor (VEGF) has an essential role in tumor metastasis by inducing the construction of abnormal blood vessels. Epidermal growth factor receptor (EGFR) is involved in different parts of cancer growth such as tumor initiation, angiogenesis and metastasis. Objectives: The aim of this study was to evaluate the expression of VEGF and EGFR in ovarian cancer in southern Iran and to assess the correlation between expression of these two markers and patients’ age, tumor stage, and grade. Patients and Methods: In this cross-sectional study, 50 paraffin blocks of serous ovarian adenocarcinomas and 50 paraffin-embedded specimens from control individuals operated for reasons other than malignancy were immunohistochemically stained using anti-human VEGF and EGFR antibodies. Results: A significant difference in the frequency of positive expression of VEGF was observed in ovarian cancer patients (25.0%) compared with the control group (8.0%) (P = 0.023). A significant difference between EGFR expression in patients (56.8%) and controls (24.0%) was also obtained (P = 0.001). No significant correlation between VEGF and EGFR expression and patients’ age, tumor grade and stage were detected (P > 0.05). Conclusions: The significant increase in both VEGF and EGFR in the patients with ovarian cancer compared to healthy individuals could have prognostic value. Identifying these markers may be useful for chemopreventive and chemotherapeutic strategies for patients with serous ovarian cancer. PMID:26478789

  10. Neurobehavioral study of borderline personality disorder.

    PubMed Central

    van Reekum, R; Conway, C A; Gansler, D; White, R; Bachman, D L

    1993-01-01

    The existence of an "organic" subgroup of borderline personality disorder (BPD) has been postulated. This report is of a case-controlled, chart-review study of BPD. The control sample consisted of patients with a variety of psychiatric diagnoses. The study found that 81% of the patients with BPD and 22% of the control patients had a history of brain injury, either developmental (44%), acquired (58%) or both. Furthermore, there was a positive correlation between the summed number of developmental and acquired brain injuries and the score on the retro-Diagnostic Interview for Borderline. A pilot neuropsychological study showed that seven of nine subjects with BPD had evidence of frontal system dysfunction. These results help to support the hypothesized existence of an organic BPD subgroup. PMID:8499428

  11. Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma.

    PubMed

    Zhou, Jun; Gong, Guanghui; Tan, Hong; Dai, Furong; Zhu, Xin; Chen, Yile; Wang, Junpu; Liu, Ying; Chen, Puxiang; Wu, Xiaoying; Wen, Jifang

    2015-06-01

    MicroRNAs (miRNAs) can serve as biomarkers in human cancer. To determine the clinical value of urinary miRNAs for ovarian serous adenocarcinoma, we collected urine samples from 39 ovarian serous adenocarcinoma patients, 26 patients with benign gynecological disease and 30 healthy controls. The miRNA microarray data showed that only miR-30a-5p was upregulated and 37 miRNAs were downregulated in the urine samples of ovarian serous adenocarcinoma patients, when compared to healthy controls, which was confirmed after conducting quantitative PCR. The upregulation of urinary miR-30a-5p was closely associated with early stage of ovarian serous adenocarcinoma as well as lymphatic metastasis. Receiver operator characteristic (ROC) analysis demonstrated the potential use of urinary miR-30a-5p as a diagnostic marker for ovarian serous adenocarcinoma. Furthermore, a lower urine level of miR-30a-5p was found in 20 gastric cancer and 20 colon carcinoma patients when compared to ovarian serous adenocarcinoma, suggesting that the upregulation of urinary miR-30a-5p may be specific for ovarian serous adenocarcinoma. miR-30a-5p was also upregulated in ovarian serous adenocarcinoma tissues and cell lines, while urinary miR-30a-5p from ovarian cancer patients was notably reduced following the surgical removal of ovarian serous adenocarcinoma, suggesting that urinary miR-30a-5p was derived from the ovarian serous adenocarcinoma tissue. Notably, miR-30a-5p was concentrated with exosomes from the ovarian cancer cell supernatant or urine from ovarian serous adenocarcinoma patients, supporting a pathway for excretion into the urine. The results also showed that the knockdown of miR-30a-5p significantly inhibited the proliferation and migration of ovarian cancer cells. In summary, to the best of our knowledge, the present study provided the first evidence of increased miR-30a-5p in the urine of ovarian serous adeno-carcinoma patients, while the inhibition of miR-30a-5p suppressed the

  12. Relationship management and the borderline patient.

    PubMed Central

    Dawson, D. F.

    1993-01-01

    Treating a patient with borderline personality disorder is fraught with peril. Some psychotherapies and medications seem to make matters worse, yet these very patients are some of the most persistent in demanding help. This happens because the context of treatment, the traditional physician-patient social contract, and the personal and professional impulses of the physician can actually feed and reinforce the patient's pathological behaviour. Relationship management offers a way to understand the problem and to handle it. PMID:8495141

  13. Borderline personality traits in hysterical neurosis.

    PubMed

    Ohshima, T

    2001-04-01

    The objective of the present study is to demonstrate the traits of the psychopathology of Borderline Personality Disorder (BPD) compared with hysterical neurosis. A total of 48 subjects with BPD and 40 subjects with hysterical neurosis both defined by DSM-III-R were assessed by Diagnostic Interview for Borderlines (DIB). Statistical analysis was done by quantification of the second type, a multivariate data analysis. The total scores of DIB were BPD group, 6.13 +/- 1.52; hysterical neurosis group, 4.9 +/- 2.12 (t = 3.05, P = 0.0016). The correlation ratio (index of to what extent the two groups are discriminated) was 0.2442. Among the four parameters of: (i) affect, (ii) cognition, (iii) impulse-action pattern, (iv), and interpersonal relationships, the partial coefficient correlations of (iii) and (iv) were significantly high (0.342, 0.287, P < 0.01). The question items with high independent coefficients were manipulation (0.4416), intolerance of aloneness (0.3797), demanding nature (0.3768), self-mutilation (0.3609), visual hallucination (0.3395). Those with low score of independent coefficients were counterdependency (0.0533), identity disturbance (0.1010), depression (0.1551), loneliness (0.1752), hypomanic episode (0.1936). Both of BPD and hysterical neurosis groups were not so fairly well discriminated. However, these results suggested that impulse-action pattern and disorder of interpersonal relationships were traits of borderline personality disorder. We could admit manipulation, intolerance of aloneness as its symptoms. In addition, counterdependency, identity disturbance were comparatively common to both. There were some borderline personality traits symptomatically in hysterical neurosis. PMID:11285092

  14. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.

    PubMed

    Creighton, Chad J; Fountain, Michael D; Yu, Zhifeng; Nagaraja, Ankur K; Zhu, Huifeng; Khan, Mahjabeen; Olokpa, Emuejevoke; Zariff, Azam; Gunaratne, Preethi H; Matzuk, Martin M; Anderson, Matthew L

    2010-03-01

    MicroRNAs (miRNA) regulate complex patterns of gene expression, and the relevance of altered miRNA expression to ovarian cancer remains to be elucidated. By comprehensively profiling expression of miRNAs and mRNAs in serous ovarian tumors and cell lines and normal ovarian surface epithelium, we identified hundreds of potential miRNA-mRNA targeting associations underlying cancer. Functional overexpression of miR-31, the most underexpressed miRNA in serous ovarian cancer, repressed predicted miR-31 gene targets including the cell cycle regulator E2F2. MIR31 and CDKN2A, which encode p14(ARF) and p16(INK4A), are located at 9p21.3, a genomic region commonly deleted in ovarian and other cancers. p14(ARF) promotes p53 activity, and E2F2 overexpression in p53 wild-type cells normally leads via p14(ARF) to an induction of p53-dependent apoptosis. In a number of serous cancer cell lines with a dysfunctional p53 pathway (i.e., OVCAR8, OVCA433, and SKOV3), miR-31 overexpression inhibited proliferation and induced apoptosis; however, in other lines (i.e., HEY and OVSAYO) with functional p53, miR-31 had no effect. Additionally, the osteosarcoma cell line U2OS and the prostate cancer cell line PC3 (p14(ARF)-deficient and p53-deficient, respectively) were also sensitive to miR-31. Furthermore, miR-31 overexpression induced a global gene expression pattern in OVCAR8 associated with better prognosis in tumors from patients with advanced stage serous ovarian cancer, potentially affecting many genes underlying disease progression. Our findings reveal that loss of miR-31 is associated with defects in the p53 pathway and functions in serous ovarian cancer and other cancers, suggesting that patients with cancers deficient in p53 activity might benefit from therapeutic delivery of miR-31. PMID:20179198

  15. Focal choroidal excavation in patients with central serous chorioretinopathy

    PubMed Central

    Luk, F O J; Fok, A C T; Lee, A; Liu, A T W; Lai, T Y Y

    2015-01-01

    Purpose To evaluate the prevalence and clinical features of focal choroidal excavation (FCE) in patients presenting with central serous chorioretinopathy (CSC). Methods This is a retrospective consecutive case series of consecutive patients with CSC who were referred for spectral domain optical coherence tomography (SD-OCT) between January 2010 and December 2011. Medical records were reviewed and clinical features including presence of FCE in SD-OCT, fluorescence angiography (FA), and indocyanine green angiography (ICGA) were studied. Results Among the 116 CSC patients assessed, FCE was found in 11 eyes of 7 (6.0%) patients. FCE was associated with subretinal fluid in six eyes of six patients and serous pigment epithelial detachment in three eyes of two patients. The mean central subfield retinal thickness of CSC eyes with FCE was 283.7 μm, compared with 377.5 μm for CSC eyes without FCE (Mann–Whitney U-test, P=0.020). Five FCE eyes of five patients had focal leakage on FA. Choroidal hyperpermeability on ICGA was found in seven CSC eyes with FCE, with four eyes showing hypofluorescent spot corresponding to the FCE. After a mean follow-up of 16 months, visual acuity of all 11 eyes with FCE remained stable or improved at the last follow-up. Conclusion FCE is not an uncommon feature in patients with CSC and might be associated with choroidal hemodynamic disturbances. PMID:25853402

  16. Optical Coherence Tomography Angiography in Central Serous Chorioretinopathy

    PubMed Central

    Costanzo, Eliana; Cohen, Salomon Yves; Miere, Alexandra; Querques, Giuseppe; Capuano, Vittorio; Semoun, Oudy; El Ameen, Ala'a; Oubraham, Hassiba; Souied, Eric H.

    2015-01-01

    Purpose. To analyze optical coherence tomography angiography (OCTA) findings in eyes with central serous chorioretinopathy (CSC) and to compare them with those obtained with multimodal imaging. Methods. A series of consecutive patients diagnosed with CSC, underwent OCTA and multimodal imaging, including spectral domain OCT, fluorescein, and indocyanine green angiography. OCTA images were performed at three main depth intervals: automatically segmented outer retina, manually adjusted outer retina, and automatically segmented choriocapillaris. Results. Thirty-three eyes of 32 consecutive patients were analyzed. OCTA showed 3 main anomalies at the choriocapillaris: the presence of dark areas (19/33 eyes) which were frequently associated with serous retinal detachment, presence of dark spots (7/33 eyes) which were frequently associated with retinal pigment epithelium detachment, and presence of abnormal vessels (12/33 eyes) which were frequently, but not systematically, associated with choroidal neovascularization, as confirmed by multimodal imaging. Conclusions. OCTA revealed dark areas and dark spots, which were commonly observed. An abnormal choroidal pattern was also observed in one-third of cases, even when multimodal imaging did not evidence any choroidal neovascularization. Abnormal choroidal vessels should be interpreted with caution, and we could assume that this pathological choroidal vascular pattern observed in many CSC cases could be distinct from CNV. PMID:26634150

  17. [Neurocognitive functioning in borderline personality disorder].

    PubMed

    Poletti, Michele

    2009-01-01

    Neurocognitive dysfunctions in subjects with a diagnosis of borderline personality disorder (BPD) have been often reported in several recent studies, reviewed in this paper. Most marked impairments are reported for executive functions, autobiographical memory and social cognition processes. These impairments may be considered as neurocognitive correlates of some clinical symptoms of BPD: the dysexecutive impairment, particularly of those processes based on the orbitofrontal cortex, is the correlate of the increased impulsivity; the interference of negative emotions on encoding and retrieval of autobiographical memories is the correlate of the frequent dissociative symptoms; difficulties in social cognition processes (for example in emotion recognition) are the correlate of the instable interpersonal relationships. Early cognitive impairments are also detected in children and adolescents with borderline clinical symptoms, suggesting that neurocognitive functioning: (1) might be considered an indirect index of the neurobiological impact of the childhood trauma that usually BPD subjects report; (2) might be a moderator in the development of BPD. Reviewed studies suggest the utility of a neuropsychological evaluation in all those subjects, children, adolescents and adults, that present borderline clinical symptoms. PMID:20218216

  18. Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy

    PubMed Central

    2014-01-01

    Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma. PMID:24636424

  19. Functional Proteomic Analysis of Advanced Serous Ovarian Cancer using Reverse Phase Protein Array: TGFβ Pathway Signaling Indicates Response to Primary Chemotherapy

    PubMed Central

    Carey, Mark S.; Agarwal, Roshan; Gilks, Blake; Swenerton, Kenneth; Kalloger, Steve; Santos, Jennifer; Ju, Zhenlin; Lu, Yiling; Zhang, Fan; Coombes, Kevin; Miller, Dianne; Huntsman, David; Mills, Gordon B.; Hennessy, Bryan T

    2010-01-01

    Purpose: Using Reverse Phase Protein Array (RPPA) we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage high-grade serous ovarian cancer. Experimental Design: Tumor samples were obtained from forty-five patients with advanced high-grade serous cancers from the Gynecology Tumor Bank at the British Columbia Cancer Agency. Treatment consisted of platinum-based chemotherapy following debulking surgery. Protein lysates were prepared from fresh frozen tumor samples and 80 validated proteins from signaling pathways implicated in ovarian carcinogenesis were measured by RPPA. Normalization of Ca-125 by the 3rd cycle of chemotherapy was chosen as the primary outcome measure of chemotherapy response. Logistic regression was used for multivariate analysis to identify protein predictors of Ca-125 normalization, and Cox regression to test for the association between protein expression and PFS. A significance level of p ≤ 0.05 was used. Results: The mean age at diagnosis was 56.8 years. EGFR, YKL-40 and several TGFβ pathway proteins (c-Jun N-terminal kinase JNK, JNK phosphorylated at residues 183 and 185, PAI-1, Smad3, TAZ) showed significant associations with Ca-125 normalization on univariate testing. On multivariate analysis, EGFR (p < 0.02), JNK (p < 0.01), and Smad3 (p < 0.04) were significantly associated with normalization of Ca-125. Contingency table analysis of pathway-classified proteins revealed that the selection of TGFβ pathway proteins was unlikely due to false discovery (p < 0.007, Bonferroni-adjusted). Conclusion: TGFβ pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted. PMID:20460476

  20. Fallopian tube secretory cell expansion: a sensitive biomarker for ovarian serous carcinogenesis

    PubMed Central

    Wang, Yiying; Li, Li; Wang, Yue; Tang, Sarah Ngocvi; Zheng, Wenxin

    2016-01-01

    Recent advances suggest that precancerous lesions of pelvic serous carcinoma originate from tubal secretory cells. The purpose of our study was to determine if an increased number of secretory cells vary with age or location in the fallopian tube and to examine its association with serous neoplasia. Three groups (benign control, high-risk, and pelvic serous carcinoma) of age-matched patients were studied. The age data were stratified into 10-year intervals ranging from 20-29 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data were analyzed by standard contingency table and Poisson distribution methods after age justification. We found that the absolute number of tubal secretory cells increased significantly with age in all three groups. But a more dramatic increase of secretory cells was observed in high-risk and pelvic serous carcinoma patients. Secretory cell expansion is more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and is significantly associated with serous neoplasia (p < 0.001). Furthermore, age remained a significant risk factor for serous neoplasia after age adjustment. These findings suggest that secretory cell expansion could serve as a potential sensitive biomarker for early serous carcinogenesis within the fallopian tube. The study also supports a relationship between serous neoplasia and increased secretory to ciliated cell ratios, and the relationship between frequency of secretory cell expansion within the fallopian tube and increasing age and-more significantly-presence of high-risk factors or co-existing serous cancers. PMID:27069556

  1. Fallopian tube secretory cell expansion: a sensitive biomarker for ovarian serous carcinogenesis

    PubMed Central

    Wang, Yiying; Li, Li; Wang, Yue; Tang, Sarah Ngocvi; Zheng, Wenxin

    2015-01-01

    Recent advances suggest that precancerous lesions of pelvic serous carcinoma originate from tubal secretory cells. The purpose of our study was to determine if an increased number of secretory cells varies with age or location in the fallopian tube and to examine its association with serous neoplasia. Three groups (benign control, high-risk, and pelvic serous carcinoma) of age-matched patients were studied. The age data were stratified into 10-year intervals ranging from 20-29 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data were analyzed by standard contingency table and Poisson distribution methods after age justification. We found that the absolute number of tubal secretory cells increased significantly with age in all three groups. But a more dramatic increase of secretory cells was observed in high-risk and pelvic serous carcinoma patients. Secretory cell expansion is more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and is significantly associated with serous neoplasia (P < 0.001). Furthermore, age remained a significant risk factor for serous neoplasia after age adjustment. These findings suggest that secretory cell expansion could serve as a potential sensitive biomarker for early serous carcinogenesis within the fallopian tube. The study also supports a relationship between serous neoplasia and increased secretory to ciliated cell ratios, and the relationship between frequency of secretory cell expansion within the fallopian tube and increasing age and-more significantly-presence of high-risk factors or co-existing serous cancers. PMID:26692952

  2. Genomic Characterization of High-Grade Serous Ovarian Cancer: Dissecting Its Molecular Heterogeneity as a Road Towards Effective Therapeutic Strategies.

    PubMed

    Mittempergher, Lorenza

    2016-07-01

    High-grade serous ovarian carcinoma (HGSOC) accounts for the majority of the ovarian cancer deaths, but over the last years little improvement in overall survival has been achieved. HGSOC is a molecularly and clinically heterogeneous disease. At genomic level, it represents a C-class malignancy having frequent gene losses (NF1, RB1, PTEN) and gains (CCNE1, MYC). HGSOC shows a simple mutational profile with TP53 nearly always mutated and with other genes mutated at low frequency. Importantly, 50 % of all HGSOCs have genetic features indicating a homologous recombination (HR) deficiency. HR deficient tumors are highly sensitive to PARP inhibitor anticancer agents, which exhibit synthetic lethality with a defective HR pathway. Transcriptionally, HGSOCs can be grouped into different molecular subtypes with distinct biology and prognosis. Molecular stratification of HGSOC based on these genomic features may result in improved therapeutic strategies. PMID:27241520

  3. Pseudopapillary Granulosa Cell Tumor: A Case of This Rare Subtype.

    PubMed

    Heller, Debra; Haddad, Andrew; Cracchiolo, Bernadette

    2016-08-01

    Background The pseudopapillary pattern of granulosa cell tumor is rare. Case We describe the case of a 35-year-old woman who presented with an initial diagnosis of papillary serous cystadenocarcinoma. Results Evaluation, including immunohistochemistry, led to the diagnosis of pseudopapillary granulosa cell tumor. Conclusion The pseudopapillary pattern of granulosa cell tumor is rare and must be suspected in order to utilize appropriate immunohistochemistry and reach the correct diagnosis. Inhibin positivity is particularly helpful. PMID:27020373

  4. CD44 Splice Variant v8-10 as a Marker of Serous Ovarian Cancer Prognosis.

    PubMed

    Sosulski, Amanda; Horn, Heiko; Zhang, Lihua; Coletti, Caroline; Vathipadiekal, Vinod; Castro, Cesar M; Birrer, Michael J; Nagano, Osamu; Saya, Hideyuki; Lage, Kasper; Donahoe, Patricia K; Pépin, David

    2016-01-01

    CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8-10 in patient ascites samples was correlated with significantly worse prognosis (p<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be

  5. CD44 Splice Variant v8-10 as a Marker of Serous Ovarian Cancer Prognosis

    PubMed Central

    Zhang, Lihua; Coletti, Caroline; Vathipadiekal, Vinod; Castro, Cesar M.; Birrer, Michael J.; Nagano, Osamu; Saya, Hideyuki; Lage, Kasper; Donahoe, Patricia K.; Pépin, David

    2016-01-01

    CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8-10 in patient ascites samples was correlated with significantly worse prognosis (p<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be

  6. Müllerian Serous Cystadenoma of the Scrotum Following Orchiopexy

    PubMed Central

    van der Putte, Sebastian C. J.; Toonstra, Johan; Sie-Go, Daisy M. D. S.

    2009-01-01

    A 24-year-old man presented himself with a nodular lesion of about 1 cm diameter at the site of a previous orchiopexy associated with surgery for cryptorchism. Histopathology revealed the lesion to be adenomatous and confined to the scrotum. Histological and immunohistological features were not consistent neither with median raphe cysts or cutaneous adenomas nor with the intrascrotal adenomas of the rete testis, epididymis, nor with (malignant) mesotheliomas. However, the lesion did compare well with serous (papillary) cystadenomas of the testis or paratestis. These adenomas are thought to originate in remnants of the Müllerian system or of peritoneal lining altered by Müllerian metaplasia. This implies that the scrotal adenoma may have developed from an implant of such elements during orchiopexy 14 years ago. Complete excision of the lesion appears to be an adequate therapy. PMID:19343186

  7. Positive affective and cognitive states in borderline personality disorder.

    PubMed

    Reed, Lawrence Ian; Zanarini, Mary C

    2011-12-01

    The aim of the current study was to compliment previous studies identifying negative states present in borderline personality disorder (BPD) by investigating the presence of positive affective and cognitive states. Ninety-six patients with criteria-defined borderline personality disorder and 24 axis II comparison participants completed the Positive Affect Scale, a 50-item self-report measure designed to assess positive states thought to be characteristic of and discriminating for BPD. Seventeen positive states (4 affective, 10 cognitive, and 3 mixed) were found to be significantly more common among axis II comparison participants than borderline patients. Twelve of these states were common to both borderline patients and axis II comparison participants. Furthermore, four positive states, when co-occurring together, were particularly strongly associated with borderline personality disorder (three negatively and one positively): (a) Fond of myself, (b) That things around me are real, (c) That I've forgiven others, and (d) Assertive. Finally, the overall mean score on the PAS significantly distinguished patients with borderline personality disorder from axis II comparison participants. Taken together, these results suggest that borderline patients are far less likely to report experiencing positive states of an affective, cognitive, and mixed nature than axis II comparison participants. They also suggest that being assertive is a positive state particularly discriminating for borderline personality disorder. PMID:22217230

  8. Borderline Personality Disorder: Too Complex for Cognitive Therapy?

    ERIC Educational Resources Information Center

    Pretzer, James L.

    Historically, the literature on psychotherapy with borderline personality disorder has been based on object-relations theory or psychoanalytical approaches, rather than cognitive and behavioral approaches. In clinical assessment, the term borderline has been used to refer to patients with both neurotic and psychotic symptoms, a particular type of…

  9. Parenting Children with Borderline Intellectual Functioning: A Unique Risk Population

    ERIC Educational Resources Information Center

    Fenning, Rachel M.; Baker, Jason K.; Baker, Bruce L.; Crnic, Keith A.

    2007-01-01

    Parenting was examined among families of children with borderline intelligence in comparison to families of typically developing children and children with developmental delays. Parenting data were obtained at child age 5 via naturalistic home observation. Mothers of children with borderline intelligence exhibited less positive and less sensitive…

  10. Treating Obesity: Clinical Implications of Comorbid Borderline Personality Disorder.

    ERIC Educational Resources Information Center

    Sansone, Randy A.; Wiederman, Michael W.; Sansone, Lori A.

    1999-01-01

    Reviews possible links between obesity and borderline-personality disorder and discusses treatment approaches for those individuals demonstrating such comorbidity. Approaches include modification of current techniques for obesity treatment and incorporation of psychodynamic counseling specific to borderline-personality disorder. (Author/GCP)

  11. Therapeutic Self-Disclosure With Borderline Patients

    PubMed Central

    WILKINSON, SALLYE M.; GABBARD, GLEN O.

    1993-01-01

    The therapeutic use of countertransference disclosure as a means of highlighting the borderline patient’s intrapsychic and interpersonal use of the therapist is discussed. Countertransference disclosure is narrowly defined as a form of clinical honesty that focuses on the therapist’s experience of the patient in the here-and-now moment of the session. The effects of disclosure on transference exploration, neutrality, and patient revelations are explored through examination of detailed process notes of therapy sessions. Technical issues such as indirect versus direct disclosure and responses to direct questions are also addressed. PMID:22700154

  12. Parenteral and enteral nutrition: borderline substances.

    PubMed

    Hopley, P J

    1981-01-01

    The application of medicinal product legislation to products which have a possible dual function as drugs and as foods or cosmetics has been described. The approach of the Family Practitioner Services under the NHS is to allow for as much professional debate as possible over the indeterminate ground between food and drugs. The role of the Advisory Committee on Borderline Substances in this context is briefly mentioned. Finally, some practical problems which arise in hospital practise have been described and for the solution the emphasis is upon the multi-disciplinary team approach. PMID:6947663

  13. Tailoring the Psychotherapy to the Borderline Patient

    PubMed Central

    HORWITZ, LEONARD; GABBARD, GLEN O.; ALLEN, JON G.; COLSON, DONALD B.; FRIESWYK, SIEBOLT; NEWSOM, GAVIN E.; COYNE, LOLAFAYE

    1996-01-01

    Views still differ as to the optimal psychodynamic treatment of borderline patients. Recommendations range from psychoanalysis and exploratory psychotherapy to an explicitly supportive treatment aimed at strengthening adaptive defenses. The authors contend that no single approach is appropriate for all patients in this wide-ranging diagnostic category, which spans a continuum from close-to-neurotic to close-to-psychotic levels of functioning. Careful differentiations based on developmental considerations, ego structures, and relationship patterns provide the basis for the optimal treatment approach. PMID:22700301

  14. The Lifetime Course of Borderline Personality Disorder

    PubMed Central

    Biskin, Robert S

    2015-01-01

    Borderline personality disorder (BPD) has historically been seen as a lifelong, highly disabling disorder. Research during the past 2 decades has challenged this assumption. This paper reviews the course of BPD throughout life, including childhood, adolescence, and adulthood. BPD can be accurately identified in adolescence, and the course of the disorder, in adolescence and adulthood, is generally similar, with reductions in symptoms over time. Functional recovery is less consistent, and further research on factors or treatments that may improve the long-term functional outcome of patients with BPD is warranted. PMID:26175388

  15. Alcoholic liver disease and bilateral multifocal central serous retinopathy: a case report

    PubMed Central

    2013-01-01

    Introduction We present a unique case of a patient with bilateral, multifocal central serous retinopathy in a patient with alcoholic liver disease. Case presentation A 58-year-old Caucasian man with alcoholic liver disease, liver cirrhosis and ascites presented to the eye clinic. The ophthalmoscopic examination of both eyes revealed a symmetrical pattern of variably sized, slightly yellowish, translucent, raised lesions throughout the fundi which were confirmed to be caused by multifocal central serous retinopathy after optical coherence tomography and autofluoresence tests. Conclusion This case highlights the possible link between central serous retinopathy and end-stage liver disease, with potential implications for the pathogenesis of central serous retinopathy in these patients. PMID:23406548

  16. The status of epidermal growth factor receptor in borderline ovarian tumours

    PubMed Central

    Showeil, Rania; Romano, Claudia; Valganon, Mikel; Lambros, Maryou; Trivedi, Pritesh; Van Noorden, Susan; Sriraksa, Ruethairat; El-Kaffash, Dalal; El-Etreby, Nour; Natrajan, Rachael; Foroni, Letizia; Osborne, Richard; El-Bahrawy, Mona

    2016-01-01

    The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear

  17. Toward standard HER2 testing of endometrial serous carcinoma: 4-year experience at a large academic center and recommendations for clinical practice.

    PubMed

    Buza, Natalia; English, Diana P; Santin, Alessandro D; Hui, Pei

    2013-12-01

    HER2 overexpression and/or amplification have been reported in endometrial serous carcinoma, suggesting that HER2 may be a promising therapeutic target. However, there is considerable variation in the reported rates of HER2 overexpression and amplification, likely--at least in part--resulting from variability in the testing methods, interpretation, and scoring criteria used. Unlike in breast and gastric cancer, currently there are no established guidelines for HER2 testing in endometrial carcinoma. A total of 108 endometrial carcinoma cases--85 pure serous carcinomas and 23 mixed endometrial carcinomas with serous component--were identified over a 4-year period. All H&E and HER2 immunohistochemical slides were reviewed and HER2 FISH results (available on 52 cases) were retrieved from pathology reports. HER2 immunohistochemical scores were assigned according to the FDA criteria and the current breast ASCO/CAP scoring criteria. Clinical information was retrieved from the patients' medical records. Thirty-eight cases (35%) showed HER2 overexpression and/or gene amplification, 20 of which (53%) had significant heterogeneity of protein expression by immunohistochemistry. Lack of apical membrane staining resulting in a lateral/basolateral staining pattern was observed in the majority of HER2-positive tumors. Five of the HER2-positive cases (13%) demonstrated discrepant immunohistochemical scores when using the FDA versus ASCO/CAP scoring system. The overall concordance rate between HER2 immunohistochemistry and FISH was 75% (39/52) when using the FDA criteria, compared with 81% (42/52) by the ASCO/CAP scoring system. In conclusion, in this largest comprehensive study, 35% of endometrial serous carcinoma harbors HER2 protein overexpression and/or gene amplification, over half of which demonstrate significant heterogeneity of protein expression. The current breast ASCO/CAP scoring criteria provide the highest concordance between immunohistochemistry and FISH. Assessment of

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

    PubMed Central

    Casella, Antonio Marcelo Barbante; Berbel, Rodrigo Fabri; Bressanim, Gláucio Luciano; Malaguido, Marcus Rudolph; Cardillo, José Augusto

    2012-01-01

    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 pylori-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. PMID:23018302

  19. Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma.

    PubMed

    Zhao, Siming; Choi, Murim; Overton, John D; Bellone, Stefania; Roque, Dana M; Cocco, Emiliano; Guzzo, Federica; English, Diana P; Varughese, Joyce; Gasparrini, Sara; Bortolomai, Ileana; Buza, Natalia; Hui, Pei; Abu-Khalaf, Maysa; Ravaggi, Antonella; Bignotti, Eliana; Bandiera, Elisabetta; Romani, Chiara; Todeschini, Paola; Tassi, Renata; Zanotti, Laura; Carrara, Luisa; Pecorelli, Sergio; Silasi, Dan-Arin; Ratner, Elena; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Stiegler, Amy L; Mane, Shrikant; Boggon, Titus J; Schlessinger, Joseph; Lifton, Richard P; Santin, Alessandro D

    2013-02-19

    Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. We analyzed the mutational landscape of USC by whole-exome sequencing of 57 cancers, most of which were matched to normal DNA from the same patients. The distribution of the number of protein-altering somatic mutations revealed that 52 USC tumors had fewer than 100 (median 36), whereas 5 had more than 3,000 somatic mutations. The mutations in these latter tumors showed hallmarks of defects in DNA mismatch repair. Among the remainder, we found a significantly increased burden of mutation in 14 genes. In addition to well-known cancer genes (i.e., TP53, PIK3CA, PPP2R1A, KRAS, FBXW7), there were frequent mutations in CHD4/Mi2b, a member of the NuRD-chromatin-remodeling complex, and TAF1, an element of the core TFIID transcriptional machinery. Additionally, somatic copy-number variation was found to play an important role in USC, with 13 copy-number gains and 12 copy-number losses that occurred more often than expected by chance. In addition to loss of TP53, we found frequent deletion of a small segment of chromosome 19 containing MBD3, also a member of the NuRD-chromatin-modification complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (an upstream activator of PIK3CA), and CCNE1 (a target of FBXW7-mediated ubiquitination). These findings identify frequent mutation of DNA damage, chromatin remodeling, cell cycle, and cell proliferation pathways in USC and suggest potential targets for treatment of this lethal variant of endometrial cancer. PMID:23359684

  20. Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma

    PubMed Central

    Zhao, Siming; Choi, Murim; Overton, John D.; Bellone, Stefania; Roque, Dana M.; Cocco, Emiliano; Guzzo, Federica; English, Diana P.; Varughese, Joyce; Gasparrini, Sara; Bortolomai, Ileana; Buza, Natalia; Hui, Pei; Abu-Khalaf, Maysa; Ravaggi, Antonella; Bignotti, Eliana; Bandiera, Elisabetta; Romani, Chiara; Todeschini, Paola; Tassi, Renata; Zanotti, Laura; Carrara, Luisa; Pecorelli, Sergio; Silasi, Dan-Arin; Ratner, Elena; Azodi, Masoud; Schwartz, Peter E.; Rutherford, Thomas J.; Stiegler, Amy L.; Mane, Shrikant; Boggon, Titus J.; Schlessinger, Joseph; Lifton, Richard P.; Santin, Alessandro D.

    2013-01-01

    Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. We analyzed the mutational landscape of USC by whole-exome sequencing of 57 cancers, most of which were matched to normal DNA from the same patients. The distribution of the number of protein-altering somatic mutations revealed that 52 USC tumors had fewer than 100 (median 36), whereas 5 had more than 3,000 somatic mutations. The mutations in these latter tumors showed hallmarks of defects in DNA mismatch repair. Among the remainder, we found a significantly increased burden of mutation in 14 genes. In addition to well-known cancer genes (i.e., TP53, PIK3CA, PPP2R1A, KRAS, FBXW7), there were frequent mutations in CHD4/Mi2b, a member of the NuRD–chromatin-remodeling complex, and TAF1, an element of the core TFIID transcriptional machinery. Additionally, somatic copy-number variation was found to play an important role in USC, with 13 copy-number gains and 12 copy-number losses that occurred more often than expected by chance. In addition to loss of TP53, we found frequent deletion of a small segment of chromosome 19 containing MBD3, also a member of the NuRD–chromatin-modification complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (an upstream activator of PIK3CA), and CCNE1 (a target of FBXW7-mediated ubiquitination). These findings identify frequent mutation of DNA damage, chromatin remodeling, cell cycle, and cell proliferation pathways in USC and suggest potential targets for treatment of this lethal variant of endometrial cancer. PMID:23359684

  1. Phyllodes Tumor of the Breast

    SciTech Connect

    Belkacemi, Yazid Bousquet, Guilhem; Marsiglia, Hugo; Ray-Coquard, Isabelle; Magne, Nicolas; Malard, Yann; Lacroix, Magalie; Gutierrez, Cristina; Senkus, Elzbieta; Christie, David; Drumea, Karen; Lagneau, Edouard; Kadish, Sidney P.; Scandolaro, Luciano; Azria, David; Ozsahin, Mahmut

    2008-02-01

    Purpose: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. Methods and Materials: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapy (RT). Results: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size tumor necrosis for overall survival. In the malignant and borderline subgroup multivariate analysis TM was the only favorable independent prognostic factor for disease-free survival. Conclusions: This study showed that phyllodes tumor patients with no RD after treatment have better local control. Benign tumors have a good prognosis after surgery alone. In borderline and malignant tumors, TM had better results than BCS. Thus, in these forms adjuvant RT should be considered according to histologic criteria.

  2. A Primary Retroperitoneal Mucinous Tumor

    PubMed Central

    Heelan Gladden, Alicia A.; Wohlauer, Max; McManus, Martine C.; Gajdos, Csaba

    2015-01-01

    A twenty-five-year-old female presented with a large retroperitoneal mass. Workup included history and physical exam, imaging, biopsy, colonoscopy, and gynecologic exam. After surgical resection, the mass was determined to be a primary retroperitoneal mucinous tumor (PRMT). Clinically and histologically, these tumors are similar pancreatic and ovarian mucinous neoplasms. PRMTs are rare and few case reports have been published. PRMTs are divided into mucinous cystadenomas, mucinous borderline tumors of low malignant potential, and mucinous carcinoma. These tumors have malignant potential so resection is indicated and in some cases adjuvant chemotherapy and/or surveillance imaging. PMID:25874152

  3. Defining the mechanisms of borderline personality disorder.

    PubMed

    Clarkin, John F; Posner, Michael

    2005-01-01

    Understanding the biological connections to mental processes was one of the original goals of psychoanalysis, and the development of cognitive and affective neuroscience and its methods might contribute to actualizing this goal. Personality disorders provide an opportunity to examine the complex mental structures of individuals experiencing extreme difficulties in interacting with their social environment. We provide initial information on a collaboration exploring an approach to one of the most serious personality disorders, borderline personality disorder, based upon the study of normal attention, individual differences in temperament, self definition and attachment organization, with the potential to illuminate the psychology and psychobiology of the disorder and to contribute to psychotherapeutic intervention. This developing model of borderline personality disorder can relate the symptoms to more enduring temperamental aspects of the patients. The goal is to understand the development of neural networks that underlie the abnormalities of adults, and eventually work out the interaction between temperament, genes, and experience that produce the disorder, and potentially inform intervention. PMID:15802943

  4. Evaluations of others by borderline patients.

    PubMed

    Arntz, A; Veen, G

    2001-08-01

    This study investigated evaluations of other people in specific emotional situations by patients with borderline personality disorder (BPD). BPD patients (N = 16), control patients with cluster C personality disorder (PD; N = 12) and normal controls (N = 15) saw film clips with emotional themes centering on abandonment, rejection and abuse, hypothesized to be specific for borderline pathology. Subjects wrote down their spontaneous reactions to six film personalities, divided over three clips, including what they thought to be characteristic traits of these persons. Spontaneous reactions were coded on two dimensions, based on earlier studies by Westen and colleagues: a) affect-tone of ascribed qualities and b) complexity of evaluations of people. The number of trait dimensions constituted the third scale. The overall pattern of findings suggests that the BPD group, as well as the cluster C group, show poorly differentiated evaluations with a low number of dimensions. Thus, this seems characteristic for personality disorders in general. The BPD group shows a lower affect-tone, reflecting a stronger tendency to view others negatively, compared with both control groups. PMID:11531203

  5. Synergetic regulatory networks mediated by oncogene-driven microRNAs and transcription factors in serous ovarian cancer

    PubMed Central

    Zhao, Min; Sun, Jingchun; Zhao, Zhongming

    2013-01-01

    Although high-grade serous ovarian cancer (OVC) is the most lethal gynecologic malignancy in women, little is known about the regulatory mechanisms in the cellular processes that lead to this cancer. Recently, accumulated lines of evidence have shown that the interplay between transcription factors (TFs) and microRNAs (miRNAs) is critical in cellular regulation during tumorigenesis. A comprehensive investigation of TFs and miRNAs, and their target genes, may provide a deeper understanding of the regulatory mechanisms in the pathology of OVC. In this study, we have integrated three complementary algorithms into a framework, aiming to infer the regulation by miRNAs and TFs in conjunction with gene expression profiles. We demonstrated the utility of our framework by inferring 67 OVC-specific regulatory feed-forward loops (FFL) initiated by miRNAs or TFs in high-grade serous OVC. By analyzing these regulatory behaviors, we found that all the 67 FFLs are consistent in their regulatory effects on genes that jointly targeted by miRNAs and TFs. Remarkably, we unveiled an unbalanced distribution of FFLs with different oncogenic effects. In total, 31 of the 67 coherent FFLs were mainly initiated by oncogenes. On the contrary, only 4 of the FFLs were initiated by tumor suppressor genes. These overwhelmingly observed oncogenic genes were further detected in a sub-network with 32 FFLs centered by miRNA let-7b and TF TCF7L1 to regulate cell differentiation. Closer inspection of 32 FFLs revealed that 75% of the miRNAs reportedly play functional roles in cell differentiation, especially when enriched in epithelial–mesenchymal transitions. This study provides a comprehensive pathophysiological overview of recurring coherent circuits in OVC that are co-regulated by miRNAs and TFs. The prevalence of oncogenic coherent FFLs in serous OVC suggests that oncogene-driven regulatory motifs could cooperatively act upon critical cellular process such as cell differentiation in a highly

  6. The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis.

    PubMed

    Che, Ya-Ling; Luo, Shu-Juan; Li, Gang; Cheng, Min; Gao, Yi-Meng; Li, Xue-Mei; Dai, Jie-Min; He, Huan; Wang, Jin; Peng, Hui-Juan; Zhang, Yu; Li, Wen-Yan; Wang, Hui; Liu, Bin; Linghu, Hua

    2015-04-10

    Complete resection is pivotal to improve survival to epithelial ovarian cancer (EOC). Crk SH3-domain-binding guanine nucleotide-releasing factor (C3G) is involved in multiple signaling pathways and it has opposite roles in different cancers. The present study aimed to identify C3G expression in ovarian tissue samples from patients with EOC and to explore its association with tumor grade. Eighty-seven archival paraffin-embedded, formalin-fixed, ovarian cancer tissues with serous histology were stained for C3G by immunohistochemistry. To evaluate the contribution of C3G to Rap1 activity, 36 patients with serous ovarian cancer (SOC) were investigated. Additionally, C3G was knocked down in SKOV3 and HEY cells. C3G regulated Rap1 activity and high Rap1 activity was correlated with poor differentiation, advanced FIGO stage, and unsuccessful cytoreductive surgery of SOC. Knockdown of C3G suppressed cell invasion, intravasation and extravasation, and reduced Rap1 activity and secretion of matrix metalloproteinase (MMP)-2 and MMP-9. C3G-mediated activation of Rap1 could direct the tumor pattern of human SOC by promoting the secretion of MMP-2 and MMP-9. These results suggest that C3G is involved in the metastatic spread of EOC. PMID:25617801

  7. Solid serous cystadenoma of the pancreas: a case report of 2 patients revealing vimentin, β-catenin, α-1 antitrypsin, and α-1 antichymotrypsin as new immunohistochemistry staining markers.

    PubMed

    Wu, Wenming; Hong, Xiafei; Li, Ji; Dai, Menghua; Wang, Wenze; Tong, Anli; Zhu, Zhaohui; Dai, Hongmei; Zhao, Yupei

    2015-03-01

    Solid serous cystadenoma (SCA) of the pancreas is a rare type of pancreatic solid tumors. Postoperative pathological evaluation is of particular importance for distinguishing solid SCA of the pancreas from other pancreatic solid tumors. Here we present 2 cases of solid SCA of the pancreas, both preoperatively diagnosed with pancreatic neuroendocrine tumors. One case had positive OctreoScan test. Surgical resections were done for both cases. Postoperative immunohistochemistry assays were conducted with marker panels for SCA and 2 types of pancreatic solid tumors, which were neuroendocrine tumor (pNET) and solid pseudopapillary tumor (SPT). Two cases showed typical staining patterns for SCA markers. Notably, both cases showed positivity for 4 SPT markers (vimentin, β-catenin, α-1 antitrypsin, and α-1 antichymotrypsin). Emphasis should be paid to those 4 new markers for future pathological diagnosis of solid SCA of the pancreas. PMID:25816032

  8. Solid Serous Cystadenoma of the Pancreas: A Case Report of 2 Patients Revealing Vimentin, β-Catenin, α-1 Antitrypsin, and α-1 Antichymotrypsin as New Immunohistochemistry Staining Markers

    PubMed Central

    Wu, Wenming; Hong, Xiafei; Li, Ji; Dai, Menghua; Wang, Wenze; Tong, Anli; Zhu, Zhaohui; Dai, Hongmei; Zhao, Yupei

    2015-01-01

    Abstract Solid serous cystadenoma (SCA) of the pancreas is a rare type of pancreatic solid tumors. Postoperative pathological evaluation is of particular importance for distinguishing solid SCA of the pancreas from other pancreatic solid tumors. Here we present 2 cases of solid SCA of the pancreas, both preoperatively diagnosed with pancreatic neuroendocrine tumors. One case had positive OctreoScan test. Surgical resections were done for both cases. Postoperative immunohistochemistry assays were conducted with marker panels for SCA and 2 types of pancreatic solid tumors, which were neuroendocrine tumor (pNET) and solid pseudopapillary tumor (SPT). Two cases showed typical staining patterns for SCA markers. Notably, both cases showed positivity for 4 SPT markers (vimentin, β-catenin, α-1 antitrypsin, and α-1 antichymotrypsin). Emphasis should be paid to those 4 new markers for future pathological diagnosis of solid SCA of the pancreas. PMID:25816032

  9. Accumulated Metabolites of Hydroxybutyric Acid Serve as Diagnostic and Prognostic Biomarkers of Ovarian High-Grade Serous Carcinomas.

