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

Expression of GLUT-1 glucose transporter in borderline and malignant epithelial tumors of the ovary.

PubMed

Cantuaria, G; Magalhaes, A; Penalver, M; Angioli, R; Braunschweiger, P; Gomez-Marin, O; Kanhoush, R; Gomez-Fernandez, C; Nadji, M

2000-10-01

Cancer cells have increased rates of glucose metabolism when compared to normal cells. One of the mechanisms proposed for the accelerated glucose use in malignant cells is the overexpression of glucose transporters. In this study we evaluated the expression of the GLUT-1 glucose transporter in borderline and malignant epithelial neoplasms of the ovary. Histologic sections of tumor tissues from 21 borderline and 82 malignant epithelial neoplasms of the ovary were stained for GLUT-1 using polyclonal GLUT-1 antibody (Dako, Carpinteria, CA) and the labeled streptavidin biotin procedure. DAB was used as chromagen and tissues were counterstained with hematoxylin. Normal ovarian surface epithelial cells were either negative or weakly positive. Of the 82 carcinomas, 81 (98.8%) were positive for GLUT-1. The staining intensity was significantly associated with the grade of tumor (P = 0.001). Of the 21 borderline neoplasms, 20 (95.2%) were positive for GLUT-1. Carcinomas had a significantly stronger stain than borderline tumors (P = 0.0001). The intensity of the stain was also stronger in serous carcinomas compared to other subtypes (P = 0. 0001). Positive cells demonstrated a cytoplasmic membrane staining that was more intense in tumor cells farther away from blood supply. Overexpression of the GLUT-1 transporter is associated with the histology and grade of the tumors. Our findings show a progressive increase in the expression of the GLUT-1 transporter from the borderline tumor to the high-grade carcinomas. These data suggest that the expression of this transporter may be closely related to the malignant transformation of epithelial ovarian tumors. Copyright 2000 Academic Press.

Allelic imbalance on chromosome 17p13 in borderline (low malignant potential) epithelial ovarian tumors.

PubMed

Zanotti, K M; Hart, W R; Kennedy, A W; Belinson, J L; Casey, G

1999-07-01

Borderline epithelial ovarian tumors (BEOTs) possess clinical and pathologic features intermediate between cystadenomas and cystadenocarcinomas. Although the clinical and pathologic characteristics of BEOTs are well described, the molecular aspects are poorly understood. Three regions of loss of heterozygosity (often referred to as allelic imbalance [AI] when identified by polymerase chain reaction) on chromosome 17p13, one of which includes the p53 gene, have been implicated in the development of ovarian and breast cancers. To provide evidence that genes in these regions also may be involved in the development of BEOTs, we undertook a detailed analysis of AI at all three loci in BEOTs from 21 patients. Seventeen of the BEOTs were serous and four were mucinous. Five of 21 tumors (24%) had AI at one or more loci. Four tumors had AI using the D17S695 marker, two of which showed AI only at this locus. In addition, three tumors exhibited AI at the D17S654 locus, one of which showed AI only at this locus. These data suggest that there may be two tumor suppressor genes distal to p53 involved in the development of at least a subset of BEOTs. Peritoneal implants from a subset of serous BEOTs also were evaluated for AI and were found to be concordant with the primary tumor in all cases. Their genetic similarity is consistent with the implantation theory of peritoneal spread of serous BEOTs in these cases.

Optical Biomarkers of Serous and Mucinous Human Ovarian Tumor Assessed with Nonlinear Optics Microscopies

PubMed Central

Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; Baratti, Mariana O.; Almeida, Diogo B.; Andrade, L. A. L. A.; Bottcher-Luiz, Fátima; Carvalho, Hernandes F.; Cesar, Carlos L.

2012-01-01

Background Nonlinear optical (NLO) microscopy techniques have potential to improve the early detection of epithelial ovarian cancer. In this study we showed that multimodal NLO microscopies, including two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third-harmonic generation (THG) and fluorescence lifetime imaging microscopy (FLIM) can detect morphological and metabolic changes associated with ovarian cancer progression. Methodology/Principal Findings We obtained strong TPEF + SHG + THG signals from fixed samples stained with Hematoxylin & Eosin (H&E) and robust FLIM signal from fixed unstained samples. Particularly, we imaged 34 ovarian biopsies from different patients (median age, 49 years) including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous tumors with the multimodal NLO platform developed in our laboratory. We have been able to distinguish adenomas, borderline, and adenocarcinomas specimens. Using a complete set of scoring methods we found significant differences in the content, distribution and organization of collagen fibrils in the stroma as well as in the morphology and fluorescence lifetime from epithelial ovarian cells. Conclusions/Significance NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for serous and mucinous ovarian tumors. The results provide a basis to interpret future NLO images of ovarian tissue and lay the foundation for future in vivo optical evaluation of premature ovarian lesions. PMID:23056557

Risk factors for benign serous and mucinous epithelial ovarian tumors.

PubMed

Jordan, Susan J; Green, Adèle C; Whiteman, David C; Webb, Penelope M

2007-03-01

To investigate the risk factors for benign serous and mucinous epithelial ovarian tumors. Cases were women newly diagnosed with benign serous ovarian tumors (n=230) or benign mucinous tumors (n=133) between 2002 and 2005. Control women were selected at random from the general population (n=752). All participants completed a comprehensive reproductive and lifestyle questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and to simultaneously adjust for potential confounding factors. Current smoking was associated with a three-fold increase in risk of benign mucinous tumors (OR 3.25, 95% CI 1.97-5.34), and there was a trend of increasing risk with increasing amount smoked (P<.001). Both recent obesity (OR 1.93, 95% CI 1.30-2.88) and obesity at age 20 (OR 4.38, 95% CI 1.88-10.20) were associated with increased risk of benign serous ovarian tumors, and having had a hysterectomy was also related to increased risk of serous (OR 2.75, 95% CI 1.90-3.96), but not mucinous tumors. Ever having had a term pregnancy was inversely associated with both tumor types (combined OR 0.65, 95% CI 0.43-0.97), although greater numbers of pregnancies did not decrease risk further. Use of hormonal contraceptives was unrelated to risk. Our results suggest some differences in risk factors between benign serous and mucinous epithelial ovarian tumors and that risk factors for benign serous tumors differ from those well established for ovarian cancer. The results also suggest that there is potential for prevention of these common conditions through avoidance of smoking and obesity. II.

Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case-control study.

PubMed

Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian; Baandrup, Louise; Junge, Jette; Vang, Russell; Kurman, Robert J; Kjaer, Susanne K

2017-03-01

Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p<0.01). Older age at first birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0.26-0.62). Our nationwide study with expert histopathologic review of all SBTs showed that parity, infertility, use of HRT, and use of OCs, respectively, were strongly associated with the risk of SBTs. This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use. This supports that SBTs and serous ovarian cancer share similar risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

KRAS mutation testing in borderline ovarian tumors and low-grade ovarian carcinomas with a rapid, fully integrated molecular diagnostic system.

PubMed

Sadlecki, Pawel; Antosik, Paulina; Grzanka, Dariusz; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

2017-10-01

Epithelial ovarian neoplasms are a heterogeneous group of tumors, including various malignancies with distinct clinicopathologic and molecular features. Mutations in BRAF and KRAS genes are the most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous and mucinous borderline tumors. Implementation of targeted therapeutic strategies requires access to highly specific and highly sensitive diagnostic tests for rapid determination of mutation status. One candidate for such test is fully integrated, real-time polymerase chain reaction-based Idylla™ system for quick and simple detection of KRAS mutations in formaldehyde fixed-paraffin embedded tumor samples. The primary aim of this study was to verify whether fully integrated real-time polymerase chain reaction-based Idylla system may be useful in determination of KRAS mutation status in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 37 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland) between January 2009 and June 2012. Based on histopathological examination of surgical specimens, 30 lesions were classified as low-grade ovarian carcinomas and 7 as borderline ovarian tumors. Seven patients examined with Idylla KRAS Mutation Test tested positive for KRAS mutation. No statistically significant association was found between the incidence of KRAS mutations and histopathological type of ovarian tumors. Mean survival of the study subjects was 48.51 months (range 3-60 months). Presence of KRAS mutation did not exert a significant effect on the duration of survival in our series. Our findings suggest that Idylla KRAS Mutation Test may be a useful tool for rapid detection of KRAS mutations in ovarian tumor tissue.

Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers.

PubMed

Sadlecki, Pawel; Walentowicz, Pawel; Bodnar, Magdalena; Marszalek, Andrzej; Grabiec, Marek; Walentowicz-Sadlecka, Malgorzata

2017-05-01

Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla™ system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla™. Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were

Genomic aberrations in borderline ovarian tumors

PubMed Central

2010-01-01

Background According to the scientific literature, less than 30 borderline ovarian tumors have been karyotyped and less than 100 analyzed for genomic imbalances by CGH. Methods We report a series of borderline ovarian tumors (n = 23) analyzed by G-banding and karyotyping as well as high resolution CGH; in addition, the tumors were analyzed for microsatellite stability status and by FISH for possible 6q deletion. Results All informative tumors were microsatellite stable and none had a deletion in 6q27. All cases with an abnormal karyotype had simple chromosomal aberrations with +7 and +12 as the most common. In three tumors with single structural rearrangements, a common breakpoint in 3q13 was detected. The major copy number changes detected in the borderline tumors were gains from chromosome arms 2q, 6q, 8q, 9p, and 13q and losses from 1p, 12q, 14q, 15q, 16p, 17p, 17q, 19p, 19q, and 22q. The series included five pairs of bilateral tumors and, in two of these pairs, informative data were obtained as to their clonal relationship. In both pairs, similarities were found between the tumors from the right and left side, strongly indicating that bilaterality had occurred via a metastatic process. The bilateral tumors as a group showed more aberrations than did the unilateral ones, consistent with the view that bilaterality is a sign of more advanced disease. Conclusion Because some of the imbalances found in borderline ovarian tumors seem to be similar to imbalances already known from the more extensively studied overt ovarian carcinomas, we speculate that the subset of borderline tumors with detectable imbalances or karyotypic aberrations may contain a smaller subset of tumors with a tendency to develop a more malignant phenotype. The group of borderline tumors with no imbalances would, in this line of thinking, have less or no propensity for clonal evolution and development to full-blown carcinomas. PMID:20184781

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

PubMed

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

2018-05-01

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

Prognostic Factors for Recurrence After Fertility-Preserving Surgery in Patients With Borderline Ovarian Tumors: A Systematic Review and Meta-analysis of Observational Studies.

PubMed

Jiao, Xiaobing; Hu, Jun; Zhu, Lirong

2017-11-01

The aim of this study was to find the unfavorable prognostic factors for recurrence after fertility-preserving surgery (FPS) in patients with borderline ovarian tumors (BOTs). To perform a meta-analysis to compare the recurrence rates of BOT patients after FPS according to different prognostic factors, we searched PubMed, EMBASE, and Cochrane for observational studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with a fixed-effects model. We analyzed 32 studies that included 2691 BOT patients who underwent FPS, 383 patients of whom had a relapse in the follow-up. In meta-analysis, risks associated with recurrence in patients with unilateral cystectomy (OR, 2.49; 95% CI, 1.86-3.33) or serous borderline ovarian tumors (OR, 3.15; 95% CI, 1.97-5.02) were significantly increased, and there was no significantly increased OR for patients with laparoscopy compared with those with laparotomy (OR, 0.96; 95% CI, 0.57-1.60). Unilateral cystectomy (19.4%) and serous BOTs (19.2%) are significantly associated with higher recurrence rates, and no negative impact of laparoscopy on recurrence can be demonstrated when compared with laparotomy in the meta-analysis.

Biomolecular pathogenesis of borderline ovarian tumors: focusing target discovery through proteogenomics.

PubMed

Vergara, D; Tinelli, A; Martignago, R; Malvasi, A; Chiuri, V E; Leo, G

2010-02-01

Tumors of the epithelial surface account for about 80% of all ovarian neoplasms and exhibit a heterogeneous histological classification affecting survival. Tumors of low malignant potential, defined as borderline ovarian tumors(BOTs), have a markedly better survival and low recurrence, even if surgery still represents the common management for this type of cancer. It is still debated in the literature if BOTs can be considered as intermediate precursors in the progression to high grade ovarian tumors. Evidences now propose that high-grade serous carcinomas are not associated with a defined precursor lesion. Together with histopathological studies, mutations of KRAS, BRAF and p53 genes, microsatellite instability (MSI)and under- or over-expression of many genes and proteins have been used to address this question. Despite the large body of data summarized, a limited number of molecules proved to be useful in elucidating BOTs pathogenesis and only a few of these showed possible application in the therapy. We believe that high-throughput technologies would help to overcome these limitations offering the promise of a better understanding of BOTs classification. The aim is to guide the diagnosis and prognosis of BOTs to develop new possible therapeutic molecular targets avoiding surgery.

Primary borderline parovarian tumor in pregnancy

PubMed Central

Kim, Jong-Hyun

2015-01-01

There are few reports of pregnancy complicated by a primary borderline parovarian tumor. A 32-year-old pregnant woman was found to have an ovarian tumor. At 13 weeks of gestation, cystectomy was performed and a diagnosis of primary borderline parovarian tumor was made. At 38 weeks of gestation, she underwent cesarean section combined with a restaging operation. A normal infant was delivered and there were no signs of recurrence. Currently, the patient is being followed for 24 months after the initial treatment and all imaging data show no evidence of recurrence. This report includes a short review of the existing literature on this topic and documents this case in detail. This case demonstrates the appropriate procedure for evaluating and treating a primary borderline parovarian tumor during pregnancy. PMID:26623422

Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies

PubMed Central

Rasmussen, Christina B.; Kjaer, Susanne K.; Albieri, Vanna; Bandera, Elisa V.; Doherty, Jennifer A.; Høgdall, Estrid; Webb, Penelope M.; Jordan, Susan J.; Rossing, Mary Anne; Wicklund, Kristine G.; Goodman, Marc T.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Edwards, Robert P.; Schildkraut, Joellen M.; Berchuck, Andrew; Olson, Sara H.; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; Narod, Steven A.; Phelan, Catherine M.; Anton-Culver, Hoda; Ziogas, Argyrios; Wu, Anna H.; Pearce, Celeste L.; Risch, Harvey A.; Jensen, Allan

2017-01-01

Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. PMID:27941069

Borderline tumors of the ovary: A clinicopathological study

PubMed Central

Yasmeen, Samia; Hannan, Abdul; Sheikh, Fareeha; Syed, Amir Ali; Siddiqui, Neelam

2017-01-01

Objective: To report experience with borderline ovarian tumors (BOTs) in a developing country like Pakistan with limited resources and weak database of health system. Methods: Patients with BOTs managed at Shaukat Khanum Cancer hospital, Lahore, Pakistan from 2004 to 2014 were included and reviewed retrospectively. Data was recorded on histopathological types, age, CA-125, stage of disease, treatment modalities and outcomes. Results: Eighty-six patients with BOT were included with a median age of 35 years. Forty-two (49%) patients had serous BOTs and 43 (50%) had mucinous BOTs, while one (1%) had mixed type. Using FIGO staging, 80 patients had stage I; two patients had IIA, IIB and stage III each. Median follow-up time was 31.5 months. All patients had primary surgery. Seventy (81%) patients underwent complete surgical resection of tumor. Forty-three (50%) patients had fertility preserving surgery. Seventy-three (85%) patients remained in remission. Recurrent disease was observed in 13 (15%) patients. Median time to recurrence was 22 months. On further analysis, age above forty years, late stage at diagnosis and incomplete surgery were significantly associated with invasive recurrence. Conclusion: Despite a low malignant potential, relapses may occur in patients above forty years of age, incomplete surgery and staging information and advanced stage at presentation. Fertility sparing surgery should be considered in young patients. Complete excision of tumor and prolonged follow-up are advised because recurrence and transformation to invasive carcinoma may occur. PMID:28523039

Histopathologic features of ovarian borderline tumors are not predictive of clinical outcome.