    PubMed

    Hilvo, Mika; de Santiago, Ines; Gopalacharyulu, Peddinti; Schmitt, Wolfgang D; Budczies, Jan; Kuhberg, Marc; Dietel, Manfred; Aittokallio, Tero; Markowetz, Florian; Denkert, Carsten; Sehouli, Jalid; Frezza, Christian; Darb-Esfahani, Silvia; Braicu, Elena Ioana

    2016-02-15

    Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but it is often challenging because the symptoms of ovarian cancer are subtle and become apparent only during advanced stages of the disease. Therefore, the identification of robust biomarkers of early disease is a clinical priority. Metabolomic profiling is an emerging diagnostic tool enabling the detection of biomarkers reflecting alterations in tumor metabolism, a hallmark of cancer. In this study, we performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ovarian cancer (HGSOC) and 100 control patients with benign or non-neoplastic lesions. We report metabolites of hydroxybutyric acid (HBA) as novel diagnostic and prognostic biomarkers associated with tumor burden and patient survival. The accumulation of HBA metabolites caused by HGSOC was also associated with reduced expression of succinic semialdehyde dehydrogenase (encoded by ALDH5A1), and with the presence of an epithelial-to-mesenchymal transition gene signature, implying a role for these metabolic alterations in cancer cell migration and invasion. In conclusion, our findings represent the first comprehensive metabolomics analysis in HGSOC and propose a new set of metabolites as biomarkers of disease with diagnostic and prognostic capabilities. PMID:26685161

  10. Accumulated metabolites of hydroxybutyric acid serve as diagnostic and prognostic biomarkers of ovarian high-grade serous carcinomas

    PubMed Central

    Hilvo, Mika; de Santiago, Ines; Gopalacharyulu, Peddinti; Schmitt, Wolfgang D.; Budczies, Jan; Kuhberg, Marc; Dietel, Manfred; Aittokallio, Tero; Markowetz, Florian; Denkert, Carsten; Sehouli, Jalid; Frezza, Christian

    2016-01-01

    Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but is often challenging because the symptoms of ovarian cancer are subtle and become apparent only during advanced stages of the disease. Therefore, the identification of robust biomarkers of early disease is a clinical priority. Metabolomic profiling is an emerging diagnostic tool enabling the detection of biomarkers reflecting alterations in tumor metabolism, a hallmark of cancer. In this study, we performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ovarian cancer (HGSOC) and 100 control patients with benign or non-neoplastic lesions. We report metabolites of hydroxybutyric acid (HBA) as novel diagnostic and prognostic biomarkers associated with tumor burden and patient survival. The accumulation of HBA metabolites caused by HGSOC was also associated with reduced expression of succinic semialdehyde dehydrogenase (encoded by ALDH5A1), and with the presence of an epithelial-to-mesenchymal transition (EMT) gene signature, implying a role for these metabolic alterations in cancer cell migration and invasion. In conclusion, our findings represent the first comprehensive metabolomics analysis in HGSOC and propose a new set of metabolites as biomarkers of disease with diagnostic and prognostic capabilities. PMID:26685161

  11. Comprehensive Mutation Profiling by Next-Generation Sequencing of Effusion Fluids From Patients With High-Grade Serous Ovarian Carcinoma

    PubMed Central

    Shah, Ronak H.; Scott, Sasinya N.; Brannon, A. Rose; Levine, Douglas A.; Lin, Oscar; Berger, Michael F.

    2016-01-01

    BACKGROUND Mutation analysis for personalized treatment has become increasingly important in the management of different types of cancer. The advent of new DNA extraction protocols and sequencing platforms with reduced DNA input requirements might allow the use of cytology specimens for high-throughput mutation analysis. In this study, the authors evaluated the use of effusion fluid for next-generation sequencing-based, multigene mutation profiling. METHODS Four specimens from each of 5 patients who had at least stage III, high-grade serous ovarian carcinoma were selected: effusion fluid; frozen tumor; formalin-fixed, paraffin embedded tumor; and matched normal blood. Frozen tumors from each patient were previously characterized by The Cancer Genomic Atlas (TCGA). DNA was extracted from all specimens and was sequenced using a custom hybridization capture-based assay. Genomic alterations were compared among all specimens from each patient as well as with mutations reported in TCGA for the same tumors. RESULTS In total, 17 distinct somatic mutations were identified in the cohort. Ten of 17 mutations were reported in TCGA and were called in all 3 malignant specimens procured from the patients. Of the remaining 7 mutations, 2 were called in all 3 specimens, and the other 5 were sample-specific. Two mutations were detected only in the cytology specimens. Copy number profiles were concordant among the tumors analyzed. CONCLUSIONS Cytology specimens represent suitable material for high-throughput sequencing, because all mutations described by TCGA were independently identified in the effusion fluid. Differences in mutations detected in samples procured from the same patient may reflect tumor heterogeneity. PMID:25655233

  12. Borderline personality features in depressed or anxious patients.

    PubMed

    Distel, Marijn A; Smit, Johannes H; Spinhoven, Philip; Penninx, Brenda W J H

    2016-07-30

    Anxiety and depression frequently co-occur with borderline personality disorder. Relatively little research examined the presence of borderline personality features and its main domains (affective instability, identity problems, negative relationships and self-harm) in individuals with remitted and current anxiety and depression. Participants with current (n=597) or remitted (n=1115) anxiety and/or depression and healthy controls (n=431) were selected from the Netherlands Study of Depression and Anxiety. Assessments included the Personality Assessment Inventory - Borderline Features Scale and several clinical characteristics of anxiety and depression. Borderline personality features were more common in depression than in anxiety. Current comorbid anxiety and depression was associated with most borderline personality features. Anxiety and depression status explained 29.7% of the variance in borderline personality features and 3.8% (self-harm) to 31% (identity problems) of the variance in the four domains. A large part of the variance was shared between anxiety and depression but both disorders also explained a significant amount of unique variance. The severity of anxiety and depression and the level of daily dysfunctioning was positively associated with borderline personality features. Individuals with a longer duration of anxiety and depression showed more affective instability and identity problems. These findings suggest that patients with anxiety and depression may benefit from an assessment of personality pathology as it may have implications for psychological and pharmacological treatment. PMID:27183108

  13. Borderline Personality and the Detection of Angry Faces

    PubMed Central

    Hepp, Johanna; Hilbig, Benjamin E.; Kieslich, Pascal J.; Herzog, Julia; Lis, Stefanie; Schmahl, Christian; Niedtfeld, Inga

    2016-01-01

    Background Many studies have assessed emotion recognition in patients with Borderline Personality Disorder and considerable evidence has been accumulated on patients’ ability to categorize emotions. In contrast, their ability to detect emotions has been investigated sparsely. The only two studies that assessed emotion detection abilities found contradictory evidence on patients’ ability to detect angry faces. Methods To clarify whether patients with Borderline Personality Disorder show enhanced detection of angry faces, we conducted three experiments: a laboratory study (n = 53) with a clinical sample and two highly powered web studies that measured Borderline features (n1 = 342, n2 = 220). Participants in all studies completed a visual search paradigm, and the reaction times for the detection of angry vs. happy faces were measured. Results Consistently, data spoke against enhanced detection of angry faces in the Borderline groups, indicated by non-significant group (Borderline vs. healthy control) × target (angry vs. happy) interactions, despite highly satisfactory statistical power to detect even small effects. Conclusions In contrast to emotion categorization, emotion detection appears to be intact in patients with Borderline Personality Disorder and individuals high in Borderline features. The importance of distinguishing between these two processes in future studies is discussed. PMID:27031611

  14. [The phenomenology and psychodynamics of affects in borderline patients].

    PubMed

    Leichsenring, Falk

    2004-01-01

    This paper presents a review of the phenomenology and psychodynamics of affects in borderline patients. The first part demonstrates that in most current conceptions of the borderline disorder affective disturbances are regarded as to be characteristic. In this context, the strong overlap between borderline disorders and affective disorders found in many empirical studies is described and different hypotheses are presented to explain this phenomenon. The second part of this review is concerned with the psychodynamics of affects in borderline patients. The role of affects in thinking, behaviour, self perception and the regulation of object relations is discussed. Borderline and other severe personality disorders are assessed from the perspective of affective disturbances. The psychodynamic functions of particularly characteristic affects such as anger, anxiety, depression and boredom are discussed. The close connection between affective and cognitive functioning in borderline patients is described and evaluated with regard to modern theories of affect and cognition. Finally, the role of affects in the treatment of borderline patients is discussed. PMID:15510348

  15. Preclinical 89Zr Immuno-PET of High-Grade Serous Ovarian Cancer and Lymph Node Metastasis

    PubMed Central

    Sharma, Sai Kiran; Sevak, Kuntal K.; Monette, Sebastien; Carlin, Sean D.; Knight, James C.; Wuest, Frank R.; Sala, Evis; Zeglis, Brian M.; Lewis, Jason S.

    2016-01-01

    The elevation of cancer antigen 125 (CA125) levels in the serum of asymptomatic patients precedes the radiologic detection of high-grade serous ovarian cancer by at least 2 mo and the final clinical diagnosis by 5 mo. PET imaging of CA125 expression by ovarian cancer cells may enhance the evaluation of the extent of disease and provide a roadmap to surgery as well as detect recurrence and metastases. Methods 89Zr-labeled mAb-B43.13 was synthesized to target CA125 and evaluated via PET imaging and biodistribution studies in mice bearing OVCAR3 human ovarian adenocarcinoma xenografts. Ex vivo analysis of tumors and lymph nodes was performed via autoradiography, histopathology, and immunohistochemistry. Results PET imaging using 89Zr-DFO-mAb-B43.13 (DFO is desferrioxamine) clearly delineated CA125-positive OVCAR3 xenografts as early as 24 h after the administration of the radioimmunoconjugate. Biodistribution studies revealed accretion of 89Zr-DFO-mAb-B43.13 in the OVCAR3 tumors, ultimately reaching 22.3 ± 6.3 percentage injected dose per gram (%ID/g) at 72 h after injection. Most interestingly, activity concentrations greater than 50 %ID/g were observed in the ipsilateral lymph nodes of the xenograft-bearingmice. Histopathologic analysis of the immuno-PET–positive lymph nodes revealed the presence of grossly metastasized ovarian cancer cells within the lymphoid tissues. In control experiments, only low-level, non-specific uptake of 89Zr-labeled isotype IgG was observed in OVCAR3 tumors; similarly, low-activity concentrations of 89Zr-DFO-mAb-B43.13 accumulated in CA125-negative SKOV3 tumors. Conclusion Immuno-PET with 89Zr-labeled mAb-B43.13 is a potential strategy for the noninvasive delineation of extent of disease and may add value in treatment planning and treatment monitoring of high-grade serous ovarian cancer. PMID:26837339

  16. Molecular Mechanism Linking BRCA1 Dysfunction to High Grade Serous Epithelial Ovarian Cancers with Peritoneal Permeability and Ascites

    PubMed Central

    Desai, A; Xu, J; Aysola, K; Akinbobuyi, O; White, M; Reddy, VE; Okoli, J; Clark, C; Partridge, EE; Childs, Ed; Beech, DJ; Rice, MV; Reddy, ESP; Rao, VN

    2015-01-01

    Ovarian cancer constitutes the second most common gynecological cancer with a five-year survival rate of 40%. Among the various histotypes associated with hereditary ovarian cancer, high-grade serous epithelial ovarian carcinoma (HGSEOC) is the most predominant and women with inherited mutations in BRCA1 have a lifetime risk of 40–60%. HGSEOC is a challenge for clinical oncologists, due to late presentation of patient, diagnosis and high rate of relapse. Ovarian tumors have a wide range of clinical presentations including development of ascites as a result of deregulated endothelial function thereby causing increased vascular permeability of peritoneal vessels. The molecular mechanisms remain elusive. Studies have shown that fallopian tube cancers develop in women with BRCA1 gene mutations more often than previously suspected. Recent studies suggest that many primary peritoneal cancers and some high-grade serous epithelial ovarian carcinomas actually start in the fallopian tubes. In this article we have addressed the molecular pathway of a recently identified potential biomarker Ubc9 whose deregulated expression due to BRCA1 dysfunction can result in HGSEOC with peritoneal permeability and formation of ascites. We also discuss the role of downstream targets Caveolin-1 and Vascular Endothelial Growth Factor (VEGF) in the pathogenesis of ascites in ovarian carcinomas. Finally we hypothesize a signaling axis between Ubc9 over expression, loss of Caveolin-1 and induction of VEGF in BRCA1 mutant HGSEOC cells. We suggest that Ubc9-mediated stimulation of VEGF as a novel mechanism underlying ovarian cancer aggressiveness and ascites formation. Agents that target Ubc9 and VEGF signaling may represent a novel therapeutic strategy to impede peritoneal growth and spread of HGSEOC. PMID:26665166

  17. Oral mineralocorticoid antagonists for recalcitrant central serous chorioretinopathy

    PubMed Central

    Chin, Eric K; Almeida, David RP; Roybal, C Nathaniel; Niles, Philip I; Gehrs, Karen M; Sohn, Elliott H; Boldt, H Culver; Russell, Stephen R; Folk, James C

    2015-01-01

    Purpose To evaluate the effect and tolerance of oral mineralocorticoid antagonists, eplerenone and/or spironolactone, in recalcitrant central serous chorioretinopathy. Methods Retrospective consecutive observational case series. Primary outcome measures included central macular thickness (CMT, μm), macular volume (MV, mm3), Snellen visual acuity, and prior treatment failures. Secondary outcomes included duration of treatment, treatment dosage, and systemic side effects. Results A total of 120 patients with central serous chorioretinopathy were reviewed, of which 29 patients were treated with one or more mineralocorticoid antagonists. The average age of patients was 58.4 years. Sixteen patients (69.6%) were recalcitrant to other interventions prior to treatment with oral mineralocorticoid antagonists, with an average washout period of 15.3 months. The average duration of mineralocorticoid antagonist treatment was 3.9±2.3 months. Twelve patients (52.2%) showed decreased CMT and MV, six patients (26.1%) had increase in both, and five patients (21.7%) had negligible changes. The mean decrease in CMT of all patients was 42.4 μm (range, −136 to 255 μm): 100.7 μm among treatment-naïve patients, and 16.9 μm among recalcitrant patients. The mean decrease in MV of all patients was 0.20 mm3 (range, −2.33 to 2.90 mm3): 0.6 mm3 among treatment-naïve patients, and 0.0 mm3 among recalcitrant patients. Median visual acuity at the start of therapy was 20/30 (range, 20/20–20/250), and at final follow-up it was 20/40 (range, 20/20–20/125). Nine patients (39.1%) experienced systemic side effects, of which three patients (13.0%) were unable to continue therapy. Conclusion Mineralocorticoid antagonist treatment had a positive treatment effect in half of our patients. The decrease in CMT and MV was much less in the recalcitrant group compared to the treatment-naïve group. An improvement in vision was seen only in the treatment-naïve group. Systemic side effects, even at

  18. The nosologic status of borderline personality: clinical and polysomnographic study.

    PubMed

    Akiskal, H S; Yerevanian, B I; Davis, G C; King, D; Lemmi, H

    1985-02-01

    The REM latencies of 24 nonschizotypal borderline outpatients--who were not in the midst of a major depressive episode--were in the range of those of 30 patients with primary major depression but were significantly shorter than those of 16 patients with nonborderline personality disorders and 14 nonpsychiatric controls. Also, more of the borderline subjects had lifetime diagnoses of affective disorder, such as dysthymic, cyclothymic, and bipolar II disorder, and of a spectrum of anxiety and somatization disorders. The authors conclude that contemporary operational criteria for borderline disorder identify a wide net of temperamental disorders with strong affective coloring rather than a unitary nosologic entity. PMID:3970243

  19. Psychopharmacologic treatment of borderline personality disorder.

    PubMed

    Ripoll, Luis H

    2013-06-01

    The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning. PMID:24174895

  20. Borderline intellectual functioning: a systematic literature review.

    PubMed

    Peltopuro, Minna; Ahonen, Timo; Kaartinen, Jukka; Seppälä, Heikki; Närhi, Vesa

    2014-12-01

    The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health problems. When adults with BIF were compared with the general population, they held lower-skilled jobs and earned less money. Although some risk factors (e.g., low birth weight) and preventive factors (e.g., education) were reported, they were not specific to BIF. The review finds that, despite the obvious everyday problems, BIF is almost invisible in the field of research. More research, societal discussion, and flexible support systems are needed. PMID:25409130

  1. Psychopharmacologic treatment of borderline personality disorder

    PubMed Central

    Ripoll, Luis H.

    2013-01-01

    The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning. PMID:24174895

  2. Cervical cytology in serous and endometrioid endometrial cancer.

    PubMed

    Roelofsen, Thijs; Geels, Yvette P; Pijnenborg, Johanna M A; van Ham, Maaike A P C; Zomer, Saskia F; van Tilburg, Johanna M Wiersma; Snijders, Marc P M L; Siebers, Albert G; Bulten, Johan; Massuger, Leon F A G

    2013-07-01

    The aim of this study was to determine the frequency of abnormal cervical cytology in preoperative cervical cytology of patients diagnosed with uterine papillary serous carcinoma (UPSC) and endometrioid endometrial carcinoma (EEC). In addition, associations between abnormal cervical cytology and clinicopathologic factors were evaluated. In this multicentre study, EEC patients diagnosed at two hospitals from 1999 to 2009 and UPSC patients diagnosed at five hospitals from 1992 to 2009, were included. Revision of the histologic slides was performed systematically and independently by 3 gynecopathologists. Cervical cytology within six months before histopathologic diagnosis of endometrial carcinoma was available for 267 EEC and 80 UPSC patients. Cervical cytology with atypical, malignant, or normal endometrial cells in postmenopausal women was considered as abnormal cytology, specific for endometrial pathology. Abnormal cervical cytology was found in 87.5% of UPSC patients, compared with 37.8% in EEC patients. In UPSC, abnormal cytology was associated with extrauterine spread of disease (P=0.043). In EEC, abnormal cytology was associated with cervical involvement (P=0.034). In both EEC and UPSC patients, abnormal cervical cytology was not associated with survival. In conclusion, abnormal cervical cytology was more frequently found in UPSC patients. It was associated with extrauterine disease in UPSC patients, and with cervical involvement in EEC patients. More prospective research should be performed to assess the true clinical value of preoperative cervical cytology in endometrial cancer patients. PMID:23722512

  3. Central serous chorioretinopathy: what we have learnt so far.

    PubMed

    Wong, Kah Hie; Lau, Kin Pong; Chhablani, Jay; Tao, Yong; Li, Qing; Wong, Ian Y

    2016-06-01

    Central serous chorioretinopathy (CSCR) is a common retinal cause of visual loss. The mainstays of management are observation, photodynamic therapy (PDT) and laser procedures. Over the past decade, there has been rapid development in the existing and novel imaging techniques, functional testing and management of CSCR. However, there is no convincing treatment designed for CSCR yet. In recent years, the advances in PDT, with various adjustments in fluence and verteporfin dosage, and the comparisons between different types of PDT for acute and chronic CSCR in recent studies have provided greater insights into the role of PDT in treating CSCR. Novel laser procedures, such as the diode micropulse laser, have shown comparable efficacy to conventional lasers without laser-induced damage. Antivascular endothelial growth factor, which was originally developed for treating cancers, has emerged to be a potentially effective treatment for CSCR. The potential role of mineralocorticoid receptor antagonists in treating CSCR has provided greater understanding of the pathogenesis. Based on the relevant studies, mainly from the past decade, we discuss updates to the management of CSCR according to the risk factor modifications, pharmacological interventions, PDT and laser procedures and concluded that PDT is the current best option for CSCR. PMID:26132864

  4. Axial length in unilateral idiopathic central serous chorioretinopathy

    PubMed Central

    Moon, Hoseok; Lee, Dae Yeong; Nam, Dong Heun

    2016-01-01

    AIM To evaluate the axial length (AXL) in unilateral idiopathic central serous chorioretinopathy (CSC). METHODS This retrospective case-control study was comprised of a consecutive case series of 35 patients with acute unilateral idiopathic CSC, and age- and sex-matched 50 control eyes. AXL of both eyes of unilateral CSC patients and the control eyes were investigated. AXL was measured by ultrasonic biometry, and the adjusted AXL was calculated for CSC eyes as measured AXL plus differences of foveal thickness between CSC and normal fellow eyes in millimeters. The main outcome measures were comparison of AXL between CSC, fellow and control eyes. RESULTS The mean age of 35 CSC patients was 45.5y, and 31 males were included. The adjusted AXL of CSC eyes was 23.52 mm, and the AXL of fellow eyes was 23.46 mm, and of control eyes 23.94 mm. The AXL of both CSC and fellow eyes were significantly shorter than control eyes (CSC vs control, P=0.044; fellow vs control, P=0.026). There was no statistically significant difference in AXL between CSC and fellow eyes. CONCLUSION In unilateral idiopathic CSC, the AXL of CSC and fellow eyes are shorter than that of control eyes. Short AXL may be related with choroidal circulation abnormality in CSC. PMID:27275428

  5. Low-dose aspirin as treatment for central serous chorioretinopathy

    PubMed Central

    Caccavale, Antonio; Romanazzi, Filippo; Imparato, Manuela; Negri, Angelo; Morano, Anna; Ferentini, Fabio

    2010-01-01

    Purpose: To evaluate the effectiveness of low-dose aspirin for the treatment of central serous chorioretinopathy (CSCR). Patients and methods: Patients with classical or multifocal CSCR were treated with aspirin 100 mg per day orally for 1 month followed by 100 mg on alternate days for 5 months. Treated patients were compared with historic controls consisting of patients with classical or multifocal CSCR previously followed up at our institution. Results: Mean visual acuity in the group treated with aspirin started to improve after the first week of therapy and continued to improve throughout the following 3 months. Visual recovery was slower in the untreated control group than in the treated group and achieved better visual acuity between the first and third month from the onset of the disease. There were no adverse events related to the administration of aspirin. Conclusion: The results indicate that treatment with low-dose aspirin may result in more rapid visual rehabilitation with fewer recurrences in patient with CSCR compared with untreated historic controls. The effectiveness of treatment with aspirin supports our hypothesis regarding the role of impaired fibrinolysis and increased platelet aggregation in the choriocapillaris in the pathogenesis of CSCR. PMID:20714368

  6. Clinical Significance of Positive Pelvic Washings in Uterine Papillary Serous Carcinoma Confined to an Endometrial Polyp.

    PubMed

    Hanley, Krisztina Z; Fadare, Oluwole; Fisher, Kevin E; Atkins, Kristen A; Mosunjac, Marina B

    2016-05-01

    Uterine papillary serous carcinoma (UPSC) represents 10% of endometrial carcinomas. Significant number of patients initially present with extrauterine disease. The role of adjuvant treatment in low stage, especially polyp-confined UPSC is controversial. This multi-institutional study evaluated the significance of positive pelvic washing (PW) and adjuvant treatment on disease recurrence in a setting of endometrial polyp-confined UPSC. Surgical pathology files from 3 institutions were searched for cases of endometrial polyp-confined UPSC. Following histologic review, cases were clinically staged as Stage I, without myoinvasion or lymphovascular invasion. Clinicopathologic characteristics, results of PW, and type of adjuvant therapy were recorded. Statistical analysis using the Kaplan-Meier method for survival and Fisher exact test were performed. Thirty-three patients were included in the study. All patients were diagnosed with polyp-confined UPSC. The size of the polyp ranged from 0.3 to 4.3 cm. PW was positive for tumor cells in 8/33 (24%) patients. Twenty-two patients (66.6%) received some type of adjuvant treatment. Six patients (18%) developed recurrent disease. There was no significant difference in disease-free survival in the patients receiving adjuvant treatment versus not (P=0.375). However, there was significant association (P=0.0013) between positive PW and disease recurrence. Data are conflicting whether positive PW affects prognosis in low-stage endometrial carcinomas. Our study showed that in UPSC, malignant cells can be present in PW without lymphovascular invasion or myoinvasion and may have negative prognostic implication. Our data also reflect the controversies in the role of adjuvant treatment in endometrium-confined UPSC. PMID:26535985

  7. Parenting Children With Borderline Intellectual Functioning: A Unique Risk Population

    PubMed Central

    Fenning, Rachel M.; Baker, Jason K.; Baker, Bruce L.; Crnic, Keith A.

    2009-01-01

    Parenting was examined among families of children with borderline intelligence in comparison to families of typically developing children and children with developmental delays. Parenting data were obtained at child age 5 via naturalistic home observation. Mothers of children with borderline intelligence exhibited less positive and less sensitive parenting behaviors than did other mothers and were least likely to display a style of positive engagement. Children with borderline intelligence were not observed to be more behaviorally problematic than other children; however, their mothers perceived more externalizing symptoms than did mothers of typically developing children. Findings suggest the importance of mothers’ explanatory models for child difficulties and highlight children with borderline intelligence as uniquely at risk for poor parenting. PMID:17295551

  8. Parental qualities as perceived by borderline personality disorders.

    PubMed

    Goldberg, R L; Mann, L S; Wise, T N; Segall, E A

    1985-01-01

    This study explores the contribution of parental qualities to the borderline personality disorder. The Parental Bonding Inventory is used to compare four parental qualities (caring mother, caring father, overprotective father, and overprotective mother) across three groups (borderline personality disorders, assorted psychiatric controls and normal controls). The major finding was that the borderline patients perceived their parents to be significantly less caring and more overprotective than both the psychiatric control or nonclinical control groups. This study was verified previous reports that patients diagnosed with an affective illness (in either the borderline group or psychiatric control group) reported no significant differences on the inventory. Pinpointing parental characteristics which antecede mental disorders may be an important first step in devising primary preventive interventions for adult disorders. PMID:4077030

  9. Borderline Personality Disorder and Development: Counseling University Students.

    ERIC Educational Resources Information Center

    Tryon, Georgiana Shick; And Others

    1988-01-01

    Discusses problems and methodology of diagnosis and counseling of college students with borderline personality disorder. Recommends that providing these students with structure through consistent limit setting can produce positive changes in their behavior. (Author/ABL)

  10. [The practical significance of the concept of borderline disorders].

    PubMed

    Fleischer, J; Koníková, M; Majercíková, L; Strecko, A

    1989-02-01

    There is not agreement on borderline disorders. The authors support the view that borderline disorders are related to other classified mental disorders, i.e. that they are their abortive forms. There is a continuous transition between abortive and non-abortive forms of those classified mental disorders which are the basis of non-specific manifestations of borderline mental disorders. The authors feel that is of practical importance to differente a small circle of abortive forms which resemble various non-psychotic disorders where an axial disposition is assumed but where, contrary to recognized abortive forms (e.g. pseudoneurotic schizophrenia or hysteriform depression), they cannot be identified at a psychopathological level. The diagnosis of a borderline disorder corresponding to this narrow basic circle of abortive forms makes it possible to avoid inadequately founded diagnoses of psychosis or an authoritative refusal of the diagnosis of psychosis, and it makes the doctor search for symptoms of latent axial disposition. PMID:2647308

  11. Sex Bias in Classifying Borderline and Narcissistic Personality Disorder.

    PubMed

    Braamhorst, Wouter; Lobbestael, Jill; Emons, Wilco H M; Arntz, Arnoud; Witteman, Cilia L M; Bekker, Marrie H J

    2015-10-01

    This study investigated sex bias in the classification of borderline and narcissistic personality disorders. A sample of psychologists in training for a post-master degree (N = 180) read brief case histories (male or female version) and made DSM classification. To differentiate sex bias due to sex stereotyping or to base rate variation, we used different case histories, respectively: (1) non-ambiguous case histories with enough criteria of either borderline or narcissistic personality disorder to meet the threshold for classification, and (2) an ambiguous case with subthreshold features of both borderline and narcissistic personality disorder. Results showed significant differences due to sex of the patient in the ambiguous condition. Thus, when the diagnosis is not straightforward, as in the case of mixed subthreshold features, sex bias is present and is influenced by base-rate variation. These findings emphasize the need for caution in classifying personality disorders, especially borderline or narcissistic traits. PMID:26421970

  12. Cultures of human tracheal gland cells of mucous or serous phenotype

    PubMed Central

    Finkbeiner, Walter E.; Zlock, Lorna T.; Mehdi, Irum

    2009-01-01

    There are two main epithelial cell types in the secretory tubules of mammalian glands: serous and mucous. The former is believed to secrete predominantly water and antimicrobials, the latter mucins. Primary cultures of human airway gland epithelium have been available for almost 20 yr, but they are poorly differentiated and lack clear features of either serous or mucous cells. In this study, by varying growth supports and media, we have produced cultures from human airway glands that in terms of their ultrastructure and secretory products resemble either mucous or serous cells. Of four types of porous-bottomed insert tested, polycarbonate filters (Transwells) most strongly promoted the mucous phenotype. Coupled with the addition of epidermal growth factor (EGF), this growth support produced “mucous” cells that contained the large electron-lucent granules characteristic of native mucous cells, but lacked the small electron-dense granules characteristic of serous cells. Furthermore, they showed high levels of mucin secretion and low levels of release of lactoferrin and lysozyme (markers of native serous cells). By contrast, growth on polyethylene terephthalate filters (Cyclopore) in medium lacking EGF produced “serous” cells in which small electron-dense granules replaced the electron-lucent ones, and the cells had high levels of lactoferrin and lysozyme but low levels of mucins. Measurements of transepithelial resistance and short-circuit current showed that both “serous” and “mucous” cell cultures possessed tight junctions, had become polarized, and were actively secreting Cl. PMID:19998060

  13. [Complementary methods of rehabilitation in borderline mental disorders].

    PubMed

    Elfimov, M A; Kotenko, K V; Korchazhkina, N B; Filatova, E V; Portnov, V V; Chervinskaya, A V; Mikhailova, A A

    2016-01-01

    The article covers treatment results of 417 patients (186 males and 231 females) aged 18 to 71 years, with borderline mental disorders. Findings are that using specified complementary methods, more when treatment complex is applied, causes better psycho-emotional state in patients with borderline mental disorders, that is supported by results of medical diagnostic tests including psychometry tests (abridged minnesota multiphasic personality inventory, Beck depression inventory, Spielberger-Hanin, test "feeling, activity, mood"). PMID:27164743

  14. Axis I diagnostic comorbidity and borderline personality disorder.

    PubMed

    Zimmerman, M; Mattia, J I

    1999-01-01

    Borderline personality disorder (PD) has been the most studied PD. Research has examined the relationship between borderline PD and most axis I diagnostic classes such as eating disorders, mood disorders, and substance use disorders. However, there is little information regarding the relationship of borderline PD and overall comorbidity with all classes of axis I disorders assessed simultaneously. In the present study, 409 patients were evaluated with semistructured diagnostic interviews for axis I and axis II disorders. Patients with a diagnosis of borderline PD versus those who did not receive the diagnosis were assigned significantly more current axis I diagnoses (3.4 v 2.0). Borderline PD patients were twice as likely to receive a diagnosis of three or more current axis I disorders (69.5% v 31.1%) and nearly four times as likely to have a diagnosis of four or more disorders 147.5% v 13.7%). In comparison to nonborderline PD patients, borderline PD patients more frequently received a diagnosis of current major depressive disorder (MDD), bipolar I and II disorder, panic disorder with agoraphobia, social and specific phobia, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), eating disorder NOS, and any somatoform disorder. Similar results were observed for lifetime diagnoses. Overall, borderline PD patients were more likely to have multiple axis I disorders than nonborderline PD patients, and the differences between the two groups were present across mood, anxiety, substance use, eating, and somatoform disorder categories. These findings highlight the importance of performing thorough evaluations of axis I pathology in patients with borderline PD in order not to overlook syndromes that are potentially treatment-responsive. PMID:10428182

  15. Neoadjuvant chemoradiation therapy for borderline pancreatic adenocarcinoma: report of two cases.

    PubMed

    Galindo, José; Gabrielli, Mauricio; Guerra, Juan Francisco; Cassina, Juan Carlos; Garrido, Marcelo; Jarufe, Nicolás; Borghero, Yerko; Madrid, Jorge; Zoroquiain, Pablo; Roa, Juan Carlos; Martínez, Jorge

    2013-01-01

    Pancreatic cancer remains as one of the most aggressive human neoplasms, with overall poor survival rates. Radical surgery of the primary lesion is the best option for treatment. Borderline resectable pancreatic tumors (BRPT), defined as partial involvement of peripancreatic vasculature, may benefit from neoadjuvant therapy. We report on the first two BRPT cases treated with neoadjuvant chemoradiation at our institution. Preoperative CT and MRI demonstrated pancreatic tumors encasing the porto-mesenteric confluence suggestive of BRPT. Patients received neoadjuvant chemotherapy (gemcitabine/cisplatin), followed by radiochemotherapy. After treatment, follow-up images demonstrated tumor downsize, allowing for the tumors to be considered then as resectable. They underwent partial pancreatoduodenectomies (Whipple procedure). In case 1, histopathology revealed a complete, margin-free resection, whereas in case 2 there was a complete pathological response, with no evidence of residual tumor. According to the literature, our initial experience using neoadjuvant chemoradiotherapy on BRPT allowed us to downsize the tumor and, subsequently, to perform a curative surgery. PMID:23379413

  16. Improvement in Borderline Personality Disorder in Relationship to Age

    PubMed Central

    Shea, M. Tracie; Edelen, Maria Orlando; Pinto, Anthony; Yen, Shirley; Gunderson, John G.; Skodol, Andrew E.; Markowitz, John; Sanislow, Charles A.; Grilo, Carlos M.; Ansell, Emily; Daversa, Maria T.; Zanarini, Mary C.; McGlashan, Thomas H.; Morey, Leslie C.

    2008-01-01

    Objective It is commonly believed that some features of borderline personality disorder improve as individuals reach their late 30s and 40s. The current study examined age-related change in borderline criteria and functional impairment, testing the hypothesis that older age would be associated with relatively more improvement than younger age. Method 216 male and female participants with borderline personality disorder were followed prospectively with yearly assessments over 6 years. Results Participants showed similar rates of improvement in borderline features regardless of age. A significant age by study year interaction showed functioning in older subjects to reverse direction and begin to decline in the latter part of the follow-up, in contrast to younger subjects who maintained or continued improvement over the six years. Despite the decline, functioning for the older subjects was comparable to or slightly better at year 6 than at year 1. Conclusion Improvement in borderline features is not specific to the late 30s and 40s. There may be a reversal of improvement in functioning in some borderline patients in this older age range. PMID:18851719

  17. Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes.

    PubMed

    Murakami, Ryusuke; Matsumura, Noriomi; Mandai, Masaki; Yoshihara, Kosuke; Tanabe, Hiroshi; Nakai, Hidekatsu; Yamanoi, Koji; Abiko, Kaoru; Yoshioka, Yumiko; Hamanishi, Junzo; Yamaguchi, Ken; Baba, Tsukasa; Koshiyama, Masafumi; Enomoto, Takayuki; Okamoto, Aikou; Murphy, Susan K; Mori, Seiichi; Mikami, Yoshiki; Minamiguchi, Sachiko; Konishi, Ikuo

    2016-05-01

    Recently, The Cancer Genome Atlas data revealed four molecular subtypes of high-grade serous ovarian carcinoma (HGSOC) exhibiting distinct prognoses. We developed four novel HGSOC histopathological subtypes by focusing on tumor microenvironment: mesenchymal transition, defined by a remarkable desmoplastic reaction; immune reactive by lymphocytes infiltrating the tumor; solid and proliferative by a solid growth pattern; and papilloglandular by a papillary architecture. Unsupervised hierarchical clustering revealed four clusters correlated with histopathological subtypes in both Kyoto and Niigata HGSOC transcriptome data sets (P < 0.001). Gene set enrichment analysis revealed pathways enriched in our histopathological classification significantly overlapped with the four molecular subtypes: mesenchymal, immunoreactive, proliferative, and differentiated (P < 0.0001, respectively). In 132 HGSOC cases, progression-free survival and overall survival were best in the immune reactive, whereas overall survival was worst in the mesenchymal transition (P < 0.001, respectively), findings reproduced in 89 validation cases (P < 0.05, respectively). The CLOVAR_MES_UP single-sample gene set enrichment analysis scores representing the mesenchymal molecular subtype were higher in paclitaxel responders than nonresponders (P = 0.002) in the GSE15622 data set. Taxane-containing regimens improved survival of cases with high MES_UP scores compared with nontaxane regimens (P < 0.001) in the GSE9891 data set. Our novel histopathological classification of HGSOC correlates with distinct prognostic transcriptome subtypes. The mesenchymal transition subtype might be particularly sensitive to taxane. PMID:26993207

  18. TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers.

    PubMed

    Schultheis, Anne M; Martelotto, Luciano G; De Filippo, Maria R; Piscuglio, Salvatore; Ng, Charlotte K Y; Hussein, Yaser R; Reis-Filho, Jorge S; Soslow, Robert A; Weigelt, Britta

    2016-07-01

    Endometrial carcinomas (ECs) are heterogeneous at the genetic level. Although TP53 mutations are highly recurrent in serous endometrial carcinomas (SECs), these are also present in a subset of endometrioid endometrial carcinomas (EECs). Here, we sought to define the frequency, pattern, distribution, and type of TP53 somatic mutations in ECs by performing a reanalysis of the publicly available data from The Cancer Genome Atlas (TCGA). A total of 228 EECs (n=186) and SECs (n=42) from the TCGA data set, for which an integrated genomic characterization was performed, were interrogated for the presence and type of TP53 mutations, and for mutations in genes frequently mutated in ECs. TP53 mutations were found in 15% of EECs and 88% of SECs, and in 91% of copy-number-high and 35% of polymerase (DNA directed), epsilon, catalytic subunit (POLE) integrative genomic subtypes. In addition to differences in prevalence, variations in the type and pattern of TP53 mutations were observed between histologic types and between integrative genomic subtypes. TP53 hotspot mutations were significantly more frequently found in SECs (46%) than in EECs (15%). TP53-mutant EECs significantly more frequently harbored a co-occurring PTEN mutation than TP53-mutant SECs. Finally, a subset of TP53-mutant ECs (22%) was found to harbor frameshift or nonsense mutations. Given that nonsense and frameshift TP53 mutations result in distinct p53 immunohistochemical results that require careful interpretation, and that EECs and SECs display different patterns, types, and distributions of TP53 mutations, the use of the TP53/p53 status alone for the differential diagnosis of EECs and SECs may not be sufficient. PMID:26556035

  19. Subthreshold micropulse yellow laser treatment for nonresolving central serous chorioretinopathy

    PubMed Central

    Abd Elhamid, Ahmed Hosni

    2015-01-01

    Purpose To report the efficacy and safety of micropulse 577 nm yellow laser in the treatment of nonresolving central serous chorioretinopathy (CSC) cases. Patients and methods The study included 15 eyes with nonresolving CSC lasting more than 3 months. All the patients were subjected to complete ophthalmic examination, in addition to contrast sensitivity measurement, fundus fluorescein angiography, and optical coherence tomography. All eyes were subjected to 577 nm subthreshold micropulse laser treatment, using the IQ 577 device, and followed up after 4 weeks, 2 months, 3 months, and 6 months. The outcome measures were change in best-corrected visual acuity, contrast sensitivity, subretinal fluid height, and change in macular thickness measured by optical coherence tomography. Results The average age of the patients was 36.4 years; eleven were males and four were females. Average duration of the leakage was 4.6 months. The mean best-corrected visual acuity measured 6 months after laser treatment was 0.85±0.097, in comparison to 0.67±0.097 before laser treatment (statistically significant [SS], P<0.05). The mean central macular thickness before laser was 389.6±46.4 µm, in comparison to 263.6±24 µm after 6 months (SS, P<0.05). The mean post-laser log contrast sensitivity measured using the Pelli–Robson contrast sensitivity chart was 1.73±0.14, while the initial log contrast sensitivity was 1.48±0.28 (SS, P<0.05). Conclusion Subthreshold micropulse laser treatment is an effective and safe treatment option for patients with nonresolving CSC. PMID:26664043

  20. Is myopia a protective factor against central serous chorioretinopathy?

    PubMed Central

    Manayath, George J.; Arora, Saurabh; Parikh, Hardik; Shah, Parag K.; Tiwari, Sarvesh; Narendran, Venkatapathy

    2016-01-01

    AIM To evaluate if any association exists between central serous chorioretinopathy (CSCR) and the refractive status of the eye. METHODS This retrospective, institutional, case control study included 499 patients, wherein 262 patients diagnosed as acute CSCR, were compared with an age and gender matched control group of 237 patients. All patients were evaluated with a detailed systemic and ocular history, objective and subjective refractions for both eyes and complete ocular examination by a retina specialist, at all visits. Optical coherence tomography confirmed the diagnosis of CSCR. RESULTS The mean age was found to be 40±7y in the study group (Group 1) compared to 38±10y in the control group (Group 2). Most common refractive status in the study group, was emmetropia seen in 191 patients (72.9%), followed by hypermetropia seen in 47 patients (17.9%) and astigmatism seen in 21 patients (8.0%). Only 3 subjects (1.1%) had myopia, which was less than or equal to 1.0 D, compared to 70 subjects (29.5%) in the control group, suggesting a statistically significant lower incidence of CSCR among the myopic patients (P< 0.0001). With respect to the systemic factors, 26 (9.9%) patients were using systemic steroids in the study group (Group 1) compared to none in the control group (Group 2) suggesting a statistically significant association of CSCR with systemic steroid use (P<0.05). No other significant systemic risk factors were noted. CONCLUSION Though CSCR is a multifactorial disease, myopia serves as a protective factor for CSCR. Thus, myopic eyes are less likely to develop CSCR. Since both retinal pigment epithelium (RPE) and choriocapillaris are postulated in the pathogenesis of CSCR, chorio-retinal thinning and atrophy seen in myopic eyes are less likely to cause CSCR. PMID:26949648

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

    PubMed Central

    Ambiya, Vikas; Goud, Abhilash; Mathai, Annie; Rani, Padmaja Kumari; Chhablani, Jay