PubMed

Avril, Stefanie; Hahn, Ellen; Specht, Katja; Hauptmann, Steffen; Höss, Cornelia; Kiechle, Marion; Höfler, Heinz; Schmalfeldt, Barbara

2012-12-01

Ovarian borderline tumors (BOTs) generally have an excellent prognosis, although recurrences and malignant transformation can occur. Our aim was to compare clinicopathologic features of BOT with clinical outcome. In seventy consecutive BOTs clinicopathologic parameters, tumor cell proliferation (Ki67) and in selected cases KRAS, BRAF and p53 mutational status were analyzed with recurrence-free and overall survival as the endpoints. Sixty-one (87%) patients presented with FIGO stage I, 3 stage II, and 6 stage III. Thirty-four patients had serous and 36 mucinous BOT (30 intestinal and 6 endocervical subtypes). Non-invasive peritoneal implants occurred in 9 patients, and no invasive implants were observed. Recurrence-free and overall survival rates were 91% and 99%, respectively, at a mean follow-up of 63 months. Disease recurrence occurred in 6 cases (all FIGO stage I) including 3 serous, 1 mucinous-intestinal, and 2 mucinous-endocervical subtypes. Mean time to recurrence was 27 months (range 8-68). The recurrence rate following fertility-conserving surgery was 31% (5/16) compared to 2% (1/54) after bilateral salpingo-oophorectomy. Neither peritoneal implants (9/70), micropapillary pattern (2/34), microinvasion (4/70), nor increased tumor cell proliferation was associated with a higher recurrence rate. The frequency of KRAS or BRAF mutations was 50% (3/6 recurrences and 3/6 controls; 4 KRAS, 2 BRAF mutations). No p53 mutations (0/12) were detected in primary or recurrent BOTs. Histopathologic parameters were not predictive of BOT recurrence including previously suggested risk factors such as micropapillary pattern and microinvasion. However, fertility-conserving surgery and incomplete surgical staging were associated with a higher risk for recurrence. Copyright © 2012 Elsevier B.V. All rights reserved.

Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

PubMed

Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

2017-04-01

Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT. Copyright © 2017 Elsevier GmbH. All rights reserved.

Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.

PubMed

Horn, Lars-Christian; Höhn, Anne K; Einenkel, Jens; Siebolts, Udo

2014-11-01

Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.

Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies.

PubMed

Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna; Bandera, Elisa V; Doherty, Jennifer A; Høgdall, Estrid; Webb, Penelope M; Jordan, Susan J; Rossing, Mary Anne; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Edwards, Robert P; Schildkraut, Joellen M; Berchuck, Andrew; Olson, Sara H; Kiemeney, Lambertus A; Massuger, Leon F A G; Narod, Steven A; Phelan, Catherine M; Anton-Culver, Hoda; Ziogas, Argyrios; Wu, Anna H; Pearce, Celeste L; Risch, Harvey A; Jensen, Allan

2017-01-01

Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Value of Serum CA125 in the Diagnosis of Borderline Tumors of the Ovary: A Subanalysis of the Prospective Multicenter ROBOT Study.

PubMed

Fotopoulou, Christina; Sehouli, Jalid; Ewald-Riegler, Nina; de Gregorio, Nikolaus; Reuss, Alexander; Richter, Rolf; Mahner, Sven; Kommoss, Friedrich; Schmalfeldt, Barbara; Fehm, Tanja; Hanker, Lars; Wimberger, Pauline; Canzler, Ulrich; Pfisterer, Jacobus; Kommoss, Stefan; Hauptmann, Steffen; du Bois, Andreas

2015-09-01

The value of the serum tumor marker CA125 in borderline tumors of the ovary (BOTs) is not well defined, with unclear benefit in both diagnosis and follow-up. The aim of the present project was to identify the predictive value of CA125 for stage and relapse. CA125 data were extracted from the ROBOT multicenter study of patients with BOT treated between 1998 and 2008 in 24 German centers. While patients' data were retrieved retrospectively from hospital records and clinical tumor registries, follow-up and independent central pathology review were performed prospectively. We identified 127 patients from the ROBOT database fulfilling the eligibility criterion of available CA125 at initial diagnosis. Eighty-three (65.3%) patients had increased CA125 levels (>35 U/L). Of the patients, 85.0% presented with serous and 13.4% with mucinous BOT histology, whereas 29.9% had stage I disease. Fifteen (11.8%) patients experienced a relapse. Multivariate analysis identified raised CA125, young age, and serous histology as independent predictors of peritoneal implants of any type at initial presentation. Raised CA125 at initial diagnosis was, however, not an independent predictor of future relapse. Elevated CA125 seems to be associated with the presence of peritoneal implants of any type at initial diagnosis of serous BOT, but failed to have any independent predictive value on future relapse. Prospective multicenter studies are warranted to evaluate CA125 measurements in the follow-up management of BOT.

Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors: Results from a Danish case-control study.

PubMed

Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan

2015-01-01

Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. From 1995 through 1999, we included 267 women with ovarian cancer, 115 women with borderline ovarian tumors and 911 randomly selected control women. All women completed a beverage frequency questionnaire with detailed information on coffee and tea consumption. Analyses were performed using multiple logistic regression models. Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer. No relation between tea consumption and ovarian cancer risk was observed. The risk estimates for borderline ovarian tumors resembled those observed for ovarian cancer, but did not reach statistical significance. Our results indicate that coffee consumption and total caffeine consumption from coffee and tea combined is associated with a modest decreased risk of ovarian cancer. However, more biological studies are needed to identify bioactive chemical compounds in coffee that potentially could affect ovarian cancer development.

Collecting Tumor Samples From Patients With Gynecological Tumors

ClinicalTrials.gov

2016-10-26

Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell

Selumetinib Sulfate in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer

ClinicalTrials.gov

2018-03-30

Borderline Ovarian Epithelial Tumor; Low Grade Ovarian Serous Adenocarcinoma; Primary Peritoneal Carcinoma; Primary Peritoneal Low Grade Serous Adenocarcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor

Borderline ovarian tumors, fertility-sparing surgery and pregnancy outcome.

PubMed

Frega, A; Coluccia, A C; Di Martino, G; Catalano, A; Milazzo, G N; Assorgi, C; Manzara, F; Romeo, G D; Gentile, M; Marziani, R; Moscarini, M

2014-01-01

Borderline ovarian tumors (BOTs) represent a type of epithelial tumors having a biologic intermediate behavior between clearly malignant and straight benign tumors. Most of BOTs interest women during fertile age, for which it is necessary to consider a fertility sparing surgery. To evaluate the clinical aspects and pregnancy rate of women affected by borderline ovarian tumors who have undergone fertility sparing surgery. A study of 22 patients affected by BOTs who have been treated with a fertility sparing surgery was conducted between January 2005 and October 2011 at Sant'Andrea Hospital, "Sapienza" University of Rome. The patients' characteristics analyzed were: age, histological type, tumor size, adnexal surgery, pre-operative serum CA-125, diagnostic circumstances, number of patients who became pregnant and number of overall pregnancies. Among the 22 patients treated with a fertility sparing surgery, only sixteen wanted to get pregnant. Eleven patents out of 16 accomplished it. The pregnancy rate was 68.7%. Fertility sparing surgery can be considered a safe procedure for young women affected by borderline ovarian tumors.

p14 expression differences in ovarian benign, borderline and malignant epithelial tumors.