    2016-01-01

    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. PMID:27570446

  2. Therapeutic benefit of melatonin in refractory central serous chorioretinopathy

    PubMed Central

    Gramajo, A L; Marquez, G E; Torres, V E; Juárez, C P; Rosenstein, R E; Luna, J D

    2015-01-01

    Purpose To evaluate the efficacy and safety of melatonin for the treatment of chronic central serous chorioretinopathy (CSCR). Methods Prospective comparative case series. A total of 13 patients with chronic CSCR were treated for 1 month: 8 patients were treated orally with 3 mg melatonin t.i.d., and 5 with placebo. All patients had 20/40 or worse Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) in the affected eye or presented an incapacitating scotoma. Most of the patients had previous failed treatments for their condition. Observational procedures included ETDRS BCVA, and complete ophthalmic examination. Optical coherence tomography (OCT) was performed at day 1 and week 4. Fluorescein angiography was performed at baseline only for diagnostic purposes. Data were subjected to two-sample t-test statistical analysis. P-values of <0.05 were considered statistically significant. Results At 1-month follow-up, BCVA significantly improved in 87.5% of patients treated with melatonin (7 of 8 patients, P<0.05). All patients showed a mean significant reduction (P<0.01) of central macular thickness (CMT) when compared with the baseline, with 3 patients (37.5%) exhibiting complete resolution of subretinal fluid at 1-month follow-up. No significant side effects were observed. No changes in BCVA or CMT were noted in the control group. Conclusions These results suggest that melatonin is safe, well tolerated, and effective in the treatment of chronic CSCR, as it significantly improved BCVA and CMT in patients with this pathology. Further evaluations with longer follow-up and a larger patient population are desirable. PMID:26160525

  3. Finasteride is effective for the treatment of central serous chorioretinopathy.

    PubMed

    Moisseiev, E; Holmes, A J; Moshiri, A; Morse, L S

    2016-06-01

    PurposeTo evaluate the safety and efficacy of finasteride treatment in patients with central serous chorioretinopathy (CSC).MethodsRetrospective review of 29 eyes of 23 patients who were treated with finasteride for CSC. Previous medical and ocular history, steroid use, length of finasteride treatment, additional treatments for CSC, visual acuity (VA), central macular thickness (CMT), and presence of subretinal fluid (SRF) throughout the follow-up period, and the occurrence of any complications were recorded.ResultsInitial VA was 0.29±0.31 logMAR, and a trend towards improved VA was noted after 3 months (0.25±0.36 logMAR; P=0.07). VA was significantly improved at the final follow-up (0.23±0.27 logMAR; P=0.024). Initial CMT was 354±160 μm, and was significantly reduced after 1 month of treatment (284±77 μm; P=0.002) and this was maintained to the end of follow-up (247±85 μm; P=0.001). A significant reduction in SRF presence was found at all time points, with an overall 75.9% rate of complete resolution. Following discontinuation, SRF recurrence was noted in 37.5% of cases. No adverse events were recorded.ConclusionsFinasteride is a safe and effective treatment for CSC. It may be a possible new option for the initial management of patient with CSC, and a suggested treatment approach is presented. PMID:27055675

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

    PubMed Central

    Dagli, Necati; Turgut, Burak; Tanyildizi, Rumeysa; Kobat, Sabiha; Kobat, Mehmet Ali; Dogdu, Orhan

    2015-01-01

    AIM To evaluate QT dispersion (QTD) in patients with central serous chorioretinopathy (CSC). METHODS This clinical, comperative, case-control study included 30 patients with CSC at acute phase (Group 1) and 30 age- and sex-matched healthy subjects (Group 2, the control group). From all subjects, a 12-lead surface electrocardiography was obtained. The heart rate (HR), QT maximum (QTmax), QT minimum (QTmin), QT corrected (QTc), QTD and Tmean were manually measured and analyzed. Student's t-test and Pearson's method of correlation were used for statistical analysis. RESULTS The patient and control groups were matched for age, smoking status (rate and duration) and gender. There were no significant differences with regard to these among the groups (P>0.05). The participants included 19 men (63.3%) and 11 women (36.7%) in Group 1, 20 men (66.7%) and 10 women (33.3%) in Group 2. QTmax, QTD and QTc were significantly higher than those of healthy controls (P<0.001 for QTmax, P=0.01 for QTD and P=0.001 for QTc). QTmin, Tmean and HR did not differ significantly between the study groups (P=0.28 for QTmin, P=0.56 for Tmean and P>0.05 for HR). No significant correlation was found between duration of the disorder and QTD values (r=0.13, P>0.05). CONCLUSION These findings suggest that CSC may be associated with an increase in QTD and that the patients might be at risk for ventricular arrhythmia. PMID:25709909

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

    PubMed Central

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

    2014-01-01

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

  6. Molecular Requirements for Transformation of Fallopian Tube Epithelial Cells into Serous Carcinoma12

    PubMed Central

    Jazaeri, Amir A; Bryant, Jennifer L; Park, Hong; Li, Hui; Dahiya, Neetu; Stoler, Mark H; Ferriss, James Stuart; Dutta, Anindya

    2011-01-01

    Although controversial, recent studies suggest that serous ovarian carcinomas may arise from fallopian tube fimbria rather than ovarian surface epithelium. We developed an in vitro model for serous carcinogenesis in which primary human fallopian tube epithelial cells (FTECs) were exposed to potentially oncogenic molecular alterations delivered by retroviral vectors. To more closely mirror in vivo conditions, transformation of FTECs was driven by the positive selection of growth-promoting alterations rather antibiotic selection. Injection of the transformed FTEC lines in SCID mice resulted in xenografts with histologic and immunohistochemical features indistinguishable from poorly differentiated serous carcinomas. Transcriptional profiling revealed high similarity among the transformed and control FTEC lines and patient-derived serous ovarian carcinoma cells and was used to define a malignancy-related transcriptional signature. Oncogene-treated FTEC lines were serially analyzed using quantitative reverse transcription-polymerase chain reaction and immunoblot analysis to identify oncogenes whose expression was subject to positive selection. The combination of p53 and Rb inactivation (mediated by SV40 T antigen), hTERT expression, and oncogenic C-MYC and HRAS accumulation showed positive selection during transformation. Knockdown of each of these selected components resulted in significant growth inhibition of the transformed cell lines that correlated with p27 accumulation. The combination of SV40 T antigen and hTERT expression resulted in immortalized cells that were nontumorigenic in mice, whereas forced expression of a dominant-negative p53 isoform (p53DD) and hTERT resulted in senescence. Thus, our investigation supports the tubal origin of serous carcinoma and provides a dynamic model for studying early molecular alterations in serous carcinogenesis. PMID:22028616

  7. P53 AUTOANTIBODIES AS POTENTIAL DETECTION AND PROGNOSTIC BIOMARKERS IN SEROUS OVARIAN CANCER

    PubMed Central

    Anderson, Karen S.; Wong, Jessica; Vitonis, Allison; Crum, Christopher P.; Sluss, Patrick M.; LaBaer, Joshua; Cramer, Daniel

    2010-01-01

    Background: This study examined the value of serum p53 autoantibodies (p53-AAb) as detection and prognostic biomarkers in ovarian cancer. Methods: p53-AAb were detected by ELISA in sera obtained pre-operatively from women undergoing surgery for a pelvic mass. This group included women subsequently diagnosed with invasive serous ovarian cancer (N=60), non-serous ovarian cancers (N=30), and women with benign disease (N=30). Age-matched controls were selected from the general population (N=120). Receiver operating characteristic curves were constructed to compare the values of p53-AAb, CA 125, and HE4 as a screening biomarker. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess its prognostic value on survival. Results: p53-AAb were detected in 25/60 (41.7%) of serous cases, 4/30 (13.3%) non-serous cases, 3/30 (10%) benign disease cases, and 10/120 (8.3%) controls (combined p=0.0002). p53-AAb did not significantly improve detection of cases (AUC=0.69) or discrimination of benign versus malignant disease (AUC=0.64) compared with CA 125 (AUC=0.99) or HE4 (AUC=0.98). In multivariate analysis among cases, p53-AAb correlated only with a family history of breast cancer (p=0.01). Detectable p53 antibodies in pre-treatment sera were correlated with improved overall survival (p=0.04, HR=0.57 (95% CI=0.33, 0.97)) in serous ovarian cancer. Conclusions: Antibodies to p53 are detected in the sera of 42% of patients with advanced serous ovarian cancer. Impact: Although their utility as a pre-operative diagnostic biomarker, beyond CA 125 and HE4, is limited, they are prognostic for improved overall survival. PMID:20200435

  8. ADAM12 is a prognostic factor associated with an aggressive molecular subtype of high-grade serous ovarian carcinoma.

    PubMed

    Cheon, Dong-Joo; Li, Andrew J; Beach, Jessica A; Walts, Ann E; Tran, Hang; Lester, Jenny; Karlan, Beth Y; Orsulic, Sandra

    2015-07-01

    ADAM metallopeptidase domain 12 (ADAM12) is a promising biomarker because of its low expression in normal tissues and high expression in a variety of human cancers. However, ADAM12 levels in ovarian cancer have not been well characterized. We previously identified ADAM12 as one of the signature genes associated with poor survival in high-grade serous ovarian carcinoma (HGSOC). Here, we sought to determine if high levels of the ADAM12 protein and/or messenger RNA (mRNA) are associated with clinical variables in HGSOC. We show that high protein levels of ADAM12 in banked preoperative sera are associated with shorter progression-free and overall survival. Tumor levels of ADAM12 mRNA were also associated with shorter progression-free and overall survival as well as with lymphatic and vascular invasion, and residual tumor volume following cytoreductive surgery. The majority of genes co-expressed with ADAM12 in HGSOC were transforming growth factor (TGF)β signaling targets that function in collagen remodeling and cell-matrix adhesion. In tumor sections, the ADAM12 protein and mRNA were expressed in epithelial cancer cells and surrounding stromal cells. In vitro data showed that ADAM12 mRNA levels can be increased by TGFβ signaling and direct contact between epithelial and stromal cells. High tumor levels of ADAM12 mRNA were characteristic of the mesenchymal/desmoplastic molecular subtype of HGSOC, which is known to have the poorest prognosis. Thus, ADAM12 may be a useful biomarker of aggressive ovarian cancer for which standard treatment is not effective. PMID:25926422

  9. Serous retinal detachment and cystoid macular edema in a patient with Wyburn-Mason syndrome.

    PubMed

    Onder, Halil Ibrahim; Alisan, Sibel; Tunc, Murat

    2015-03-01

    Wyburn-Mason syndrome is a rare phacomatosis characterized by unilateral arteriovenous malformations (AVMs) involving the brain, retina, and (rarely) the skin. The diagnosis is concluded with dilated fundus examination and markedly dilated tortuous vascular loops with arteriovenous communications on fluorescent angiography. We present a 14-year-old male patient with Wyburn-Mason syndrome who developed serous macular neuroretinal detachment, cystoid macular edema (CME), and consequent visual deterioration in the left eye. To the best of our knowledge, this is the first report of a patient with Wyburn-Mason syndrome who developed serous retinal detachment and CME. PMID:24171831

  10. Current perspectives on pancreatic serous cystic neoplasms: Diagnosis, management and beyond

    PubMed Central

    Zhang, Xiao-Peng; Yu, Zhong-Xun; Zhao, Yu-Pei; Dai, Meng-Hua

    2016-01-01

    Pancreatic cystic neoplasms have been increasingly recognized recently. Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic neoplasms are uncommon benign lesions that are usually asymptomatic and found incidentally. Despite overall low risk of malignancy, these pancreatic cysts still generate anxiety, leading to intensive medical investigations with considerable financial cost to health care systems. This review discusses the general background of serous cystic neoplasms, including epidemiology and clinical characteristics, and provides an updated overview of diagnostic approaches based on clinical features, relevant imaging studies and new findings that are being discovered pertaining to diagnostic evaluation. We also concisely discuss and propose management strategies for better quality of life. PMID:27022447

  11. Atypical proliferative endometrioid tumor of ovary: Report of a rare case

    PubMed Central

    Jetley, S; Khetrapal, S; Ahmad, A; Jairajpuri, ZS

    2016-01-01

    Borderline ovarian tumors represent 10-20% of epithelial ovarian neoplasms that typically have an excellent prognosis. Both the oncological behavior of this group of tumors and also the diagnostic histological criteria are intermediate between the specific criteria of benign and malignant. They usually occur in the third to fourth decade of women's lives and are limited to the ovary in 80% of cases. Atypical proliferative or borderline ovarian tumors constitute a group of epithelial tumors with an excellent prognosis due to the low aggressiveness, microscopic examination is mandatory in order to establish an accurate histological diagnosis in all cases of borderline ovarian tumors and to differentiate from well differentiated adenocarcinoma. We report a case of a 45 year old female who presented with irregular bleeding per vaginum and underwent hysterectomy with bilateral salpingo-oophorectomy. Atypical proliferative endometrioid tumor of the left ovary was an incidental finding, which is a very rare occurrence. PMID:26497398

  12. Emotions and memory in borderline personality disorder.

    PubMed

    Winter, Dorina; Elzinga, Bernet; Schmahl, Christian

    2014-01-01

    Memory processes such as encoding, storage, and retrieval of information are influenced by emotional content. Because patients with borderline personality disorder (BPD) are particularly susceptible to emotional information, it is relevant to understand whether such memory processes are altered in this patient group. This systematic literature review collects current evidence on this issue. Research suggests that emotional information interferes more strongly with information processing and learning in BPD patients than in healthy controls. In general, BPD patients do not seem to differ from healthy control subjects in their ability to memorize emotional information, but they tend to have specific difficulties forgetting negative information. Also, BPD patients seem to recall autobiographical, particularly negative events with stronger arousal than healthy controls, while BPD patients also show specific temporo-prefrontal alterations in neural correlates. No substantial evidence was found that the current affective state influences learning and memory in BPD patients any differently than in healthy control subjects. In general, a depressive mood seems to both deteriorate and negatively bias information processing and memories, while there is evidence that dissociative symptoms impair learning and memory independently of stimulus valence. This review discusses methodological challenges of studies on memory and emotions in BPD and makes suggestions for future research and clinical implications. PMID:24355827

  13. Borderline Personality Disorder: Why 'fast and furious'?

    PubMed

    Brüne, Martin

    2016-01-01

    The term 'Borderline Personality Disorder' (BPD) refers to a psychiatric syndrome that is characterized by emotion dysregulation, impulsivity, risk-taking behavior, irritability, feelings of emptiness, self-injury and fear of abandonment, as well as unstable interpersonal relationships. BPD is not only common in psychiatric populations but also more prevalent in the general community than previously thought, and thus represents an important public health issue. In contrast to most psychiatric disorders, some symptoms associated with BPD may improve over time, even without therapy, though impaired social functioning and interpersonal disturbances in close relationships often persist. Another counterintuitive and insufficiently resolved question is why depressive symptoms and risk-taking behaviors can occur simultaneously in the same individual. Moreover, there is an ongoing debate about the nosological position of BPD, which impacts on research regarding sex differences in clinical presentation and patterns of comorbidity.In this review, it is argued that many features of BPD may be conceptualized within an evolutionary framework, namely behavioral ecology. According to Life History Theory, BPD reflects a pathological extreme or distortion of a behavioral 'strategy' which unconsciously aims at immediate exploitation of resources, both interpersonal and material, based on predictions shaped by early developmental experiences. Such a view is consistent with standard medical conceptualizations of BPD, but goes beyond classic 'deficit'-oriented models, which may have profound implications for therapeutic approaches. PMID:26929090

  14. Executive functions in borderline personality disorder.

    PubMed

    Hagenhoff, Meike; Franzen, Nele; Koppe, Georgia; Baer, Nina; Scheibel, Niki; Sammer, Gebhard; Gallhofer, Bernd; Lis, Stefanie

    2013-11-30

    Different domains of executive function such as working memory and response inhibition were investigated together with elementary cognitive processes in borderline personality disorder (BPD). Patients with BPD (N=28) were compared to nonpatient controls (NP, N=28) on eight tasks (e.g. n-back, Go/NoGo, CPT-AX). In order to separate impairments in different cognitive domains and to assess the influence of more elementary cognitive processes on executive functioning, tasks were embedded in a reaction-time-decomposition approach. BPD patients solved tasks with accuracies comparable to those of nonpatients. The only exception was the n-back task, for which working memory is required: here, error rates were higher and increased more prominently in BPD patients depending on working memory load. In most tasks, movement times were shorter for BPD patients than for nonpatients, while the quality of task-solving was comparable. The faster processing in the BPD group was observable starting with the simplest task, i.e. a simple reaction-time task. These findings suggest that domains of executive functioning are differentially affected in BPD. In contrast to load-dependent deficits in working memory, response inhibition processes were unimpaired. Faster action-related processes could be observed in BPD patients in a variety of tasks; however, these did not influence executive functioning. PMID:23764434

  15. Interpreting Borderline BeLPT Results

    PubMed Central

    Middleton, D.C.; Mayer, A.S.; Lewin, M.D.; Mroz, M.M.; Maier, L.A.

    2015-01-01

    Background The beryllium lymphocyte proliferation test (BeLPT) identifies persons sensitized to beryllium (BeS) and thus at risk for chronic beryllium disease (CBD). BeLPT test results are abnormal (AB), borderline (BL), or normal (NL). This manuscript addresses the predictive value and interpretation of BL BeLPT results. Methods The various three-result combinations that meet or exceed a nominal referral criteria of 1 AB + 1 BL are assessed with probability modeling and compared. Results At 2% prevalence, the three-result combinations that meet or exceed this referral criteria and associated probabilities of BeS are: (a) 1 AB + 1 BL + 1 NL (72%); (b) 3 BL (91%); (c) 2 AB + 1 NL (95%); (d) 1 AB + 2 BL (99%); (e) 2 AB + 1 BL (100%); and (f) 3 AB (100%). Conclusion These results suggest that BL results are meaningful and that three BL results predict BeS across a broad range of population prevalences. An analysis of longitudinal BeLPT results and clinical findings from an actual surveillance program is warranted to confirm the model’s predictions. PMID:20957676

  16. Social cognition in borderline personality disorder

    PubMed Central

    Roepke, Stefan; Vater, Aline; Preißler, Sandra; Heekeren, Hauke R.; Dziobek, Isabel

    2013-01-01

    Many typical symptoms of borderline personality disorder (BPD) occur within interpersonal contexts, suggesting that BPD is characterized by aberrant social cognition. While research consistently shows that BPD patients have biases in mental state attribution (e.g., evaluate others as malevolent), the research focusing on accuracy in inferring mental states (i.e., cognitive empathy) is less consistent. For complex and ecologically valid tasks in particular, emerging evidence suggests that individuals with BPD have impairments in the attribution of emotions, thoughts, and intentions of others (e.g., Preißler et al., 2010). A history of childhood trauma and co-morbid PTSD seem to be strong additional predictors for cognitive empathy deficits. Together with reduced emotional empathy and aberrant sending of social signals (e.g., expression of mixed and hard-to-read emotions), the deficits in mental state attribution might contribute to behavioral problems in BPD. Given the importance of social cognition on the part of both the sender and the recipient in maintaining interpersonal relationships and therapeutic alliance, these impairments deserve more attention. PMID:23335877

  17. [Borderline personality disorders: diagnosis and treatment].

    PubMed

    Allilaire, Jean-François

    2012-10-01

    Borderline personality disorders are complex clinical states with highly polymorphic symptoms and signs, leading to delays in their diagnosis and treatment. All international classifications emphasize certain clinical criteria such as unstable identity and interpersonal relationships, feelings of emptiness or boredom, and pathological impulsiveness. The prevalence is about 2%, with a female-male sex ratio of 2 or 3 to 1. Both adolescents and adults may be affected There is a high risk of suicide, addictive behaviors, eating disorders, and criminality. These individuals frequently have a history of trauma in early childhood, such as separation, loss, physical or sexual abuse, or affective privation. Subjective signs and symptoms are particularly important in the diagnostic and therapeutic evaluation, and this requires an empathic and subtle approach. Standardized and semi-structured interviews may help to identify comorbidities such as thymic disorders, anxiety, addiction, eating disorders, and, in some cases, psychotic symptoms. The psychiatric bio-psycho-social model takes into account multiple pathogenic factors, such as trauma during early development, temperamental instability and other emotional disorders, as well as psychosocial, neurobiological (5HT etc.) and genetic vulnerabilities. Treatment requires optimal integration of psychotherapeutic and pharmacotherapeutic approaches. Emergency intervention must be available in case of delirious or suicidal behavior The clinical course is often lengthy and complex, but outcome may be favorable, provided the principal risk--suicide--is correctly managed, PMID:23815019

  18. A prospective investigation of the development of borderline personality symptoms.

    PubMed

    Carlson, Elizabeth A; Egeland, Byron; Sroufe, L Alan

    2009-01-01

    The antecedents and developmental course of borderline personality disorder symptoms were examined prospectively from infancy to adulthood using longitudinal data from a risk sample (N = 162). Borderline personality disorder symptom counts were derived from the Structured Clinical Interview for DSM Disorders diagnostic interview at age 28 years. Correlational analyses confirmed expected relations between borderline symptoms and contemporary adult disturbance (e.g., self-injurious behavior, dissociative symptoms, drug use, relational violence) as well as maltreatment history. Antecedent correlational and regression analyses revealed significant links between borderline symptoms in adulthood and endogenous (i.e., temperament) and environmental (e.g., attachment disorganization, parental hostility) history in early childhood and disturbance across domains of child functioning (e.g., attention, emotion, behavior, relationship, self-representation) in middle childhood/early adolescence. Process analyses revealed a significant mediating effect of self-representation on the relation between attachment disorganization on borderline symptoms. The findings are discussed within a developmental psychopathology framework in which disturbance in self-processes is constructed through successive transactions between the individual and environment. PMID:19825270

  19. [The borderline patient. Diagnosis, psychodynamics and physician-patient relation].

    PubMed

    Brühlmann, T

    1995-06-01

    'Borderline' is a popular psychiatric diagnosis. The uses of the term are variable and often unclear. It is the goal of this presentation to elaborate a borderline concept for use in daily clinical practise. First, development of the term over the preanalytical, analytical and empirical areas is summarized. Next, the term of borderline for clinical practise is developed on the basis of characteristics and the global picture. Characteristics are: intensive, instable behaviour in relations, reduced control of impulse, disturbed affection and mood, psychotic manifestations, instable social adaptation. Diagnosis is founded on exploration of characteristics and on seizing of the global picture. The combination with other psychiatric disorders and separation from other personality disorders have to be considered with respect to differential diagnosis. The descriptive diagnosis has to be complemented from a psychodynamic point of view. The borderline patient has in his psychologic development failed to segregate sufficiently from his primary reference person. This results in a structural deficit and a weak ego. This latter is characterized by deficient integration and deficient separation, by disturbed perception of reality and by a non-specific general weakness of the ego. Finally, difficulties arising in the relations between physician and borderline patient are outlined. PMID:7784774

  20. Half-dose Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

    PubMed Central

    Naseripour, Masood; Falavarjani, Khalil Ghasemi; Sedaghat, Ahad; Moghaddam, Arezoo Karimi; Nasserisina, Sadaf; Alemzadeh, Sayyed Amirpooya

    2016-01-01

    Purpose: To report the outcomes of half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (CSC). Methods: A chart review of patients with chronic CSC who had received half-dose verteporfin PDT (3 mg/m2) was performed. The main outcome measures were resolution of subretinal fluid and best corrected visual acuity (BCVA). Results: Fifty-three eyes of 51 patients with mean age of 45.01 ± 8.9 years were studied. Three, 6 and 12 months after half-dose PDT, subretinal fluid was completely resolved in 51 eyes (96.2%). In 2 eyes (one patient), subretinal fluid decreased at 3 months but one year later, an increase in subretinal fluid was detected on optical coherence tomography (OCT) which completely resolved following additional PDT. Another patient with recurrence of subretinal fluid rejected further treatment. Mean baseline central subfield thickness was 385 ± 113.0 μm which was decreased to 235 ± 39.7, 247 ± 49.7, and 244 ± 49.52 μm after 3, 6 and 12 months, respectively (all P-values < 0.001). Mean BCVA was 0.33 ± 0.27 LogMAR before PDT and 0.11 ± 0.18, 0.11 ± 0.17, 0.17 ± 0.26 and 0.10 ± 0.23 LogMAR, 3, 6 and 12 months and at final visit (up to 60 months) after PDT, respectively (all P-values < 0.001). Improvement ≥2 lines in BCVA occurred in 20 eyes (37.7%). Statistically significant correlations were found between improvement in BCVA and baseline BCVA, baseline central subfield thickness and central subfield thickness after resorption of subretinal fluid (P < 0.001, P= 0.04 and P= 0.01, respectively). No complications attributed to PDT were observed. Conclusion: Half-dose PDT is effective for treatment of patients with chronic CSC. PMID:27195088

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

    PubMed Central

    Lawrenson, Kate; Pakzamir, Elham; Liu, Biao; Lee, Janet M.; Delgado, Melissa K.; Duncan, Kara; Gayther, Simon A.; Liu, Song; Roman, Lynda; Mhawech-Fauceglia, Paulette

    2015-01-01

    Background 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. Methodology/Principal Findings 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). Conclusion 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. PMID:26132201

  2. Borderline personality disorder, stigma, and treatment implications.

    PubMed

    Aviram, Ron B; Brodsky, Beth S; Stanley, Barbara

    2006-01-01

    Borderline personality disorder (BPD) is often viewed in negative terms by mental health practitioners and the public. The disorder may have a stigma associated with it that goes beyond those associated with other mental illnesses. The stigma associated with BPD may affect how practitioners tolerate the actions, thoughts, and emotional reactions of these individuals. It may also lead to minimizing symptoms and overlooking strengths. In society, people tend to distance themselves from stigmatized populations, and there is evidence that some clinicians may emotionally distance themselves from individuals with BPD. This distancing may be especially problematic in treating patients with BPD; in addition to being unusually sensitive to rejection and abandonment, they may react negatively (e.g., by harming themselves or withdrawing from treatment) if they perceive such distancing and rejection. Clinicians' reactivity may be self-protective in response to actual behavior associated with the pathology. As a consequence, however, the very behaviors that make it difficult to work with these individuals contribute to the stigma of BPD. In a dialectical relationship, that stigma can influence the clinician's reactivity, thereby exacerbating those same negative behaviors. The result is a self-fulfilling prophecy and a cycle of stigmatization to which both patient and therapist contribute. The extent to which therapist distancing is influenced by stigma is an important question that highlights the possibility that the stigma associated with BPD can have an independent contribution to poor outcome with this population. A final issue concerns the available means for identifying and limiting the impact of stigmatization on the treatment of individuals with BPD. PMID:16990170

  3. [Borderline leprosy as a rare differential diagnosis].

    PubMed

    Trawinski, Henning; Brüning, Jan-Hinnerk; Baum, Petra; Ziemer, Mirjana; Schubert, Stefan; Lübbert, Christoph

    2016-06-01

    History and clinical findings | A 42-year-old migrant from Brazil presented with persistent sensory disturbances, skin discolorations and local alopecia in the upper limbs. Decisive for the presentation in our Tropical Medicine Clinic were new occurrences of severe pain and redness and swelling in the area of the lesions that had already been assessed by a number of medical specialists without a clear diagnosis could be made. Investigations and diagnosis | The histological analysis of skin biopsies showed perivascular, perineural, periadnexial lymphocytic and granulomatous dermatitis. In a direct microbiological preparation individual acid fast bacilli could be detected (Ziehl-Neelsen stain). The electroneurographical examination demonstrated a sensitive peripheral-neurogenic damage with emphasis on the right median nerve and the left ulnar and radial nerves. Thermography revealed an increased heating or cooling threshold. The serological investigation by ELISA for IgM antibodies against the phenolic glycolipid (PGL-1) was positive (titer 1 : 1200). In summary, the diagnosis of borderline leprosy (infection with Mycobacterium leprae) with transition to multibacillary leprosy (according to WHO) and leprosy reaction type 1 was made. Treatment and course | We initiated an oral antimycobacterial therapy (multidrug therapy, MDT) with rifampin, clofazimine and dapsone for 12 months (WHO regimen for multibacillary leprosy). Leprosy reaction type 1 was treated with prednisolone and by increasing the dose of clofazimine. Analgesic therapy on demand was carried out with nonsteroidal anti-inflammatory drugs (ibuprofen). MDT and successful management of leprosy reaction lead to a rapid improvement of symptoms. Conclusions | Leprosy is an infectious disease occurring only rarely in Germany (average incidence of 1-2 cases per year) that is diagnosed almost exclusively among migrants. Main symptoms comprise non-itchy, reddish, touch insensitive skin lesions or nerve deficits. The

  4. Informed consent for research in Borderline Personality Disorder

    PubMed Central

    Dew, Rachel E

    2007-01-01

    Background Previous research on informed consent for research in psychiatric patients has centered on disorders that affect comprehension and appreciation of risks. Little has been written about consent to research in those subjects with Borderline Personality Disorder, a prevalent and disabling condition. Discussion Despite apparently intact cognition and comprehension of risks, a borderline subject may deliberately choose self-harm in order to fulfill abnormal psychological needs, or due to suicidality. Alternatively, such a subject may refuse enrollment due to transference or the desire to harm him or herself. Such phenomena could be precipitated or prevented by the interpersonal dynamics of the informed consent encounter. Summary Caution should be exercised in obtaining informed consent for research from subjects with Borderline Personality Disorder. A literature review and recommendations for future research are discussed. PMID:17493277

  5. Emotional hyper-reactivity in borderline personality disorder.

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2010-09-01

    According to clinical experience, the Diagnostic and Statistical Manual of Mental Disorders, and authorities in the field, patients with borderline personality disorder tend to be hyper-reactive to environmental stimuli. In addition to the preceding clinical impressions and experiences, the majority of empirical studies in this area have concluded that patients with borderline personality disorder are indeed hyper-responsive to experimental environmental stimuli, whether the stimuli are negative, positive, or even neutral or ambiguous. While two empirical studies did not find hyper-responsiveness, both were undertaken in inpatients with borderline personality disorder, and the potential for emotional blunting from psychotropic medications may have been a potential confound. These findings have several clinical implications in both mental health and primary care settings. PMID:20941347

  6. Examining the Relationship between Childhood Sexual Abuse and Borderline Personality Disorder: Does Social Support Matter?

    ERIC Educational Resources Information Center

    Elzy, Meredith B.

    2011-01-01

    The relationship between childhood sexual abuse and borderline personality disorder is a prominent issue in the etiological research on borderline personality disorder. This study further explored the relationship between childhood sexual abuse and the development of borderline personality features while evaluating the moderating role of a primary…

  7. Increased Lead and Cadmium Burdens among Mentally Retarded Children and Children with Borderline Intelligence.

    ERIC Educational Resources Information Center

    Marlowe, Mike; And Others

    1983-01-01

    The relationship between subtoxic metal levels and mild mental retardation and borderline intelligence was investigated through comparison of hair metal concentrations in 135 secondary students with mild retardation or borderline intelligence. Children in the retarded/borderline group had significantly higher lead and cadmium concentrations.…

  8. Art Therapy for Individuals with Borderline Personality: Using a Dialectical Behavior Therapy Framework

    ERIC Educational Resources Information Center

    Drass, Jessica Masino

    2015-01-01

    Art therapy has shown benefits for people with borderline personality disorder and borderline personality traits by alleviating interpersonal difficulties such as affect regulation, an unstable sense of self, self-injurious behaviors, and suicidal ideation. Borderline personality disorder is currently viewed as a trauma spectrum disorder, because…

  9. Autonomic mechanisms underpinning the stress response in borderline hypertensive rats

    PubMed Central

    Šarenac, Olivera; Lozić, Maja; Drakulić, Srdja; Bajić, Dragana; Paton, Julian F; Murphy, David; Japundžić-Žigon, Nina

    2011-01-01

    This study investigates blood pressure (BP) and heart rate (HR) short-term variability and spontaneous baroreflex functioning in adult borderline hypertensive rats and normotensive control animals kept on normal-salt diet. Arterial pulse pressure was recorded by radio telemetry. Systolic BP, diastolic BP and HR variabilities and baroreflex were assessed by spectral analysis and the sequence method, respectively. In all experimental conditions (baseline and stress), borderline hypertensive rats exhibited higher BP, increased baroreflex sensitivity and resetting, relative to control animals. Acute shaker stress (single exposure to 200 cycles min-1 shaking platform) increased BP in both strains, while chronic shaker stress (3-day exposure to shaking platform) increased systolic BP in borderline hypertensive rats alone. Low- and high-frequency HR variability increased only in control animals in response to acute and chronic shaker (single exposure to restrainer) stress. Acute restraint stress increased BP, HR, low- and high-frequency variability of BP and HR in both strains to a greater extent than acute shaker stress. Only normotensive rats exhibited a reduced ratio of low- to high-frequency HR variability, pointing to domination of vagal cardiac control. In borderline hypertensive rats, but not in control animals, chronic restraint stress (9-day exposure to restrainer) increased low- and high-frequency BP and HR variability and their ratio, indicating a shift towards sympathetic cardiovascular control. It is concluded that maintenance of BP in borderline hypertensive rats in basal conditions and during stress is associated with enhanced baroreflex sensitivity and resetting. Imbalance in sympathovagal control was evident only during exposure of borderline hypertensive rats to stressors. PMID:21421701

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

    PubMed

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

    2016-01-01

    High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among all gynecological cancers. Patients are generally diagnosed in an advanced stage with the majority of cases displaying platinum resistant relapses. Recent genomic interrogation of large numbers of HGSOC patient samples indicated high complexity in terms of genetic aberrations, intra- and intertumor heterogeneity and underscored their lack of targetable oncogenic mutations. Sub-classifications of HGSOC based on expression profiles, termed 'differentiated', 'immunoreactive', 'mesenchymal' and 'proliferative', were shown to have prognostic value. In addition, in almost half of all HGSOC patients, a deficiency in homologous recombination (HR) was found that potentially can be targeted using PARP inhibitors. Developing precision medicine requires advanced experimental models. In the current review, we discuss experimental HGSOC models in which resistance to platinum therapy and the use of novel therapeutics can be carefully studied. Panels of better-defined primary cell lines need to be established to capture the full spectrum of HGSOC subtypes. Further refinement of cell lines is obtained with a 3-dimensional culture model mimicking the tumor microenvironment. Alternatively, ex vivo ovarian tumor tissue slices are used. For in vivo studies, larger panels of ovarian cancer patient-derived xenografts (PDXs) are being established, encompassing all expression subtypes. Ovarian cancer PDXs grossly retain tumor heterogeneity and clinical response to platinum therapy is preserved. PDXs are currently used in drug screens and as avatars for patient response. The role of the immune system in tumor responses can be assessed using humanized PDXs and immunocompetent genetically engineered mouse models. Dynamic tracking of genetic alterations in PDXs as well as patients during treatment and after relapse is feasible by sequencing circulating cell-free tumor DNA and analyzing circulating tumor cells. We

  11. Augmentation of Response to Chemotherapy by microRNA-506 Through Regulation of RAD51 in Serous Ovarian Cancers

    PubMed Central

    Liu, Guoyan; Yang, Da; Rupaimoole, Rajesha; Pecot, Chad V.; Sun, Yan; Mangala, Lingegowda S.; Li, Xia; Ji, Ping; Cogdell, David; Hu, Limei; Wang, Yingmei; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Shmulevich, Ilya; De Cecco, Loris; Chen, Kexin; Mezzanzanica, Delia; Xue, Fengxia; Sood, Anil K.

    2015-01-01

    Background: Chemoresistance is a major challenge in cancer treatment. miR-506 is a potent inhibitor of the epithelial-to-mesenchymal transition (EMT), which is also associated with chemoresistance. We characterized the role of miR-506 in chemotherapy response in high-grade serous ovarian cancers. Methods: We used Kaplan-Meier and log-rank methods to analyze the relationship between miR-506 and progression-free and overall survival in The Cancer Genome Atlas (TCGA) (n = 468) and Bagnoli (n = 130) datasets, in vitro experiments to study whether miR-506 is associated with homologous recombination, and response to chemotherapy agents. We used an orthotopic ovarian cancer mouse model (n = 10 per group) to test the effect of miR-506 on cisplatin and PARP inhibitor sensitivity. All statistical tests were two-sided. Results: MiR-506 was associated with better response to therapy and longer progression-free and overall survival in two independent epithelial ovarian cancer patient cohorts (PFS: high vs low miR-506 expression; Bagnoli: hazard ratio [HR] = 3.06, 95% confidence interval [CI] = 1.90 to 4.70, P < .0001; TCGA: HR = 1.49, 95% CI = 1.00 to 2.25, P = 0.04). MiR-506 sensitized cells to DNA damage through directly targeting the double-strand DNA damage repair gene RAD51. Systemic delivery of miR-506 in 8–12 week old female athymic nude mice statistically significantly augmented the cisplatin and olaparib response (mean tumor weight ± SD, control miRNA plus cisplatin vs miR-506 plus cisplatin: 0.36±0.05g vs 0.07±0.02g, P < .001; control miRNA plus olaparib vs miR-506 plus olaparib: 0.32±0.13g vs 0.05±0.02g, P = .045, respectively), thus recapitulating the clinical observation. Conclusions: MiR-506 is a robust clinical marker for chemotherapy response and survival in serous ovarian cancers and has important therapeutic value in sensitizing cancer cells to chemotherapy. PMID:25995442

  12. NGS-based BRCA1/2 mutation testing of high-grade serous ovarian cancer tissue: results and conclusions of the first international round robin trial.

    PubMed

    Endris, Volker; Stenzinger, Albrecht; Pfarr, Nicole; Penzel, Roland; Möbs, Markus; Lenze, Dido; Darb-Esfahani, Silvia; Hummel, Michael; Sabine-Merkelbach-Bruse; Jung, Andreas; Lehmann, Ulrich; Kreipe, Hans; Kirchner, Thomas; Büttner, Reinhard; Jochum, Wolfram; Höfler, Gerald; Dietel, Manfred; Weichert, Wilko; Schirmacher, Peter

    2016-06-01

    With the approval of olaparib as monotherapy treatment in platinum-sensitive, relapsed high-grade serous ovarian cancer by the European Medical Agency (EMA), comprehensive genotyping of BRCA1 and BRCA2 in tumor tissue has become a mandatory pre-therapeutic test. This requires significant advances in routine tumor test methodologies due to the large size of both genes and the lack of mutational hot spots. Classical focused screening approaches, like Sanger sequencing, do not allow for a sensitive, rapid, and economic analysis of tumor tissue. Next-generation sequencing (NGS) approaches employing targeted panels for BRCA1/2 to interrogate formalin-fixed and paraffin-embedded tumor samples from either surgical resection or biopsy specimens can overcome these limitations. Although focused NGS methods have been implemented by few centers in routine molecular diagnostics for the analysis of some druggable oncogenic mutations, the reliable diagnostic testing of the entire coding regions of BRCA1 and BRCA2 was a new challenge requiring extensive technological improvement and quality management. Here, we describe the implementation and results of the first round robin trial for BRCA1/2 mutation testing in tumor tissue that was conducted in central Europe on May 2015, shortly after the approval and prior to the official release of olaparib. The high success rate of 81 % (21/26 test centers) demonstrates that BRCA1/2 multicenter mutation testing is well feasible in FFPE tumor tissue, extending to other tumor entities beyond ovarian cancer. The high number of test centers passing the trial demonstrates the success of the concerted efforts by German, Swiss, and Austrian pathology centers to ensure quality-controlled NGS-based testing and proves the potential of this technology in routine molecular pathology. On the basis of our results, we provide recommendations for predictive testing of tumor tissue for BRCA1/2 to clinical decision making in ovarian cancer patients. PMID

  13. [Grading of gynecological tumors : Current aspects].

    PubMed

    Horn, L-C; Mayr, D; Brambs, C E; Einenkel, J; Sändig, I; Schierle, K

    2016-07-01

    Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3‑tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract. PMID:27379622

  14. Expression of REG4 in ovarian mucinous tumors.

    PubMed

    Huang, Qiong; Chen, Xiaoduan; Lu, Weiguo; Lai, Maode; Lu, Bingjian

    2014-04-01

    Regenerating islet-deprived gene family, number 4 (REG4), is a novel marker for intestinal differentiation. We performed immunohistochemical studies on REG4, cytokeratin (CK)7, CK20, and caudal type homeobox 2 (CDX2) in 291 ovarian mucinous tumors. There were 226 primary tumors and 65 metastatic tumors. The primary tumors comprised 69/226 mucinous cystadenomas, 79/226 mucinous borderline tumors (64/79 intestinal-type and 15/79 endocervical-like tumors), and 78/226 mucinous carcinomas. We found that REG4 expression was significantly higher in mucinous borderline tumors (30/79, 38.0%) and primary mucinous carcinomas (26/78, 33.3%) than in mucinous cystadenomas (4/69, 5.8%; P<0.05). However, REG4 expression was more commonly associated with intestinal-type, borderline, mucinous tumors rather than the endocervical-like type (30/64 vs. 0/15, P<0.001). There was a significant correlation between the REG4 and CDX2 expression profiles in primary ovarian mucinous tumors (r=0.772, P<0.001). REG4, CDX2, and diffuse CK20 had higher expression frequencies in metastatic lower gastrointestinal adenocarcinoma than in primary mucinous tumors (P<0.01). The CK7/REG4 coordinate expression profile was comparable in diagnostic value to CK7/CK20 or CK7/CDX2 profile. We conclude that REG4 expression is common in mucinous borderline tumors of the intestinal type as it is absent in the endocervical-like form in this series. Expression of CK7/REG4 may contribute to the differential diagnosis between primary and metastatic ovarian mucinous tumors. PMID:23958547

  15. Carcinoembryonic antigen-related cell adhesion molecule 1 is expressed and as a function histotype in ovarian tumors.

    PubMed

    Li, Ning; Yang, Jing-Yan; Wang, Xiao-Ying; Wang, Hai-Tao; Guan, Bing-Xin; Zhou, Cheng-Jun

    2016-02-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell-cell adhesion receptor and is implicated in several cellular functions. It is rarely reported in ovarian tumors. The aim of this study is to determine the expression of CEACAM1 in ovarian tumors, trying to see whether CEACAM1 has different expression patterns as a function of histotype. Antigen expression was examined by immunohistochemistry with mouse anti-human antibody for CEACAM1. Immunohistochemistry was performed using avidin-biotin-diaminobenzide staining. The results were expressed as average score ± SD (0, negative; 8, highest) for each histotype. In ovarian tumors, the benign serous and mucinous cystadenoma negatively or weakly expressed CEACAM1, the malignant epithelial tumors strongly expressed CEACAM1, and there was significant difference between benign epithelial tumor and adenocarcinoma (P < .05). The well-differentiated serous adenocarcinoma expressed CEACAM1 mainly with membrane pattern, and the intermediately and poorly differentiated serous adenocarcinomas expressed CEACAM1 mainly with cytoplasmic pattern (P < .05). In addition, CEACAM1 expression is elevated in solid tumors of ovary but variable as a function of histotype. Compared with membranous expression, the cytoplasmic expression was observed almost in metastatic carcinoma that might decrease the adhesive interactions of the carcinoma cells with the surrounding cells, especially with tumor cells, and this could facilitate the tumor cells to metastasize to distant regions. So, we thought that cytoplasmic CEACAM1 might play an important role in tumor progression, especially in tumor metastasis. PMID:26653024

  16. Hyperadrenergic borderline hypertension is characterized by suppressed aggression.

    PubMed

    Perini, C; Müller, F B; Rauchfleisch, U; Battegay, R; Bühler, F R

    1986-01-01

    The effect of suppressed aggression on the reactivity of the sympathetic nervous and cardiovascular systems has been investigated in two groups of 24 subjects each with either borderline hypertension or normal blood pressure and no family history of hypertension. Groups were matched for sex and age (18-24 years). Suppressed aggression was defined by the newly standardized Rosenzweig Picture-Frustration test, a projective method assessing the reaction to everyday stress. Responses of blood pressure, heart rate, and venous plasma catecholamines were measured before and during application of mental stressors, using the Stroop color-word conflict test and mental arithmetic. In an analysis of covariance for repeated measures, which eliminates the influence of anxiety, borderline hypertensive subjects with suppressed aggression had significantly higher heart rates and diastolic blood pressures and a greater noradrenaline reactivity than borderline hypertensive subjects without suppressed aggression or normotensive subjects. Suppressed aggression may lead to a hyperadrenergic form of early borderline hypertension and thereby contribute to higher blood pressure. PMID:2427886

  17. Borderline-lepromatous leprosy manifesting as granulomatous mastitis.

    PubMed

    Pandhi, Deepika; Verma, Prashant; Sharma, Sonal; Dhawan, Amit Kumar

    2012-06-01

    Leprosy is characterised by a chronic granulomatous inflammation of the skin and peripheral nerves. Dissemination of the lepra bacilli may cause involvement of other tissues as well. We describe an unusual case of the granulomatous involvement of the nipple-areola complex in a 35-year-old male consequent to borderline-lepromatous leprosy. PMID:22997696

  18. The Objective Borderline Method: A Probabilistic Method for Standard Setting

    ERIC Educational Resources Information Center

    Shulruf, Boaz; Poole, Phillippa; Jones, Philip; Wilkinson, Tim

    2015-01-01

    A new probability-based standard setting technique, the Objective Borderline Method (OBM), was introduced recently. This was based on a mathematical model of how test scores relate to student ability. The present study refined the model and tested it using 2500 simulated data-sets. The OBM was feasible to use. On average, the OBM performed well…

  19. Borderline Personality Disorder: A Dysregulation of the Endogenous Opioid System?

    ERIC Educational Resources Information Center

    Bandelow, Borwin; Schmahl, Christian; Falkai, Peter; Wedekind, Dirk

    2010-01-01

    The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids…

  20. Development and Validation of the Minnesota Borderline Personality Disorder Scale

    ERIC Educational Resources Information Center

    Bornovalova, Marina A.; Hicks, Brian M.; Patrick, Christopher J.; Iacono, William G.; McGue, Matt

    2011-01-01

    Although large epidemiological data sets can inform research on the etiology and development of borderline personality disorder (BPD), they rarely include BPD measures. In some cases, however, proxy measures can be constructed using instruments already in these data sets. In this study, the authors developed and validated a self-report measure of…

  1. Borderline Personality Disorder and Posttraumatic Stress Disorder: Time for Integration?

    ERIC Educational Resources Information Center

    Hodges, Shannon

    2003-01-01

    An increasing prevalence of borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) diagnoses among women illustrates problems and limitations of the medical model system. Article explores overlapping relationship between BPD and PTSD and critiques how both are viewed within the mental health community. Previous research is…

  2. Is Anakin Skywalker suffering from borderline personality disorder?

    PubMed

    Bui, Eric; Rodgers, Rachel; Chabrol, Henri; Birmes, Philippe; Schmitt, Laurent

    2011-01-30

    Anakin Skywalker, one of the main characters in the "Star Wars" films, meets the criteria for borderline personality disorder (BPD). This finding is interesting for it may partly explain the commercial success of these movies among adolescents and be useful in educating the general public and medical students about BPD symptoms. PMID:20537718

  3. Interpersonal Precipitants and Suicide Attempts in Borderline Personality Disorder

    ERIC Educational Resources Information Center

    Brodsky, Beth S.; Groves, Shelly A.; Oquendo, Maria A.; Mann, J. John; Stanley, Barbara

    2006-01-01

    Borderline personality disorder (BPD) is often characterized by multiple low lethality suicide attempts triggered by seemingly minor incidents, and less commonly by high lethality attempts that are attributed to impulsiveness or comorbid major depression. The relationships among life events, impulsiveness, and type of suicidal behavior has hardly…

  4. Autonomic Impairment in Borderline Personality Disorder: A Laboratory Investigation

    ERIC Educational Resources Information Center

    Weinberg, Anna; Klonsky, E. David; Hajcak, Greg

    2009-01-01

    Recent research suggests that emotional dysfunction in psychiatric disorders can be reflected in autonomic abnormalities. The present study examines sympathetic and parasympathetic autonomic nervous system activity in individuals with Borderline Personality Disorder (BPD) before, during, and following a social stressor task. Data were obtained…

  5. Treatment of Borderline Adolescents in Family Court Services.

    ERIC Educational Resources Information Center

    Green, Maurice R.

    A recent revision of the proposed DSM III description of the borderline category is presented with reference to the work of Masterson and Grinker. The contributions of Roger Shapiro and his group to a psychoanalytic formulation of the developmental and familial dynamics are summarized with reference to genetic factors and the lack of validation,…

  6. The Borderline Personality Diagnosis in Adolescents: Gender Differences and Subtypes

    ERIC Educational Resources Information Center

    Bradley, Rebekah; Zittel Conklin, Carolyn; Westen, Drew

    2005-01-01

    Background: This study aimed to identify personality features characterizing adolescent girls and boys with borderline personality disorder (BPD) and to see whether meaningful patterns of heterogeneity exist among adolescents diagnosed with the disorder. Methods: Two hundred and ninety-four randomly selected doctoral-level clinicians described…

  7. Borderline Personality in Adolescence: An Overview for Counselors.

    ERIC Educational Resources Information Center

    Craig, Stephen E.; Fall, Kevin A.

    1998-01-01

    Borderline-personality disorder in adolescence is thought to develop through environmental sources, and object-relations theory posits a developmental arrest in the separation-individuation phase of development. This article discusses gender and race considerations, issues related to counseling, general treatment strategies such as coping-skills…

  8. Obesity is associated with worse overall survival in women with low grade papillary serous epithelial ovarian cancer

    PubMed Central

    Previs, Rebecca; Kilgore, Joshua; Craven, Renatta; Broadwater, Gloria; Bean, Sarah; Wobker, Sara; DiFurio, Megan; Bae-Jump, Victoria; Gehrig, Paola A.; Secord, Angeles Alvarez

    2015-01-01

    Objective To evaluate prognostic risk factors for survival in women with low grade serous epithelial ovarian cancer (LGSC). Methods A multicenter retrospective analysis of patients with LGSC was conducted. Potential epidemiologic risk factors evaluated included obesity, age, parity, race, smoking, oral contraceptive pill and/or hormonal replacement therapy use, and previous hysterectomy or surgery on fallopian tubes and/or ovaries. Additional factors included stage, extent of debulking, residual disease, and disease status. Results Eighty-one patients were identified, and pathological diagnosis was independently confirmed. Median age of diagnosis was 56 years (range: 21 to 86). Thirty-four percent were obese, and 80% had optimally debulked disease. Forty-six percent were alive, 14% with disease; while 25% were dead of disease; 2% died of intercurrent disease; and 27% had an unknown status. In a univariate analysis, optimal surgical debulking was associated with improved PFS (p=0.01), DSS (p=0.03), and OS (p<0.001 and BMI with worse OS (p=0.05). On multivariate analysis, obesity (HR=2.8; 95% CI=1.05-7.3; p=0.04) and optimal tumor debulking (HR=0.05; 95% CI=0.008-0.29; p=0.001) were a significant predictor of OS. Conclusions In a multivariate analysis, obesity and optimal tumor cytoreduction were significant predictors of OS. However, obesity was not associated with worse DSS, suggesting that mortality of obese patients with LGSC may result from other co-morbidities. Interventions addressing obesity may improve survival for women diagnosed with LGSC and further study is warranted to address the role of obesity in LGSC. PMID:24614825

  9. [Tattoos and piercings: motives for body modification in women suffering from borderline symptomatology].

    PubMed

    Höhner, Gesche; Teismann, Tobias; Willutzki, Ulrike

    2014-02-01

    Do women suffering from borderline symptomatology differ from women without these symptoms regarding their motives for body modifications?A sample of 289 women with body modifications were questioned about their tattoos, piercings and motives for body modifications as well as about symptoms of borderline personality disorder. Women with borderline symptomatology were compared to women without borderline symptomatology concerning the extent of and motives for body modification.The 2 groups showed no differences in regard to amount and extent of body modifications. The "borderline"-group considered individuality, coping and management of negative life-events to be more crucial reasons for body modification than the non-borderline females.The degree of a person's body modification is not a feasible indicator for psychopathological strain. Though, for people with borderline tendency body modification may serve as a coping strategy similar to self-injury. PMID:23784796

  10. The incidence of pelvic and para-aortic lymph node metastasis in uterine papillary serous and clear cell carcinoma according to the SEER registry

    PubMed Central

    Lee, Jennifer C.; Metzger, Daniel J.; Ashamalla, Hani; Katsoulakis, Evangelia

    2015-01-01

    Objective In this study we utilized the Surveillance, Epidemiology and End-Results (SEER) registry to identify risk factors for lymphatic spread and determine the incidence of pelvic and para-aortic lymph node metastases in patients with uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) who underwent complete surgical staging and lymph node dissection. Methods Nine hundred seventy-two eligible patients diagnosed between 1998 to 2009 with International Federation of Gynecology and Obstetrics (FIGO) 1988 stage IA-IVA UPSC (n=685) or UCCC (n=287) were identified for analysis. Binomial logistic regression was used to determine risk factors for lymph node metastasis, with the incidence of pelvic and para-aortic lymph node metastases reported for each FIGO primary tumor stage. The Cox proportional hazards regression model was used to determine factors associated with overall survival. Results FIGO primary tumor stage was the only independent risk factor for lymph node metastasis (p<0.01). The incidence of pelvis-only and para-aortic lymph node involvement according to the FIGO primary tumor stage were as follows: IA (2.3%/3.8%), IB (7.5%/5.2%), IC (22.5%/16.9%), IIA (20.8%/13.2%), IIB (25.7%/14.9%), and III/IV (25.7%/24.3%). Prognostic factors for overall survival included lymph node involvement (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.09 to 1.85; p<0.01), patient age >60 years (HR, 1.70; 95% CI, 1.21 to 2.41; p<0.01), and advanced FIGO primary tumor stage (p<0.01). Tumor grade, histologic subtype, and patient race did not predict for either lymph node metastasis or overall survival. Conclusion There is a high incidence of both pelvic and para-aortic lymph node metastases for FIGO stages IC and above uterine papillary serous and clear cell carcinomas, suggesting a potential role for lymph node-directed therapy for these patients. PMID:25310855

  11. Pharmacological interventions for borderline personality disorder

    PubMed Central

    Stoffers, Jutta; Völlm, Birgit A; Rücker, Gerta; Timmer, Antje; Huband, Nick; Lieb, Klaus

    2014-01-01

    Background Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders (“off-label use”), mostly targeting affective or impulsive symptom clusters. Objectives To assess the effects of drug treatment in BPD patients. Search methods We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field. Selection criteria Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects. Data collection and analysis Two authors selected trials, assessed quality and extracted data, independently. Main results Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants. The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed. Adverse event data were scarce

  12. A Weeping Tumor in a Young Girl: An Unusual Presentation of Nodular Hidradenoma.

    PubMed

    Das, Anupam; Gayen, Tirthankar; Podder, Indrashis; Shome, Kaushik; Bandyopadhyay, Debabrata

    2016-01-01

    A 10-year-old girl presented with a swelling on her left thigh that was associated with dripping of serous fluid from the lesion. Based on histological features of the excised tumor, a diagnosis of nodular hidradenoma was made. Atypical features including large size of the tumor, location on the lower limb, a weeping presentation, and histological finding of a nodular hidradenoma with an unusually large cystic cavity discharging fluid prompted us to report the case. PMID:27293255

  13. A Weeping Tumor in a Young Girl: An Unusual Presentation of Nodular Hidradenoma

    PubMed Central

    Das, Anupam; Gayen, Tirthankar; Podder, Indrashis; Shome, Kaushik; Bandyopadhyay, Debabrata

    2016-01-01

    A 10-year-old girl presented with a swelling on her left thigh that was associated with dripping of serous fluid from the lesion. Based on histological features of the excised tumor, a diagnosis of nodular hidradenoma was made. Atypical features including large size of the tumor, location on the lower limb, a weeping presentation, and histological finding of a nodular hidradenoma with an unusually large cystic cavity discharging fluid prompted us to report the case. PMID:27293255

  14. Central serous chorioretinopathy after ocular trauma in the fellow eye during a water-polo game.

    PubMed

    Moschos, Marilita M; Gouliopoulos, Nikolaos Stefanos

    2015-01-01

    A 35-year-old water polo player was struck in his right eye during a water polo game. At presentation to our hospital, his visual acuity, intraocular pressure, fundus examination and neurological examination were normal. He received the appropriate treatment (no corticosteroids were applied), but 1 week later he reported blurred vision in his left eye. Visual acuity in the left eye was 6/10 Snellen chart, fluorescein angiography showed a focal retinal pigment epithelium leakage, while optical coherence tomography through the macula revealed mild neurosensory retinal detachment with an increase in retinal thickness. Two weeks later, the situation improved, and 1 month later no signs or symptoms of central serous chorioretinopathy were present. Currently, 9 months later, the situation remains unchanged. Post-traumatic stress was recognised as the key factor for development of central serous chorioretinopathy in our patient, since it was followed by excessive release of catecholamines and increased endogenous cortisol levels. PMID:26392445

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

    PubMed Central

    Gawęcki, Maciej

    2015-01-01

    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. PMID:26180649

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

    PubMed Central

    2013-01-01

    Purpose The capacity of nadir CA-125 levels to predict the prognosis of epithelial ovarian cancer remains controversial. This study aimed to explore whether the nadir CA-125 serum levels could predict the durations of overall survival (OS) and progression free survival (PFS) in patients with high-grade serous ovarian cancer (HG-SOC) from the USA and PRC. Materials and methods A total of 616 HG-SOC patients from the MD Anderson Cancer Center (MDACC, USA) between 1990 and 2011 were retrospectively analyzed. The results of 262 cases from the Jiangsu Institute of Cancer Research (JICR, PRC) between 1992 and 2011 were used to validate the MDACC data. The CA-125 immunohistochemistry assay was performed on 280 tissue specimens. The Cox proportional hazards model and the log-rank test were used to assess the associations between the clinicopathological characteristics and duration of survival. Results The nadir CA-125 level was an independent predictor of OS and PFS (p < 0.01 for both) in the MDACC patients. Lower nadir CA-125 levels (≤10 U/mL) were associated with longer OS and PFS (median: 61.2 and 16.8 months with 95% CI: 52.0–72.4 and 14.0–19.6 months, respectively) than their counterparts with shorter OS and PFS (median: 49.2 and 10.5 months with 95% CI: 41.7–56.7 and 6.9–14.1 months, respectively). The nadir CA-125 levels in JICR patients were similarly independent when predicting the OS and PFS (p < 0.01 for both). Nadir CA-125 levels less than or equal to 10 U/mL were associated with longer OS and PFS (median: 59.9 and 15.5 months with 95% CI: 49.7–70.1 and 10.6–20.4 months, respectively), as compared with those more than 10 U/mL (median: 42.0 and 9.0 months with 95% CI: 34.4–49.7 and 6.6–11.2 months, respectively). Baseline serum CA-125 levels, but not the CA-125 expression in tissues, were associated with the OS and PFS of HG-SOC patients in the MDACC and JICR groups. However, these values were not independent. Nadir CA-125

  17. How to approach phyllodes tumors of the breast?

    PubMed Central

    Acar, Turan; Tarcan, Ercüment; Hacıyanlı, Mehmet; Kamer, Erdinç; Peşkersoy, Mustafa; Yiğit, Seyran; Gür, Özlem; Cin, Necat; Sarı, Ayşegül Akder; Tatar, Fatma

    2015-01-01

    Objective: Phyllodes tumor of the breast is a rare fibroepithelial breast tumor that comprise 0.3–0.9% of primary breast neoplasms. In this study, we aimed to present clinicopathologic symptoms of our patients along with their treatment modality. Material and Methods: Clinicopathologic properties and treatment modality of 20 phyllodes tumor patients who underwent surgery between January 2008 and January 2013 were retrospectively evaluated. Results: Median patient age was 47 years (22–75). Fine-needle aspiration biopsy was applied to 19 patients. Biopsy results were reported as suspicious in four, malignant in three, benign in 11, and as non-diagnostic in one patient. Final histopathology reports revealed two benign, one malignant and one borderline tumor out of the four patients with suspicious findings on fine needle aspiration biopsy; all patients with malignant cytology had malignancy. There were two borderline and nine benign lesions within the benign biopsy group. Sixteen patients underwent segmental mastectomy, four patients underwent mastectomy with/without axillary dissection. The median tumor size was 6 (1–13) cm. Histopathologically, 11 (55%) tumors were benign, 5 (25%) were borderline, and 4 (20%) were malignant. Two of the four patients with malignancy underwent radiotherapy and chemotherapy, and one patient only received chemotherapy as adjuvant treatment. Conclusion: Phyllodes tumors are rare, mix-type breast tumors. Due to high rates of local recurrence and potential for malignancy, preoperative diagnosis and accurate management are important. PMID:26668526

  18. Mixed and Ambiguous Endometrial Carcinomas: A Heterogenous Group of Tumors With Different Clinicopathologic and Molecular Genetic Features.

    PubMed

    Espinosa, Iñigo; D'Angelo, Emanuela; Palacios, José; Prat, Jaime

    2016-07-01

    Besides endometrioid, serous, and clear cell carcinomas, there are endometrial carcinomas exhibiting mixed and ambiguous morphologic features. We have analyzed the immunophenotype (p53, p16, β-catenin, ER, HNF-1B, MLH1, and Ki-67) and mutational status (PTEN, KRAS, PIK3CA, and POLE) of 7 mixed carcinomas and 13 ambiguous carcinomas, all of them classified initially as mixed carcinomas. Only 2 of the 7 (28%) mixed carcinomas showed different immunophenotypes in different components. All but 2 tumors (5/7, 71%) overexpressed p53 and p16 and were negative for ER. Both carcinomas (2/7, 28%) showed a prominent micropapillary component that resembled an ovarian low-grade serous carcinoma and merged with villoglandular endometrioid carcinoma. The ambiguous carcinomas exhibited glandular architecture, high nuclear grade, and overlapping features of endometrioid and serous carcinomas. All tumors overexpressed p53 and p16, and the majority of cases (12/13, 92%) were negative for ER. KRAS mutations were identified in 3 of 7 (42%) mixed carcinomas, including the 2 cases with a "low-grade" serous-like component. PIK3CA mutations occurred in 2 (2/13, 15%) ambiguous carcinomas and PTEN mutations in 1 (1/7, 14%) mixed and 1 (1/13, 8%) ambiguous carcinoma. POLE exonuclease domain mutations were encountered in a case of mixed undifferentiated and well-differentiated (dedifferentiated) carcinoma. Two of the 7 (29%) mixed endometrial carcinomas and 5 of the 13 (38%) ambiguous carcinomas had extended beyond the pelvis (stages III and IV). Two of the 7 (29%) patients with mixed endometrial carcinoma and 6 of 12 (50%) patients with ambiguous endometrial carcinoma were alive with disease or had died of tumor. Our results show that, biologically, many so-called mixed carcinomas represent serous carcinomas with ambiguous morphology. Our series include 2 true mixed endometrial carcinomas with a "low-grade serous"-like component, microcystic, elongated, or fragmented features, KRAS mutations

  19. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer.

    PubMed

    Bowtell, David D; Böhm, Steffen; Ahmed, Ahmed A; Aspuria, Paul-Joseph; Bast, Robert C; Beral, Valerie; Berek, Jonathan S; Birrer, Michael J; Blagden, Sarah; Bookman, Michael A; Brenton, James D; Chiappinelli, Katherine B; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G; Iwanicki, Marcin; Karlan, Beth Y; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A; Lu, Karen H; McNeish, Iain A; Menon, Usha; Narod, Steven A; Nelson, Brad H; Nephew, Kenneth P; Pharoah, Paul; Powell, Daniel J; Ramos, Pilar; Romero, Iris L; Scott, Clare L; Sood, Anil K; Stronach, Euan A; Balkwill, Frances R

    2015-11-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

  20. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

    PubMed Central

    Bowtell, David D.; Böhm, Steffen; Ahmed, Ahmed A.; Aspuria, Paul-Joseph; Bast, Robert C.; Beral, Valerie; Berek, Jonathan S.; Birrer, Michael J.; Blagden, Sarah; Bookman, Michael A.; Brenton, James; Chiappinelli, Katherine B.; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G.; Iwanicki, Marcin; Karlan, Beth Y.; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A.; Lu, Karen H.; McNeish, Iain A.; Menon, Usha; Narod, Steve A.; Nelson, Brad H.; Nephew, Kenneth P.; Pharoah, Paul; Powell, Daniel J.; Ramos, Pilar; Romero, Iris L.; Scott, Clare L.; Sood, Anil K.; Stronach, Euan A.; Balkwill, Frances R.

    2016-01-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This ‘roadmap’ for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

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

    PubMed Central

    Fabry, Annelies; Blanckaert, Johan; Leys, Anita

    2011-01-01

    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.

  2. Nystagmus in patients with unilateral acute otitis media complicated by serous labyrinthitis.

    PubMed

    Kim, Chang-Hee; Yang, Young Soo; Im, Donghyuk; Shin, Jung Eun

    2016-06-01

    Conclusion The patients with serous labyrinthitis caused by acute otitis media (AOM) exhibited various patterns of nystagmus in which direction-fixed irritative-type nystagmus was the most common pattern. Differential effects on inner ear function by toxic or inflammatory mediators may be responsible for the various manifestation of nystagmus. Objective This study aimed to investigate nystagmus patterns in patients with serous labyrinthitis, and discuss possible mechanisms. Methods From October 2011 to March 2014, 13 consecutive patients with serous labyrinthitis were included. Eye movements of the patients were serially examined using video-nystagmography, and patterns of nystagmus were investigated. Results The most commonly observed pattern was direction-fixed nystagmus (nine of 13 patients). Of these, eight showed irritative-type, and one showed paretic-type. Direction of nystagmus, although the intensity gradually decreased, was not changed during the course of treatment. One patient showed direction-changing spontaneous nystagmus, which changed into paretic-type direction-fixed nystagmus 1 day after myringotomy. Three patients exhibited persistent direction-changing positional nystagmus in a supine head-roll test. Of them, two showed apogeotropic and one showed geotropic type. In all 13 patients, vertigo and hearing loss were improved after the treatment. PMID:26797398

  3. Use of antisera to epithelial membrane antigen for the cytodiagnosis of malignancy in serous effusions.

    PubMed Central

    To, A; Coleman, D V; Dearnaley, D P; Ormerod, M G; Steele, K; Neville, A M

    1981-01-01

    A new human antigen, designated epithelial membrane antigen (EMA), has recently been described on surface membranes of a wide variety of normal epithelium but not on connective tissue cells. The antigen is only weakly expressed on normal or reactive mesothelium. Increased expression of the antigen has been observed in most neoplasms of epithelial origin and in malignant mesothelioma. We have investigated the possibility of using this difference in the expression of the antigen to distinguish between mesothelial cells and malignant cells in cytological smears of serous effusions. This distinction cannot always be made on morphological grounds alone and problems of differential diagnosis are encountered in about 15% of all specimens of serous effusions sent for cytological examination. Using antisera to EMA we have applied an indirect immunoalkaline phosphatase technique to alcohol-fixed smears prepared from serous effusions and have found that intense staining of the antigen is confined to effusions from patients in whom there is either clinical or cytological evidence of malignancy. The technique proved to be especially useful in cytologically equivocal cases, where there were problems of differential diagnosis. Images PMID:7035498

  4. An automated framework for 3D serous pigment epithelium detachment segmentation in SD-OCT images

    PubMed Central

    Sun, Zhuli; Chen, Haoyu; Shi, Fei; Wang, Lirong; Zhu, Weifang; Xiang, Dehui; Yan, Chenglin; Li, Liang; Chen, Xinjian

    2016-01-01

    Pigment epithelium detachment (PED) is an important clinical manifestation of multiple chorioretinal diseases, which can cause loss of central vision. In this paper, an automated framework is proposed to segment serous PED in SD-OCT images. The proposed framework consists of four main steps: first, a multi-scale graph search method is applied to segment abnormal retinal layers; second, an effective AdaBoost method is applied to refine the initial segmented regions based on 62 extracted features; third, a shape-constrained graph cut method is applied to segment serous PED, in which the foreground and background seeds are obtained automatically; finally, an adaptive structure elements based morphology method is applied to remove false positive segmented regions. The proposed framework was tested on 25 SD-OCT volumes from 25 patients diagnosed with serous PED. The average true positive volume fraction (TPVF), false positive volume fraction (FPVF), dice similarity coefficient (DSC) and positive predictive value (PPV) are 90.08%, 0.22%, 91.20% and 92.62%, respectively. The proposed framework can provide clinicians with accurate quantitative information, including shape, size and position of the PED region, which can assist clinical diagnosis and treatment. PMID:26899236

  5. Automated segmentation of serous pigment epithelium detachment in SD-OCT images

    NASA Astrophysics Data System (ADS)

    Sun, Zhuli; Shi, Fei; Xiang, Dehui; Chen, Haoyu; Chen, Xinjian

    2015-03-01

    Pigment epithelium detachment (PED) is an important clinical manifestation of multiple chorio-retinal disease processes, which can cause the loss of central vision. A 3-D method is proposed to automatically segment serous PED in SD-OCT images. The proposed method consists of five steps: first, a curvature anisotropic diffusion filter is applied to remove speckle noise. Second, the graph search method is applied for abnormal retinal layer segmentation associated with retinal pigment epithelium (RPE) deformation. During this process, Bruch's membrane, which doesn't show in the SD-OCT images, is estimated with the convex hull algorithm. Third, the foreground and background seeds are automatically obtained from retinal layer segmentation result. Fourth, the serous PED is segmented based on the graph cut method. Finally, a post-processing step is applied to remove false positive regions based on mathematical morphology. The proposed method was tested on 20 SD-OCT volumes from 20 patients diagnosed with serous PED. The average true positive volume fraction (TPVF), false positive volume fraction (FPVF), dice similarity coefficient (DSC) and positive predictive value (PPV) are 97.19%, 0.03%, 96.34% and 95.59%, respectively. Linear regression analysis shows a strong correlation (r = 0.975) comparing the segmented PED volumes with the ground truth labeled by an ophthalmology expert. The proposed method can provide clinicians with accurate quantitative information, including shape, size and position of the PED regions, which can assist diagnose and treatment.

  6. 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

    PubMed Central

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

    2015-01-01

    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. PMID:25995637

  7. Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201).

    PubMed

    El-Sahwi, Karim; Bellone, Stefania; Cocco, Emiliano; Casagrande, Francesca; Bellone, Marta; Abu-Khalaf, Maysa; Buza, Natalia; Tavassoli, Fattaneh A; Hui, Pei; Rüttinger, Dominik; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Pecorelli, Sergio; Santin, Alessandro D

    2010-01-01

    We evaluated the expression of epithelial cell adhesion molecule (EpCAM) and the potential of MT201 (adecatumumab), a human monoclonal antibody against EpCAM, in uterine serous papillary carcinoma (USPC). EpCAM expression was evaluated by real-time PCR and immunohistochemistry in a total of 56 USPC fresh-frozen biopsies and paraffin-embedded tissues. EpCAM surface expression was also evaluated by flow cytometry and immunohistochemistry in six USPC cell lines. Sensitivity to MT201 antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity was tested against a panel of primary USPC cell lines expressing different levels of EpCAM in standard 5-h (51)Cr release assays. EpCAM transcript was significantly overexpressed in fresh-frozen USPC when compared with normal endometrial cells (NEC). Median (minimum-maximum) copy number was 943.8 (31.5-1568.3) in tumor samples versus 12.9 (1.0-37.0) in NEC (P < 0.001). By immunohistochemistry, EpCAM expression was found in 96% (26 out of 27) of USPC samples with significantly higher expression compared with NECs (P < 0.001). High surface expression of EpCAM was found in 83% (five out of six) of the USPC cell lines tested by flow cytometry. EpCAM-positive cell lines were found highly sensitive to MT201-mediated antibody-dependent cellular cytotoxicity in vitro, whereas primary USPC cell lines were resistant to natural killer cell-dependent cytotoxicity. Human plasma IgG did not significantly inhibit MT201-mediated cytotoxicity against USPC. EpCAM is highly expressed in uterine serous carcinoma at mRNA and protein levels, and primary USPC are highly sensitivity to MT201-mediated cytotoxicity. MT201 might represent a novel therapeutic strategy in patients harboring advanced/recurrent or metastatic USPC refractory to standard treatment modalities. PMID:20053761

  8. Overexpression of EpCAM in Uterine Serous Papillary Carcinoma: Implications for EpCAM-specific Immunotherapy with Human Monoclonal Antibody Adecatumumab (MT201)

    PubMed Central

    El-Sahwi, Karim; Bellone, Stefania; Cocco, Emiliano; Casagrande, Francesca; Bellone, Marta; Abu-Khalaf, Maysa; Buza, Natalia; Tavassoli, Fattaneh A.; Hui, Pei; Rüttinger, Dominik; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Rutherford, Thomas J.; Pecorelli, Sergio; Santin, Alessandro D.

    2009-01-01

    We evaluated the expression of epithelial-cell-adhesion-molecule (EpCAM) and the potential of MT201 (adecatumumab), a human monoclonal antibody against EpCAM, in uterine serous papillary carcinoma (USPC). EpCAM expression was evaluated by real-time-PCR and immunohistochemistry (IHC) in a total of 56 USPC fresh-frozen biopsies and paraffin-embedded-tissues. EpCAM surface expression was also evaluated by flow cytometry and IHC in 6 USPC cell lines. Sensitivity to MT201 antibody-dependent-cellular-cytotoxicity (ADCC) and complement-dependent-cytotoxicity (CDC) was tested against a panel of primary USPC cell lines expressing different levels of EpCAM in standard 5-h 51Cr release-assays. EpCAM transcript was significantly overexpressed in fresh-frozen USPC when compared to normal-endometrial-cells (NEC). Median (minimum–maximum) copy number was 943.8 (31.5–1568.3) in tumor samples versus 12.9 (1.0–37.0) in NEC (P < 0.001). By immunohistochemistry, EpCAM expression was found in 96% (26 out of 27) of USPC samples with significantly higher expression compared to normal endometrial cells (P < 0.001). High surface expression of EpCAM was found in 83% (5 out of 6) of the USPC cell lines tested by flow cytometry. EpCAM-positive cell lines were found highly sensitive to MT201-mediated ADCC in vitro, while primary USPC cell lines were resistant to natural killer (NK) cell-dependent cytotoxicity. Human plasma IgG did not significantly inhibit MT201-mediated-cytotoxicity against USPC. EpCAM is highly expressed in uterine serous carcinoma at mRNA and protein levels and primary USPC are highly sensitivity to MT201-mediated cytotoxicity. MT201 might represent a novel therapeutic strategy in patients harboring advanced/recurrent or metastatic USPC refractory to standard treatment modalities. PMID:20053761

  9. Decreased expression of 14-3-3σ is predictive of poor prognosis for patients with human uterine papillary serous carcinoma.

    PubMed

    Suzuki, Fumihiko; Nagase, Satoru; Suzuki, Kichiya; Oba, Etsuko; Hiroki, Eri; Matsuda, Yukika; Akahira, Jun-Ichi; Nishigori, Hidekazu; Sugiyama, Takashi; Otsuki, Takeo; Yoshinaga, Kousuke; Takano, Tadao; Niikura, Hitoshi; Ito, Kiyoshi; Sasano, Hironobu; Yaegashi, Nobuo

    2013-01-01

    Uterine papillary serous carcinoma (UPSC) morphologically resembles ovarian serous carcinoma and is categorized as a type II endometrial cancer. UPSC comprises about 10% of all types of endometrial cancer and has an aggressive clinical course and a poor prognosis. The 14-3-3σ gene was originally discovered as a p53-inducible gene; its expression is induced by DNA damage in a p53-dependent manner, which leads to G2 arrest and repair of damaged DNA. Moreover, it has been reported that expression of 14-3-3σ is frequently lost in various types of human cancer, including ovarian cancer. We therefore examined the association between 14-3-3σ expression determined by immunohistochemistry and clinical outcomes of 51 patients with UPSC. UPSC was considered positive for 14-3-3σ when > 30% of tumor cells were stained with a specific antibody. Of these patients, 29 (58.7%) showed positive immunoreactivity for 14-3-3σ and 22 (41.3%) had decreased 14-3-3σ staining. Decreased immunoreactivity for 14-3-3σ was associated with stage (P = 0.001) and lymphovascular space involvement (P = 0.005). Moreover, decreased 14-3-3σ expression was an independent risk factor for reduced overall survival (P = 0.0416) in multivariate analysis. Direct bisulfite sequencing was performed to evaluate the methylation status of the 27 CpG islands in the promoter region and first exon of the 14-3-3σ gene. These CpG islands were hypermethylated in 30% of 14-3-3σ-positive UPSC and 80% of 14-3-3σ-negative UPSC, although the difference was not statistically significant. These findings suggest that decreased expression of immunoreactive 14-3-3σ may be a predictor of poor prognosis in patients with UPSC. PMID:24201220

  10. Assessment of Borderline Personality Features in Population Samples: Is the Personality Assessment Inventory-Borderline Features Scale Measurement Invariant across Sex and Age?

    ERIC Educational Resources Information Center

    De Moor, Marleen H. M.; Distel, Marijn A.; Trull, Timothy J.; Boomsma, Dorret I.

    2009-01-01

    Borderline personality disorder (BPD) is more often diagnosed in women than in men, and symptoms tend to decline with age. Using a large community sample, the authors investigated whether sex and age differences in four main features of BPD, measured with the "Personality Assessment Inventory-Borderline Features" scale (PAI-BOR; Morey, 1991), are…

  11. A Further Validation of the Minnesota Borderline Personality Disorder Scale

    PubMed Central

    Rojas, Elizabeth, E.; Cummings, Jenna, R.; Bornovalova, Marina A.; Hopwood, Christopher J.; Racine, Sarah E.; Keel, Pamela K.; Sisk, Cheryl, L.; Neale, Michael; Boker, Steven; Burt, Alexandra S.; Klump, Kelly L.

    2014-01-01

    Previous research indicates that Borderline Personality Disorder (BPD) is well conceptualized as a dimensional construct that can be represented using normal personality traits. A previous study successfully developed and validated a BPD measure embedded within a normal trait measure, the Minnesota Borderline Personality Disorder Scale (MBPD). The current study performed a further validation of the MBPD by examining its convergent validity, external correlates, and heritability in a sample of 429 female twins. The MBPD correlated strongly with the SCID-II screener for BPD and moderately with external correlates. Moreover, the MBPD and SCID-II screener exhibited very similar patterns of external correlations. Additionally, results indicated that the genetic and environmental influences on MBPD overlap with the genetic and environmental influences on the SCID-II screener, which suggests that these scales are measuring the same construct. This data provide further evidence for the construct validity of the MBPD. PMID:24364505

  12. A further validation of the Minnesota Borderline Personality Disorder Scale.

    PubMed

    Rojas, Elizabeth C; Cummings, Jenna R; Bornovalova, Marina A; Hopwood, Christopher J; Racine, Sarah E; Keel, Pamela K; Sisk, Cheryl L; Neale, Michael; Boker, Steven; Burt, S Alexandra; Klump, Kelly L

    2014-04-01

    Previous research indicates that borderline personality disorder (BPD) is well conceptualized as a dimensional construct that can be represented using normal personality traits. A previous study successfully developed and validated a BPD measure embedded within a normal trait measure, the Minnesota Borderline Personality Disorder Scale (MBPD). The current study performed a further validation of the MBPD by examining its convergent validity, external correlates, and heritability in a sample of 429 female twins. The MBPD correlated strongly with the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) screener for BPD and moderately with external correlates. Moreover, the MBPD and SCID-II screener exhibited very similar patterns of external correlations. Additionally, results indicated that the genetic and environmental influences on MBPD overlap with the genetic and environmental influences on the SCID-II screener, which suggests that these scales are measuring the same construct. These data provide further evidence for the construct validity of the MBPD. PMID:24364505

  13. Construct validity of the five factor borderline inventory.

    PubMed

    DeShong, Hilary L; Lengel, Gregory J; Sauer-Zavala, Shannon E; O'Meara, Madison; Mullins-Sweatt, Stephanie N

    2015-06-01

    The Five Factor Borderline Inventory (FFBI) is a new self-report measure developed to assess traits of borderline personality disorder (BPD) from the perspective of the Five Factor Model of general personality. The current study sought to first replicate initial validity findings for the FFBI and then to further validate the FFBI with predispositional risk factors of the biosocial theory of BPD and with commonly associated features of BPD (e.g., depression, low self-esteem) utilizing two samples of young adults (N = 87; 85) who have engaged in nonsuicidal self-injury. The FFBI showed strong convergent and discriminant validity across two measures of the Five Factor Model and also correlated strongly with measures of impulsivity, emotion dysregulation, and BPD. The FFBI also related to two measures of early childhood emotional vulnerability and parental invalidation and measures of depression, anxiety, and self-esteem. Overall, the results provide support for the FFBI as a measure of BPD. PMID:25155158

  14. Promoting Good Psychiatric Management for Patients With Borderline Personality Disorder.

    PubMed

    Links, Paul S; Ross, James; Gunderson, John G

    2015-08-01

    General psychiatric management for patients with borderline personality disorder was devised to be an outpatient intervention that could be readily learned and easily delivered by independent community mental health professionals. To disseminate the approach, Drs. Gunderson and Links developed the Handbook of Good Psychiatric Management for Borderline Personality Disorder (Gunderson & Links, ) that presented the basics of the approach, videos to illustrate the appropriate clinical skills, and case examples to practice adherence to the approach. Unfortunately, the inclusion of "psychiatric" in the treatment's name may discourage psychologists and other mental health professionals from using this therapy. In this article, we review the basic principles and approaches related to general psychiatric management. With a case example, we illustrate how psychologists can use all the general psychiatric management principles for their patients with BPD, except medications and, as a result, provide and deliver this approach effectively. PMID:26197971

  15. Interobserver Variability by Pathologists in the Distinction Between Cellular Fibroadenomas and Phyllodes Tumors

    PubMed Central

    Lawton, Thomas J.; Acs, Geza; Argani, Pedram; Farshid, Gelareh; Gilcrease, Michael; Goldstein, Neal; Koerner, Frederick; Rowe, J. Jordi; Sanders, Melinda; Shah, Sejal S.; Reynolds, Carol

    2015-01-01

    Fibroepithelial lesions with cellular stroma are frequently termed cellular fibroadenomas although criteria for distinguishing them from a phyllodes tumor are vague and subjective. However, the clinical implications and surgical management for these 2 lesions may be different. We randomly selected 21 cases of fibroepithelial lesions sent in consultation to the senior author that were challenging to classify as cellular fibroadenoma or phyllodes tumor. One to 2 representative slides of each case along with patient age were sent to 10 pathologists who specialize in breast pathology. The World Health Organization criteria for phyllodes tumors and a diagnosis form were included with the study set. For the purposes of data reporting, fibroadenoma and cellular fibroadenoma are considered together. In only 2 cases was there uniform agreement as to whether the tumor represented a fibroadenoma or phyllodes tumor. Of the remaining 19 cases, if the diagnoses of fibroadenoma and benign phyllodes tumor were combined and separated from borderline and malignant phyllodes tumors, there was 100% agreement in 53% of cases and 90% agreement in 79% of cases. This study highlights the difficulty that exists in distinguishing some cellular fibroadenomas from phyllodes tumors even for pathologists who specialize in breast pathology. However, there appears to be considerable agreement when cellular fibroadenomas and benign phyllodes tumors are distinguished from borderline and malignant phyllodes tumors. Further studies are needed to determine if there is a clinically significant difference between cellular fibroadenomas and benign phyllodes tumors and how to better distinguish them from borderline and malignant phyllodes tumors. PMID:25161205

  16. [Repetitive thermal self-manipulation in borderline personality disorder].

    PubMed

    von Wild, T; Namdar, T; Stollwerck, P L; Mailänder, P; Siemers, F

    2011-10-01

    Self-mutilations are one of the major characteristics of patients with borderline personality disorder (BPD). Thermal injuries of BPD should be treated by a plastic surgeon who is faced to a challenge in the plastic-reconstructive strategy because of the most complex psychiatric disease. This means the need of a multidisciplinary strategy. Based on 3 case reports such conflict between best plastic reconstructive treatment of the burns wound and the psychiatric limit with the appropriate therapy options are presented. PMID:21863546

  17. Co-occurrence of dissociative identity disorder and borderline personality disorder.

    PubMed

    Ross, Colin A; Ferrell, Lynn; Schroeder, Elizabeth

    2014-01-01

    The literature indicates that, among individuals with borderline personality disorder, pathological dissociation correlates with a wide range of impairments and difficulties in psychological function. It also predicts a poorer response to dialectical behavior therapy for borderline personality disorder. We hypothesized that (a) dissociative identity disorder commonly co-occurs with borderline personality disorder and vice versa, and (b) individuals who meet criteria for both disorders have more comorbidity and trauma than individuals who meet criteria for only 1 disorder. We interviewed a sample of inpatients in a hospital trauma program using 3 measures of dissociation. The most symptomatic group was those participants who met criteria for both borderline personality disorder and dissociative identity disorder on the Dissociative Disorders Interview Schedule, followed by those who met criteria for dissociative identity disorder only, then those with borderline personality disorder only, and finally those with neither disorder. Greater attention should be paid to the relationship between borderline personality disorder and dissociative identity disorder. PMID:24377974

  18. Changes in expression of differentiation markers between normal ovarian cells and derived tumors.

    PubMed Central

    Van Niekerk, C. C.; Ramaekers, F. C.; Hanselaar, A. G.; Aldeweireldt, J.; Poels, L. G.