PubMed

Cabral, Vinicius Duarte; Cerski, Marcelle Reesink; Sa Brito, Ivana Trindade; Kliemann, Lucia Maria

2016-10-22

Abnormalities in tumor suppressors p14, p16 and p53 are reported in several human cancers. In ovarian epithelial carcinogenesis, p16 and p53 show higher immunohistochemical staining frequencies in malignant tumors and are associated with poor prognoses. p14 was only analyzed in carcinomas, with conflicting results. There are no reports on its expression in benign and borderline tumors. This study aims to determine p14, p16 and p53 expression frequencies in ovarian benign, borderline and malignant tumors and their associations with clinical parameters. A cross-sectional study utilizing immunohistochemistry was performed on paraffin-embedded ovarian epithelial tumor samples. Clinical data were collected from medical records. Fisher's exact test and the Bonferroni correction were performed for frequency associations. Survival comparisons utilized Kaplan-Meier and log rank testing. Associations were considered significant when p < 0.05. p14 absent expression was associated with malignant tumors (60 % positive) (p = 0.000), while 93 % and 94 % of benign and borderline tumors, respectively, were positive. p16 was positive in 94.6 % of carcinomas, 75 % of borderline and 45.7 % of benign tumors (p = 0.000). p53 negative staining was associated with benign tumors (2.9 % positive) (p = 0.016) but no difference was observed between borderline (16.7 %) and malignant tumors (29.7 %) (p = 0.560). No associations were found between expression rates, disease-free survival times or clinical variables. Carcinoma subtypes showed no difference in expression. This is the first description of p14 expression in benign and borderline tumors. It remains stable in benign and borderline tumors, while carcinomas show a significant absence of staining. This may indicate that p14 abnormalities occur later in carcinogenesis. p16 and p53 frequencies increase from benign to borderline and malignant tumors, similarly to previous reports, possibly reflecting the

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

Differentiation between borderline and benign ovarian tumors: combined analysis of MRI with tumor markers for large cystic masses (≥5 cm).

PubMed

Park, Sung Yoon; Oh, Young Taik; Jung, Dae Chul

2016-05-01

There is overlap in imaging features between borderline and benign ovarian tumors. To analyze diagnostic performance of magnetic resonance imaging (MRI) combined with tumor markers for differentiating borderline from benign ovarian tumor. Ninety-nine patient with MRI and surgically confirmed ovarian tumors 5 cm or larger (borderline, n = 37; benign, n = 62) were included. On MRI, tumor size, septal number (0; 1-4; 5 or more), and presence of solid portion such as papillary projection or septal thickening 0.5 cm or larger were investigated. Serum tumor markers (carbohydrate antigen 125 [CA 125] and CA 19-9) were recorded. Multivariate analysis was conducted for assessing whether combined MRI with tumor markers could differentiate borderline from benign tumor. The diagnostic performance was also analyzed. Incidence of solid portion was 67.6% (25/37) in borderline and 3.2% (2/62) in benign tumors (P < 0.05). In all patients, without combined analysis of MRI with tumor markers, multivariate analysis revealed solid portion (P < 0.001) and CA 125 (P = 0.039) were significant for predicting borderline tumors. When combined analysis of MRI with CA 125 ((i) the presence of solid portion or (ii) CA 125 > 44.1 U/mL with septal number ≥5 for borderline tumor) is incorporated to multivariate analysis, it was only significant (P = 0.001). The sensitivity, specificity, PPV, NPV, and accuracy of combined analysis of MRI with CA 125 were 89.1%, 91.9%, 86.8%, 93.4, and 90.9%, respectively. Combined analysis of MRI with CA 125 may allow better differentiation between borderline and benign ovarian tumor compared with MRI alone. © The Foundation Acta Radiologica 2015.

High Grade Serous Cystadenocarcinoma of Testis-Case Report of a Rare Ovarian Epithelial Type Tumour

PubMed Central

Nayanar, Sangeetha K; Varadharajaperumal, R; Satheeshbabu, TV; Balasubramanian, Satheesan

2017-01-01

Ovarian epithelial type tumour of testis are extremely rare tumours that resemble ovarian surface epithelial tumours. They usually present as testicular or paratesticular tumours and can be serous, mucinous, endometrioid or Brenner tumour. Serous and mucinous types account for the majority of tumours. The tumours are benign, borderline or malignant, commonly borderline. Here, we report a case of high grade serous cyst adenocarcinoma of testis which manifested as extensive metastasis in supraclavicular, mediastinal and abdominopelvic groups of lymph nodes, lung and adrenal gland without clinical evidence of an overt primary tumour. We report this case so as to make clinicians and pathologists aware of this rare entity and to stress on the fact that this rare entity should be kept in mind when evaluating cases of metastatic adenocarcinoma in male patients. PMID:28764180

A binary histologic grading system for ovarian serous carcinoma is an independent prognostic factor: a population-based study of 4317 women diagnosed in Denmark 1978-2006.

PubMed

Hannibal, Charlotte Gerd; Vang, Russell; Junge, Jette; Kjaerbye-Thygesen, Anette; Kurman, Robert J; Kjaer, Susanne K

2012-06-01

To evaluate the prognostic significance of histologic grade on survival of ovarian serous cancer in Denmark during nearly 30 years. Using the nationwide Danish Pathology Data Bank, we evaluated 4317 women with ovarian serous carcinoma in 1978-2006. All pathology reports were scrutinized and tumors classified as either low-grade serous carcinomas (LGSC) or high-grade serous carcinomas (HGSC). Tumors in which the original pathology reports were described as well-differentiated were classified as LGSC, and those that were described as moderately or poorly differentiated were classified as HGSC. We obtained histologic slides from the pathology departments for women with a diagnosis of well-differentiated serous carcinoma during 1997-2006, which were then reviewed by expert gynecologic pathologists. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression analysis with follow-up through June 2009. Women with HGSC had a significantly increased risk of dying (HR=1.9; 95% CI: 1.6-2.3) compared with women with LGSC while adjusting for age and stage. Expert review of 171 women originally classified as well-differentiated in 1997-2006 were interpreted as LGSC in 30% of cases, whereas 12% were interpreted as HGSC and 50% as serous borderline ovarian tumors (SBT). Compared with women with confirmed LGSC, women with SBT at review had a significantly lower risk of dying (HR=0.5; 95% CI: 0.22-0.99), and women with HGSC at review had a non-significantly increased risk of dying (HR=1.6; 95% CI: 0.7-3.4). A binary grading system is a significant predictor of survival for ovarian serous carcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.

Is target oriented surgery sufficient with borderline ovarian tumors? - Role of accompanying pathologies.

PubMed

Gungor, Tayfun; Cetinkaya, Nilufer; Yalcin, Hakan; Ozdal, Bulent; Ozgu, Emre; Baser, Eralp; Yilmaz, Nafiye; Caglar, Mete; Zergeroglu, Sema; Erkaya, Salim

2014-01-01

There are limited data in the literature related to concomitant genital or extra-genital organ pathologies in patients with borderline ovarian tumors (BOTs). The aim of this study was to evaluate our experience with 183 patients to draw attention to the accompanying organ pathologies with BOTs. One hundred eighty-three patients with BOTs, diagnosed and/or treated in our center between January of 2000 and March of 2013 were evaluated retrospectively. Data related to age, tumor histology, lesion side, disease stage, accompanying incidental ipsilateral and/or contralateral ovarian pathologies, treatment approaches, and follow-up periods were investigated. Incidental gynecologic and non-gynecologic concomitant organ pathologies were also recorded. The mean age at diagnosis was 40.6 years (range: 17-78). Ninety- five patients (51%) were ≤40 years. A hundred and forty-seven patients (80%) were at stage IA of the disease. The most common type of BOT was serous in histology. Non-invasive tumor implants were diagnosed in 4% and uterine involvement was found 2% among patients who underwent hysterectomies. There were 12 patients with positive peritoneal washings. Only 17 and 84 patients respectively had concomitant ipsilateral and concomitant contralateral incidental ovarian pathologies. The most common type of uterine, appendicular and omental pathologies were chronic cervicitis, lymphoid hyperplasia and chronic inflammatory reaction. According to our findings most of accompanying pathologies for BOT are benign in nature. Nevertheless, there were additional malignant diseases necessitating further therapy. We emphasize the importance of the evaluation of all abdominal organs during surgery.

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

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

PubMed

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

2015-02-17

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. 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). 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. 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.

Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

PubMed

Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

2017-09-01

Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

HtrA3 Is Downregulated in Cancer Cell Lines and Significantly Reduced in Primary Serous and Granulosa Cell Ovarian Tumors.

PubMed

Singh, Harmeet; Li, Ying; Fuller, Peter J; Harrison, Craig; Rao, Jyothsna; Stephens, Andrew N; Nie, Guiying

2013-01-01

Objective. The high temperature requirement factor A3 (HtrA3) is a serine protease homologous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of cancers, suggesting a widespread loss of these proteases in cancer. This study examined how extensively the HtrA (HtrA1-3) proteins are downregulated in commonly used cancer cell lines and primary ovarian tumors.Methods. RT-PCR was applied to various cancer cell lines (n=17) derived from the ovary, endometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian tumors [granulosa cell tumors (n=19), mucinous cystadenocarcinomas (n=6), serous cystadenocarcinomas (n=8)] and normal ovary (n = 9). HtrA3 protein was localized by immunohistochemistry.Results. HtrA3 was extensively downregulated in the cancer cell lines examined including the granulosa cell tumor-derived cell lines. In primary ovarian tumors, the HtrA3 was significantly lower in serous cystadenocarcinoma and granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and tumors. In normal postmenopausal ovary, HtrA3 protein was localized to lutenizing stromal cells and corpus albicans. In serous cystadenocarcinoma, HtrA3 protein was absent in the papillae but detected in the mesenchymal cyst wall.Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian serous cystadenocarcinoma and granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian malignancy.

Long-term follow-up of borderline ovarian tumors clinical outcome and prognostic factors.

PubMed

Lazarou, Anastasia; Fotopoulou, Christina; Coumbos, Alexandra; Sehouli, Jalid; Vasiljeva, Jekaterina; Braicu, Ioana; Burger, Heinz; Kuehn, Wolfgang

2014-11-01

The aim of the present study was to evaluate the characteristics of borderline ovarian tumors (BOTs). Data of 151 patients with BOTs were retrospectively evaluated. A total of 151 cases with BOTs were diagnosed. Histopathological evaluation identified 82.8% with serous, 10.6% with mucinous and 5.3% with mixed histology. Overall, 67.5% had International Federation of Gynecology and Obstetrics (FIGO) stage I, 10.6% FIGO stage II, 14.6% FIGO stage III and 4% FIGO stage IV. A total of 21.9% had peritoneal implants; of which 2.7% were invasive, 17.2% non-invasive and 2% both invasive and non-invasive. Microinvasion was observed in 5.3% and a micropapillary pattern in 12.6%. A total of 12.6% of patients presented second neoplasms. During a median follow-up period of 86 (range=0.1-432) months, there were relapses in 16.8%, of which 52.6% had invasive implants. Overall, 6.2% died of their disease, 28.5% with invasive implants. The median time-to-progression was 48 (range=8-120) months. Patients with BOTs have an excellent prognosis. Long-term follow-up is recommended, since recurrence occurs. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Parameters of blood count and tumor markers in patients with borderline ovarian tumors: a retrospective analysis and relation to staging.

PubMed

Nomelini, Rosekeila Simões; da Silva, Taísa Morete; Tavares Murta, Beatriz Martins; Murta, Eddie Fernando Candido

2012-01-01

The aim of this paper was to evaluate the parameters of blood count and tumor markers in borderline ovarian tumors. We evaluated 21 patients who had confirmed histopathologic diagnosis of borderline ovarian tumor. We recorded age, parity, tumor type, stage of cancer, serum levels of tumor markers (CA-125, CA-15.3, CA-19.9, CEA, AFP), and the parameters of blood count, fasting glucose, disease-free survival and overall. The patients were divided into two groups, stage IA (n = 13) and stage IB-IIIC (n = 8). The unpaired t-test and Fisher's exact test were used, with P values of less than 0.05 being considered to indicate statistical significance. Levels of red blood cells, hematocrit, and hemoglobin were significantly higher in stage IA when compared with stage IB-IIIC (P < 0.05). The levels of tumor marker CEA had a tendency to be higher in the group stage IB-IIIC (0.08). Abnormal levels of CEA and CA-19.9 were found more frequently in stages IB-IIIC. Therefore, parameters of blood count, CEA, and CA-19.9 should be targeted for further research in identifying prognostic factors in borderline tumors.

Ultrasonographic diagnosis and longitudinal follow-up of recurrences after conservative surgery for borderline ovarian tumors.

PubMed

Franchi, Dorella; Boveri, Sara; Radice, Davide; Portuesi, Rosalba; Zanagnolo, Vanna; Colombo, Nicoletta; Testa, Antonia Carla

2016-12-01

Borderline ovarian tumors are generally diagnosed in young women. Because of the young age of patients at first diagnosis and at recurrence, and given the good prognosis of borderline ovarian tumors, a conservative surgical approach in those women who wish to preserve their fertility is advised. In this scenario, transvaginal ultrasound examination plays a key role in the detection of borderline ovarian tumor recurrence, and in assessment of amount of normal functioning parenchyma remaining. To date, no data are available about the natural history of borderline ovarian tumor recurrence. The aim of the study was to determine growth rate of recurrent ovarian cysts by a scheduled follow-up by ultrasound examination, in women previously treated with fertility-sparing surgery due to borderline ovarian tumors. In this prospective observational study, we collected data from 34 patients previously treated with fertility-sparing surgery due to borderline ovarian tumors, who had a suspicious recurrent lesion. The patients underwent transvaginal ultrasonographic examination every 3 months, until the clinical setting recommended proceeding with surgery. According to cyst size at study entry, they were categorized into 3 groups: ≤10 mm, 10-20 mm, and >20 mm. Summary statistics for cyst size, growth rate, and the probability of remaining within the same dimension category at first ultrasound during the follow-up were also obtained. For each cyst the growth rate was calculated as the slope of the linear interpolation between 2 consecutive measurements. Follow-up timing (P < .001), cyst size (P < .001), and micropapillary pattern (P < .001) were factors significantly affecting the cyst growth both in univariate and multivariate analysis. According to size category at first ultrasound, growth rate ranges from a minimum of 0.06 mm/mo for cysts <10 mm up to 1.92 mm/mo for cysts >20 mm. The final histology of all recurrent lesions confirmed the same histotype of primary borderline

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

Borderline Brenner tumor of the ovary: a case report with immunohistochemical and molecular study.

PubMed

De Cecio, Rossella; Cantile, Monica; Collina, Francesca; Marra, Laura; Santonastaso, Clemente; Scaffa, Cono; Botti, Gerardo; Losito, Nunzia Simona

2014-10-29

Borderline Brenner tumor of the ovary is a rare entity characterized by papillary structures with a fibro-vascular core, covered by a transitional epithelium, and by the absence of stromal infiltration. It is associated, by definition, with a benign component of Brenner tumor. We report a case of a 68-year-old woman, with a right ovarian mass, whose morphology and immuno-profile were consistent with the diagnosis of a borderline Brenner tumor. Immunohistochemistry carried out on selected markers may help to formulate the diagnosis, more than the molecular analyses.

Miscellaneous rare paratesticular tumors.