    1993-01-01

    The marker profile of 18 samples of normal human ovarian tissues and 138 samples of their derived tumors was established using 51 monoclonal antibodies directed against intermediate filaments, ovarian carcinoma-specific antigens, general tumor-associated antigens and MHC-I/II antigens. Our data show that vimentin and keratins 7, 8, 18, and 19 were found in both epithelial and some nonepithelial ovarian tumors. Several tumor samples contained additional keratins 4, 10, 13, and 14, as well as desmin. BW 495/36 and to a lesser extent HMFG-2 were usually found in all ovarian tumors that contained simple epithelial keratins, except the absence of HMFG-2 in gonadal tumors as well as in dysgerminomas. In contrast to the keratin antibodies, these two panepithelial antibodies were negative in normal mesothelial cells and granulosa cells of the ovarian follicles. In general, the marker TAG-72 appeared useful for its discrimination between positively stained mucinous adenomas, the ovarian carcinomas as well as germ cell tumors, and the negatively stained gonadal tumors, serous adenomas, and cystomas. OV632 appeared useful in the distinction between negatively stained serous adenomas and positively stained serous carcinomas. In contrast, the monoclonal antibodies OC 125, OV-TL 3, OV-TL 16, and MOv 18 can be considered as pan-ovarian carcinoma markers, however without the discriminative capability as seen for OV632. These ovarian carcinoma-associated antigens were hardly found expressed in gonadal and germ cell tumors, except in the group of endodermal sinus tumors. HLA-I was found to be expressed in almost all nucleated cells, although loss of HLA-I expression was seen in areas of tumor cells. HLA-DR was negative in normal ovarian tissue, but heterogeneous expression was noticed in most of the epithelial tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7678716

  19. Preoperative Neutrophil-to-Lymphocyte Ratio as a Predictive and Prognostic Factor for High-Grade Serous Ovarian Cancer

    PubMed Central

    Bi, Rui; Ju, Xingzhu; Chen, Xiaojun; Yang, Wentao; Wu, Xiaohua

    2016-01-01

    Objective We aimed to demonstrate the clinical and prognostic significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) in high-grade serous ovarian cancer (HGSC). Methods We retrospectively investigated 875 patients who underwent primary staging or debulking surgery for HGSC between April 2005 and June 2013 at our institution. None of these patients received neoadjuvant chemotherapy. NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which were expressed as hazard ratios (HRs). Results The NLRs ranged from 0.30 to 24.0. The median value was 3.24 and used as the cutoff value to discriminate between the high-NLR (≥3.24) and low-NLR (<3.24) groups. A high preoperative NLR level was associated with an advanced FIGO stage, increased CA125 level, more extensive ascites, worse cytoreduction outcome and chemoresistance. For univariate analyses, a high NLR was associated with reduced PFS (p<0.001) and OS (p<0.001). In multivariate analyses, a high NLR was still an independent predictor of PFS (p = 0.011), but not OS (p = 0.148). Conclusion Our study demonstrated that NLR could reflect tumor burden and clinical outcomes to a certain extent and should be regarded as a predictive and prognostic parameter for HGSC. PMID:27203425

  20. Psychophysiological ambulatory assessment of affective dysregulation in borderline personality disorder.

    PubMed

    Ebner-Priemer, Ulrich W; Welch, Stacy S; Grossman, Paul; Reisch, Thomas; Linehan, Marsha M; Bohus, Martin

    2007-04-15

    Many experts now believe that pervasive problems in affect regulation constitute the central area of dysfunction in borderline personality disorder (BPD). However, data is sparse and inconclusive. We hypothesized that patients with BPD, in contrast to healthy gender and nationality-matched controls, show a higher frequency and intensity of self-reported emotions, altered physiological indices of emotions, more complex emotions and greater problems in identifying specific emotions. We took a 24-hour psychophysiological ambulatory monitoring approach to investigate affect regulation during everyday life in 50 patients with BPD and in 50 healthy controls. To provide a typical and unmanipulated sample, we included only patients who were currently in treatment and did not alter their medication schedule. BPD patients reported more negative emotions, fewer positive emotions, and a greater intensity of negative emotions. A subgroup of non-medicated BPD patients manifested higher values of additional heart rate. Additional heart rate is that part of a heart rate increase that does not directly result from metabolic activity, and is used as an indicator of emotional reactivity. Borderline participants were more likely to report the concurrent presence of more than one emotion, and those patients who just started treatment in particular had greater problems in identifying specific emotions. Our findings during naturalistic ambulatory assessment support emotional dysregulation in BPD as defined by the biosocial theory of [Linehan, M.M., 1993. Cognitive-Behavioral Treatment of Borderline Personality Disorder. The Guildford Press, New York.] and suggest the potential utility for evaluating treatment outcome. PMID:17321599

  1. [Stalemates and opportunities in the treatment of borderline personality disorder].

    PubMed

    Bouchard, Sébastien

    2010-01-01

    Borderline personality disorder is a serious mental health problem for which one of its main characteristics is significant difficulties in relationships with others. These relational problems have the unfortunate consequence of fostering negative attitudes among mental health professionals and contributing to the stigmatization of people suffering from this disorder. In this article, the author emphasizes the importance of taking into account the parameter of the therapeutic frame within which the feeling of facing a stalemate in the treatment of borderline personality disorder patients occurs. Six general strategies are presented that enable the therapist to limit or hinder the risk of stalemate in treatment. This article then presents the commonalities between treatments teams that tend to feel comfortable and efficacious in their management of borderline personality disorder patients. Finally, a case history is used to illustrate how some stalemates can in fact be seen as opportunities for growth for both the patient and the therapist. In order to avoid the vicious circle of negative interactions with patients already hypersensitive to inconsistencies and rejection, the author concludes by insisting on the necessity that more mental health professional have access to training programs and workshops specifically addressing how to better manage and treat people with BPD. PMID:21761087

  2. Expression of c-myc and mutation of the KRAS gene in patients with ovarian mucinous tumors.

    PubMed

    Li, X S; Sun, J; He, X L

    2015-01-01

    We examined the expression of c-myc and mutations in the KRAS gene in ovarian mucinous tumors to explore the pathogenesis of these tumors and the feasibility of targeted gene therapy. Expression of c-myc protein and mutations in the KRAS gene in 24 cases of ovarian mucinous cystadenoma, 46 cases of ovarian borderline mucinous cystadenoma, and 46 cases of ovarian mucinous cystadenocarcinoma were detected using the immunohistochemistry PV-9000 2-step method and polymerase chain reaction-restriction fragment length polymorphism. The positive expression rates of c-myc in ovarian mucinous cystadenoma, borderline mucinous cystadenoma, and cystadenocarcinoma were 0, 39.1, and 65.2%, respectively (P < 0.01), while the mutation rates in KRAS were 0, 39.1 and 13.0%, respectively. The mutation rate of the borderline group was significantly higher, while rates in the other 2 groups were similar (P > 0.05). c-myc was not correlated with clinical stage, pathological grade, or age of patients with ovarian mucinous cystadenocarcinoma or borderline mucinous cystadenoma (P > 0.05), but was correlated with tumor size (P < 0.05). Mutations in KRAS were not correlated with clinical stage or tumor size in patients with borderline mucinous cystadenoma (P > 0.05), whereas it was correlated with age (P < 0.05). In borderline mucinous cystadenoma, c-myc expression and KRAS mutations were not correlated (P > 0.05). c-myc is involved in the formation of ovarian borderline mucinous cystadenoma and mucinous cystadenocarcinoma, and the KRAS gene may contribute to the formation of borderline mucinous cystadenoma. PMID:26400304

  3. Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer

    PubMed Central

    2013-01-01

    Background Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. In this series, we report the pathologic outcomes in the subset of patients who underwent surgery after neoadjuvant SBRT. Methods Patients with borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with SBRT followed by resection were included. Chemotherapy was to the discretion of the medical oncologist and preceded SBRT for most patients. Results Twelve patients met inclusion criteria. Most (92%) received neoadjuvant chemotherapy, and gemcitabine/capecitabine was most frequently utilized (n = 7). Most were treated with fractionated SBRT to 36 Gy/3 fractions (n = 7) and the remainder with single fraction to 24 Gy (n = 5). No grade 3+ acute toxicities attributable to SBRT were found. Two patients developed post-surgical vascular complications and one died secondary to this. The mean time to surgery after SBRT was 3.3 months. An R0 resection was performed in 92% of patients (n = 11/12). In 25% (n = 3/12) of patients, a complete pathologic response was achieved, and an additional 16.7% (n = 2/12) demonstrated <10% viable tumor cells. Kaplan-Meier estimated median progression free survival is 27.4 months. Overall survival is 92%, 64% and 51% at 1-, 2-, and 3-years. Conclusions This study reports the pathologic response in patients treated with neoadjuvant chemotherapy and SBRT for borderline resectable and locally-advanced pancreatic cancer. In our experience, 92% achieved an R0 resection and 41.7% of patients demonstrated either complete or extensive pathologic response to treatment. The results of a phase II study of this novel approach will be forthcoming. PMID:24175982

  4. Ablative therapies for renal tumors

    PubMed Central

    Ramanathan, Rajan; Leveillee, Raymond J.

    2010-01-01

    Owing to an increased use of diagnostic imaging for evaluating patients with other abdominal conditions, incidentally discovered kidney masses now account for a majority of renal tumors. Renal ablative therapy is assuming a more important role in patients with borderline renal impairment. Renal ablation uses heat or cold to bring about cell death. Radiofrequency ablation and cryoablation are two such procedures, and 5-year results are now emerging from both modalities. Renal biopsy at the time of ablation is extremely important in order to establish tissue diagnosis. Real-time temperature monitoring at the time of radiofrequency ablation is very useful to ensure adequacy of ablation. PMID:21789083

  5. Novel high-grade serous epithelial ovarian cancer cell lines that reflect the molecular diversity of both the sporadic and hereditary disease

    PubMed Central

    Carmona, Euridice; Portelance, Lise; Arcand, Suzanna L.; Rahimi, Kurosh; Tonin, Patricia N.; Provencher, Diane; Mes-Masson, Anne-Marie

    2015-01-01

    Few cell line models of epithelial ovarian cancer (EOC) have been developed for the high-grade serous (HGS) subtype, which is the most common and lethal form of gynaecological cancer. Here we describe the establishment of six new EOC cell lines spontaneously derived from HGS tumors (TOV2978G, TOV3041G and TOV3291G) or ascites (OV866(2), OV4453 and OV4485). Exome sequencing revealed somatic TP53 mutations in five of the cell lines. One cell line has a novel BRCA1 splice-site mutation, and another, a recurrent BRCA2 nonsense mutation, both of germline origin. The novel BRCA1 mutation induced abnormal splicing, mRNA instability, resulting in the absence of BRCA1 protein. None of the cell lines harbor mutations in KRAS or BRAF, which are characteristic of other EOC subtypes. SNP arrays showed that all of the cell lines exhibited structural chromosomal abnormalities, copy number alterations and regions of loss of heterozygosity, consistent with those described for HGS. Four cell lines were able to produce 3D-spheroids, two exhibited anchorage-independent growth, and three (including the BRCA1 and BRCA2 mutated cell lines) formed tumors in SCID mice. These novel HGS EOC cell lines and their detailed characterization provide new research tools for investigating the most common and lethal form of EOC. PMID:26622941

  6. Targeting the mitogen-activated protein kinase pathway in low-grade serous carcinoma of the ovary.

    PubMed

    McLachlan, Jennifer; Gore, Martin; Banerjee, Susana

    2016-08-01

    Until recently, there has been little change in the management of epithelial ovarian cancer with the majority of women receiving identical systemic therapy, regardless of histological subtype. The heterogeneity of epithelial ovarian cancer is now well established, with distinct subtypes characterized by specific molecular alterations and patterns of clinical behavior. Low-grade serous carcinoma is a rare subtype associated with an indolent biological behavior and inherent resistance to chemotherapy. The mitogen-activated protein kinase pathway plays a prominent role in the pathogenesis of low-grade serous carcinoma, and provides an attractive target for novel therapeutic agents. Selumetinib, a MEK1/2 inhibitor, demonstrates promising efficacy in women with relapsed low-grade serous carcinoma, and further trials of MEK-inhibition are underway. Translational research will be essential to identify predictive biomarkers for this treatment approach. PMID:27469379

  7. Topical difluprednate for treatment of serous retinal detachment and panuveitis associated with Vogt-Koyanagi-Harada disease

    PubMed Central

    Lu, Stacey; Taban, Mehran

    2016-01-01

    Summary Patients with bilateral serous retinal detachments and panuveitis related to Vogt-Koyanagi-Harada disease are commonly managed with oral corticosteroids, immunosuppressive agents, and/or intravitreal injections. We present the case of a 56-year-old Hispanic man with Harada disease whose bilateral serous retinal detachments and panuveitis were treated with topical corticosteroid difluprednate alone. Functional and anatomical recoveries were assessed by fluorescein angiograms and optical coherence tomography studies over a period of 9 months. The patient’s serous retinal detachments resolved, and his vision and panuveitis improved dramatically over a period of 2 weeks, after which he was placed on a drop taper and maintenance therapy for the remainder of the 9 months. PMID:27582676

  8. Topical difluprednate for treatment of serous retinal detachment and panuveitis associated with Vogt-Koyanagi-Harada disease.

    PubMed

    Lu, Stacey; Taban, Mehran

    2016-01-01

    Patients with bilateral serous retinal detachments and panuveitis related to Vogt-Koyanagi-Harada disease are commonly managed with oral corticosteroids, immunosuppressive agents, and/or intravitreal injections. We present the case of a 56-year-old Hispanic man with Harada disease whose bilateral serous retinal detachments and panuveitis were treated with topical corticosteroid difluprednate alone. Functional and anatomical recoveries were assessed by fluorescein angiograms and optical coherence tomography studies over a period of 9 months. The patient's serous retinal detachments resolved, and his vision and panuveitis improved dramatically over a period of 2 weeks, after which he was placed on a drop taper and maintenance therapy for the remainder of the 9 months. PMID:27582676

  9. Diagnostic Accuracy of Calretinin for Malignant Mesothelioma in Serous Effusions: a Meta-analysis

    PubMed Central

    Li, Diandian; Wang, Bo; Long, Hongyu; Wen, Fuqiang

    2015-01-01

    Numerous studies have investigated the utility of calretinin in differentiating malignant mesothelioma (MM) from metastatic carcinoma (MC) in serous effusions. However, the results remain controversial. The aim of this study is to determine the overall accuracy of calretinin in serous effusions for MM through a meta-analysis of published studies. Publications addressing the accuracy of calretinin in the diagnosis of MM were selected from the Medline (Ovid), PubMed, the Cochrane Library Database and the Web of Science. Data from selected studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Statistical analysis was performed by Meta-Disc 1.4 and STATA 12.0 softwares. 18 studies met the inclusion criteria and the summary estimating for calretinin in the diagnosis of MM were: sensitivity 0.91 (95%CI: 0.87–0.94), specificity 0.96 (95%CI: 0.95–0.96), positive likelihood ratio (PLR) 14.42 (95%CI: 7.92–26.26), negative likelihood ratio (NLR) 0.1 (95%CI: 0.05–0.2) and diagnostic odds ratio 163.03 (95%CI: 54.62–486.63). The SROC curve indicated that the maximum joint sensitivity and specificity (Q-value) was 0.92; the area under the curve was 0.97. Our findings suggest that calretinin may be a useful diagnostic tool for confirming MM in serous effusions. PMID:25821016

  10. Phyllodes tumor: diagnostic imaging and histopathology findings.

    PubMed

    Venter, Alina Cristiana; Roşca, Elena; Daina, Lucia Georgeta; Muţiu, Gabriela; Pirte, Adriana Nicoleta; Rahotă, Daniela

    2015-01-01

    Phyllodes tumors are rare breast tumors, accounting for less than 1% of all primary tumors of the breast. Histologically, phyllodes tumors can be divided into benign (60%), borderline (20%) and malignant (20%). The mammography examination was performed by means of a digital mammography system Giotto 3D Images; the ultrasound examination was performed through a GE Logiq P6 device and histological confirmation was possible after surgery or following the histological biopsy. We grouped the nine patients who presented clinically palpable nodules into two groups, namely: the six patients presenting histological benign results into Group I, and Group II where we included those with borderline and malignant histological results. Mammography performed in 77.7% revealed a well-circumscribed round or oval opacity or with contour lobules. Ultrasound examination was performed in all patients. Mammography and ultrasound have limitation in differentiating between benign lesion and phyllodes tumor. In the nine analyzed cases, mammographic and ultrasound examinations did not allow the differentiation into the three groups of phyllodes tumor. Histopathological examination is considered the golden standard for their diagnosis. Correlations between mammographic and microscopic aspects were inconclusive for determining the degree of differentiation, ultrasound changes could be correlated with the histopathological aspects. PMID:26743286

  11. Late Isolated Central Nervous System Relapse from Ovarian Serous Adenocarcinoma: A Case Report and Literature Review

    PubMed Central

    de Castria, Tiago Biachi; Rodrigues, Sylvia Regina Quintanilha; Diz, Maria del Pilar Estevez

    2014-01-01

    Central nervous system involvement by ovarian serous adenocarcinoma is rare. We report a case of a 60-year-old woman that developed brain metastasis as isolated site of relapse 4.5 years after a complete resection and adjuvant chemotherapy for a stage Ic disease. She proceeded to a craniotomy with resection of the lesion and, subsequently, to a whole brain radiotherapy. Nineteen months later, she developed carcinomatous meningitis as isolated site of recurrence. Patient was submitted to intrathecal chemotherapy with methotrexate; however, she died from progressive neurologic involvement disease few weeks later. PMID:25506007

  12. Annexin A2 and S100A10 are independent predictors of serous ovarian cancer outcome.

    PubMed

    Lokman, Noor A; Pyragius, Carmen E; Ruszkiewicz, Andrew; Oehler, Martin K; Ricciardelli, Carmela

    2016-05-01

    Annexin A2, a calcium phospholipid binding protein, has been shown to play an important role in ovarian cancer metastasis. This study examined whether annexin A2 and S100A10 can be used as prognostic markers in serous ovarian cancer. ANXA2 and S100A10 gene expressions were assessed in publicly available ovarian cancer data sets and annexin A2 and S100A10 protein expressions were assessed by immunohistochemistry in a uniform cohort of stage III serous ovarian cancers (n = 109). Kaplan-Meier and Cox regression analyses were performed to assess the relationship between annexin A2 or S100A10 messenger RNA (mRNA) and protein expressions with clinical outcome. High ANXA2 mRNA levels in stage III serous ovarian cancers were associated with reduced progression-free survival (PFS; P = 0.023) and overall survival (OS; P = 0.0038), whereas high S100A10 mRNA levels predicted reduced OS (P = 0.0019). Using The Cancer Genome Atlas data sets, ANXA2 but not S100A10 expression was associated with higher clinical stage (P = 0.005), whereas both ANXA2 and S100A10 expressions were associated with the mesenchymal molecular subtype (P < 0.0001). Kaplan-Meier and Cox regression analyses showed that high stromal annexin A2 immunostaining was significantly associated with reduced PFS (P = 0.013) and OS (P = 0.044). Moreover, high cytoplasmic S100A10 staining was significantly associated with reduced OS (P = 0.027). Multivariate Cox regression analysis showed stromal annexin A2 (P = 0.009) and cytoplasmic S100A10 (P = 0.016) levels to be independent predictors of OS. Patients with high stromal annexin A2 and high cytoplasmic S100A10 expressions had a 3.4-fold increased risk of progression (P = 0.02) and 7.9-fold risk of ovarian cancer death (P = 0.04). Our findings indicate that together annexin A2 and S100A10 expressions are powerful predictors of serous ovarian cancer outcome. PMID:26925708

  13. Identification of predictive factors of response to the BH3-mimetic molecule ABT-737: an ex vivo experiment in human serous ovarian carcinoma.

    PubMed

    Lheureux, Stéphanie; N'Diaye, Monique; Blanc-Fournier, Cécile; Dugué, Audrey Emmanuelle; Clarisse, Bénédicte; Dutoit, Soizic; Giffard, Florence; Abeilard, Edwige; Briand, Mélanie; Labiche, Alexandre; Grellard, Jean-Michel; Crouet, Hubert; Martin, Sandrine; Joly, Florence; Poulain, Laurent

    2015-03-01

    Ovarian cancers are addicted to Bcl-xL and Mcl-1, antiapoptotic members of the Bcl-2 family. Bcl-xL can be inhibited by the BH3-mimetic ABT-737. In vitro, ABT-737 can induce apoptosis of cancer cells, and its activity is potentiated by Mcl-1 inactivation. Herein, we assessed the sensitivity of human ovarian tumor nodes to ABT-737 when combined with carboplatin, which can indirectly inhibit Mcl-1. Fresh samples from 25 patients with high-grade serous ovarian cancer (HGSOC) who were chemo-naïve and had undergone surgery were prospectively exposed ex vivo to ABT-737 ± carboplatin. The treatment effect was studied on sliced tumor nodes by assessment of cleaved-caspase 3 immunostaining. We also studied the association between baseline Bcl-2 family protein expression (via immunohistochemistry) and the response of nodes to treatment. ABT-737 induced apoptosis as a single agent but its efficacy was not improved by the addition of carboplatin. Bim was frequently expressed (20/25) and its absence or low expression was associated with the absence of response to ABT-737, p value = 0.019 by Fisher's test and sensitivity = 93%, (95% confidence interval, 66-100). Moreover, we observed that in tumors in which Bim was expressed, a low expression of phospho-Erk1/2 or Mcl-1 improved the proportion of responses. This pilot study showed that ABT-737 has promise as monotherapy for HGSOC in a specific subgroup of tumors. Bim, Mcl-1, and phospho-Erk1/2 appeared to be relevant biomarkers that could be used for the selection of patients in the design of clinical trials using Navitoclax (an orally available compound related to ABT-737). PMID:25066666

  14. The Borderline/Schizoid Marriage: The Holding Environment as an Essential Treatment Construct.

    ERIC Educational Resources Information Center

    McCormack, Charles C.

    1989-01-01

    Discusses the borderline/schizoid marital constellation as the prominent constellation among borderline patients on a long-term inpatient unit. Contends that treatment of this marital constellation requires application of the concept of the holding environment as an essential treatment construct with the therapist as manager of the holding…

  15. Emotion Regulation Training for Adolescents with Borderline Personality Disorder Traits: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Schuppert, H. Marieke; Timmerman, Marieke E.; Bloo, Josephine; van Gemert, Tonny G.; Wiersema, Herman M.; Minderaa, Ruud B.; Emmelkamp, Paul M. G.; Nauta, Maaike H.

    2012-01-01

    Objective: To evaluate the effectiveness of Emotion Regulation Training (ERT), a 17-session weekly group training for adolescents with borderline personality disorder (BPD) symptoms. Method: One hundred nine adolescents with borderline traits (73% meeting the full criteria for BPD) were randomized to treatment as usual only (TAU) or ERT + TAU.…

  16. Adolescent Borderline Symptoms in the Community: Prognosis for Functioning over 20 Years

    ERIC Educational Resources Information Center

    Winograd, Greta; Cohen, Patricia; Chen, Henian

    2008-01-01

    Background: The long-term prognosis associated with adolescent symptoms of borderline personality disorder (BPD) in the general population is virtually unknown. In this study, the relationship of early borderline symptoms to subsequent psychosocial functioning and attainment was investigated based on data from the Children in the Community cohort.…

  17. Use of Dialectical Behavior Therapy in Borderline Personality Disorder: A View from Residency

    ERIC Educational Resources Information Center

    Sharma, Binali; Dunlop, Boadie W.; Ninan, Philip T.; Bradley, Rebekah

    2007-01-01

    Objective: The authors describe the use of dialectical behavior therapy (DBT) in treating borderline personality disorder during psychiatry residency, and assess the status of DBT education within psychiatry residencies in the United States. Method: The authors present a patient with borderline personality disorder treated by a resident using DBT,…

  18. Social Information Processing in Boys with Autistic Spectrum Disorder and Mild to Borderline Intellectual Disabilities

    ERIC Educational Resources Information Center

    Embregts, P.; van Nieuwenhuijzen, M.

    2009-01-01

    Background: Children with autistic spectrum disorders (ASD) and mild to borderline intellectual disability (ID) have less adaptive behaviour and more behaviour problems than children with mild to borderline ID. Social information processing appears to be an important mechanism in the explanation of the socially inadequate behaviour of children…

  19. Using Student Ability and Item Difficulty for Making Defensible Pass/Fail Decisions for Borderline Grades

    ERIC Educational Resources Information Center

    Shulruf, Boaz; Jones, Phil; Turner, Rolf

    2015-01-01

    The determination of Pass/Fail decisions over Borderline grades, (i.e., grades which do not clearly distinguish between the competent and incompetent examinees) has been an ongoing challenge for academic institutions. This study utilises the Objective Borderline Method (OBM) to determine examinee ability and item difficulty, and from that…

  20. Women's Views on Their Diagnosis and Management for Borderline Gestational Diabetes Mellitus

    PubMed Central

    Han, Shanshan; Middleton, Philippa F.; Bubner, Tanya K.; Crowther, Caroline A.

    2015-01-01

    Introduction. Little is known about women's views relating to a diagnosis of borderline gestational diabetes mellitus (GDM) and the subsequent management. This study aimed to explore women's experiences after being diagnosed with borderline GDM, their attitudes about treatment, and factors important to them for achieving any lifestyle changes. Methods. We conducted face-to-face, semistructured interviews with women diagnosed with borderline GDM. Results. A total of 22 women were interviewed. After a diagnosis of borderline GDM, 14 (64%) women reported not being concerned or worried. Management of borderline GDM was thought by 21 (95%) women to be very important or important. Eighteen (82%) women planned to improve their diet and/or exercise to manage their borderline GDM. The most frequently mentioned enabler for achieving intended lifestyle change was being more motivated to improve the health of their baby and/or themselves (15 women). The most frequent barrier was tiredness and/or being physically unwell (11 women). Conclusions. A diagnosis of borderline GDM caused some concern to one-third of women interviewed. The majority of women believed managing their borderline GDM was important and they planned to improve their lifestyle. Women's own and their babies' future health were powerful motivators for lifestyle change. PMID:25785278

  1. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential.

    PubMed

    Shenouda, Mina; Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-01-01

    Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified

  2. A Case of Oncocytic Adrenocortical Neoplasm of Borderline (Uncertain) Malignant Potential

    PubMed Central

    Brown, Linda G; Denning, Krista L; Pacioles, Toni

    2016-01-01

    Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified

  3. [Impulse control disorders in borderline and antisocial personality disorder].

    PubMed

    Herpertz, S

    2007-01-18

    A borderline personality disorder is associated with highly impulsive acts that cannot be controlled by cognitive inhibition. In a psychopathic/antisocial personality disorder emotional inhibition of hostile acts is lacking. The patient has a high proclivity for risk-seeking, and is incapable of responding appropriately to punishment. In both disorders, the result is (auto)aggressive behavior. The family doctor must refer such patients to a specialist, when there is an acute danger of self-harm or when a grave functional limitation in the areas of work or interpersonal relationship has persisted over a long period of time. PMID:17619383

  4. The Family, Family Therapy, and Borderline Personality Disorder

    PubMed Central

    GLICK, IRA D.; DULIT, REBECCA A.; WACHTER, EILEEN; CLARKIN, JOHN F.

    1995-01-01

    The authors review recent controlled studies on the interrelationship of the family and its members with borderline disorder and propose a new model for understanding and managing this relationship. The focus of the model is on psychopathology, evaluation, and treatment of patient and family as they influence each other. In the authors’ view this illness originates in cerebral dysfunction, in the patient in combination with impaired relationships among family members. When the family is available, we believe that the treatment of choice is a multimodal approach involving family psychoeducation and family systems or dynamic intervention where possible, in combination with medications, individual psychotherapy, or both. PMID:22700254

  5. Neurocognitive deficits in borderline personality disorder: implications for treatment.

    PubMed

    Judd, Patricia A

    2012-03-01

    The cognitive dimension of Borderline Personality Disorder has received relatively little attention in the clinical literature and is poorly understood. This article illustrates how a range of cognitive problems including attention deficit disorder and learning disabilities may contribute to the cognitive disturbances identified in the disorder including dissociation, paranoia, all or nothing thinking, overvalued ideas, and denial and splitting. A review of relevant research supporting the presence of cognitive deficits is summarized along with a developmental pathway for the expression of the cognitive dimension. Clinical examples are provided. Recommendations for inclusion of assessment and treatment strategies that address cognitive deficits within a psychodynamically based psychotherapy are discussed. PMID:23006031

  6. Borderline viability: controversies in caring for the extremely premature infant.

    PubMed

    Leuthner, Steven R

    2014-12-01

    Controversy surrounding the decision to resuscitate at the limits or borderline of viability has been at the center of neonatal ethical debate for decades. This debate has led to numerous reports from individual institutions, councils, and advisory committees that all have remarkable consistency in the development of gestational age-based guidelines. This article reviews legal or regulatory concerns that may contradict ethical discussion and guidelines, discriminatory and scientific basis concerns with consensus guidelines, and personal controversy about how to determine best interest. Guidelines are a reasonable place to start in helping determine parental authority and autonomy. The article also addresses controversies raised in counseling and costs. PMID:25459775

  7. Borderline Personality Characteristics and Treatment Outcome in Cognitive-Behavioral Treatments for PTSD in Female Rape Victims

    ERIC Educational Resources Information Center

    Clarke, Stephanie B.; Rizvi, Shireen L.; Resick, Patricia A.

    2008-01-01

    Many studies report that comorbid borderline personality pathology is associated with poorer outcomes in the treatment of Axis I disorders. Given the high rates of comorbidity between borderline personality pathology and posttraumatic stress disorder (PTSD), it is essential to determine whether borderline symptomatology affects PTSD treatment…

  8. Association between schizotypal and borderline personality disorder traits, and cannabis use in young adults.

    PubMed

    Raynal, Patrick; Chabrol, Henri

    2016-09-01

    The aim of the study was to examine the association of schizotypal and borderline personality traits to cannabis use. Participants were 476 college students (95 males; 381 females; mean age of males=21; mean age of females=20.7) who completed self-report questionnaires assessing cannabis use, schizotypal and borderline personality traits. Problematic cannabis use, depressive symptoms, borderline and schizotypal traits were significantly inter-correlated. A logistic regression analysis showed that only borderline traits contributed significantly to cannabis use in the total sample. A multiple regression analysis showed that only schizotypal traits were positively and uniquely associated to problematic cannabis use symptoms among users. These results may imply that schizotypal traits are not a risk factor for initiating use, but may facilitate the development of problematic use symptoms among users. This study showed the necessity of taking into account schizotypal traits when exploring the relationships between depressive symptoms, borderline traits and cannabis use. PMID:27149691

  9. Borderline Personality Features in Childhood: The Role of Subtype, Developmental Timing and Chronicity of Child Maltreatment

    PubMed Central

    Hecht, Kathryn F.; Cicchetti, Dante; Rogosch, Fred A.; Crick, Nicki

    2014-01-01

    Child maltreatment has been established as a risk factor for borderline personality disorder (BPD), yet few studies consider how maltreatment influences the development of BPD features through childhood and adolescence. Subtype, developmental timing and chronicity of child maltreatment were examined as factors in the development of borderline personality features in childhood. Children (M age = 11.30, SD = 0.94), including 314 maltreated and 285 nonmaltreated children from comparable low socioeconomic backgrounds, provided self-reports of developmentally salient borderline personality traits. Maltreated children had higher overall borderline feature scores, higher scores on each individual subscale and were more likely to be identified as at high risk for development of BPD through raised scores on all 4 subscales. Chronicity of maltreatment predicted higher overall borderline feature scores and patterns of onset and recency of maltreatment significantly predicted whether a participant would meet criteria for the high-risk group. Implications of findings and recommendations for intervention are discussed. PMID:25047300

  10. The influence of borderline personality features on inpatient adolescent suicide risk.

    PubMed

    Yalch, Matthew M; Hopwood, Christopher J; Fehon, Dwain C; Grilo, Carlos M

    2014-01-01

    Suicide is a leading cause of death among adolescents and suicidal behavior is one of the primary risk factors for youth psychiatric hospitalizations. A number of studies indicate that depression and substance abuse are associated with suicide risk in this population, but less is known about the role of borderline personality features or their incremental influence over other known risk factors in indicating suicidal behavior among adolescents. This study examined whether borderline features were associated with suicide risk when controlling for symptoms of depression and substance abuse in a sample of adolescents hospitalized in an inpatient psychiatric facility. Self-report data from 477 adolescent psychiatric inpatients were used to test hypotheses about the association of borderline features with suicide risk after controlling for other common risk factors. Borderline features were significantly related to suicide risk even after accounting for symptoms of depression and substance abuse. These findings underscore the clinical value of routinely assessing borderline features among adolescents. PMID:24128121

  11. Distinct pattern of P3a event-related potential in borderline personality disorder.

    PubMed

    Meares, Russell; Melkonian, Dmitriy; Gordon, Evian; Williams, Leanne

    2005-02-28

    P3a and P3b event-related brain potentials to auditory stimuli were recorded for 17 unmedicated patients with borderline personality disorder, 17 matched healthy controls and 100 healthy control participants spanning five decades. Using high-resolution fragmentary decomposition for single-trial event-related potential analysis, distinctive disturbances in P3a in borderline personality disorder patients were found: abnormally enhanced amplitude, failure to habituate and a loss of temporal locking with P3b. Normative age dependencies from 100 controls suggest that natural age-related decline in P3a amplitude is reduced in borderline personality disorder patients and is likely to indicate failure of frontal maturation. On the basis of the theories of Hughlings Jackson, this conceptualization of borderline personality disorder is consistent with an aetiological model of borderline personality disorder. PMID:15706238

  12. Analysis of rare high-DNA cell populations in serous effusions using continuous-motion imaging.

    PubMed

    Tucker, J H; Stark, M H; Eason, P; Duvall, E

    1991-07-01

    The rare high-DNA cell sub-populations in a series of serous effusion specimens were analysed to determine whether such measurements could provide a basis for the improved diagnosis of malignancy. Monolayer specimens stained with gallocyanin chrome-alum were scanned with the CERVIFIP continuous-motion image analyser to locate and measure the highest-DNA cells in the sample. Two types of features were obtained for the detected sub-populations; firstly, 'percentile ploidy' values which characterise the ploidy levels above which specified proportions of the total cells are found; and secondly 'percentage abnormal' values which characterise the proportion of the cells diagnosed as malignant during examination by a cytopathologist. The classification accuracy for one or both of these features was then obtained by comparison with the clinical outcome of each patient. The results gave a classification error of 9/44 (20%) using the 0.01% percentile ploidy alone, 6/44 (14%) using the 75% percentage abnormal feature alone, but only 2/44 (5%) from a box discriminant using both features. It was therefore concluded that the analysis of the high-DNA cell population could be of value in the diagnosis of malignancy in serous effusion specimens. PMID:1883747

  13. Primary peritoneal serous carcinoma, an extremely rare malignancy: A case report and review of the literature

    PubMed Central

    YUN, WOO-SUNG; BAE, JUNG-MIN

    2016-01-01

    Primary peritoneal serous carcinoma (PPSC) is an extremely rare malignancy that was first described in 1959. This type of cancer arises from the peritoneal epithelium and is similar to serous ovarian carcinoma. A diagnosis of PPSC is typically made based on the Gynecology Oncology Group criteria; however, a correct differential diagnosis of PPSC is difficult preoperatively. The current study describes the case of a 66 year-old female patient presenting with abdomen distension. A computed tomography (CT) scan revealed abundant ascites in the abdominal cavity and omental infiltration. The results of positron emission tomography/CT showed hot uptake in the greater omentum. Furthermore, preoperative serum cancer antigen-125 levels were 1,032 U/ml. Upon surgical exploration, a whitish mass and nodule were found in the greater omentum. Therefore, omentectomy was performed. Pathological examination of the resected specimen revealed a diagnosis of PPSC. PPSC is extremely rare with few cases cited in the current literature. The present study describes a rare case of PPSC with a review of the literature. PMID:27313741

  14. Serous retinal detachment following panretinal photocoagulation (PRP) using Pattern Scan Laser (PASCAL) photocoagulator

    PubMed Central

    Azar, Georges; Wolff, Benjamin; Cornut, Pierre-Loïc; Mauget-Faÿsse, Martine

    2012-01-01

    Objective: To report a case of serous retinal detachment after Pattern Scan Laser (PASCAL) treatment in a diabetic woman. Methods: A 34-year-old diabetic woman presented with florid diabetic retinopathy after a miscarriage during the 20th week of pregnancy. Her Best Corrected Visual Acuity (BCVA) was 20/40 right eye (OD) and 20/30 left eye (OS). Fundus exam showed multiple microaneurysms, large blot hemorrhages and venous dilation both eyes (OU). Fundus fluorescein angiography (FFA) revealed large areas of capillary nonperfusion and panretinal neovascularisation in all quadrants OU. Macular Spectral-Domain Optical Coherence Tomography scan (SD-OCT) did not show any foveal thickening. Panretinal photocoagulation (PRP) was immediately performed OU during the same day. Results: Two days after PASCAL treatment, her BCVA decreased to 20/80 OU and worsened to Count Fingers (CF) during the following days. Fundus exam revealed an extensive serous retinal detachment confirmed on SD-OCT. 2 sub-conjunctival injections of 0.1 ml Betamethasone were done OU. One month later, BCVA improved to 20/30 and SD-OCT confirmed regression of retinal detachment. Conclusions: PASCAL is considered to be a safe treatment, but one has to be aware of its potential side effects. It has to be used with caution in pregnant women.

  15. Molecular Subtyping of Serous Ovarian Cancer Based on Multi-omics Data

    PubMed Central

    Zhang, Zhe; Huang, Ke; Gu, Chenglei; Zhao, Luyang; Wang, Nan; Wang, Xiaolei; Zhao, Dongsheng; Zhang, Chenggang; Lu, Yiming; Meng, Yuanguang

    2016-01-01

    Classification of ovarian cancer by morphologic features has a limited effect on serous ovarian cancer (SOC) treatment and prognosis. Here, we proposed a new system for SOC subtyping based on the molecular categories from the Cancer Genome Atlas project. We analyzed the DNA methylation, protein, microRNA, and gene expression of 1203 samples from 599 serous ovarian cancer patients. These samples were divided into nine subtypes based on RNA-seq data, and each subtype was found to be associated with the activation and/or suppression of the following four biological processes: immunoactivity, hormone metabolic, mesenchymal development and the MAPK signaling pathway. We also identified four DNA methylation, two protein expression, six microRNA sequencing and four pathway subtypes. By integrating the subtyping results across different omics platforms, we found that most RNA-seq subtypes overlapped with one or two subtypes from other omics data. Our study sheds light on the molecular mechanisms of SOC and provides a new perspective for the more accurate stratification of its subtypes. PMID:27184229

  16. Morphologic Changes in Acute Central Serous Chorioretinopathy Using Spectral Domain Optical Coherence Tomography

    PubMed Central

    Cho, Won Bin; Chung, Hyewon

    2012-01-01

    Purpose To investigate morphologic changes of acute central serous chorioretinopathy (CSC) using spectral domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy. Methods This retrospective study included 63 eyes of 63 patients with unilateral acute CSC. All patients underwent simultaneous SD-OCT and fluorescein angiography examination using Spectralis HRA+OCT. Results The external limiting membrane could be seen on SD-OCT, although the junction between photoreceptor inner and outer segments (IS/OS) was not detected in all eyes with retinal detachment (RD). However, IS/OS became visible after resolution of serous RD in 51 eyes (81.0%). SD-OCT images at the leakage sites showed a bump of retinal pigment epithelium (RPE) in in 47 cases (68.1%) and pigment epithelial detachment (PED) in 22 of 69 leakage sites (31.9%). In 14 of 69 leakage sites (20.3%), highly reflective areas suggesting fibrinous exudate were observed in the subretinal space. In nine leakage sites (13.0%), sagging or dipping of the posterior retinal layer was seen. Abnormal RPE changes such as RPE bump and PED were observed in 12 of 22 fellow eyes (54.5%). Conclusions A variety of morphologic changes could be identified on SD-OCT, and those findings may contribute more information to our understanding of the pathophysiology of CSC. PMID:23060721

  17. High Expression of Ecto-Nucleotidases CD39 and CD73 in Human Endometrial Tumors

    PubMed Central

    Aliagas, Elisabet; Vidal, August; Texidó, Laura; Ponce, Jordi; Condom, Enric; Martín-Satué, Mireia

    2014-01-01

    One of the strategies used by tumors to evade immunosurveillance is the accumulation of extracellular adenosine, which has immunosupressive and tumor promoting effects. The study of the mechanisms leading to adenosine formation at the tumor interstitium are therefore of great interest in oncology. The dominant pathway generating extracellular adenosine in tumors is the dephosphorylation of ATP by ecto-nucleotidases. Two of these enzymes acting sequentially, CD39 and CD73, efficiently hydrolyze extracellular ATP to adenosine. They have been found to play a crucial role in a variety of tumors, but there were no data concerning endometrial cancer, the most frequent of the invasive tumors of the female genital tract. The aim of the present work is to study the expression of CD39 and CD73 in human endometrial cancer. We have analyzed protein and gene expression, as well as enzyme activity, in type I endometrioid adenocarcinomas and type II serous adenocarcinomas and their nonpathological endometrial counterparts. High levels of both enzymes were found in tumor samples, with significantly increased expression of CD39 in type II serous tumors, which also coincided with the higher tumor grade. Our results reinforce the involvement of the adenosinergic system in cancer, emphasizing the relevance of ecto-nucleotidases as emerging therapeutic targets in oncology. PMID:24707115

  18. Ovarian cancer survival by tumor dominance, a surrogate for site of origin

    PubMed Central

    Ivanova, Anna; Loo, Anneli; Tworoger, Shelley; Crum, Christopher P.; Fan, Isabel; McLaughlin, John R.; Rosen, Barry; Risch, Harvey; Narod, Steven A.; Kotsopoulos, Joanne

    2015-01-01

    Objectives Recent studies suggest that a proportion of ovarian tumors may actually originate in the distal fallopian tube. The objective of this study was to examine the relationship between dominance (a surrogate for site of origin) and survival following a diagnosis of epithelial ovarian cancer. Methods We classified 1,386 tumors as dominant (putatively originating in the ovary and non-dominant (putatively originating in the fallopian tube), using parameters obtained from pathology reports. Dominant tumors were restricted to one ovary or one involved ovary that exceeded the other in dimension by at least two-fold, while non-dominant tumors were identified as having a greater likelihood of a tubal origin if the disease was equally distributed across the ovaries. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with dominance. Results Non-dominant tumors were more likely to be serous, stage III/IV, and be associated with a BRCA1/2 mutation, increasing parity and use of estrogen hormone replacement therapy (P ≤ 0.01). In contrast, 46% and 26% of the dominant tumors were serous and endometrioid, respectively, with a more even distribution of stage (P < 0.0001). Women with a non-dominant tumor had an increased risk of death compared to women with a dominant tumor (multivariate HR = 1.28; 95%CI 1.02–1.60). Findings were similar in our analysis restricted to serous only subtypes (HR = 1.28; 95%CI 1.01–1.63). Conclusion These preliminary findings suggest significantly worse survival among women diagnosed with a tumor putatively arising from fallopian tube. PMID:25771796

  19. Defining the neurocircuitry of borderline personality disorder: functional neuroimaging approaches.

    PubMed

    Brendel, Gary R; Stern, Emily; Silbersweig, David A

    2005-01-01

    Functional neuroimaging recently has been used to localize brain dysfunction in borderline personality disorder (BPD). Initial studies have examined baseline activity or emotional reactivity, and our group has investigated what we consider to be a crucial interaction between negative emotion and behavioral (dys)control. This research is beginning to identify abnormal frontolimbic circuitry likely underlying core clinical features of this condition. We review the evidence for dysfunction in specific frontolimbic regions, leading to a mechanistic model of symptom formation in BPD. In addition, we offer an integration of these neuroimaging findings with developmental perspectives on the emergence of borderline psychopathology, focusing on the ways in which early psychosocial experience may interact with developing brain systems. We also consider possible mechanisms of psychotherapeutic change at the neural systems level in BPD. Finally, we propose that future neuroimaging studies of BPD should integrate multiple levels of observation (structural, functional, neurochemical, genetic, and clinical) in a model-driven fashion to further understand the dynamic relationship between biological and psychological factors in the development and treatment of this difficult condition. PMID:16613437

  20. Working around a contested diagnosis: borderline personality disorder in adolescence.

    PubMed

    Koehne, Kristy; Hamilton, Bridget; Sands, Natisha; Humphreys, Cathy

    2013-01-01

    This discourse analytic study sits at the intersection of everyday communications with young people in mental health settings and the enduring sociological critique of diagnoses in psychiatry. The diagnosis of borderline personality disorder (BPD) is both contested and stigmatized, in mental health and general health settings. Its legitimacy is further contested within the specialist adolescent mental health setting. In this setting, clinicians face a quandary regarding the application of adult diagnostic criteria to an adolescent population, aged less than 18 years. This article presents an analysis of interviews undertaken with Child and Adolescent Mental Health Services (CAMHS) clinicians in two publicly funded Australian services, about their use of the BPD diagnosis. In contrast with notions of primacy of diagnosis or of transparency in communications, doctors, nurses and allied health clinicians resisted and subverted a diagnosis of BPD in their work with adolescents. We delineate specific social and discursive strategies that clinicians displayed and reflected on, including: team rules which discouraged diagnostic disclosure; the lexical strategy of hedging when using the diagnosis; the prohibition and utility of informal 'borderline talk' among clinicians; and reframing the diagnosis with young people. For clinicians, these strategies legitimated their scepticism and enabled them to work with diagnostic uncertainty, in a population identified as vulnerable. For adolescent identities, these strategies served to forestall a BPD trajectory, allowing room for troubled adolescents to move and grow. These findings illuminate how the contest surrounding this diagnosis in principle is expressed in everyday clinical practice. PMID:22674745

  1. Genomic landscapes of breast fibroepithelial tumors.

    PubMed

    Tan, Jing; Ong, Choon Kiat; Lim, Weng Khong; Ng, Cedric Chuan Young; Thike, Aye Aye; Ng, Ley Moy; Rajasegaran, Vikneswari; Myint, Swe Swe; Nagarajan, Sanjanaa; Thangaraju, Saranya; Dey, Sucharita; Nasir, Nur Diyana Md; Wijaya, Giovani Claresta; Lim, Jing Quan; Huang, Dachuan; Li, Zhimei; Wong, Bernice Huimin; Chan, Jason Yong Sheng; McPherson, John R; Cutcutache, Ioana; Poore, Gregory; Tay, Su Ting; Tan, Wai Jin; Putti, Thomas Choudary; Ahmad, Buhari Shaik; Iau, Philip; Chan, Ching Wan; Tang, Anthony P H; Yong, Wei Sean; Madhukumar, Preetha; Ho, Gay Hui; Tan, Veronique Kiak Mien; Wong, Chow Yin; Hartman, Mikael; Ong, Kong Wee; Tan, Benita K T; Rozen, Steven G; Tan, Patrick; Tan, Puay Hoon; Teh, Bin Tean

    2015-11-01

    Breast fibroepithelial tumors comprise a heterogeneous spectrum of pathological entities, from benign fibroadenomas to malignant phyllodes tumors. Although MED12 mutations have been frequently found in fibroadenomas and phyllodes tumors, the landscapes of genetic alterations across the fibroepithelial tumor spectrum remain unclear. Here, by performing exome sequencing of 22 phyllodes tumors followed by targeted sequencing of 100 breast fibroepithelial tumors, we observed three distinct somatic mutation patterns. First, we frequently observed MED12 and RARA mutations in both fibroadenomas and phyllodes tumors, emphasizing the importance of these mutations in fibroepithelial tumorigenesis. Second, phyllodes tumors exhibited mutations in FLNA, SETD2 and KMT2D, suggesting a role in driving phyllodes tumor development. Third, borderline and malignant phyllodes tumors harbored additional mutations in cancer-associated genes. RARA mutations exhibited clustering in the portion of the gene encoding the ligand-binding domain, functionally suppressed RARA-mediated transcriptional activation and enhanced RARA interactions with transcriptional co-repressors. This study provides insights into the molecular pathogenesis of breast fibroepithelial tumors, with potential clinical implications. PMID:26437033

  2. Etiological features of borderline personality related characteristics in a birth cohort of 12-year-old children

    PubMed Central

    BELSKY, DANIEL W.; CASPI, AVSHALOM; ARSENEAULT, LOUISE; BLEIDORN, WIEBKE; FONAGY, PETER; GOODMAN, MARIANNE; HOUTS, RENATE; MOFFITT, TERRIE E.