PubMed

Henley, J D; Ferry, J; Ulbright, T M

2000-11-01

A few uncommon but distinctive tumors may preferentially involve the paratestis. The 3 unusual tumors that represent the focus of this discussion are the ovarian-type epithelial tumors (OTET), the desmoplastic small round cell tumor (DSRCT), and the melanotic neuroectodermal tumor of infancy (MNTI). The OTETs are testicular homologues of their more common namesake counterparts that arise in the ovary. Most frequent of these are serous tumors of borderline malignancy, with fewer cases of serous carcinomas or other forms of mullerian differentiation. DSRCT is an increasingly recognized, aggressive, "small blue cell" neoplasm with distinctive clinical and pathologic features. These polyphenotypic tumors characteristically, but not invariably, arise in intimate association with the serosal membrane of the peritoneal cavity and harbor a signature translocation-t(11;22)(p13,q12). In the paratestis they often involve the surface of the epididymis. The MNTI is an enigmatic, histologically distinctive, low-grade neoplasm occasionally encountered in the epididymis. Recognition of its features is essential to avoid misdiagnosis as a more aggressive "small blue cell" neoplasm and consequent therapeutic mismanagement. Primary hematopoietic tumors of the paratesticular structures are rare. There appears to be a tendency for young men to have low-grade lymphomas with an indolent course and older patients to develop higher-grade tumors. Plasmacytoma and granulocytic sarcoma of the paratestis are even more rare and are often susceptible to misinterpretation. Finally, metastatic tumors and a variety of other very rare neoplasms are discussed.

Is the two-tier ovarian serous carcinoma grading system potentially useful in stratifying uterine serous carcinoma? A large multi-institutional analysis.

PubMed

Ahmed, Quratulain; Hussein, Yaser; Hayek, Kinda; Bandyopadhyay, Sudeshna; Semaan, Assaad; Abdul-Karim, Fadi; Al-Wahab, Zaid; Munkarah, Adnan R; Elshaikh, Mohamed A; Alosh, Baraa; Nucci, Marisa R; Van de Vijver, Koen K; Morris, Robert T; Oliva, Esther; Ali-Fehmi, Rouba

2014-02-01

A subset of uterine serous carcinoma (USC) may have better clinical behavior bringing up the possibility that there may be morphologic features, which would help in their categorization. The aim of this study is to evaluate the potential use of the MD Anderson Cancer Center 2-tier grading system for ovarian carcinoma in USC. Tumors assigned a combined score included in this analysis were 1) low-grade: tumors without marked atypia and 12 mitoses/10 high power field (HPF) and 2) high grade: tumors with severe nuclear atypia and >12 mitoses/10 HPF. Clinicopathologic parameters evaluated included patients' age, tumor size, myometrial invasion (MI), lymphovascular invasion (LVI), lymph node (LN), FIGO stage, and patient outcome. 140 patients with USC were included, 30 low grade uterine serous carcinoma (LGUSC) and 110 high grade uterine serous carcinoma (HGUSC). Of all parameters only 2 (MI and stage IA) reached statistical significance. 67% of LGUSC cases showed myometrial invasion versus 93.6% HGUSC cases (p = 0.003). A higher percentage of LGUSC (63.3%) versus HGUSC (32.7%) were in stage IA (p = 0.01). However, by multivariate analysis including age, LVI, stage and tumor grade only stage was an independent prognostic factor. The presence of atypia and mitosis across a uterine serous carcinoma is notoriously variable in magnitude and extent, potentially making evaluation of these features difficult and subsequent grading subjective. Our findings thus show that actual prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma may not be applicable. Copyright © 2013 Elsevier Inc. All rights reserved.

The frequency and significance of WT-1 expression in serous endometrial carcinoma.

PubMed

Hedley, Catherine; Sriraksa, Ruethairat; Showeil, Rania; Van Noorden, Susan; El-Bahrawy, Mona

2014-09-01

Serous endometrial carcinoma is an aggressive type of endometrial carcinoma. Wilms tumor gene 1 (WT-1) is commonly expressed in ovarian serous carcinomas and considered a diagnostic marker of these tumors. However, it is generally believed that WT-1 is rarely expressed by endometrial serous carcinoma. The aim of this study was to evaluate the frequency and significance of WT-1 expression in endometrial serous carcinoma. We studied the expression of WT-1 in formalin-fixed, paraffin-embedded tumor sections from 77 cases of endometrial serous carcinoma. Thirty-four tumors showed positive expression for WT-1 (44%). There was a statistically significant association between the presence of WT-1 expression and disease-free survival (DFS), where patients with tumors expressing WT-1 had a shorter DFS compared with those with no WT-1 expression (P = .031; median DFS, 15 and 38 months, respectively). By multivariate Cox regression analysis, DFS was independent from other clinicopathological data (tumor stage, presence of lymphovascular space invasion, cervical involvement, and extrauterine spread), indicating that WT-1 expression is independently associated with DFS. Our study shows that WT-1 is expressed in a considerable percentage of endometrial serous carcinomas, suggesting a role for WT-1 in the pathology of these tumors. This has therapeutic significance, as WT-1 is an emerging target for immunotherapy. Moreover, our results show that WT-1 has prognostic value, being predictive of DFS. As a potential prognostic marker and therapeutic target, we recommend that WT-1 expression should be included in histopathologic reports of endometrial serous carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants

PubMed Central

2013-01-01

Background Patients diagnosed for a serous ovarian borderline tumor (s-BOT) typically present with an excellent clinical outcome. However there have been controversies concerning the prognostic impact of so-called implants, an extra ovarian spread occurring alongside the s-BOT in certain cases. It remains obscure whether these implants actually resemble metastasis owning the same genetic pattern as the ovarian primary or whether they develop independently. Methods The current study, in the aim of further clarifying the genetic origin of implants, assessed BRAF/KRAS hot spot mutations and the p53/p16INK4a immunophenotype of s-BOTs and corresponding implants (n = 49) of 15 patients by pyro-sequencing and immunostaining, respectively. Results A significant proportion of both s-BOTs and implants showed KRAS or BRAF mutation and though p16INK4a was found to be abundantly expressed, p53 immunoreactivity was rather low. When genotypes of BRAF/KRAS mutated s-BOTs and corresponding implants were compared no patient presented with a fully matching mutation profile of s-BOTs and all corresponding implants. Conclusions The current study reveals genetic heterogeneity of s-BOTs and implants, as none of the markers examined showed constant reciprocity. Hence, our findings may assist to explain the different clinical presentation of s-BOTs and implants and might encourage to applying more individualized follow up protocols. PMID:24139521

KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants.

PubMed

Heublein, Sabine; Grasse, Katinka; Hessel, Harald; Burges, Alexander; Lenhard, Miriam; Engel, Jutta; Kirchner, Thomas; Jeschke, Udo; Mayr, Doris

2013-10-18

Patients diagnosed for a serous ovarian borderline tumor (s-BOT) typically present with an excellent clinical outcome. However there have been controversies concerning the prognostic impact of so-called implants, an extra ovarian spread occurring alongside the s-BOT in certain cases. It remains obscure whether these implants actually resemble metastasis owning the same genetic pattern as the ovarian primary or whether they develop independently. The current study, in the aim of further clarifying the genetic origin of implants, assessed BRAF/KRAS hot spot mutations and the p53/p16INK4a immunophenotype of s-BOTs and corresponding implants (n=49) of 15 patients by pyro-sequencing and immunostaining, respectively. A significant proportion of both s-BOTs and implants showed KRAS or BRAF mutation and though p16INK4a was found to be abundantly expressed, p53 immunoreactivity was rather low. When genotypes of BRAF/KRAS mutated s-BOTs and corresponding implants were compared no patient presented with a fully matching mutation profile of s-BOTs and all corresponding implants. The current study reveals genetic heterogeneity of s-BOTs and implants, as none of the markers examined showed constant reciprocity. Hence, our findings may assist to explain the different clinical presentation of s-BOTs and implants and might encourage to applying more individualized follow up protocols.

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. © The Author(s) 2015.

Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG).

PubMed

Dahm-Kähler, Pernilla; Borgfeldt, Christer; Holmberg, Erik; Staf, Christian; Falconer, Henrik; Bjurberg, Maria; Kjölhede, Preben; Rosenberg, Per; Stålberg, Karin; Högberg, Thomas; Åvall-Lundqvist, Elisabeth

2017-01-01

The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy. Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2013-07-01

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

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

[Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumors: Guidelines from the French national network dedicated to rare gynaecological cancer].

PubMed

Rousset-Jablonski, Christine; Selle, Fréderic; Adda-Herzog, Elodie; Planchamp, François; Selleret, Lise; Pomel, Christophe; Chabbert-Buffet, Nathalie; Daraï, Emile; Pautier, Patricia; Trémollières, Florence; Guyon, Frederic; Rouzier, Roman; Laurence, Valérie; Chopin, Nicolas; Faure-Conter, Cécile; Bentivegna, Enrica; Vacher-Lavenu, Marie-Cécile; Lhomme, Catherine; Floquet, Anne; Treilleux, Isabelle; Lecuru, Fabrice; Gouy, Sébastien; Kalbacher, Elsa; Genestie, Catherine; de la Motte Rouge, Thibault; Ferron, Gwenael; Devouassoux-Shisheboran, Mojgan; Kurtz, Jean-Emmanuel; Namer, Moise; Joly, Florence; Pujade-Lauraine, Eric; Grynberg, Michael; Querleu, Denis; Morice, Philippe; Gompel, Anne; Ray-Coquard, Isabelle

2018-03-01

Rare ovarian tumors include complex borderline ovarian tumors, sex-cord tumors, germ cell tumors, and rare epithelial tumors. Indications and modalities of fertility preservation, infertility management and contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and of experts in reproductive medicine and gynaecology have worked on guidelines about fertility preservation, contraception and menopause hormone therapy in women treated for ovarian rare tumors. A panel of 39 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review, and then rated through two successive rounds. Thirty-five recommendations were selected, and concerned indications for fertility preservation, contraindications for ovarian stimulation (in the context of fertility preservation or for infertility management), contraceptive options (especially hormonal ones), and menopause hormone therapy for each tumor type. Overall, prudence has been recommended in the case of potentially hormone-sensitive tumors such as sex cord tumors, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumors. In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

PubMed

Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

2017-09-25

von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: A systematic review and meta-analysis

PubMed Central

ZENG, SHIYAN; ZHANG, XINDAN; YANG, DEJUAN; WANG, XIAOYI; REN, GUOSHENG

2015-01-01

The standard treatment for borderline and malignant phyllodes tumors is wide local excision (margins ≥1 cm), in the context of either breast-conserving surgery (BCS) or total mastectomy (TM). Due to the high risk of local recurrence (LR) following surgical intervention alone, the addition of adjuvant radiotherapy (RT) has been previously investigated; however, the conclusions have been inconsistent. This systematic review and meta-analysis was designed to assess the efficacy of adjuvant RT for borderline and malignant phyllodes tumors. Pubmed and Web of Science were systematically searched to identify relevant studies assessing the effect of adjuvant RT on borderline and malignant phyllodes tumors from the inception of this technique through May, 2014. A total of 8 studies were identified among 332 citations. In this meta-analysis, patients who received adjuvant RT had a lower relative risk of LR [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.23–0.64]. The absolute risk difference was 10.1% (95% CI: 4.9–17.6), corresponding to a number needed to treat of 10. Our pooled meta-analysis clearly demonstrated a decreased risk of LR in patients with borderline and malignant phyllodes tumors who received RT following BCS (HR=0.31, 95% CI: −0.10–0.72). However, the combined HR for LR in the TM group did not demonstrate that adjuvant RT was superior to no RT (HR=0.68, 95% CI: −0.28–1.64). No significant differences were observed in overall survival (OS) or disease-free survival (DFS) between the two groups. Our analysis suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS. However, adjuvant RT was not found to exert an effect on OS or DFS. PMID:26137284

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. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

PubMed Central

Ardighieri, Laura; Zeppernick, Felix; Hannibal, Charlotte G; Vang, Russell; Cope, Leslie; Junge, Jette; Kjaer, Susanne K; Kurman, Robert J; Shih, Ie-Ming

2014-01-01

There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced-stage disease identified from a nation-wide tumour registry in Denmark. Mutational analysis for hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed KRAS mutations in 34 (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST–implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST–implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11 SBT/APST–implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST–implant (non-invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non-invasive and invasive, harbour the identical KRAS or BRAF mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour. PMID:24307542

Immunohistochemical localization of HE4 in benign, borderline, and malignant lesions of the ovary.

PubMed

Georgakopoulos, Penelope; Mehmood, Saira; Akalin, Ali; Shroyer, Kenneth R

2012-11-01

Despite advances in the development of novel methods to improve treatment, ovarian carcinoma is still the leading cause of gynecologic cancer death in the United States and other industrialized nations. Improvements in the clinical outcome of ovarian cancer will be achieved if methods can be developed to enable the detection of these tumors at the earliest possible stage. Thus, it is critically important to identify and validate new biomarkers of ovarian cancer. HE4 expression was defined by immunohistochemical analysis of a wide range of benign, borderline, and malignant ovarian lesions, including serous, endometrioid, mucinous, and clear cell lesions of the ovary and in primary tubal carcinomas and the normal fallopian tube. At the cellular level, HE4 was highly expressed in malignant ovarian tumors and in a wide range of benign and borderline ovarian lesions. In addition, HE4 was highly expressed in primary fallopian tube carcinomas and benign fallopian tubal epithelial cells. These results support the conclusion that HE4 is widely expressed in most benign, borderline, and malignant lesions of the ovary and the fallopian tube. The detection of HE4 expression at high levels in some benign lesions and normal tissues suggests that HE4 could have limited specificity as a marker of ovarian or tubal carcinoma. Furthermore, the relatively weak expression that was observed in many ovarian carcinomas indicates that HE4 could fail to detect some cases of primary or recurrent disease.

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

PubMed

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

2013-03-01

To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7 months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7-85.2; p = 0.006, log-rank statistic). PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ. Copyright © 2013. Published by Elsevier B.V.

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

PubMed

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

2010-10-01

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

Wilms tumor gene product: sensitive and contextually specific marker of serous carcinomas of ovarian surface epithelial origin.

PubMed

Hwang, Harry; Quenneville, Louise; Yaziji, Hadi; Gown, Allen M

2004-06-01

Carcinomas of ovarian surface epithelial origin can arise from, and often present at, extraovarian sites. There are few available markers for the positive identification of carcinomas of ovarian surface epithelial origin, which might aid in distinguishing them from metastatic carcinomas, such as of breast, colon, or lung origin. Recently, the Wilms tumor gene product (WT-1) has been shown to be expressed in ovarian surface and mesothelial epithelium. We tested the hypothesis that WT-1 would be a sensitive and specific marker of ovarian surface epithelium carcinomas. An archived series of 116 ovarian carcinomas (57 serous [43 ovarian, 14 extraovarian], 31 mucinous, 15 clear cell, 13 endometrioid), 118 breast carcinomas, 46 colonic carcinomas, and 45 nonsmall cell lung cancers were selected. A polyclonal antibody to the WT-1 gene product was applied to deparaffinized, formalin-fixed tissue sections after epitope retrieval. Fifty-two of 57 (93%) serous carcinomas of ovarian surface epithelial origin were WT-1-positive, in a nuclear pattern, with virtually all the tumor cell population positive in the majority of cases. None of the mucinous, clear cell, or endometrioid ovarian cancers were positive, and only 8 of 118 breast, 0 of 46 colonic, and 0 of 45 lung nonsmall cell carcinomas were WT-1-positive. These findings demonstrate that WT-1 is a highly sensitive and specific marker of serous carcinomas of ovarian surface epithelial origin (both ovarian and extraovarian). These results also contradict recent reports demonstrating WT-1 expression in both breast and lung carcinomas.