    2012-01-01

    It has been reported that borderline personality related characteristics can be observed in children, and that these characteristics are associated with increased risk for the development of borderline personality disorder. It is not clear whether borderline personality related characteristics in children share etiological features with adult borderline personality disorder. We investigated the etiology of borderline personality related characteristics in a longitudinal cohort study of 1,116 pairs of same-sex twins followed from birth through age 12 years. Borderline personality related characteristics measured at age 12 years were highly heritable, were more common in children who had exhibited poor cognitive function, impulsivity, and more behavioral and emotional problems at age 5 years, and co-occurred with symptoms of conduct disorder, depression, anxiety, and psychosis. Exposure to harsh treatment in the family environment through age 10 years predicted borderline personality related characteristics at age 12 years. This association showed evidence of environmental mediation and was stronger among children with a family history of psychiatric illness, consistent with diathesis–stress models of borderline etiology. Results indicate that borderline personality related characteristics in children share etiological features with borderline personality disorder in adults and suggest that inherited and environmental risk factors make independent and interactive contributions to borderline etiology. PMID:22293008

  3. Expression of AQP6 and AQP8 in epithelial ovarian tumor.

    PubMed

    Ma, Jiong; Zhou, Chunxia; Yang, Jianhua; Ding, Xiaoyan; Zhu, Yunshan; Chen, Xuejun

    2016-04-01

    Aquaporins (AQPs), the rapid transition pores for water molecules, play an important role in maintenance of intracellular water balance. Studies showed that AQPs were also involved in occurrence, development, invasion and metastasis of tumors. In this study, we aimed to explore the distribution and expression differences of aquaporin 6 (AQP6) and aquaporin 8 (AQP8) in epithelial ovarian tumors. The expression of AQP6 and AQP8 in 47 cases of epithelial ovarian tumors were measured by immunochemical technique and Western blotting. AQP6 was strongly expressed in benign ovarian tumors, but weak signal was shown in malignant tumors. The difference was not statistically significant (P > 0.05). Compared with serous adenoma and normal tissues, AQP6 expression in serous carcinoma was obviously decreased (P < 0.05). AQP8 expressions were both identified in benign and malignant tumors, but there was no significantly statistical difference (P > 0.05). For patients with large volume of malignant ascites (>1000 ml), AQP8 expression was increased (P < 0.05). AQP8 expression in malignant tumors was not related to different clinical stages, presence of lymphatic metastasis, and differentiation degrees (P > 0.05). These data showed that AQP6 and AQP8 had different expression degrees in epithelial ovarian tissues, which suggests that AQP6 and AQP8 may play certain roles in epithelial ovarian tumors. PMID:26779650

  4. Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients.

    PubMed

    Kamieniak, Marta M; Rico, Daniel; Milne, Roger L; Muñoz-Repeto, Ivan; Ibáñez, Kristina; Grillo, Miguel A; Domingo, Samuel; Borrego, Salud; Cazorla, Alicia; García-Bueno, José M; Hernando, Susana; García-Donas, Jesús; Hernández-Agudo, Elena; Y Cajal, Teresa Ramón; Robles-Díaz, Luis; Márquez-Rodas, Ivan; Cusidó, Maite; Sáez, Raquel; Lacambra-Calvet, Carmen; Osorio, Ana; Urioste, Miguel; Cigudosa, Juan C; Paz-Ares, Luis; Palacios, José; Benítez, Javier; García, María J

    2015-02-01

    Standard treatments for advanced high-grade serous ovarian carcinomas (HGSOCs) show significant side-effects and provide only short-term survival benefits due to disease recurrence. Thus, identification of novel prognostic and predictive biomarkers is urgently needed. We have used 42 paraffin-embedded HGSOCs, to evaluate the utility of DNA copy number alterations, as potential predictors of clinical outcome. Copy number-based unsupervised clustering stratified HGSOCs into two clusters of different immunohistopathological features and survival outcome (HR = 0.15, 95%CI = 0.03-0.81; Padj = 0.03). We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life. PMID:25454820

  5. Predicting Ovarian Cancer Patients' Clinical Response to Platinum-Based Chemotherapy by Their Tumor Proteomic Signatures.

    PubMed

    Yu, Kun-Hsing; Levine, Douglas A; Zhang, Hui; Chan, Daniel W; Zhang, Zhen; Snyder, Michael

    2016-08-01

    Ovarian cancer is the deadliest gynecologic malignancy in the United States with most patients diagnosed in the advanced stage of the disease. Platinum-based antineoplastic therapeutics is indispensable to treating advanced ovarian serous carcinoma. However, patients have heterogeneous responses to platinum drugs, and it is difficult to predict these interindividual differences before administering medication. In this study, we investigated the tumor proteomic profiles and clinical characteristics of 130 ovarian serous carcinoma patients analyzed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), predicted the platinum drug response using supervised machine learning methods, and evaluated our prediction models through leave-one-out cross-validation. Our data-driven feature selection approach indicated that tumor proteomics profiles contain information for predicting binarized platinum response (P < 0.0001). We further built a least absolute shrinkage and selection operator (LASSO)-Cox proportional hazards model that stratified patients into early relapse and late relapse groups (P = 0.00013). The top proteomic features indicative of platinum response were involved in ATP synthesis pathways and Ran GTPase binding. Overall, we demonstrated that proteomic profiles of ovarian serous carcinoma patients predicted platinum drug responses as well as provided insights into the biological processes influencing the efficacy of platinum-based therapeutics. Our analytical approach is also extensible to predicting response to other antineoplastic agents or treatment modalities for both ovarian and other cancers. PMID:27312948

  6. Maternal empathy, family chaos, and the etiology of borderline personality disorder.

    PubMed

    Golomb, A; Ludolph, P; Westen, D; Block, M J; Maurer, P; Wiss, F C

    1994-01-01

    Psychoanalytic writers have traced the etiology of borderline personality disorder (BPD) to be a preoedipal disturbance in the mother-child relationship. Despite the prevalence of theories focusing on the role of mothering in the development of BPD, few empirical studies have tested the hypothesis that borderlines were the recipients of unempathic mothering. The current preliminary study compared 13 mothers of borderline adolescents with 13 mothers of normal adolescents. This study found that mothers of borderlines tended to conceive of their children egocentrically, as need-gratifying objects, rather than as individuals with distinct and evolving personalities. This study also found that the mothers of borderlines reported raising their daughters in extremely chaotic families struggling to cope with multiple hardships, including divorce and financial worries. The stressful environmental circumstances reported by the mothers likely affected the borderline daughters directly as well as the mothers' ability to parent effectively and empathically. The results of this study suggest that, as predicted by psychoanalytic theory, a problematic mother-child relationship may play a significant role in the genesis of borderline pathology; however, the life circumstances that contextualize the mother-child relationship also need to be considered when accounting for the etiology of BPD. PMID:8040554

  7. A rare case of three different tumors in the same pancreatic specimen: a case report and brief review of the literature

    PubMed Central

    Paiella, Salvatore; Luchini, Claudio; Amodio, Antonio; Rusev, Borislav; Bassi, Claudio; Manfredi, Riccardo; Frulloni, Luca

    2016-01-01

    Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms mainly affecting young women. Pancreatic serous cystadenomas (SCAs) and pancreatic neuroendocrine tumors (PanNETs) account for about 2% of all pancreatic neoplasms. The combination of these three lesions, to our knowledge, has never been described in literature. Here we report a case of combined SPT, SCA and PanNET affecting a 33-year-old woman. PMID:27284489

  8. Tubulin-β-III Overexpression by Uterine Serous Carcinomas is a Marker for Poor Overall Survival after Platinum/Taxane Chemotherapy and Sensitivity to Epothilones

    PubMed Central

    Roque, Dana M.; Bellone, Stefania; English, Diana P.; Buza, Natalia; Cocco, Emiliano; Gasparrini, Sara; Bortolomai, Ileana; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Rutherford, Thomas J.; Schwartz, Peter E.; Santin, Alessandro D.

    2013-01-01

    BACKGROUND Uterine serous carcinoma (USC) is a subtype of endometrial cancer associated with chemoresistance and poor outcome. Overexpression of tubulin-β-III and p-glycoprotein has been linked to paclitaxel resistance in many cancers but has been undercharacterized among USC. Epothilones have demonstrated activity in certain paclitaxel-resistant malignancies. In this study, we clarify in USC relative to ovarian serous carcinomas (OSC) the relationships between tubulin-β-III and p-glycoprotein expression, clinical outcome, and in vitro chemoresponsiveness to epothilone B, ixabepilone and paclitaxel. METHODS Tubulin-β-III and p-glycoprotein were quantified by real time polymerase chain reaction (qRT-PCR) in 48 fresh-frozen tissue samples and 13 cell lines. Copy number was correlated with immunohistochemistry and overall survival. IC50 was determined using viability and metabolic assays. Impact of tubulin-β-III knockdown on IC50 was assessed with siRNAs. RESULTS USC overexpressed tubulin-β-III but not p-glycoprotein relative to OSC in both fresh-frozen tissues (552.9±106.7 versus 202.0±43.99, p=0.01) and cell lines (1701.0±.376.4 versus 645.1±157.9, p=0.02). Tubulin-β-III immunohistochemistry reflected qRT-PCR copy number and overexpression stratified patients by overall survival (copy number ≤400: 615 days; copy number >400: 165 days, p=0.049); p-glycoprotein did not predict clinical outcome. USC remained exquisitely sensitive to patupilone in vitro despite tubulin-β-III overexpression (IC50, USC 0.245±0.11 nM versus IC50, OSC 1.01±0.13 nM, p=0.006). CONCLUSIONS Tubulin-β-III overexpression in USC discriminates poor prognosis, serves as a marker for sensitivity to epothilones, and may contribute to paclitaxel resistance. Immunohistochemistry reliably identifies tumors with overexpression of tubulin-β-III, and a subset of individuals likely to respond to patupilone and ixabepilone. Epothilones warrant clinical investigation for treatment of USC. PMID

  9. Management of borderline personality disorder: a review of psychotherapeutic approaches

    PubMed Central

    STONE, MICHAEL H.

    2006-01-01

    There are currently three major psychotherapeutic approaches to the management of borderline personality disorder (BPD): the psychodynamic, the cognitive-behavioral, and the supportive. There are special varieties within each: e.g., transference-focused psychotherapy (psychodynamic) or dialectic behavioral therapy (cognitive-behavioral). Though differing in basic conceptions and in methodology, all approaches aim at the amelioration of both the symptom-aspects that dominate the clinical picture at the outset, and the personality difficulties that remain apparent after the symptoms have been alleviated. The term "management" implies a focus on the more serious aspects of the borderline picture. These can be pictured hierarchically as to their level of seriousness, and there is universal agreement about the nature of this hierarchy. Therapists must pay attention first to suicidal and self-mutilative behaviors. Next, one deals with any threats to interrupt therapy prematurely. Third in order of seriousness: non-suicidal symptoms such as (mild to moderate) depression, substance abuse, panic and other anxiety manifestations, or dissociation. Psychopharmacological treatment will often be used adjunctively to help control any target symptoms, which usually fall into such categories as cognitive-perceptual, affect dysregulation, or impulsive/ behavioral dyscontrol. Therapists must then be alert to any signs of withholding, dishonesty, or antisocial tendencies, since these have an adverse effect on prognosis. When all these disruptive influences are (to the extent possible) dealt with, therapists will next take up milder symptoms such as social anxiety or lability of mood. Throughout this initial process, the personality-disorder attributes of BPD will become more apparent, and will usually emerge with greater clarity, once the serious symptoms have been dealt with. The management issues will gradually be supplanted with the overlapping and enduring personality issues

  10. Management of borderline personality disorder: a review of psychotherapeutic approaches.

    PubMed

    Stone, Michael H

    2006-02-01

    There are currently three major psychotherapeutic approaches to the management of borderline personality disorder (BPD): the psychodynamic, the cognitive-behavioral, and the supportive. There are special varieties within each: e.g., transference-focused psychotherapy (psychodynamic) or dialectic behavioral therapy (cognitive-behavioral). Though differing in basic conceptions and in methodology, all approaches aim at the amelioration of both the symptom-aspects that dominate the clinical picture at the outset, and the personality difficulties that remain apparent after the symptoms have been alleviated. The term "management" implies a focus on the more serious aspects of the borderline picture. These can be pictured hierarchically as to their level of seriousness, and there is universal agreement about the nature of this hierarchy. Therapists must pay attention first to suicidal and self-mutilative behaviors. Next, one deals with any threats to interrupt therapy prematurely. Third in order of seriousness: non-suicidal symptoms such as (mild to moderate) depression, substance abuse, panic and other anxiety manifestations, or dissociation. Psychopharmacological treatment will often be used adjunctively to help control any target symptoms, which usually fall into such categories as cognitive-perceptual, affect dysregulation, or impulsive/ behavioral dyscontrol. Therapists must then be alert to any signs of withholding, dishonesty, or antisocial tendencies, since these have an adverse effect on prognosis. When all these disruptive influences are (to the extent possible) dealt with, therapists will next take up milder symptoms such as social anxiety or lability of mood. Throughout this initial process, the personality-disorder attributes of BPD will become more apparent, and will usually emerge with greater clarity, once the serious symptoms have been dealt with. The management issues will gradually be supplanted with the overlapping and enduring personality issues

  11. The experience of borderline phenomena through cinema: Guentin Tarantino's Reservoir dogs, true romance, and pulp fiction.

    PubMed

    Ross, Donald R; Favero, Marcus

    2002-01-01

    The experience of many patients with borderline personality is intense and kaleidoscopic. These qualities may be represented in film in ways that reflect and convey their essential features that are less readily captured in words. Quentin Tarantino has produced a trilogy of films that bring to light and to life the borderline experience. We use these movies to illustrate and discuss five key borderline themes: the fluid nature of drive derivatives, the discontinuous experience of time and space, the coniflicted search for an idealized parent, antisocial distortions of the superego, and the organizing and stabilizing function of a central romantic fantasy. PMID:12389520

  12. Serous cutaneous glands in anurans: Fourier transform analysis of the repeating secretory granule substructure

    NASA Astrophysics Data System (ADS)

    Nosi, D.; Delfino, G.; Quercioli, F.

    2013-03-01

    A combined transmission electron microscopy (TEM) and Fourier transform analysis has been performed on the secretory granules storing active peptides/proteins in serous cutaneous glands of n = 12 anuran species. Previous TEM investigation showed that the granules are provided with remarkable repeating substructures based on discrete subunits, arranged into a consistent framework. Furthermore, TEM findings revealed that this recurrent arrangement is acquired during a prolonged post-Golgian (or maturational) processing that affects the secretory product. Maturation leads to a variety of patterns depending on the degree of subunit clustering. This variety of recurrent patterns has been plotted into a range of frequency spectra. Through this quantitative approach, we found that the varying granule substructure can be reduced to a single mechanism of peptide/protein aggregation.

  13. Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer

    PubMed Central

    Black, Jonathan D; English, Diana P; Roque, Dana M; Santin, Alessandro D

    2014-01-01

    Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer. Although it only represents less than 10% of all cases, it accounts for a disproportionate number of deaths from endometrial cancer. Comprehensive surgical staging followed by carboplatin and paclitaxel chemotherapy represents the mainstay of USC therapy. Vaginal cuff brachytherapy is also of potential benefit in USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. These results emphasize the relevance of these novel therapeutic targets for biologic therapy of chemotherapy-resistant recurrent USC. PMID:24328598

  14. Should all patients with serous and clear cell endometrial carcinoma receive adjuvant chemotherapy?

    PubMed

    Boren, Todd P; Miller, David S

    2010-11-01

    Uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC) represent two rare subtypes that have an increased risk of recurrence and worse overall survival compared with the more common endometrioid endometrial cancers. Meaningful data in the form of prospective randomized trials is lacking for both advanced and early-stage UPSC and UCCC. Data extrapolated from prospective trials in advanced endometrioid endometrial cancer and retrospective trials on early-stage UPSC suggest that adjuvant platinum and taxane-based chemotherapy may provide a survival benefit for these patients. Future trials specifically examining UPSC and UCCC are needed to elucidate the optimal treatment regimen for these patients. Given the current data, the option of chemotherapy should be considered in treatment-planning discussions for all patients with UPSC and UCCC. PMID:21118038

  15. Long-term survival in uterine clear cell carcinoma and uterine papillary serous carcinoma.

    PubMed

    Lindahl, Bengt; Persson, Jan; Ranstam, Jonas; Willén, Roger

    2010-09-01

    Uterine clear cell carcinoma (UCC) and uterine papillary serous carcinoma (UPSC) are rare entities that differ in clinical behavior from endometrial adenocarcinoma. Compared with endometrioid adenocarcinoma, they more often metastasize early and more commonly in the upper abdomen including the omentum. Treatment programs of UCC and UPSC at different stages vary and range from no adjuvant therapy in stage Ia to a wide variety of chemotherapies and radiotherapies in more advanced stages. This study presents the outcome of 109 patients with UCC or UPSC treated according to essentially the same treatment program from May 1993 to December 2004. Most patients were treated with a simple hysterectomy with no further adjuvant treatment. In stage Ia, 2/46 patients died of their disease and amongst all the stages, 30/109 patients died of their disease. These survival outcomes are comparable to or better than those presented previously. PMID:20944161

  16. Diagnosis of serous tubal intraepithelial carcinoma based on morphologic and immunohistochemical features: a reproducibility study.

    PubMed

    Visvanathan, Kala; Vang, Russell; Shaw, Patricia; Gross, Amy; Soslow, Robert; Parkash, Vinita; Shih, Ie-Ming; Kurman, Robert J

    2011-12-01

    There is compelling evidence that serous tubal intraepithelial carcinoma (STIC) is a precursor of high-grade serous ovarian carcinoma. Large-scale studies are now required to determine its biological significance and clinical implication. Before conducting these studies, a reproducible classification for STIC is needed, and that is the goal of this study. This study involved 6 gynecologic pathologists from 4 academic institutions and 3 independent rounds of review. In round 1, sixty-seven lesions ranging from normal, atypical, to STICs were classified by 5 pathologists on the basis of predetermined morphologic criteria. Interobserver agreement for the diagnosis of STIC versus not STIC was fair [κ = 0.39; 95% confidence interval (CI) 0.26, 0.52], and intraobserver reproducibility ranged from fair to moderate on the basis of percentage agreement and κ. Round 2 involved testing revised criteria that incorporated morphology and immunohistochemistry (IHC) for p53 protein expression and Ki-67 labeling in 10 sets by 3 of the pathologists. The result was an improvement in interobserver agreement for the classification of STIC (κ = 0.62; 95% CI 0.18, 1.00). An algorithm was then created combining morphology and IHC for p53 and Ki-67, and reproducibility was assessed as part of round 3. In 37 lesions reviewed by 6 pathologists, substantial agreement for STIC versus no STIC was observed (κ = 0.73; 95% CI 0.58, 0.86). In conclusion, we have developed reproducible criteria for the diagnosis of STIC that incorporate morphologic and IHC markers for p53 and Ki-67. The algorithm we propose is expected to help standardize the classification of STIC for future studies. PMID:21989347

  17. Relationships between thought suppression and symptoms of borderline personality disorder.

    PubMed

    Sauer, Shannon E; Baer, Ruth A

    2009-02-01

    The current study examined relationships among childhood emotional vulnerability, an invalidating childhood environment, thought suppression, and symptoms of borderline personality disorder (BPD). Emotional vulnerability and an invalidating childhood environment are described by Linehan (1993) as important biosocial precursors to the development of BPD. Using a student sample selected to have a wide range of BPD symptoms, we examined whether thought suppression mediates the relationship between these biosocial precursors and symptoms of BPD. Results supported the hypothesis that thought suppression fully mediates the relationship between invalidating environment and BPD symptoms. Mixed support was found for the hypothesis that thought suppression mediates the relationship between emotional vulnerability and BPD symptoms. We also examined whether fear of emotions mediates the relationship between the biosocial precursors and thought suppression. Results supported this hypothesis, and also suggested that fear of emotion contributes independently to mediating the relationship between biosocial precursors and BPD symptoms. PMID:19267661

  18. Use of Clozapine for Borderline Personality Disorder: A Case Report

    PubMed Central

    Amamou, Badii; Salah, Walid Bel Hadj; Mhalla, Ahmed; Benzarti, Nejla; Elloumi, Hend; Zaafrane, Ferid; Gaha, Lotfi

    2016-01-01

    Patients with borderline personality disorder (BPD) show significant impairment in functioning, particularly in the interpersonal and social domains. Prior reports suggest that clozapine may be effective in the management of BPD. We present the case of a patient with BPD who experienced persistent suicidal ideation and was treated with clozapine at a state psychiatric hospital. After treatment failure with other psychotropic medications, clozapine medication was initiated; not only did suicidal ideation cease, but social and professional functioning also greatly improved to the point of no longer requiring intensive levels of observation or restrictive procedures. Clozapine appears to be efficacious in the management of suicide attempts and self-injurious behavior. Moreover, it appears to be promising as a therapeutic measure for ameliorating the global functioning of patients with severe BPD. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings and to determine optimal dosage. PMID:27121437

  19. Schemas and Borderline Personality Disorder symptoms in incarcerated women.

    PubMed

    Specht, Matt W; Chapman, Alex; Cellucci, Tony

    2009-06-01

    There is increasing interest regarding the role of maladaptive cognition in Borderline Personality Disorder (BPD). The current study examined the relationship between early maladaptive schema (EMS) domains and BPD symptoms as well as whether schema domains account for the relationship between childhood maltreatment and BPD severity. Incarcerated women (N=105) were assessed for BPD symptoms via semi-structured diagnostic interview. Disconnection/Rejection and Impaired Limits were associated with BPD pathology although these domains shared variance with depression and antisocial personality disorder pathology, respectively. In addition, the relationship between childhood abuse and BPD severity was non-significant after controlling for schema domains. Related findings and the implications for cognitive treatment of BPD are discussed. PMID:19159865

  20. Patient-reported outcomes in borderline personality disorder

    PubMed Central

    Hasler, Gregor; Hopwood, Christopher J.; Jacob, Gitta A.; Brändle, Laura S.; Schulte-Vels, Thomas

    2014-01-01

    Patient-reported outcome (PRO) refers to measures that emphasize the subjective view of patients about their health-related conditions and behaviors. Typically, PROs include self-report questionnaires and clinical interviews. Defining PROs for borderline personality disorder (BPD) is particularly challenging given the disorder's high symptomatic heterogeneity, high comorbidity with other psychiatric conditions, highly fluctuating symptoms, weak correlations between symptoms and functional outcomes, and lack of valid and reliable experimental measures to complement self-report data. Here, we provide an overview of currently used BPD outcome measures and discuss them from clinical, psychometric, experimental, and patient perspectives. In addition, we review the most promising leads to improve BPD PROs, including the DSM-5 Section III, the Recovery Approach, Ecological Momentary Assessments, and novel experimental measures of social functioning that are associated with functional and social outcomes. PMID:25152662

  1. The role of mindfulness in borderline personality disorder features.

    PubMed

    Wupperman, Peggilee; Neumann, Craig S; Whitman, Jeannie B; Axelrod, Seth R

    2009-10-01

    This study investigated whether deficits in mindfulness (attention, awareness, and acceptance of the present moment) underlie variability in borderline personality disorder (BPD) features and related impairments in interpersonal functioning, impulsivity, and emotion regulation. A path analytic approach was used to examine the relationships of trait mindfulness with BPD features, interpersonal effectiveness, impulsive and passive emotion-regulation, and neuroticism in a psychiatric sample of adults (N = 70). As hypothesized, mindfulness was associated inversely with BPD features and core areas of dysfunction, and these associations continued when controlling for neuroticism. Furthermore, mindfulness deficits continued to predict BPD features even when interpersonal effectiveness, passive and impulsive emotion-regulation, and neuroticism were controlled. These findings suggest that mindfulness may be a unique predictor for the expression of BPD pathology. An emphasis on mindfulness may thus be crucial in enhancing the formulation and treatment of BPD. PMID:19829206

  2. The Rejection-Rage Contingency in Borderline Personality Disorder

    PubMed Central

    Berenson, Kathy R.; Downey, Geraldine; Rafaeli, Eshkol; Coifman, Karin; Leventhal, Nina

    2011-01-01

    Though longstanding clinical observation reflected in the DSM-IV suggests that the rage characteristic of borderline personality disorder (BPD) often appears in response to perceived rejection, the role of perceived rejection in triggering rage in BPD has never been empirically tested. Extending basic personality research on rejection sensitivity to a clinical sample, a priming-pronunciation experiment and a 21-day experience-sampling diary examined the contingent relationship between perceived rejection and rage in participants diagnosed with BPD compared to healthy controls. Despite the differences in these two assessment methods, the indices of rejection-contingent rage that they produced were both elevated in the BPD group, and were strongly interrelated. They provide corroborating evidence that reactions to perceived rejection significantly explain the rage seen in BPD. PMID:21500875

  3. Adult attachment in the clinical management of borderline personality disorder.

    PubMed

    Fossati, Andrea

    2012-05-01

    Borderline personality disorder (BPD) is a common psychiatric disorder associated with severe functional impairment, high rates of suicide and comorbid psychiatric illness, intensive use of treatment, and high costs to society. The etiology and pathogenesis of BPD are still uncertain, although an interaction between biological and psychosocial factors has been proposed to explain how the condition develops. Attachment disturbances represent one of the developmental risk factors that have been most consistently found to be associated with BPD, with a number of studies reporting a significant strong association between insecure attachment and BPD, notwithstanding the variety of measures and attachment types employed in these studies. In this article, the author first reviews clinical descriptions and research findings concerning the association between attachment disturbances and BPD and then discusses how attachment theory may help clinicians who work with patients with BPD better understand the psychopathology of the illness and plan treatment. PMID:22617081

  4. Suicidal risk and management in borderline personality disorder.

    PubMed

    Goodman, Marianne; Roiff, Tracey; Oakes, Allison H; Paris, Joel

    2012-02-01

    This paper reviews recent advances in our understanding of suicidality in borderline personality disorder (BPD), with a focus on suicide risk assessment, guidelines for treatment, and medicolegal concerns. Relevant material on distinctions between suicide completers and suicide attempters, contributions of published American Psychiatric Association Guidelines, the controversial role of hospitalization, and management strategies regarding litigation is addressed. Despite accumulating data on suicidality in BPD, the current state of knowledge offers only partial clues to help identify the BPD patients most at risk of death by suicide, and offers a limited armamentarium of treatment targeted to suicide prevention, creating discomfort in clinicians and fears regarding litigation in the event of a successful suicide. Promising new interventions include less resource-intensive psychotherapies as well as brief crisis intervention. PMID:22113831

  5. The neurobiology of empathy in borderline personality disorder.

    PubMed

    Ripoll, Luis H; Snyder, Rebekah; Steele, Howard; Siever, Larry J

    2013-03-01

    We present a neurobiological model of empathic dysfunction in borderline personality disorder (BPD) to guide future empirical research. Empathy is a necessary component of interpersonal functioning, involving two distinct, parallel neural networks. One form of empathic processing relies on shared representations (SR) of others' mental states, while the other is associated with explicit mental state attribution (MSA). SR processing is visceral and automatic, contributing to attunement, but also emotional contagion. MSA processing contributes to deliberate, perspectival forms of empathic understanding. Empathic dysfunction in BPD may involve hyper-reactivity of SR networks and impairment of MSA networks. Nevertheless, this empathic dysfunction is subtle, but contributes to interpersonal difficulties. Interaction between genetic factors and traumatic attachment stressors may contribute to development of BPD, with painful attachment insecurity and disorganization affecting SR and MSA network functioning. Future avenues for BPD research will include developmental assessment of attachment and neurobiological functioning under varying conditions. PMID:23389774

  6. Reactivity to sensations in borderline personality disorder: a preliminary study.

    PubMed

    Rosenthal, M Zachary; Ahn, Roianne; Geiger, Paul J

    2011-10-01

    Individuals with borderline personality disorder (BPD) are widely considered to have problems with emotional reactivity. However, the specific kinds of stimuli that are associated with heightened emotional reactivity in BPD have not been well characterized. Thus, it is unclear whether the emotional dysfunction in BPD occurs in response to any emotionally evocative stimuli, or to specific classes of stimuli. In this study, we used subjective measures (self-report and interview-based) to compare reactivity to sensations (auditory, gustatory, olfactory, tactile, visual) between participants with BPD (n = 30) and healthy controls (n = 50). Controlling for trait negative emotional reactivity, individuals with BPD reported being significantly more reactive across sensory stimuli. However, the difference between controls and BPD was significantly greater for reactivity to auditory stimuli compared to other sensory stimuli. Findings from this study provide preliminary data suggesting individuals with BPD may be characterized by heightened self-reported reactivity to aversive sounds. PMID:22023306

  7. Altered state and trait disgust in borderline personality disorder.

    PubMed

    Schienle, Anne; Haas-Krammer, Alexandra; Schöggl, Helmut; Kapfhammer, Hans-Peter; Ille, Rottraut

    2013-02-01

    Clinical experience suggests that the emotion disgust plays an important role in borderline personality disorder (BPD). We investigated 30 female patients with BPD and 30 healthy women who answered different measures of trait disgust, specifically disgust proneness, disgust sensitivity, and self-disgust. Moreover, all participants rated affective facial expressions as well as affective scenes according to perceived or elicited basic emotions. The patients with BPD reported elevated trait disgust, especially for the area of self-disgust. They also rated facial expressions of disgust as more intense than did the healthy women but only when the person who displayed this emotion was male. This sex-specific disgust bias was independent of depression and experienced sexual/physical abuse in the clinical group. Altogether, the patients with BPD showed a broad spectrum of altered disgust processes, which was positively correlated with disorder severity. Consequently, the assessment of disgust reactivity should be introduced as a diagnostic tool for this disorder. PMID:23364118

  8. [Borderline personality disorder: the patients and their relatives].

    PubMed

    Apfelbaum, Sergio; Gagliesi, Pablo

    This present paper reviews the current theories about the borderline personality disorder and their relations with their families and significant others. The biosocial theory states that the relationship between emotional vulnerability and the interactions with family relations seems to explain the problems with DLP clients. This disorder is defined then as an interaction disease. Relatives and significant others usually have symptoms, beliefs, and emotions produced by this interaction. A list of general strategies for the assistance of these clients and their families is introduced: The transformation of the complaint into a problem, the psycho education, the reduction of expressed emotions, the acceptance and the training in different abilities. At the end, the experience with psycho education approach workshops is commented, as well as the use of a psycho educational manual. PMID:15597126

  9. Dream analysis in the psychodynamic psychotherapy of borderline patients.

    PubMed

    Stone, Michael H

    2012-06-01

    Despite Freud's dictum that dreams are the royal road to the unconscious, the use of dream analysis by therapists working with Borderline Personality Disorder and other severe psychiatric conditions has in the past two decades has fallen into a state of decline, if not outright neglect. The reasons why are not altogether clear, though some have said that the growing popularity of ego psychology and other movements in the domain of psychoanalysis have perhaps pushed dream analysis to one side. To me this marginalization seems unjustified. I hope to demonstrate in this article the enduring utility of dream analysis in working with the more severely disordered patients, with the aim of revivifying its application--and its efficacy--in our work with such patients. PMID:23006120

  10. Use of Clozapine for Borderline Personality Disorder: A Case Report.

    PubMed

    Amamou, Badii; Salah, Walid Bel Hadj; Mhalla, Ahmed; Benzarti, Nejla; Elloumi, Hend; Zaafrane, Ferid; Gaha, Lotfi

    2016-05-31

    Patients with borderline personality disorder (BPD) show significant impairment in functioning, particularly in the interpersonal and social domains. Prior reports suggest that clozapine may be effective in the management of BPD. We present the case of a patient with BPD who experienced persistent suicidal ideation and was treated with clozapine at a state psychiatric hospital. After treatment failure with other psychotropic medications, clozapine medication was initiated; not only did suicidal ideation cease, but social and professional functioning also greatly improved to the point of no longer requiring intensive levels of observation or restrictive procedures. Clozapine appears to be efficacious in the management of suicide attempts and self-injurious behavior. Moreover, it appears to be promising as a therapeutic measure for ameliorating the global functioning of patients with severe BPD. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings and to determine optimal dosage. PMID:27121437

  11. Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

    ClinicalTrials.gov

    2016-08-24

    Acinar Cell Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bladder Adenocarcinoma; Bronchioloalveolar Carcinoma; Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Endometrial Adenocarcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; 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 Skin Neoplasm; Malignant Testicular Sex Cord-Stromal Tumor; Metastatic Malignant Neoplasm of Unknown Primary Origin; 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; 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; Pseudomyxoma Peritonei; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous

  12. Identifying Trajectories of Borderline Personality Features in Adolescence

    PubMed Central

    Haltigan, John D.

    2016-01-01

    Objective: To examine trajectories of adolescent borderline personality (BP) features in a normative-risk cohort (n = 566) of Canadian children assessed at ages 13, 14, 15, and 16 and childhood predictors of trajectory group membership assessed at ages 8, 10, 11, and 12. Method: Data were drawn from the McMaster Teen Study, an on-going study examining relations among bullying, mental health, and academic achievement. Participants and their parents completed a battery of mental health and peer relations questionnaires at each wave of the study. Academic competence was assessed at age 8 (Grade 3). Latent class growth analysis, analysis of variance, and logistic regression were used to analyze the data. Results: Three distinct BP features trajectory groups were identified: elevated or rising, intermediate or stable, and low or stable. Parent- and child-reported mental health symptoms, peer relations risk factors, and intra-individual risk factors were significant predictors of elevated or rising and intermediate or stable trajectory groups. Child-reported attention-deficit hyperactivity disorder (ADHD) and somatization symptoms uniquely predicted elevated or rising trajectory group membership, whereas parent-reported anxiety and child-reported ADHD symptoms uniquely predicted intermediate or stable trajectory group membership. Child-reported somatization symptoms was the only predictor to differentiate the intermediate or stable and elevated or rising trajectory groups (OR 1.15, 95% CI 1.04 to 1.28). Associations between child-reported reactive temperament and elevated BP features trajectory group membership were 10.23 times higher among children who were bullied, supporting a diathesis–stress pathway in the development of BP features for these youth. Conclusions: Findings demonstrate the heterogeneous course of BP features in early adolescence and shed light on the potential prodromal course of later borderline personality disorder. PMID:27254092

  13. Toward a genetically-informed model of borderline personality disorder.

    PubMed

    Livesley, John

    2008-02-01

    This article describes a conceptual framework for describing borderline personality disorder (BPD) based on empirical studies of the phenotypic structure and genetic architecture of personality. The proposed phenotype has 2 components: (1) a description of core self and interpersonal pathology-the defining features of personality disorder-as these features are expressed in the disorder; and (2) a set of traits based on the anxious-dependent or emotional dysregulation factor of the four-factor model of PD. Four kinds of traits are described: emotional (anxiousness, emotional reactivity, emotional intensity, and pessimistic-anhedonia), interpersonal (submissiveness, insecure attachment, social apprehensiveness, and need for approval), cognitive (cognitive dysregulation), and self-harm (behaviors and ideas). Formulation of the phenotype was guided by the conceptualization of personality as a system of interrelated sub-systems. The psychopathology associated with BPD involves most components of the system. The trait structure of the disorder is assumed to reflect the genetic architecture of personality and individual traits are assumed to be based on adaptive mechanisms. It is suggested that borderline traits are organized around the trait of anxiousness and that an important feature of BPD is dysregulation of the threat management system leading to pervasive fearfulness and unstable emotions. The interpersonal traits are assumed to be heritable characteristics that evolved to deal with interpersonal threats that arose as a result of social living. The potential for unstable and conflicted interpersonal relationships that is inherent to the disorder is assumed to result from the interplay between the adaptive structure of personality and psychosocial adversity. The etiology of the disorder is discussed in terms of biological and environmental factors associated with each component of the phenotype. PMID:18312122

  14. Borderline personality disorder: a disorder in search of advocacy.

    PubMed

    Zimmerman, Mark

    2015-01-01

    Compared with bipolar disorder, borderline personality disorder (BPD) is as frequent (if not more frequent), as impairing (if not more impairing), and as lethal (if not more lethal). Yet, BPD has received less than one-tenth the funding from the National Institutes of Health than has bipolar disorder. More than other reviewers of the literature on the interface between bipolar disorder and BPD, Paris and Black (Paris J and Black DW (2015) Borderline Personality Disorder and Bipolar Disorder: What is the Difference and Why Does it Matter? J Nerv Ment Dis 203:3-7) emphasize the clinical importance of correctly diagnosing BPD and not overdiagnosing bipolar disorder, with a focus on the clinical feature of affective instability and how the failure to recognize the distinction between sustained and transient mood perturbations can result in misdiagnosing patients with BPD as having bipolar disorder. The review by Paris and Black, then, is more of an advocacy for BPD than other reviews in this area have been. In the present article, the author will illustrate how the bipolar disorder research community has done a superior job of advocating for and "marketing" their disorder compared with researchers of BPD. Specifically, researchers of bipolar disorder have conducted multiple studies highlighting the problem with underdiagnosis, written commentaries about the problem with underdiagnosis, developed and promoted several screening scales to improve diagnostic recognition, published numerous studies of the operating characteristics of these screening measures, attempted to broaden the definition of bipolar disorder by advancing the concept of the bipolar spectrum, and repeatedly demonstrated the economic costs and public health significance of bipolar disorder. In contrast, researchers of BPD have almost completely ignored each of these issues and thus have been less successful in highlighting the public health significance of the disorder. PMID:25536098

  15. Phyllodes tumor of the breast

    PubMed Central

    Herazo, Fernando; Gil, Monica; Echeverri, Carolina; Ángel, Gonzalo; Borrero, Mauricio; Madrid, Jorge; Jaramillo, Ricardo

    2015-01-01

    Introduction: Breast Phyllodes tumors are rare breast tumors present in less than 1% of new cases of breast cancer, usually occurring among middle-aged women (40-50 yrs). Objective: This study shows diagnostic experience, surgical management and follows up of patients with this disease during a period of ten years in a oncology referral center. Methods: Retrospectively, breast cancer registries at the institution were reviewed, identifying 77 patients with Phyllodes tumors between 2002 and 2012, who had been operated on at the Instituto de Cancerología - Clínica Las Américas, in Medellín (Colombia). Clinical and histopathological data belonging to these cases was captured and analyzed and descriptive statistics were used. Results: The follow up median was 22.5 months (IQR: 10.5-60.0), average age was 47.2 yrs (SD: 12.4), mean tumor size was 3.6 cm (SD: 4.6), 88.3% of the patients (68 cases) presented negative margins and none of them received adjuvant chemotherapy. Of the patients with Phyllodes tumors; 33.8% had benign, 31.2% had borderline and 35.0% had malignant tumor. Disease-free survival was 85.8% and overall survival was 94.5%. Discussion: Reported data in this article is in accordance with what has been reported in worldwide literature. In our cohort even the high mean size of the tumors, the risk of local relapse and metastatic disease is low than previously reported in literature. Trials with longer follow up and molecular trials in Phyllodes tumors are necessary to understand the behavior of these tumors in Hispanics population. PMID:26600624

  16. Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma

    PubMed Central

    2010-01-01

    Background Most patients with ovarian cancer are diagnosed with advanced stage disease (i.e., stage III-IV), which is associated with a poor prognosis. Differentially expressed genes (DEGs) in stage III serous ovarian carcinoma compared to normal tissue were screened by a new differential display method, the annealing control primer (ACP) system. The potential targets for markers that could be used for diagnosis and prognosis, for stage III serous ovarian cancer, were found by cluster and survival analysis. Methods The ACP-based reverse transcriptase polymerase chain reaction (RT PCR) technique was used to identify DEGs in patients with stage III serous ovarian carcinoma. The DEGs identified by the ACP system were confirmed by quantitative real-time PCR. Cluster analysis was performed on the basis of the expression profile produced by quantitative real-time PCR and survival analysis was carried out by the Kaplan-Meier method and Cox proportional hazards multivariate model; the results of gene expression were compared between chemo-resistant and chemo-sensitive groups. Results A total of 114 DEGs were identified by the ACP-based RT PCR technique among patients with stage III serous ovarian carcinoma. The DEGs associated with an apoptosis inhibitory process tended to be up-regulated clones while the DEGs associated with immune response tended to be down-regulated clones. Cluster analysis of the gene expression profile obtained by quantitative real-time PCR revealed two contrasting groups of DEGs. That is, a group of genes including: SSBP1, IFI6 DDT, IFI27, C11orf92, NFKBIA, TNXB, NEAT1 and TFG were up-regulated while another group of genes consisting of: LAMB2, XRCC6, MEF2C, RBM5, FOXP1, NUDCP2, LGALS3, TMEM185A, and C1S were down-regulated in most patients. Survival analysis revealed that the up-regulated genes such as DDAH2, RNase K and TCEAL2 might be associated with a poor prognosis. Furthermore, the prognosis of patients with chemo-resistance was predicted to be

  17. The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

    PubMed Central

    Kamieniak, Marta M.; Muñoz-Repeto, Ivan; Borrego, Salud; Hernando, Susana; Hernández-Agudo, Elena; Heredia Soto, Victoria; Márquez-Rodas, Ivan; Echarri, María José; Lacambra-Calvet, Carmen; Sáez, Raquel; Redondo, Andrés; Benítez, Javier

    2016-01-01

    Objective We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. Methods In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients’ survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Results Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. Conclusion Low

  18. Clinicopathological and prognostic impact of human epidermal growth factor receptor type 2 (HER2) and hormone receptor expression in uterine papillary serous carcinoma.

    PubMed

    Togami, Shinichi; Sasajima, Yuko; Oi, Takateru; Ishikawa, Mitsuya; Onda, Takashi; Ikeda, Shun-Ichi; Kato, Tomoyasu; Tsuda, Hitoshi; Kasamatsu, Takahiro

    2012-05-01

    Uterine papillary serous carcinoma (UPSC) is a rare and aggressive variant of endometrial carcinoma. Little is known about the pathological and biological features of this tumor. Human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) expression have an important role in tumor behavior and clinical outcome, but their relevance in UPSC is not clear. In the present study, the immunohistochemical expression of HER2 and HR was assessed in 27 patients with Stage I disease, 13 with Stage II disease, 25 with Stage III disease, and 6 with Stage IV disease. Correlations between HER2 and HR expression and the clinicopathological parameters of UPSC were evaluated using Cox's univariate and multivariate analyses. For all patients, the 5-year recurrence-free survival (RFS) and overall survival (OS) rates were 51% and 66%, respectively; in patients with Stage I, II, III and IV disease, the RFS and OS were 67%/81%, 59%/77%, 43%/54% and 0%/0%, respectively. Of all 71 patients, 14% (10/71) were positive for HER2 and 52% (37/71) were positive for HR. Overexpression of HER2 was correlated with lower OS (P = 0.01), whereas HR overexpression was correlated with higher OS (P = 0.008). In multivariate models, HER2, HR, and histologic subtype were identified as independent prognostic indicators for RFS (P = 0.022, P = 0.018, and P = 0.01, respectively), but HR was the only independent factor associated with OS (P = 0.044). Thus, HER2 and HR are prognostic variables in UPSC, with HR an independent prognostic factor for OS. PMID:22329832

  19. BORDERLINE PERSONALITY DISORDER IN THE MEDICAL SETTING: Suggestive Behaviors, Syndromes, and Diagnoses

    PubMed Central

    Sansone, Lori A.

    2015-01-01

    Borderline personality disorder is a personality dysfunction that is characterized by disinhibition and impulsivity, which oftentimes manifest as self-regulation difficulties. Patients with this disorder have always been present in medical settings, but have been described as “difficult patients” rather than patients with borderline personality disorder. According to empirical findings, a number of behaviors and medical syndromes/diagnoses are suggestive of borderline personality disorder. Suggestive behaviors in the medical setting may include aggressive or disruptive behaviors, the intentional sabotage of medical care, and excessive healthcare utilization. Suggestive medical syndromes and diagnoses in the medical setting may include alcohol and substance misuse (including the abuse of prescription medications), multiple somatic complaints, chronic pain, obesity, sexual impulsivity, and hair pulling. While not all-inclusive or diagnostic, these behaviors and syndromes/diagnoses may invite further clinical evaluation of the patient for borderline personality disorder. PMID:26351624

  20. Primary process thinking, primitive defensive operations and object relationships in borderline and neurotic patients.

    PubMed

    Leichsenring, F

    1991-01-01

    In the present paper Kernberg's hypothesis concerning the connection between primary process thinking on the one hand and primitive defense mechanisms and modes of object relationships on the other hand were tested empirically in a sample of 30 hospitalized borderline and 30 hospitalized neurotic patients. The diagnoses of the patients were given according to the 'Diagnostic Interview for Borderlines' of Gunderson and Kolb, the functions mentioned above were assessed on the basis of the Holtzman Inkblot Technique applying scoring systems of Lerner and coworkers for primitive defense mechanisms and of Urist for the scoring of object relationships to the Holtzman Inkblot Technique. According to the results the hypothesis derived from assumptions of Kernberg could be corroborated. Primary process thinking in borderline patients seems to be closely connected with high levels of anxiety and hostility, projective identification/projection, primitive denial and sadomasochistic relationships. A model for the coming about of primary process thinking in borderline patients is proposed. PMID:2023983

  1. BORDERLINE PERSONALITY DISORDER IN THE MEDICAL SETTING: Suggestive Behaviors, Syndromes, and Diagnoses.

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2015-01-01

    Borderline personality disorder is a personality dysfunction that is characterized by disinhibition and impulsivity, which oftentimes manifest as self-regulation difficulties. Patients with this disorder have always been present in medical settings, but have been described as "difficult patients" rather than patients with borderline personality disorder. According to empirical findings, a number of behaviors and medical syndromes/diagnoses are suggestive of borderline personality disorder. Suggestive behaviors in the medical setting may include aggressive or disruptive behaviors, the intentional sabotage of medical care, and excessive healthcare utilization. Suggestive medical syndromes and diagnoses in the medical setting may include alcohol and substance misuse (including the abuse of prescription medications), multiple somatic complaints, chronic pain, obesity, sexual impulsivity, and hair pulling. While not all-inclusive or diagnostic, these behaviors and syndromes/diagnoses may invite further clinical evaluation of the patient for borderline personality disorder. PMID:26351624

  2. Reasons for Change in Borderline Personality Disorder (and Other Axis II Disorders)

    PubMed Central

    Zanarini, Mary C.

    2008-01-01

    Borderline personality disorder (BPD) is a slow moving disorder. Most patients with BPD improve over time. The reasons for this change are unclear. Both therapy as usual and the reparations that adult life offers can facilitate these changes. PMID:18638649

  3. Stepped care: an alternative to routine extended treatment for patients with borderline personality disorder.

    PubMed

    Paris, Joel

    2013-10-01

    This review examined evidence supporting stepped care for borderline personality disorder as an alternative to routine extended treatment. Empirical studies have shown that patients with borderline personality disorder have a heterogeneous course, but symptomatic improvement can sometimes be relatively rapid. Currently, there is no evidence that any long-term treatment is superior to briefer interventions for borderline personality disorder. Long-term therapy may not be necessary for all patients, and its routine use leads to access problems. A stepped-care model, similar to models applied to other severe mental disorders, might provide a better use of resources. Stepped care can be used to limit the use of expensive programs and reduce waiting lists. Not all patients with borderline personality disorder can be treated briefly, but a stepped-care model allows those with less severe symptoms to be managed with fewer resources, freeing up more time and personnel for the treatment of those who need treatment the most. PMID:23945913

  4. Sinus Tumors

    MedlinePlus

    ... Tumors Nasal Deformities Choanal Atresia Epiphora (Excessive Tearing) Disclosure Statement Printer Friendly Sinus Tumors Abtin Tabaee, MD Introduction Tumors of the nose and paranasal sinuses are rare, accounting for fewer than 1% of all tumors. These ...

  5. Bone tumor

    MedlinePlus

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  6. Recent concepts of ovarian carcinogenesis: type I and type II.

    PubMed

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2014-01-01

    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. PMID:24868556

  7. Mucinous tumors of the ovary: current thoughts on diagnosis and management.

    PubMed

    Brown, Jubilee; Frumovitz, Michael

    2014-06-01

    Mucinous tumors of the ovary represent a spectrum of neoplastic disorders, including benign mucinous cystadenoma, pseudomyxoma peritonei, mucinous tumors of low malignant potential (borderline), and invasive mucinous ovarian carcinoma. These tumors are related closely to each other and are distinct from other histologic subtypes of epithelial ovarian neoplasms from a clinical, histologic, and molecular standpoint. A continuum appears to be present from benign to borderline to malignant, which is different from other types of epithelial ovarian cancer. Mutational profiles are also distinct, as KRAS mutations are common, but p53 and BRCA mutations are infrequent. These characteristics lead to specific biologic behavior and guide both clinical management and research efforts in patients with mucinous ovarian tumors. PMID:24777667

  8. Borderline personality and emotional reactivity to theoretical media events: A pilot study.

    PubMed

    Sansone, Randy A; Wiederman, Michael W; Hatic, Anna; Flath, Laura

    2010-06-01

    Abstract Objective. The purpose of this study was to determine if patients with borderline personality emotionally react any differently than controls to theoretical media events of different valences. Methods. In this cross-sectional sample of convenience, we examined among 70 primary care patients the relationship between borderline personality disorder, according to two diagnostic measures (the borderline personality scale of the Personality Diagnostic Questionaire-4 and the Self-Harm Inventory), and emotional reactions to three types of theoretical media events - positive, negative, and neutral events. Results. Participants with versus without borderline personality evidenced no emotional differences to the various media events according to the Personality Diagnostic Questionnaire-4. However, according to the Self-Harm Inventory, participants with borderline personality symptomatology were more likely to rate neutral events with greater emotional intensity, but not positive or negative events. Conclusions. These findings suggest that patients with borderline personality may tend to respond more dramatically to ambiguous stimuli, such as neutral environmental events. We discuss the potential implications of these findings. PMID:24922472

  9. Banff Borderline Changes Suspicious for Acute T Cell-Mediated Rejection: Where Do We Stand?

    PubMed

    Becker, J U; Chang, A; Nickeleit, V; Randhawa, P; Roufosse, C

    2016-09-01

    The definition of Banff Borderline became ambiguous when the Banff 2005 consensus modified the lower threshold from i1t1 (10-25% interstitial inflammation with mild tubulitis) to i0t1 (0-10% interstitial inflammation with mild tubulitis). We conducted a worldwide survey among members of the Renal Pathology Society about their approach to this diagnostic category. A web-based survey was sent out to all 503 current members (153 respondents). A database search yielded which threshold for Banff i was applied in the most influential manuscripts about Borderline. Among the 139 nephropathologists using the Borderline category, 67% use the Banff 1997 definition, requiring Banff i1. Thirty-seven percent admitted to sometimes exaggerating Banff i in the presence of tubulitis, to reach a diagnosis of Borderline. Forty-eight percent were dissatisfied with the definition of Borderline. The majority of the most influential manuscripts used the 1997 definition, contrary to the current one. There is considerable dissatisfaction with Borderline, and practice in Banff i thresholds is variable. Until additional studies inform a revision, we suggest leaving it to each pathologist's discretion whether to use i0 or i1 as the minimal threshold. In order to avoid future ambiguity, a web-based synopsis of all scattered current Banff definitions and rules should be created. PMID:26988137

  10. Detection of Human Papillomavirus-16 E6-Oncoprotein in Epithelial Ovarian Tumors Samples of Iraqi Patients

    PubMed Central

    Mahmood, Fahem Mohsin; Kadhim, Haider Sabah; Mousa Al Khuzaee, Liqaa Riadh

    2014-01-01

    Background: Human papillomavirus (HPV) is the causal factor for cervical cancer. However, the role of HPV infection in ovarian cancer is unclear. Objectives: This study aimed to determine the presence of human papillomavirus-16 (HPV-16) in ovarian tumor tissues. Patients and Methods: This was a retrospective study, which included 61 Archived human ovarian tumor tissues embedded in paraffin blocks. The ovarian tumor tissues were divided into four groups. The first group was the malignant ovarian epithelial tumor group; it included 31 cases with invasive surface epithelial ovarian tumors. The second group was the borderline epithelial ovarian tumor group: it included four cases with borderline intermediate malignancy. The third group was the benign epithelial ovarian tumors group: it included 18 cases with benign epithelial ovarian tumors. The fourth group had functional ovarian cystic lesions: it included eight cases with non-neoplastic functional ovarian cysts. Sections were made from each of the paraffin embedded blocks and examined using immunohistochemistry to detect HPV 16-E6-oncoprotein in ovarian tumor tissues. Results: Out of the eight cases with functional cysts only one case (12.5%) expressed HPV. No HPV expression was seen in cases with benign and borderline tumors. Out of the 31 cases with one malignant surface epithelial ovarian tumor only three (9.67%) cases expressed HPV. There was no significant statistical difference in HPV expression among neoplastic and non-neoplastic ovarian tumors included in the present study (P= 0.476). Conclusions: HPV type 16 was detected in only 9.67% of malignant epithelial tumors. It appears that HPV infection plays a relatively minor role in the pathogenesis of ovarian carcinomas. PMID:25485061

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

    PubMed

    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

  12. Vitrectomy, argon laser, and gas tamponade for serous retinal detachment associated with an optic disc pit: a case report.

    PubMed Central

    Snead, M P; James, N; Jacobs, P M

    1991-01-01

    We report the case of a 9-year-old boy with a right optic disc pit and associated serous retinal detachment of the macula. This was treated by vitrectomy, endolaser, and gas tamponade as a primary procedure, which resulted in complete resolution. We review the literature and conclude that further reports of the management of this uncommon condition are required so that firmer guidelines on treatment can be established. Images PMID:2043587

  13. Kinase fusions are frequent in Spitz tumors and spitzoid melanomas

    PubMed Central

    Esteve-Puig, Rosaura; Botton, Thomas; Yeh, Iwei; Lipson, Doron; Otto, Geoff; Brennan, Kristina; Murali, Rajmohan; Garrido, Maria; Miller, Vincent A.; Ross, Jeffrey S; Berger, Michael F.; Sparatta, Alyssa; Palmedo, Gabriele; Cerroni, Lorenzo; Busam, Klaus J.; Kutzner, Heinz; Cronin, Maureen T; Stephens, Philip J; Bastian, Boris C.

    2014-01-01

    Spitzoid neoplasms are a group of melanocytic tumors with distinctive histopathologic features. They include benign tumors (Spitz nevi), malignant tumors (spitzoid melanomas), and tumors with borderline histopathologic features and uncertain clinical outcome (atypical Spitz tumors). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbor kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%), and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signaling pathways, are tumorigenic, and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz nevi, 56% of atypical Spitz tumors, and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signaling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms, and may serve as therapeutic targets for metastatic spitzoid melanomas. PMID:24445538

  14. The Effect of Attending Good Psychiatric Management (GPM) Workshops on Attitudes Toward Patients With Borderline Personality Disorder.

    PubMed

    Keuroghlian, Alex S; Palmer, Brian A; Choi-Kain, Lois W; Borba, Christina P C; Links, Paul S; Gunderson, John G

    2016-08-01

    The effect that attending a 1-day workshop on Good Psychiatric Management (GPM) had on attitudes about borderline personality disorder (BPD) was assessed among 297 clinicians. Change was recorded by comparing before and after scores on a 9-item survey previously developed to assess the effects of workshops on Systems Training for Emotional Predictability and Problem Solving (STEPPS). Participants reported decreased inclination to avoid borderline patients, dislike of borderline patients, and belief that BPD's prognosis is hopeless, as well as increased feeling of competence, belief that borderline patients have low self-esteem, feeling of being able to make a positive difference, and belief that effective psychotherapies exist. Less clinical experience was related to an increased feeling of competence and belief that borderline patients have low self-esteem. These findings were compared to those from the STEPPS workshop. This assessment demonstrates GPM's potential for training clinicians to meet population-wide needs related to borderline personality disorder. PMID:26111249

  15. Adopting a Uniform Approach to Site Assignment in Tubo-Ovarian High-Grade Serous Carcinoma: The Time has Come.

    PubMed

    Singh, Naveena; Gilks, C Blake; Hirshowitz, Lynn; Wilkinson, Nafisa; McCluggage, W Glenn

    2016-05-01

    There is currently sufficient evidence that nonuterine high-grade serous carcinoma (HGSC) originates in the fallopian tube in the majority of cases, but this is not uniformly reflected in our diagnostic terminology. This is because there remains wide variation in awareness and acceptance of this evidence, which conflicts with traditional views on origin. Accurate disease classification is fundamental to routine clinical practice and research, particularly at a time when exciting new approaches to therapy, early detection, and prevention are appearing on the horizon. We feel the time has come to minimize individual and institutional variations in practice, and agree on an evidence-based approach to uniform terminology and primary site assignment. In this paper we put forward a proposal for a unified approach based on published research evidence and discuss the reasons why it is vital to agree on a uniform protocol. We propose the term "Tubo-ovarian HGSC" in preference to "pelvic" or "Müllerian," as it accurately reflects the origin of this disease in the vast majority of cases, and is unambiguous, distinguishing it clearly from uterine serous carcinoma and ovarian low-grade serous carcinomas. A detailed protocol for primary site assignment is presented for different scenarios, which is easy to follow and has been developed with a view to promoting a uniform approach worldwide. PMID:26977579

  16. Clear Cell Renal Cell Carcinoma With Borderline Features of Clear Cell Papillary Renal Cell Carcinoma: Combined Morphologic, Immunohistochemical, and Cytogenetic Analysis.

    PubMed

    Williamson, Sean R; Gupta, Nilesh S; Eble, John N; Rogers, Craig G; Michalowski, Susan; Zhang, Shaobo; Wang, Mingsheng; Grignon, David J; Cheng, Liang

    2015-11-01

    Clear cell papillary renal cell carcinoma is increasingly recognized as a distinct tumor with unique morphology, immunohistochemistry, and cytogenetics. Histopathology often mimics clear cell renal cell carcinoma; however, metastasis has not been reported, emphasizing the clinical value of recognizing these likely nonaggressive tumors. We studied tumors with borderline morphology of clear cell papillary renal cell carcinoma, utilizing immunohistochemistry and fluorescence in situ hybridization or karyotyping. Tumors from 22 patients (ages 33 to 82 y) were analyzed. Clear cell papillary renal cell carcinoma-like morphology varied from 10% to 90% of the tumor (median 25%). Sources of resemblance included: branched glands (95%), nuclear alignment (68%), small papillary tufts (32%), focal branching papillae (27%), and prominent papillary structures (9%). Carbonic anhydrase IX uniformly revealed diffuse positivity. Staining for cytokeratin 7 (CK7) was focal (64%) or negative (18%) in most tumors (82%); however, >50% labeling was present in 4 (18%). Reactivity for both CD10 and α-methyl-acyl-CoA-racemase (AMACR) was usually present (median 80% and 60% of cells). Seven tumors showed reactivity for high-molecular weight keratin (32%). Chromosome 3p loss was confirmed in 15 tumors (68%), including 4/7 with labeling for high-molecular weight keratin or >50% reactivity for CK7. A discordant immunohistochemical pattern typically correlates with loss of material from chromosome 3p in tumors with incomplete morphology of clear cell papillary renal cell carcinoma, supporting classification as clear cell renal cell carcinoma. Diffuse labeling for CK7 can uncommonly be observed in clear cell renal cell carcinomas confirmed to have chromosome 3p loss, although these do not exhibit the expected staining pattern of clear cell papillary renal cell carcinoma, including positivity for CD10 and AMACR. PMID:26457355

  17. Standard Setting in a Small Scale OSCE: A Comparison of the Modified Borderline-Group Method and the Borderline Regression Method

    ERIC Educational Resources Information Center

    Wood, Timothy J.; Humphrey-Murto, Susan M.; Norman, Geoffrey R.

    2006-01-01

    When setting standards, administrators of small-scale OSCEs often face several challenges, including a lack of resources, a lack of available expertise in statistics, and difficulty in recruiting judges. The Modified Borderline-Group Method is a standard setting procedure that compensates for these challenges by using physician examiners and is…

  18. Pharmacologic management of borderline personality disorder: a case study.

    PubMed

    Links, Paul S; Cook, Michele; Quastel, Adam

    2005-01-01

    General principles of the "outcome-focused" model of psychopharmacologic management of patients with BPD are illustrated using the case of Ms. A, a patient with borderline personality disorder (BPD) experiencing impulsivity such as suicidal behavior, chronic insomnia and concurrent substance abuse. The model includes (1) measurement of specific behavioral outcomes related to functioning; (2) assessment of the role of substance use/abuse in patients with BPD; (3) consideration of interventions to clarify and strengthen the boundaries of the therapeutic relationship-including short lengths of time between prescription refills, medication contracts outlining consequences if substances are obtained outside of the relationship, and urine testing to ascertain compliance; (4) an understanding of the psychodynamic meanings attributed to medication while positive and negative medication effects are monitored with treatment response or transference issues, and; (5) use of the N-of-1 approach to test the new medication vs previous medications using patient specific outcomes that are anticipated to change with the pharmacologic management. PMID:16459755

  19. Borderline personality disorder: a comparison between children and adults.

    PubMed

    Sharp, Carla; Romero, Catherine

    2007-01-01

    Recently, more empirical studies have been devoted to the investigation of borderline personality disorder (BPD) in children and adolescents. Against this background, the purpose of the current review is to compare research findings on diagnostic-related phenomena in child and adolescent samples with those in adult samples to establish the utility of the BPD construct in childhood and adolescence. A search of relevant publications reported in Pubmed and PsycInfo from 1940 (the first clinical descriptions of BPD in childhood) to 2006 was carried out. A total of 58 studies were included. The review of the adult literature was not exhaustive but relied on excellent existing and comprehensive reviews of the adult literature carried out in the past 5 years. Although significant differences seem to exist between juveniles and adults in diagnostic-related phenomena associated with BPD, these can be explained by the principle of heterotypic continuity in development. Moreover, enough overlap between juvenile and adult BPD has been observed to warrant further empirical investigation into the construct of juvenile BPD. Specific areas for future research in juvenile BPD suggested by this review include studies of comorbidity, measure development, and the use of neurobiological measures such as functional neuroimaging. PMID:17666001

  20. Borderline Personality Disorder as a Female Phenotypic Expression of Psychopathy?

    PubMed Central

    Sprague, Jenessa; Javdani, Shabnam; Sadeh, Naomi; Newman, Joseph P.; Verona, Edelyn

    2011-01-01

    Evidence suggests that the combination of the interpersonal-affective (F1) and impulsive-antisocial (F2) features of psychopathy may be associated with borderline personality disorder (BPD), specifically among women (e.g., Coid, 1993; Hicks, Vaidyana-than, & Patrick, 2010). However, empirical research explicitly examining gendered relationships between BPD and psychopathy factors is lacking. To further inform this area of research, we investigated the hypothesis that the interplay between the two psychopathy factors is associated with BPD among women across two studies. Study 1 consisted of a college sample of 318 adults (51% women), and Study 2 consisted of a large sample of 488 female prisoners. The interpersonal-affective (F1) and impulsiveantisocial psychopathy (F2) scores, measured with self-report and clinician-rated indices, respectively, were entered as explanatory variables in regression analyses to investigate their unique contributions to BPD traits. Across two independent samples, results indicated that the interaction of high F1 and F2 psychopathy scores was associated with BPD in women. This association was found to be specific to women in Study 1. These results suggest that BPD and psychopathy, at least as they are measured by current instruments, overlap in women and, accordingly, may reflect gender-differentiated phenotypic expressions of similar dispositional vulnerabilities. PMID:22452756

  1. Anger, preoccupied attachment, and domain disorganization in borderline personality disorder

    PubMed Central

    Morse, Jennifer Q.; Hill, Jonathan; Pilkonis, Paul A.; Yaggi, Kirsten; Broyden, Nichaela; Stepp, Stephanie; Reed, Lawrence Ian; Feske, Ulrike

    2010-01-01

    Emotional dysregulation and attachment insecurity have been reported in borderline personality disorder (BPD). Domain disorganization, evidenced in poor regulation of emotions and behaviors in relation to the demands of different social domains, may be a distinguishing feature of BPD. Understanding the interplay between these factors may be critical for identifying interacting processes in BPD and potential subtypes of BPD. Therefore, we examined the joint and interactive effects of anger, preoccupied attachment, and domain disorganization on BPD traits in clinical sample of 128 psychiatric patients. The results suggest that these factors contribute to BPD both independently and in interaction, even when controlling for other personality disorder traits and Axis I symptoms. In regression analyses, the interaction between anger and domain disorganization predicted BPD traits. In recursive partitioning analyses, two possible paths to BPD were identified: high anger combined with high domain disorganization and low anger combined with preoccupied attachment. These results may suggest possible subtypes of BPD or possible mechanisms by which BPD traits are established and maintained. PMID:19538080

  2. Construct Validity of the Adolescent Borderline Personality Disorder: A Review

    PubMed Central

    Bondurant, Helen; Greenfield, Brian; Tse, Sze Man

    2004-01-01

    Introduction Although the term borderline personality disorder (BPD) is used to describe adolescents in clinical settings, there is confusion as to what it comprises. To further elucidate that diagnosis, this article reviews its construct validity. Method Relevant publications appearing in PsychInfo (1872 to present) were reviewed for the purposes of this article. Results Thirty-six of the approximately sixty-five publications selected for consideration were included in this review. Conclusion The construct validity of adolescent BPD is supported by internal consistency (comparable to that of adults), group differences (ie this diagnosis segregates BPD from non-BPD adolescents), convergent validity (ie multiple measures of this disorder measure the same pathology) and concurrent validity, whereby these youth manifest functional impairment and distress. By contrast, the adolescent BPD criteria manifest less construct validity than the adult diagnosis in that its criteria did not uniformly predict the overall diagnosis, and showed more criterion overlap with other personality disorders and a broader pattern of axis II comorbidity. Further diminishing its construct validity, factor analysis suggested that adolescent BPD was not a single entity, and its low predictive validity was demonstrated by little diagnostic stability through adolescence into adulthood. PMID:19030500

  3. Sleep disturbances and circadian CLOCK genes in borderline personality disorder.

    PubMed

    Fleischer, Monika; Schäfer, Michael; Coogan, Andrew; Häßler, Frank; Thome, Johannes

    2012-10-01

    Borderline personality disorder (BPD) is characterised by a deep-reaching pattern of affective instability, incoherent identity, self-injury, suicide attempts, and disturbed interpersonal relations and lifestyle. The daily activities of BPD patients are often chaotic and disorganized, with patients often staying up late while sleeping during the day. These behavioural patterns suggest that altered circadian rhythms may be associated with BPD. Furthermore, BPD patients frequently report suffering from sleep disturbances. In this review, we overview the evidence that circadian rhythms and sleep are disturbed in BPD, and we explore the possibility that personality traits that are pertinent for BPD may be associated with circadian typology, and perhaps to circadian genotypes. With regards to sleep architecture, we review the evidence that BPD patients display altered non-REM and REM sleep. A possible cue to a deeper understanding of this temporal dysregulation might be an analysis of the circadian clock at the molecular and cellular level, as well as behavioural studies using actigraphy and we suggest avenues for further exploration of these factors. PMID:22806005

  4. Psychic skin: psychotic defences, borderline process and delusions.

    PubMed

    Schmidt, Martin

    2012-02-01

    In this paper, I apply the concept of psychic skin to analytic work with people suffering from personality disorders and psychoses. When psychoses emerge, the defensive skin which protects the ego is breached and violent unconscious forces rip through the personality. Some of the patients diagnosed as schizophrenic with whom I work have identified with archetypal characters such as Christ, Satan, John Lennon and the Queen. I attempt to show how the adoption of these inflated personas can serve as secondary psychic skins. Such delusional identifications can provide a protective shield to hide the denuded self and prevent intrusion from the external world. Through clinical example, I try to demonstrate how these archetypal 'second skins' can preserve life until internal and external conditions make it possible for the self to emerge. I contrast such psychotic identifications with 'thin-skinned' and 'thick-skinned' narcissism as well as 'defences of the self' in borderline states where the psychic skin may be damaged but does not disintegrate. I also look at the ways in which Jung's own personal experience was different from this and how he managed to avert psychotic breakdown. PMID:22288539

  5. Recovery, as Experienced by Women with Borderline Personality Disorder.

    PubMed

    Larivière, Nadine; Couture, Élise; Blackburn, Catherine; Carbonneau, Manon; Lacombe, Christophe; Schinck, Shella-Ann; David, Pierre; St-Cyr-Tribble, Denise

    2015-12-01

    Studies examining recovery through the service users' perspectives have mainly included persons with schizophrenia or bipolar disorder. Giving voice to those with borderline personality disorder (BPD) would enrich our understanding of recovery, as their specific experiences may bring new dimensions, obstacles and facilitators. The objective of this study was to qualitatively capture the experience of recovery in women with BPD. Participants were women between 18 and 65 years old who had a diagnosis of BPD and completed at least 2 years in a program for persons with BPD. During the first meeting, they produced a picture collage, followed by an interview on their experience of recovery. The second meeting was a phone interview to discuss new thoughts. In addition, their medical records were reviewed. A thematic analysis of the interviews was conducted and organized with the Person-Environment-Occupation model. Although recovery was not the best term to name their experience, they all talked about a process towards stability and wellbeing (n = 12). Dimensions of recovery included, for example, letting go of the past (person), being involved in meaningful activities (occupation) and having healthy relationships (environment). Facilitators included social support and participation in a specialized therapy program. The main obstacle was unstable family relationships. The findings from this study showed similar dimensions to previous recovery studies, new perspectives on certain dimensions, as well as new ones. They also reinforced the importance to incorporate intervention outcomes that target the person with BPD, their social environment and meaningful occupations. PMID:25736797

  6. Borderlines between Sarcopenia and Mild Late-Onset Muscle Disease

    PubMed Central

    Palmio, Johanna; Udd, Bjarne

    2014-01-01

    Numerous natural or disease-related alterations occur in different tissues of the body with advancing age. Sarcopenia is defined as age-related decrease of muscle mass and strength beginning in mid-adulthood and accelerating in people older than 60 years. Pathophysiology of sarcopenia involves both neural and muscle dependent mechanisms and is enhanced by multiple factors. Aged muscles show loss in fiber number, fiber atrophy, and gradual increase in the number of ragged red fibers and cytochrome c oxidase-negative fibers. Generalized loss of muscle tissue and increased amount of intramuscular fat are seen on muscle imaging. However, the degree of these changes varies greatly between individuals, and the distinction between normal age-related weakening of muscle strength and clinically significant muscle disease is not always obvious. Because some of the genetic myopathies can present at a very old age and be mild in severity, the correct diagnosis is easily missed. We highlight this difficult borderline zone between sarcopenia and muscle disease by two examples: LGMD1D and myotonic dystrophy type 2. Muscle magnetic resonance imaging (MRI) is a useful tool to help differentiate myopathies from sarcopenia and to reach the correct diagnosis also in the elderly. PMID:25324776

  7. Enhanced emotion-induced amnesia in borderline personality disorder

    PubMed Central

    HURLEMANN, RENÉ; HAWELLEK, BARBARA; MAIER, WOLFGANG; DOLAN, RAYMOND J.

    2009-01-01

    Background Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion–episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence. Method To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls. Results BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects. Conclusion These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD. PMID:17224096

  8. Social perspective coordination in youth with borderline personality pathology.

    PubMed

    Jennings, Tarni C; Hulbert, Carol A; Jackson, Henry J; Chanen, Andrew M

    2012-02-01

    This study investigated social perspective coordination (SPC) in youth (15-24-year-olds) with first-presentation borderline personality disorder (BPD). SPC is defined as the capacity to differentiate and integrate the perspective of the self with the perspectives of others (Selman, Beardslee, Schultz, Krupa, & Podorefsky, 1986). Two groups: patients with full or sub-syndromal BPD (n = 30) and patients with major depressive disorder (MDD; n = 30) completed measures of SPC derived from the interpersonal negotiation strategies (INS) model (Selman et al., 1986). Compared with the MDD group, the BPD group responded to all vignettes with significantly lower SPC scores and SPC was a significant predictor of BPD status over and above self-reported, personality factors (Neuroticism and Agreeableness), attachment disturbance and functional impairment. These findings suggest that disturbances in social cognition are an important characteristic of individuals with BPD pathology. These difficulties extended beyond attachment contexts and were not limited to situations involving BPD-related themes of abandonment, deprivations or mistrust/abuse. PMID:22369170

  9. Aggression in borderline personality disorder: A multidimensional model.

    PubMed

    Mancke, Falk; Herpertz, Sabine C; Bertsch, Katja

    2015-07-01

    This article proposes a multidimensional model of aggression in borderline personality disorder (BPD) from the perspective of the biobehavioral dimensions of affective dysregulation, impulsivity, threat hypersensitivity, and empathic functioning. It summarizes data from studies that investigated these biobehavioral dimensions using self-reports, behavioral tasks, neuroimaging, neurochemistry as well as psychophysiology, and identifies the following alterations: (a) affective dysregulation associated with prefrontal-limbic imbalance, enhanced heart rate reactivity, skin conductance, and startle response; (b) impulsivity also associated with prefrontal-limbic imbalance, central serotonergic dysfunction, more electroencephalographic slow wave activity, and reduced P300 amplitude in a 2-tone discrimination task; (c) threat hypersensitivity associated with enhanced perception of anger in ambiguous facial expressions, greater speed and number of reflexive eye movements to angry eyes (shown to be compensated by exogenous oxytocin), enhanced P100 amplitude in response to blends of happy versus angry facial expressions, and prefrontal-limbic imbalance; (d) reduced cognitive empathy associated with reduced activity in the superior temporal sulcus/gyrus and preliminary findings of lower oxytocinergic and higher vasopressinergic activity; and (e) reduced self-other differentiation associated with greater emotional simulation and hyperactivation of the somatosensory cortex. These biobehavioral dimensions can be nicely linked to conceptual terms of the alternative Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) model of BPD, and thus to a multidimensional rather than a traditional categorical approach. PMID:26191822

  10. Facial expression of emotions in borderline personality disorder and depression.

    PubMed

    Renneberg, Babette; Heyn, Katrin; Gebhard, Rita; Bachmann, Silke

    2005-09-01

    Borderline personality disorder (BPD) is characterized by marked problems in interpersonal relationships and emotion regulation. The assumption of emotional hyper-reactivity in BPD is tested regarding the facial expression of emotions, an aspect highly relevant for communication processes and a central feature of emotion regulation. Facial expressions of emotions are examined in a group of 30 female inpatients with BPD, 27 women with major depression and 30 non-patient female controls. Participants were videotaped while watching two short movie sequences, inducing either positive or negative emotions. Frequency of emotional facial expressions and intensity of happiness expressions were examined, using the Emotional Facial Action Coding System (EMFACS-7, Friesen & Ekman, EMFACS-7: Emotional Facial Action Coding System, Version 7. Unpublished manual, 1984). Group differences were analyzed for the negative and the positive mood-induction procedure separately. Results indicate that BPD patients reacted similar to depressed patients with reduced facial expressiveness to both films. The highest emotional facial activity to both films and most intense happiness expressions were displayed by the non-clinical control group. Current findings contradict the assumption of a general hyper-reactivity to emotional stimuli in patients with BPD. PMID:15950175

  11. Comorbid antisocial and borderline personality disorders: mentalization-based treatment.

    PubMed

    Bateman, Anthony; Fonagy, Peter

    2008-02-01

    Mentalization is the process by which we implicitly and explicitly interpret the actions of ourselves and others as meaningful based on intentional mental states (e.g., desires, needs, feelings, beliefs, and reasons). This process is disrupted in individuals with comorbid antisocial (ASPD) and borderline personality disorder (BPD), who tend to misinterpret others' motives. Antisocial characteristics stabilize mentalizing by rigidifying relationships within prementalistic ways of functioning. However, loss of flexibility makes the person vulnerable to sudden collapse when the schematic representation is challenged. This exposes feelings of humiliation, which can only be avoided by violence and control of the other person. The common path to violence is via a momentary inhibition of the capacity for mentalization. In this article, the authors outline their current understanding of mentalizing and its relation to antisocial characteristics and violence. This is illustrated by a clinical account of mentalization-based treatment adapted for antisocial personality disorder. Treatment combines group and individual therapy. The focus is on helping patients maintain mentalizing about their own mental states when their personal integrity is challenged. A patient with ASPD does not have mental pain associated with another's state of mind; thus, to generate conflict in ASPD by thinking about the victim will typically be ineffective in inducing behavior change. PMID:18186112

  12. [Comorbid antisocial and borderline personality disorders: mentalization-based treatment].

    PubMed

    Bateman, Anthony; Fonagy, Peter

    2010-01-01

    Mentalization is the process by which we implicitly and explicitly interpret the actions of ourselves and others as meaningful based on intentional mental states (e.g., desires, needs, feelings, beliefs, and reasons). This process is disrupted in individuals with comorbid antisocial (ASPD) and borderline personality disorder (BPD), who tend to misinterpret others' motives. Antisocial characteristics stabilize mentalizing by rigidifying relationships within prementalistic ways of functioning. However, loss of flexibility makes the person vulnerable to sudden collapse when the schematic representation is challenged. This exposes feelings of humiliation, which can only be avoided by violence and control of the other person. The common path to violence is via a momentary inhibition of the capacity for mentalization. In this article, the authors outline their current understanding of mentalizing and its relation to antisocial characteristics and violence. This is illustrated by a clinical account of mentalization-based treatment adapted for antisocial personality disorder. Treatment combines group and individual therapy. The focus is on helping patients maintain mentalizing about their own mental states when their personal integrity is challenged. A patient with ASPD does not have mental pain associated with another's state of mind; thus, to generate conflict in ASPD by thinking about the victim will typically be ineffective in inducing behavior change. PMID:20795523

  13. Maternal Borderline Personality Disorder Symptoms and Parenting of Adolescent Daughters

    PubMed Central

    Zalewski, Maureen; Stepp, Stephanie D.; Scott, Lori N.; Whalen, Diana J.; Beeney, Joseph F.; Hipwell, Alison E.

    2014-01-01

    Maternal borderline personality disorder (BPD) symptoms are associated with poorer parenting. However, most studies conducted are with young children. In the current study, the authors examined associations between maternal BPD symptoms and parenting in an urban community sample of 15- to 17-year-old girls (n = 1,598) and their biological mothers. Additionally, the authors tested the impact of adolescent temperament on these associations. Mothers reported on their own psychopathology and their daughters' temperament. Adolescent girls reported on mothers' parenting methods in terms of psychological and behavioral control. Results demonstrated that maternal BPD symptoms were associated with aspects of psychological and behavioral control, even after controlling for maternal depression and alcohol use severity. After examining specific BPD components that may account for these associations, the authors found that affective/behavioral dysregulation, but not interpersonal dysregulation or identity disturbance, uniquely accounted for parenting. Adolescent temperament did not moderate these associations. BPD symptoms, particularly affective/behavioral dysregulation, are important targets when conducting parenting interventions. PMID:24689767

  14. Volume of hippocampal substructures in borderline personality disorder.

    PubMed

    Kreisel, Stefan Henner; Labudda, Kirsten; Kurlandchikov, Oleg; Beblo, Thomas; Mertens, Markus; Thomas, Christine; Rullkötter, Nina; Wingenfeld, Katja; Mensebach, Christoph; Woermann, Friedrich G; Driessen, Martin

    2015-03-30

    Borderline personality disorder (BPD) may be associated with smaller hippocampi in comparison to hippocampal size in controls. However, specific pathology in hippocampal substructures (i.e., head, body and tail) has not been sufficiently investigated. To address hippocampal structure in greater detail, we studied 39 psychiatric inpatients and outpatients with a DSM-IV diagnosis of BPD and 39 healthy controls. The hippocampus and its substructures were segmented manually on magnetic resonance imaging scans. The volumes of hippocampal substructures (and total hippocampal volume) did not differ between BPD patients and controls. Exploratory analysis suggests that patients with a lifetime history of posttraumatic stress disorder (PTSD) may have a significantly smaller hippocampus - affecting both the hippocampal head and body - in comparison to BPD patients without comorbid PTSD (difference in total hippocampal volume: -10.5%, 95%CI -2.6 to -18.5, significant). Also, patients fulfilling seven or more DSM-IV BPD criteria showed a hippocampal volume reduction, limited to the hippocampal head (difference in volume of the hippocampal head: -16.5%, 95%CI -6.1 to -26.8, significant). Disease heterogeneity in respect to, for example, symptom severity and psychiatric comorbidities may limit direct comparability between studies; the results presented here may reflect hippocampal volumes in patients who are "less" affected or they may simply be a chance finding. However, there is also the possibility that global effects of BPD on the hippocampus may have previously been overestimated. PMID:25624067

  15. Exploration of microstructural abnormalities in borderline personality disorder

    NASA Astrophysics Data System (ADS)

    Fritzsche, Klaus H.; Brunner, Romuald; Henze, Romy; Meinzer, Hans-Peter; Stieltjes, Bram

    2012-03-01

    As with other mental disorders, the causes of borderline personality disorder (BPD) are complex and not fully understood. In this study we aimed to determine whether adults with BPD exhibit microstructural abnormalities using diffusion tensor imaging (DTI). 56 female right-handed individuals (age range, 14-18 years), 19 with a DSM-IV diagnosis of BPD, 18 patients with a DSM-IV defined current psychiatric disorder and 19 healthy control subjects were included. Groups were matched for age and IQ. DTI Images were analyzed using Tract-Based Spatial Statistics (TBSS). The analysis revealed significanty reduced fractional anisotropy (FA) values in the group of BPD patients compared to the normal controls. Similar FA reductions could not be found comparing BPD patients to clinical controls. Several clusters of increased radial (DR), axial (DA), and mean (MD) diffusivity were consistently identified when comparing the BPD patients to clinical as well as to healthy controls. None of the measures showed significant differences between the clinical and healthy controls. Diverse possible factors have been suggested to play a role in the disease, including environmental factors, neurobiological factors, or brain abnormalities. The presented results may play an important role in this ongoing debate.

  16. Personality Profile of Women Affected with Borderline Personality Disorder

    PubMed Central

    Nasiri, Hamid; Abedi, Ahmad; Ebrahimi, Amrollah; Ameli, Sedigheh Sadr; Samouei, Rahele

    2013-01-01

    Introduction: The main objective of the present study is to review the psychological profile of female patients with borderline personality disorder in the women referring to the Centers of Counseling and Psychological Services at Isfahan city based on MMPI-2 test and comparing them with ordinary women. Method: The present study is of the type of cause-comparative and the selection of examinees was done in form of random sampling with 50 women with the BPD and 50 ordinary women and through confirmation of test recognition of MCMI-III and clinical interviews. In addition, 370 questions of MMPI-2 have also been implemented. Results: The results of this research showed a significant difference in validity of scales and the clinical scales of MMPI-2 test among women with BPD and regular women. The results of MANOVA test with the power of valuable test confirmed the existing differences. Conclusion: The obtained results shows that female patients with BPD has a specific and different psychological profile as compared with ordinary (regular) women and the obtained profile can be used in recognition and forecasting any disorder. PMID:23687463

  17. [Electroconvulsive therapy for major depression in borderline personality disorder].

    PubMed

    Gescher, D M; Malevani, J

    2012-03-01

    Depressive disorder is a serious and frequent complication in borderline personality disorder (BPD), however, its severity tends to be neglected particularly if symptoms are short-lived or inconsistent as is common in patients with BPD. Yet the high frequency in these patients requires especially rapid and effective therapy to reduce the risks of vital endangerment, chronification and psychosocial impairment. Efficient crisis intervention is essential for continuity of the disease-specific multimodal therapy enabling lasting remission and social and vocational rehabilitation in BPD. In particular with regard to the high incidence of poor or failed pharmacological responses in patients with BPD, electroconvulsive therapy (ECT) is of significant relevance among antidepressant treatment options. Despite the wide consensus on its efficacy, there are only few selected trials on ECT for major depression (MD) in BPD. This review summarises the published original studies on this issue, and critically scrutinises indication, benefits and risks of ECT for MD in BPD. It contributes to a focused, discriminating view on ECT and thus enables an optimised patient-oriented, efficient indication for MD in BPD. PMID:21678232

  18. Borderline personality disorder: a dysregulation of the endogenous opioid system?

    PubMed

    Bandelow, Borwin; Schmahl, Christian; Falkai, Peter; Wedekind, Dirk

    2010-04-01

    The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids constitute part of the underlying pathophysiology of BPD. The alarming symptoms and self-destructive behaviors of the affected patients may be explained by uncontrollable and unconscious attempts to stimulate their endogenous opioid system (EOS) and the dopaminergic reward system, regardless of the possible harmful consequences. Neurobiological findings that support this hypothesis are reviewed: Frantic efforts to avoid abandonment, frequent and risky sexual contacts, and attention-seeking behavior may be explained by attempts to make use of the rewarding effects of human attachment mediated by the EOS. Anhedonia and feelings of emptiness may be an expression of reduced activity of the EOS. Patients with BPD tend to abuse substances that target mu-opioid receptors. Self-injury, food restriction, aggressive behavior, and sensation seeking may be interpreted as desperate attempts to artificially set the body to survival mode in order to mobilize the last reserves of the EOS. BPD-associated symptoms, such as substance abuse, anorexia, self-injury, depersonalization, and sexual overstimulation, can be treated successfully with opioid receptor antagonists. An understanding of the neurobiology of BPD may help in developing new treatments for patients with this severe disorder. PMID:20438240

  19. The diagnostic value of frozen section for borderline ovarian tumours.

    PubMed

    Bozdag, Halenur; Guzin, Kadir; Gocmen, Ahmet; Kabaca, Sedef; Usta, Akın; Akdeniz Duran, Esra

    2016-07-01

    Borderline ovarian tumours (BOTs) are characterised histologically by a low degree of cellular proliferation and nuclear atypia in the absence of infiltrative growth or stromal invasion. Surgical treatment has been a crucial component of BOT therapy. Surgical decisions are established intraoperatively via the frozen section. We evaluated the accuracy of frozen section diagnosis. The rate of correct diagnosis, underdiagnosis and overdiagnosis of BOTs with frozen sections was 78%, 17% and 5%, respectively. The sensitivity and positive predictive values for the diagnosis of BOTs with frozen sections were 82.3% and 93.3%, respectively. The positive likelihood ratio was 0.82 (95% CI: 0.85-0.96). The histological classification of BOTs had a significant effect on the accuracy of diagnosis (p = 0.001). Frozen section diagnosis is not suitable to be considered as the gold standard for a definitive diagnosis. Clinicians should be aware that using frozen sections is insufficient for the accurate staging of BOTs. PMID:26790979

  20. Borderline Personality Disorder in the Emergency Department: Good Psychiatric Management.

    PubMed

    Hong, Victor

    2016-01-01

    Patients with borderline personality disorder (BPD) are high utilizers of psychiatric emergency services and present unique challenges in that setting. Frequently advised to visit an emergency department (ED) if safety is in question, their experiences once there often do not have beneficial effects. Issues specific to patients with BPD in the ED include volatile interactions with staff, repeat visits, concerns about safety (and liability), and disposition. Emergency department staff attitudes toward these patients are frequently negative when compared to patients with other diagnoses, and can detrimentally affect outcomes and perpetuate stigma regarding BPD. These attitudes are often due to lack of education and training about how to understand, approach, and treat the patient with BPD. The limited literature regarding the treatment of BPD in the ED offers few guidelines. This article presents an approach based on Good Psychiatric Management that can reduce negative reactions by ED staff and make ED visits more effective and less harmful. Relevant principles include psychoeducation, the reinforcement of the connection between symptoms and interpersonal stressors, and employment of an active, authentic therapeutic stance. Training ED staff in these principles could lead to attitudinal changes, reduced stigma, and potentially improved outcomes. PMID:27603743

  1. Brain structure and function in borderline personality disorder.

    PubMed

    O'Neill, Aisling; Frodl, Thomas

    2012-10-01

    The spotlight on borderline personality disorder (BPD) has been growing in recent years, with the number of papers discussing potential causes and triggers of the disorder rapidly on the increase. Also on the increase, though still lacking sufficient numbers to produce well-supported hypotheses, are studies employing neuroimaging techniques as investigative tools in BPD. In this review, we investigate the current state and findings of neuroimaging studies in BPD, focusing in particular, on the studies examining structural, functional, and neurometabolic abnormalities in the disorder. Some suspected trends in the data are highlighted, including reductions in the hippocampi and amygdalae of BPD patients compared to healthy controls, exaggerated amygdala activity in BPD patients when confronted with emotion-related stimulus, and negative correlations between increases in left amygdalar creatine and reductions in amygdalar volume, reductions in absolute N-acetylaspartate concentration in the dorsolateral prefrontal cortex of BPD patients, and increases in glutamate concentration in the anterior cingulate cortices of BPD patients. We also discuss the limitations of some of the current studies including hindrances due to sample effects and techniques used and the potential of future neuroimaging research in BPD. PMID:22252376

  2. Clinical and cytopathological aspects in phyllodes tumors of the breast.

    PubMed

    Pătraşcu, Anca; Popescu, Carmen Florina; Pleşea, I E; Bădulescu, Adriana; Tănase, Florentina; Mateescu, Garofiţa

    2009-01-01

    The frequency of mesenchymal breast tumors is very low, being represented mostly by tumors with biphasic proliferation (phyllodes tumors) and less by other types of non-epithelial tumors. From clinical point of view, phyllodes tumors (PT) can mimic a breast carcinoma. Therefore, the preoperative diagnosis by cytological examination on material obtained by fine needle aspiration (FNA) is very important for adequate treatment of these tumors. In current study, we assessed clinical aspects of 79 phyllodes tumors regarding patient's age and localization of the tumors. In 17 out of 79 cases, it has been performed FNA within the tumors with further cytological examination on the smears obtained. The median age of the patients was 46.07-year-old, being progressively higher with grade of the tumors with significant values between benign and borderline tumors (p=0.04954) and between benign and malignant ones (p=0.02890). The distinguish on the smears of stromal fragments and naked stromal nuclei with variable grade of atypia regarding the tumoral type, in detriment of epithelial elements have been conclusive for fibroepithelial lesion as cytopathological diagnosis. The preoperative differentiation between a breast phyllodes tumor and a breast carcinoma is extremely important for avoiding of a useless radical surgery for the patient. If the fine needle aspiration was correctly performed, the accuracy of the cytodiagnosis has been 82% in current study. PMID:19942954

  3. Endosalpingiosis in Conjunction with Ovarian Serous Cystadenoma Mimicking Metastatic Ovarian Malignancy

    PubMed Central

    Singhania, Namrata; Janakiraman, Neha; Coslett, Douglas; Ahmad, Navid

    2014-01-01

    Patient: Female, 26 Final Diagnosis: Endosalpingiosis Symptoms: Chronic pelvic pain Medication: — Clinical Procedure: Diagnostic laproscopy (conservative management) Specialty: Obstetrics and Gynecology Objective: Challenging differential diagnosis Background: Interesting and unusual case of endosalpingiosis mimicking ovarian malignancy presentation. Case Report: A 26-year-old G0P0 white female presented to our office with chronic pelvic pain. On vaginal examination, a nontender mass in left the adnexal region was palpable. Transvaginal ultrasound showed a left ovarian cyst. Laparoscopy was performed, which revealed diffuse bilateral ovarian excrescences with unusual multiple studdings throughout the peritoneum and abdominal cavity. Due to a suspicion of malignancy, a biopsy specimen was obtained for frozen sectioning. The specimen proved to be consistent with benign papillary serous cystadenofibroma. Gross appearance was still suspicious for malignancy and therefore left paraovarian cystectomy was performed. Additional specimens showed ovarian adenofibroma and endosalpingiosis. The patient’s complaint of pelvic pain improved after laparoscopy. Due to diffuse presentation of endosalpingiosis in the peritoneum, serial CT scan of abdomen and pelvis at 6-month intervals was recommended. Conclusions: To our knowledge, this is an unusual case of a young, nulliparous female presenting with diffuse-presentation endosalpingiosis in the abdomen and peritoneum, which on gross examination was suspicious for malignancy. By following a conservative approach and performing serial CT scans, the patient will be clinically monitored. PMID:25180540

  4. YAP induces high-grade serous carcinoma in fallopian tube secretory epithelial cells.

    PubMed

    Hua, G; Lv, X; He, C; Remmenga, S W; Rodabough, K J; Dong, J; Yang, L; Lele, S M; Yang, P; Zhou, J; Karst, A; Drapkin, R I; Davis, J S; Wang, C

    2016-04-28

    Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In this study, we found that the Hippo/Yes-associated protein (YAP) signaling pathway has a critical role in the initiation and progression of fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine-positive feedback loop to drive the progression of the FTSEC-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGF receptors (such as BGJ398) can provide a novel therapeutic strategy to treat fallopian tube and ovarian HGSC. PMID:26364602

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

    PubMed

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

    2015-07-01

    High-grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost-effective and high-throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman-based (low-density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin-fixed, paraffin-embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo-naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. PMID:25810134

  6. Intravitreal Injection of Dexamethasone Implant in Serous Macular Detachment Associated with Waldenström's Disease

    PubMed Central

    Fenicia, Vito; Balestrieri, Marco; Perdicchi, Andrea; Maraone, Giorgia; Recupero, Santi Maria

    2013-01-01

    Purpose To evaluate the efficacy of one intravitreal injection of dexamethasone (Ozurdex®; Allergan, Inc., Irvine, Calif., USA) in serous macular detachment (SMD) of one eye, associated with bilateral central retinal vein occlusion (CRVO) in a patient affected by Waldenström's macroglobulinemia (WM). Patients and Methods A female patient, affected by WM, complained of a progressive decrease in visual acuity, mainly in the left eye (LE). SMD in the LE associated with bilateral CRVO was diagnosed. One intravitreal injection of dexamethasone was administered in the LE and the patient was tested 1, 2, and 6 months after the injection. Results 1, 2, and 6 months after the injection, the spectral domain optical coherence tomography (SD-OCT) showed a progressive slight reduction of foveal thickness that was not related to any improvement of visual function. Conclusions Treatment with dexamethasone (Ozurdex) induced a progressive slight reduction of SMD but no improvement of visual acuity, and it is possible that this is related to the condition of hematic hyperviscosity that is present in WM. PMID:24019788

  7. Bilateral Serous Retinal Detachment Associated with Inferior Posterior Staphyloma Treated with Scleral Shortening and Vitrectomy

    PubMed Central

    Kasai, Akihito; Kanda, Naotaka; Sekiryu, Tetsuju

    2016-01-01

    Purpose We report a case of bilateral serous retinal detachment (SRD) associated with inferior posterior staphyloma (IPS) treated successfully with scleral shortening. Patient and Methods A 63-year-old woman presented with bilateral visual loss due to an SRD with IPS. The best-corrected visual acuity levels were 0.6 (20/30) and 0.5 (20/40) in the right and left eye, respectively. The patient underwent vitrectomy and scleral shortening in the right eye. The lamellar scleral crescent was resected 4 mm in width from the 5- to 8-o'clock positions. Seven interrupted 5-0 polyester sutures were placed at the edge of the lamellar scleral crescent. After 25-gauge three-port vitrectomy, the sutures were tightened. Optical coherence tomography showed decreased curvature at the staphyloma border. The choroidal thickness decreased in the superior flat portion of the fundus and increased slightly in the staphyloma. The SRD resolved 3 months postoperatively. The best-corrected visual acuity in the right eye improved to 0.8 (20/25) 6 months postoperatively. Angiography 6 months postoperatively showed decreased diffuse dye leakage at the fovea in the right eye; indocyanine green angiography did not show marked changes. Discussion Scleral shortening with vitrectomy changes the eye wall shape, may improve the retinal pigment epithelial integrity, and may be a treatment option for SRD with IPS PMID:27403132

  8. Multimodal Imaging Evaluations of Focal Choroidal Excavations in Eyes with Central Serous Chorioretinopathy

    PubMed Central

    Chen, Zhi-Qing; Wang, Wei

    2016-01-01

    Purpose. To investigate the prevalence and characteristics of focal choroidal excavation (FCE) concurrent with central serous chorioretinopathy (CSC) using multimodal imaging. Methods. This was a retrospective single-institution study. Clinical features and multimodal imaging findings were analyzed in eyes with CSC and FCEs, using imaging methods including optical coherence tomography (OCT), OCT angiography (OCTA), fluorescein angiography (FA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), and multispectral imaging. Results. Seventeen patients (4.8%) with 21 FCEs (19 eyes) were found among 351 consecutive Chinese patients with CSC. Chronic CSC represented 47.1% of those cases. Window defects in 12 lesions identified through FA and hypoautofluorescence in 13 lesions identified through FAF revealed retinal pigment epithelial attenuation. Choroidal hemodynamic disturbances characterized by localized filling defects at the excavation and circumferential hyperperfusion were validated by both ICGA and OCTA, which were similar to the angiographic features of normal chronic CSC. The hyperreflective tissue beneath FCE, observed on B-scan OCT, presented as intensive choroidal flow signals on OCTA. Conclusions. FCE is not uncommon in patients with CSC. Multimodal imaging suggested that the aberrant choroidal circulation might be a contribution factor for leakage from the dysfunctional retinal pigment epithelium at the area of excavation. PMID:27437148

  9. High levels of genomic aberrations in serous ovarian cancers are associated with better survival.

    PubMed

    Baumbusch, Lars O; Helland, Åslaug; Wang, Yun; Liestøl, Knut; Schaner, Marci E; Holm, Ruth; Etemadmoghadam, Dariush; Alsop, Kathryn; Brown, Pat; Mitchell, Gillian; Fereday, Sian; DeFazio, Anna; Bowtell, David D L; Kristensen, Gunnar B; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise

    2013-01-01

    Genomic instability and copy number alterations in cancer are generally associated with poor prognosis; however, recent studies have suggested that extreme levels of genomic aberrations may be beneficial for the survival outcome for patients with specific tumour types. We investigated the extent of genomic instability in predominantly high-grade serous ovarian cancers (SOC) using two independent datasets, generated in Norway (n = 74) and Australia (n = 70), respectively. Genomic instability was quantified by the Total Aberration Index (TAI), a measure of the abundance and genomic size of copy number changes in a tumour. In the Norwegian cohort, patients with TAI above the median revealed significantly prolonged overall survival (p<0.001) and progression-free survival (p<0.05). In the Australian cohort, patients with above median TAI showed prolonged overall survival (p<0.05) and moderately, but not significantly, prolonged progression-free survival. Results were confirmed by univariate and multivariate Cox regression analyses with TAI as a continuous variable. Our results provide further evidence supporting an association between high level of genomic instability and prolonged survival of high-grade SOC patients, possibly as disturbed genome integrity may lead to increased sensitivity to chemotherapeutic agents. PMID:23372714

  10. A novel mutation of sgk-1 gene in central serous chorioretinopathy

    PubMed Central

    Akyol, Mahmut; Erol, Muhammet Kazım; Ozdemir, Ozdemir; Coban, Deniz Turgut; Bilgin, Ahmet Burak; Sari, Esin Sogutlu; Turkoglu, Elif Betul

    2015-01-01

    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. PMID:25709902

  11. Central Serous Chorioretinopathy Misdiagnosed as Posterior Uveitis and the Vicious Circle of Corticosteroid Therapy

    PubMed Central

    Papadia, Marina; Jeannin, Bruno; Herbort, Carl P.

    2015-01-01

    Purpose: To determine the proportion of patients with central serous chorioretinopathy (CSCR) mistaken for posterior uveitis and to identify the deleterious consequences. Methods: Charts of 1,657 patients admitted in the section of inflammatory eye diseases at the Center for Ophthalmic Specialized Care (COS) in Lausanne, Switzerland from 1995 to 2013 were reviewed. CSCR cases misdiagnosed as posterior uveitis or those with superimposed disease due to steroid therapy for uveitis were studied. Delay in diagnosis, specific erroneous uveitis diagnosis and evolution of the disease were also evaluated. Retrospectively, the most useful means for a correct diagnosis of CSCR were the original fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) when available. Results: Out of a total of 1,657 patients, 15 (0.9%) cases with CSCR were identified. These included 12 subjects misdiagnosed as posterior uveitis and 3 uveitis subjects with superimposed CSCR following corticosteroid therapy for uveitis. The presentation of the disease was largely influenced by improper and continued use of corticosteroids. Conclusion: CSCR is a rare but not negligible misdiagnosis in posterior uveitis representing approximately 1% of subjects from a collective series of uveitis cases at a referral center. Investigative measures such as FA, ICGA and OCT are crucial for reaching a correct diagnosis and avoiding disease aggravation due to corticosteroid therapy. PMID:26730317

  12. YAP Induces High-Grade Serous Carcinoma in Fallopian Tube Secretory Epithelial Cells

    PubMed Central

    Hua, Guohua; Lv, Xiangmin; He, Chunbo; Remmenga, Steven W.; Rodabough, Kerry J.; Dong, Jixin; Yang, Liguo; Lele, Subodh M.; Yang, Peixin; Zhou, Jin; Karst, Alison; Drapkin, Ronny I.; Davis, John S.; Wang, Cheng

    2015-01-01

    Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from Fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In the present study, we found that the Hippo/YAP signaling pathway plays a critical role in the initiation and progression of Fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous Fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation, and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine positive feedback loop to drive the progression of the FTSECs-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGFRs (such as BGJ398) can provide a novel therapeutic strategy to treat Fallopian tube and ovarian HGSC. PMID:26364602

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

    PubMed

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

    2016-08-01

    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. PMID:27255997

  14. High-dose-rate vaginal brachytherapy with chemotherapy for surgically staged localized uterine serous carcinoma

    PubMed Central

    Higgins, Susan A.; Ratner, Elena; De Leon, Maria C.; Mani, Sheida; Silasi, Dan-Arin; Azodi, Masoud; Santin, Alessandro; Rutherford, Thomas; Schwartz, Peter E.

    2015-01-01

    Purpose To evaluate our institutional experience combining carboplatin-paclitaxel (C/T) chemotherapy with high-dose-rate (HDR) intra-vaginal brachytherapy (IVB) following comprehensive surgical staging in localized uterine serous carcinoma (USC). Material and methods Institutional chart review identified 56 patients with FIGO 2009 stage I-II USC treated between 2000-2010. Patients underwent total hysterectomy, bilateral salpingo-oopherectomy, and comprehensive surgical staging including pelvic and para-aortic lymph node dissection, omentectomy, and peritoneal cytology. Chemotherapy was 6 cycles of C/T, and the IVB dose was 14 Gy in 2 fractions, prescribed to 0.5 cm from the cylinder surface. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS) and overall survival (OS). Results The median follow-up time was 49 months (range: 9-145). The 5-yr RFS and OS were 85% and 93%, respectively. In all cases of recurrence (n = 8), the first site of failure was extra-pelvic. There were no isolated vaginal recurrences, however, there was one vaginal apex recurrence recorded at 19 months in a patient with simultaneous lung metastases. Thus, the 2-year vaginal RFS was 98%. Conclusions Excellent vaginal/pelvic control rates were observed. Further study of HDR brachytherapy dose and fractionation in combination with chemotherapy is worthwhile. PMID:25829935

  15. A Clinical and Pathologic Comparison Between Stage-Matched Endometrial Intraepithelial Carcinoma and Uterine Serous Carcinoma

    PubMed Central

    Hou, June Y.; McAndrew, Thomas C.; Goldberg, Gary L.; Whitney, Kathleen

    2014-01-01

    Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic–pathologic outcomes in patients with EIC and USC for disease limited to the endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically staged patients were retrospectively identified and relevant variables were extracted and compared. Kaplan-Meier was used to generate the survival data. More USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed higher levels of estrogen receptor-α than EIC (P = .0009 and .063 for stages 1 and 4, respectively). The survival is comparable, with 1 recurrence in each group for stage 1A disease. For stage 4 EIC and USC, the progression-free survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to what is previously published. In conclusion, EIC, whether limited to the endometrium, or widely metastatic, imparts similar outcomes and should be treated comparably with stage-matched USC. PMID:24023030

  16. Temperament and character personality profile and illness-related stress in central serous chorioretinopathy.

    PubMed

    Conrad, Rupert; Geiser, Franziska; Kleiman, Alexandra; Zur, Berndt; Karpawitz-Godt, Andrea

    2014-01-01

    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. PMID:24696654

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

    PubMed Central

    Kessler, Mirjana; Fotopoulou, Christina; Meyer, Thomas

    2013-01-01

    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. PMID:23528888

  18. STAT3 polymorphisms may predict an unfavorable response to first-line platinum-based therapy for women with advanced serous epithelial ovarian cancer

    PubMed Central

    Permuth-Wey, Jennifer; Fulp, William J.; Reid, Brett M.; Chen, Zhihua; Georgeades, Christina; Cheng, Jin Q.; Magliocco, Anthony; Chen, Dung-Tsa; Lancaster, Johnathan M.

    2016-01-01

    Cancer stem cells (CSC) contribute to epithelial ovarian cancer (EOC) progression and therapeutic response. We hypothesized that germline single nucleotide polymorphisms (SNPs) in CSC-related genes may predict an initial therapeutic response for women newly diagnosed with EOC. A nested case–control design was used to study 361 women with advanced-stage serous EOC treated with surgery followed by first-line platinum-based combination therapy at Moffitt Cancer Center or as part of The Cancer Genome Atlas Study. “Cases” included 102 incomplete responders (IRs) and “controls” included 259 complete clinical responders (CRs) to therapy. Using Illumina genotyping arrays and imputation, DNA samples were evaluated for 5,509 SNPs in 24 ovarian CSC-related genes. We also evaluated the overall significance of each CSC gene using the admixture maximum likelihood (AML) test, and correlated genotype with EOC tumor tissue expression. The strongest SNP-level associations with an IR to therapy were identified for correlated (r2 > 0.80) SNPs within signal transducer and activator of transcription 3 (STAT3) [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.32–3.78; p = 0.0027], after adjustment for age, population stratification, grade and residual disease. At the gene level, STAT3 was significantly associated with an IR to therapy (pAML 5 0.006). rs1053004, a STAT3 SNP in a putative miRNA-binding site, was associated with STAT3 expression (p = 0.057). This is the first study to identify germline STAT3 variants as independent predictors of an unfavorable therapeutic response for EOC patients. Findings suggest that STAT3 genotype may identify high-risk women likely to respond more favorably to novel therapeutic combinations that include STAT3 inhibitors. PMID:26264211

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

    PubMed

    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

    2014-10-01

    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. PMID:24890382

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

    PubMed Central

    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. PMID:24890382

  1. STAT3 polymorphisms may predict an unfavorable response to first-line platinum-based therapy for women with advanced serous epithelial ovarian cancer.

    PubMed

    Permuth-Wey, Jennifer; Fulp, William J; Reid, Brett M; Chen, Zhihua; Georgeades, Christina; Cheng, Jin Q; Magliocco, Anthony; Chen, Dung-Tsa; Lancaster, Johnathan M

    2016-02-01

    Cancer stem cells (CSC) contribute to epithelial ovarian cancer (EOC) progression and therapeutic response. We hypothesized that germline single nucleotide polymorphisms (SNPs) in CSC-related genes may predict an initial therapeutic response for women newly diagnosed with EOC. A nested case-control design was used to study 361 women with advanced-stage serous EOC treated with surgery followed by first-line platinum-based combination therapy at Moffitt Cancer Center or as part of The Cancer Genome Atlas Study. "Cases" included 102 incomplete responders (IRs) and "controls" included 259 complete clinical responders (CRs) to therapy. Using Illumina genotyping arrays and imputation, DNA samples were evaluated for 5,509 SNPs in 24 ovarian CSC-related genes. We also evaluated the overall significance of each CSC gene using the admixture maximum likelihood (AML) test, and correlated genotype with EOC tumor tissue expression. The strongest SNP-level associations with an IR to therapy were identified for correlated (r(2) > 0.80) SNPs within signal transducer and activator of transcription 3 (STAT3) [odds ratio (OR), 2.24; 95% confidence interval (CI), 1.32-3.78; p = 0.0027], after adjustment for age, population stratification, grade and residual disease. At the gene level, STAT3 was significantly associated with an IR to therapy (pAML = 0.006). rs1053004, a STAT3 SNP in a putative miRNA-binding site, was associated with STAT3 expression (p = 0.057). This is the first study to identify germline STAT3 variants as independent predictors of an unfavorable therapeutic response for EOC patients. Findings suggest that STAT3 genotype may identify high-risk women likely to respond more favorably to novel therapeutic combinations that include STAT3 inhibitors. PMID:26264211

  2. Randomized trial of oral cyclophosphamide and veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer

    PubMed Central

    Kummar, Shivaani; Oza, Amit M.; Fleming, Gini F.; Sullivan, Daniel M.; Gandara, David R.; Naughton, Michael J.; Villalona-Calero, Miguel A.; Morgan, Robert J.; Szabo, Peter M.; Youn, Ahrim; Chen, Alice P.; Ji, Jiuping; Allen, Deborah E.; Lih, Chih-Jian; Mehaffey, Michele G.; Walsh, William D.; McGregor, Paul M.; Steinberg, Seth M.; Williams, Paul M.; Kinders, Robert J.; Conley, Barbara A.; Simon, Richard M.; Doroshow, James H.

    2015-01-01

    Purpose Veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase 1 trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase 2 trial to determine the response rate of veliparib in combination with cyclophosphamide compared to cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC). Methods Adult patients were randomized to receive cyclophosphamide alone (50 mg orally once daily) or with veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the combination was allowed at disease progression. Results Seventy-five patients were enrolled and 72 were evaluable for response; 38 received cyclophosphamide alone and 37 the combination as their initial treatment regimen. Treatment was well tolerated. One complete response was observed in each arm, with three partial responses (PR) in the combination arm and six PRs in the cyclophosphamide alone arm. Genetic sequence and expression analyses were performed for 211 genes involved in DNA repair; none of the detected genetic alterations were significantly associated with treatment benefit. Conclusion This is the first trial that evaluated single agent, low dose cyclophosphamide in HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well tolerated and clinical activity was observed; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression free survival. PMID:25589624

  3. A prospective phase II study of chemoradiation followed by adjuvant chemotherapy for FIGO stage I-IIIa (1988) uterine papillary serous carcinoma of the endometrium

    PubMed Central

    Jhingran, Anuja; Ramondetta, Lois M.; Bodurka, Diane C.; Slomovitz, Brian M.; Brown, Jubilee; Levy, Lawrence B.; Garcia, Michael E.; Eifel, Patricia J.; Lu, Karen H.; Burke, Thomas W.

    2015-01-01

    Objective To prospectively evaluate tumor control, survival, and toxic effects in patients with International Federation of Gynecology and Obstetrics (1988) stage I-IIIA papillary serous carcinoma of the endometrium treated with concurrent chemoradiation and adjuvant chemotherapy. Methods Thirty-two patients were enrolled from October 2001 through July 2009. Patients underwent full surgical disease staging and postoperative concurrent weekly paclitaxel (50 mg/m2) and pelvic RT to 45 Gy plus a vaginal cuff boost followed by 4 cycles of adjuvant paclitaxel (135 mg/m2). Results Thirty patients (94%) were evaluable (3 with stage IA disease, 11 IB, 3 IC, 1 IIB, and 12 IIIA). Eighteen patients (60%) received all 5 planned courses of concurrent chemotherapy, 10 (33%) received 4 courses, and 2 (7%) received 3 courses. All 30 patients received RT; 27 (90%) received the full dose, 2 received 43.2 Gy, and 1 received 39.6 Gy owing to toxic effects. Twenty-three patients (77%) completed all 4 cycles of adjuvant paclitaxel, 3 (10%) completed 3 cycles, 2 (7%) completed 2 cycles, and 2 received no adjuvant therapy. Overall survival (OS), progression-free survival (PFS), and local control rates for all patients were 93%, 87%, and 87%, respectively, at 2 years and 85%, 83%, and 87%, respectively, at 5 years. Six patients developed (20%) grade 3/4 toxcities from the treatment. Four patients (13%) had grade 3 or more severe bowel complications and two patients developed symptomatic pelvic fractures. Conclusions Treatment with concurrent paclitaxel and pelvic RT followed by 4 courses of systemic paclitaxel produced favorable results in patients with surgically staged I-III UPSC. PMID:23385150

  4. Spinal tumor

    MedlinePlus

    Tumor - spinal cord ... spinal tumors occur in the nerves of the spinal cord itself. Most often these are ependymomas and other ... gene mutations. Spinal tumors can occur: Inside the spinal cord (intramedullary) In the membranes (meninges) covering the spinal ...

  5. Functional Connectivity of Pain-Mediated Affect Regulation in Borderline Personality Disorder

    PubMed Central

    Niedtfeld, Inga; Kirsch, Peter; Schulze, Lars; Herpertz, Sabine C.; Bohus, Martin; Schmahl, Christian

    2012-01-01

    Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD. We used psychophysiological interactions to analyze functional connectivity of (para-) limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex) in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral) affect and subsequently applying heat pain (versus warmth perception). Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-)limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen), as well areas involved in self-referential processing (precuneus and posterior cingulate). We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia. PMID:22428013

  6. Extending Extant Models of the Pathogenesis of Borderline Personality Disorder to Childhood Borderline Personality Symptoms: The Roles of Affective Dysfunction, Disinhibition, and Self-and Emotion-Regulation Deficits

    PubMed Central

    Gratz, Kim L.; Tull, Matthew T.; Reynolds, Elizabeth K.; Bagge, Courtney L.; Latzman, Robert D.; Daughters, Stacey B.; Lejuez, C. W.

    2010-01-01

    Although research has been conducted on the course, consequences, and correlates of borderline personality disorder (BPD), little is known about its emergence in childhood, and no studies have examined the extent to which theoretical models of the pathogenesis of BPD in adults are applicable to the correlates of borderline personality symptoms in children. The goal of this study was to examine the interrelationships between two BPD-relevant personality traits (affective dysfunction and disinhibition), self- and emotion regulation deficits, and childhood borderline personality symptoms among 263 children aged 9 to 13. We predicted that affective dysfunction, disinhibition, and their interaction would be associated with childhood borderline personality symptoms, and that self- and emotion-regulation deficits would mediate these relationships. Results provided support for the roles of both affective dysfunction and disinhibition (in the form of sensation seeking) in childhood borderline personality symptoms, as well as their hypothesized interaction. Further, both self- and emotion-regulation deficits partially mediated the relationship between affective dysfunction and childhood borderline personality symptoms. Finally, results provided evidence of different gender-based pathways to childhood borderline personality symptoms, suggesting that models of BPD among adults are more relevant to understanding the factors associated with borderline personality symptoms among girls than boys. PMID:19825268

  7. Confidence in facial emotion recognition in borderline personality disorder.

    PubMed

    Thome, Janine; Liebke, Lisa; Bungert, Melanie; Schmahl, Christian; Domes, Gregor; Bohus, Martin; Lis, Stefanie

    2016-04-01

    Dysfunctions of social-cognitive processes such as the recognition of emotions have been discussed to contribute to the severe impairments of interpersonal functioning in borderline personality disorder (BPD). By investigating how patients with BPD experience the intensity of different emotions in a facial expression and how confident they are in their own judgments, the current study aimed at identifying subtle alterations of emotion processing in BPD. Female patients with BPD (N = 36) and 36 healthy controls were presented with faces that displayed low-intense anger and happiness or ambiguous expressions of anger and happiness blends. Subjects were asked to rate (a) the intensity of anger and happiness in each facial expression and (b) their confidence in their judgments. Patients with BPD rated the intensity of happiness in happy faces lower than did controls, but did not differ in regard to the assessment of angry or ambiguous facial stimuli or the rating of anger. They reported lower confidence in their judgments, which was particularly pronounced for the assessment of happy facial expressions. The reduced rating of happiness was linked to higher state anger, whereas the reduced confidence in the assessment of happy faces was related to stronger feelings of loneliness and the expectation of social rejection. Our findings suggest alterations in the processing of positive social stimuli that affect both the experience of the emotional intensity and the confidence subjects experience during their assessment. The link to loneliness and social rejection sensitivity points to the necessity to target these alterations in psychotherapeutical interventions. (PsycINFO Database Record PMID:26389624

  8. Familial aggregation of candidate phenotypes for borderline personality disorder.

    PubMed

    Ruocco, Anthony C; Hudson, James I; Zanarini, Mary C; Gunderson, John G

    2015-01-01

    Borderline personality disorder (BPD) and its core Diagnostic and Statistical Manual of Mental Disorders (DSM) factor-analytically derived phenotypes aggregate in families. To potentially inform future conceptualizations of BPD, this study examined the familial aggregation and co-aggregation with BPD of 3 additional candidate phenotypes for BPD psychopathology: anxiousness, aggressiveness, and cognitive dysregulation. Participants included 347 probands (126 with BPD, 128 without BPD, and 93 with major depressive disorder) and 814 parents and siblings of probands. All participants completed diagnostic assessments and scales assessing the candidate phenotypes. The familial aggregation of phenotypes (correlation of level of phenotype between family members), the familial co-aggregation of phenotypes with BPD (correlation of phenotype with BPD between family members), and the within-individual correlation of phenotypes with BPD were assessed. All 3 candidate phenotypes showed high levels of familial aggregation (rs = .14 - .53, ps < .001), the magnitudes of which were comparable with DSM-based core sectors of psychopathology. Anxiousness and cognitive dysregulation showed strong within-individual associations with BPD (rs = .55 and .46, respectively; ps < .001) and substantial familial co-aggregation with BPD (rs = .12 and .13, respectively; ps ≤ .002). In contrast, aggressiveness showed a weak within-individual association with BPD (r = .11, p = .12) and little familial co-aggregation with BPD (r = .05, p = .21). These findings suggest that anxiousness and cognitive dysregulation are promising phenotypes for BPD psychopathology that move beyond factor-analytically based conceptualizations. In contrast, aggressiveness was only weakly related to BPD, suggesting that this phenotype may not represent an essential feature of this disorder. PMID:25046574

  9. Interpretation bias in Cluster-C and borderline personality disorders.

    PubMed

    Arntz, Arnoud; Weertman, Anoek; Salet, Sjoerd

    2011-08-01

    Cognitive therapy (CT) assumes that personality disorders (PDs) are characterized by interpretational biases that maintain the disorder. Changing interpretations is therefore a major aim of CT of PDs. This study tested whether Borderline PD (BPD), Avoidant and Dependent PD (AV/DEPD), and Obsessive-Compulsive PD (OCPD) are characterized by specific interpretations. Among the 122 participants there were 55 PD patients (17 BPD, 30 AV/DEPD, 29 OCPD diagnoses), 26 axis-1 patients, and 41 nonpatients. Participants put themselves into 10 scripts of negative events and noted feelings, thoughts and behaviors that came to mind. Next, they chose between hypothesized BPD-specific, AV/DEPD-specific, and OCPD-specific interpretations of each event (forced choice). Lastly, participants rated belief in each interpretation. Regression analyses revealed that forced choices and belief ratings supported the CT-model of BPD and AV/DEP: interpretations were specific. The alleged OCPD-beliefs were however not specifically related to OCPD, with relatively high popularity in axis-1 patients and nonpatients. The open responses were classified by judges blind for diagnoses, with the following results. BPD was characterized by low levels of solution-focused and healthy-flexible/accepting responses, and higher levels of criticizing others and malevolent interpretations of others. AV/DEPD was characterized by lower levels of solution-focused responses, and higher levels of self-criticism, negative emotions, guilt and fear of judgment, as well as lower levels of other-criticism. OCPD only showed trends for lower healthy responses, and higher compulsiveness and worry. It is concluded that the assumptions of CT are supported for BPD and AV/DEPD, but not - at least not on the explicit interpretational level - for OCPD. CT of OCPD might need a slightly different approach. PMID:21621746

  10. The 'Self' and Borderline Personality Disorder: Conceptual and Clinical Considerations.

    PubMed

    Kerr, Ian B; Finlayson-Short, Laura; McCutcheon, Louise K; Beard, Hilary; Chanen, Andrew M

    2015-01-01

    Some concept of self has been used by many, although not all, researchers and clinicians as an 'organising construct' for borderline personality disorder (BPD). There is considerable variation in this usage and how clearly researchers have defined the self. Given this diversity, and that 'self' is often used interchangeably with parallel concepts (e.g., psyche, brain-mind, 'person') or with features of self (e.g., self-awareness, identity), unqualified use of the term is problematic. This is further complicated by the heterogeneity and 'comorbidity' of BPD and the limitations of syndromally based psychiatric nosology. Still, BPD remains in current classification systems and can be reliably diagnosed. A considerable body of research on self and BPD has accrued, including a recent profusion and confluence of neuroscientific and sociopsychological findings. These have generated supporting evidence for a supra-ordinate, functionally constituted entity of the self ranging over multiple, interacting levels from an unconscious, 'core' self, through to a reflective, phenotypic, 'idiographic' and relational self constituted by interpersonal and sociocultural experience. Important insights have been generated regarding emotional and social-cognitive dysregulation, disorder of self-awareness, relationality, identity, and coherence and continuity of the self. Many of these are shared by various trauma-related, dissociative disorders. A construct of the self could be useful as an explanatory principle in BPD, which could be construed as a 'self-state' (and relational) disorder, as opposed to a less severe disorder of aspects of the self (e.g., mood or memory). We offer a tentative description of 'Self' in this context, noting that any such construct will require a clear definition and to be evaluable. PMID:26346462

  11. [Skills Training for Patients with Borderline Personality Disorder].

    PubMed

    Armbrust, Michael; Ehrig, Christian

    2016-07-01

    The emotionally instable personality disorder, mostly called borderline disorder, shows central abnormalities in impulse control as well as instability of mood and identity. It is composed of behaviour problems in creating relationships and in self-management, first of all by high psychophysiological tension. The prevalence of this disorder is 10 % in outpatients and 20 % in inpatients and has therefore high relevance for the medical-psychotherapeutic care system. The treatment is deemed to be complex and interminable. Regarding all evaluated techniques of treatment the best examined is the Dialectical Behavioral Therapy (DBT). This specific therapy, developed in the eighties by Marsha M. Linehan, can be used for inpatient and outpatient treatment and combines single and group sessions. It is essential in mental health care of this disorder, but not available everywhere. Essential part of DBT is the skill training, a specific technique for the acquirement and for exercising skills for mindfulness, modulation of tension, regulation of emotions, structuring of social competence and developing self value. The central goal of DBT is to ensure the survival of the patients, to reduce self- and external aggressive behaviour and to provide inpatient crisis interventions. For sustained crisis management skills for reality acceptance are best fitting. But before, fast available sensory and active body-related skills should be used. Radical acceptance is the most important, since most effective, skill. The skills training, although in use for only twenty years, is permanently expanding in practice and is meanwhile also used for other disorders such as, for example, PTSD or ADHD. Since 2010, there also exists an elaborated DBT-version for adolescents. For medical care politics and health-economic reasons a supply with skills training for in- and outpatients all over the country is desirable. PMID:27388871

  12. Emotional lability and affective synchrony in borderline personality disorder.

    PubMed

    Schoenleber, Michelle; Berghoff, Christopher R; Tull, Matthew T; DiLillo, David; Messman-Moore, Terri; Gratz, Kim L

    2016-07-01

    Extant research on emotional lability in borderline personality disorder (BPD) has focused almost exclusively on lability of individual emotions or emotion types, with limited research considering how different types of emotions shift together over time. Thus, this study examined the temporal dynamics of emotion in BPD at the level of both individual emotions (i.e., self-conscious emotions [SCE], anger, and anxiety) and mixed emotions (i.e., synchrony between emotions). One hundred forty-four women from the community completed a diagnostic interview and laboratory study involving 5 emotion induction tasks (each of which was preceded and followed by a 5-min resting period or neutral task). State ratings of SCE, anger, and anxiety were provided at 14 time points (before and after each laboratory task and resting period). Hierarchical linear modeling results indicate that women with BPD reported greater mean levels of SCE and Anxiety (but not Anger), and greater lability of Anxiety. Women with BPD also exhibited greater variability in lability of all 3 emotions (suggestive of within-group differences in the relevance of lability to BPD). Results also revealed synchrony (i.e., positive relations) between each possible pair of emotions, regardless of BPD status. Follow-up regression analyses suggest the importance of accounting for lability when examining the role of synchrony in BPD, as the relation of SCE-Anger synchrony to BPD symptom severity was moderated by Anger and SCE lability. Specifically, synchronous changes in SCE and Anger were associated with greater BPD symptom severity when large shifts in SCE were paired with minor shifts in Anger. (PsycINFO Database Record PMID:27362623