Identification and Characterization of Genomic Amplifications in Ovarian Serous Carcinoma

DTIC Science & Technology

2008-01-01

lower cost. As a result, we have analyzed more than 40 affinity purified ovarian serous tumors and our results demonstrated that CCNE1, Notch3 , Rsf-1...serous tumors. In addition, we have further characterized the biological functions of the two of the commonly amplified genes, Notch3 and Rsf-1, in...analyses, we have focused on two of the most frequently amplified regions, 11q13.2 (Rsf-1 locus) and 19p13 ( Notch3 locus), for detailed mapping and

Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer

PubMed Central

Grisham, Rachel N.; Sylvester, Brooke E.; Won, Helen; McDermott, Gregory; DeLair, Deborah; Ramirez, Ricardo; Yao, Zhan; Shen, Ronglai; Dao, Fanny; Bogomolniy, Faina; Makker, Vicky; Sala, Evis; Soumerai, Tara E.; Hyman, David M.; Socci, Nicholas D.; Viale, Agnes; Gershenson, David M.; Farley, John; Levine, Douglas A.; Rosen, Neal; Berger, Michael F.; Spriggs, David R.; Aghajanian, Carol A.; Solit, David B.; Iyer, Gopa

2015-01-01

Purpose No effective systemic therapy exists for patients with metastatic low-grade serous (LGS) ovarian cancers. BRAF and KRAS mutations are common in serous borderline (SB) and LGS ovarian cancers, and MEK inhibition has been shown to induce tumor regression in a minority of patients; however, no correlation has been observed between mutation status and clinical response. With the goal of identifying biomarkers of sensitivity to MEK inhibitor treatment, we performed an outlier analysis of a patient who experienced a complete, durable, and ongoing (> 5 years) response to selumetinib, a non-ATP competitive MEK inhibitor. Patients and Methods Next-generation sequencing was used to analyze this patient's tumor as well as an additional 28 SB/LGS tumors. Functional characterization of an identified novel alteration of interest was performed. Results Analysis of the extraordinary responder's tumor identified a 15-nucleotide deletion in the negative regulatory helix of the MAP2K1 gene encoding for MEK1. Functional characterization demonstrated that this mutant induced extracellular signal-regulated kinase pathway activation, promoted anchorage-independent growth and tumor formation in mice, and retained sensitivity to selumetinib. Analysis of additional LGS/SB tumors identified mutations predicted to induce extracellular signal-regulated kinase pathway activation in 82% (23 of 28), including two patients with BRAF fusions, one of whom achieved an ongoing complete response to MEK inhibitor–based combination therapy. Conclusion Alterations affecting the mitogen-activated protein kinase pathway are present in the majority of patients with LGS ovarian cancer. Next-generation sequencing analysis revealed deletions and fusions that are not detected by older sequencing approaches. These findings, coupled with the observation that a subset of patients with recurrent LGS ovarian cancer experienced dramatic and durable responses to MEK inhibitor therapy, support additional

Inhibition of nuclear factor-kappa B enhances the tumor growth of ovarian cancer cell line derived from a low-grade papillary serous carcinoma in p53-independent pathway.

PubMed

Xiao, Xue; Yang, Gong; Bai, Peng; Gui, Shunping; Nyuyen, Tri M Bui; Mercado-Uribe, Imelda; Yang, Mei; Zou, Juan; Li, Qintong; Xiao, Jianguo; Chang, Bin; Liu, Guangzhi; Wang, He; Liu, Jinsong

2016-08-02

NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer. The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells. Western blot analysis indicated increased expression of the anti-apoptotic proteins Bcl-xL and reduced expression of the pro-apoptotic proteins Bax, Bad, and Bid in HOC-7/IĸBαM cell. Further investigations validate this conclusion in KRAS wildtype cell line SKOV3. Interesting, NF-kB can exert its pro-apoptotic effect by activating mitogen-activated protein kinase (MAPK) phosphorylation in SKOV3 ovarian cancer cell, whereas opposite changes detected in p-MEK in HOC-7 ovarian cancer cell, the same as some chemoresistant ovarian cancer cell lines. In vivo animal assay performed on BALB/athymic mice showed that injection of HOC-7 induced subcutaneous tumor growth, which was completely regressed within 7 weeks. In comparison, HOC-7/IĸBαM cells caused sustained tumor growth and abrogated tumor regression, suggesting that knock-down of NF-kB by IĸBαM promoted sustained tumor growth and delayed tumor regression in HOC-7 cells. Our results demonstrated that NF-kB may function as a tumor suppressor by facilitating regression of low grade ovarian serous carcinoma through activating pro-apoptotic pathways.

Inverse expression of cystein-rich 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2) in borderline tumors and carcinomas of the ovary.

PubMed

Bartel, Frank; Balschun, Katharina; Gradhand, Elise; Strauss, Hans G; Dittmer, Jürgen; Hauptmann, Steffen

2012-09-01

Members of the CCN [cystein-rich 61 (Cyr61)/connective tissue growth factor (CTGF)/nephroblastoma (NOV)] protein family are involved in the regulation of cellular proliferation, apoptosis, and migration and are also assumed to play a role in carcinogenesis. Therefore, we performed a retrospective study to investigate the immunohistochemical expression of both Cyr61 and CTGF in 92 borderline tumors (BOTs) and 107 invasive carcinomas of the ovary (IOCs). To determine their diagnostic and prognostic value, we correlated protein expression with clinicopathologic factors including overall and disease-free survival. Cyr61 and CTGF were found to be inversely expressed in both BOTs and IOCs, with a stronger expression of Cyr61 in IOCs. Moreover, Cyr61 was found to be preferentially expressed in high-grade serous carcinomas, whereas CTGF was found more frequently in low-grade serous carcinomas. Weak Cyr61 levels correlated with both low estrogen receptor and p53 expression (P=0.038, P=0.04, respectively). However, no association was observed between CTGF, estrogen receptor, and p53 expression levels in IOCs. Regarding prognosis, Cyr61 was found to be of no value, but the loss of CTGF was found to be associated with a poor prognosis in multivariate analysis of overall (relative risk 2.8; P=0.050) and disease-free (relative risk 2.3; P=0.031) survival. Cyr61 and CTGF are inversely expressed in BOTs and IOCs, and loss of CTGF independently indicates poor prognosis in IOCs.

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.

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

Fertility preservation in women with borderline ovarian tumors - how does it impact disease outcome? A cohort study.

PubMed

Helpman, Limor; Yaniv, Assaf; Beiner, Mario E; Aviel-Ronen, Sarit; Perri, Tamar; Ben-Baruch, Gilad; Hogen Ben-David, Liat; Jakobson-Setton, Ariella; Korach, Jacob

2017-11-01

Borderline ovarian tumors are typically indolent neoplasms. Since many are diagnosed in younger women, fertility conservation is an important consideration and has been advocated based on retrospective data. The objective of this study was to identify features impacting on recurrence and survival in a series of borderline ovarian tumors, and to assess the safety of a fertility-sparing approach. A historical cohort study of consecutive borderline ovarian tumors cases treated at a single institution over 30 years (1981-2011). Data on surgical approach (fertility-sparing or otherwise), disease stage, CA125 levels, histological features, adjuvant treatment and follow-up data were collected. Recurrence and survival were assessed using the Kaplan-Meier method and associations with the variables of interest were evaluated using a multivariate Cox proportional hazards model. 213 patients were included. Of 132 women age 40 years and below at diagnosis, 112 (85%) had a fertility-sparing procedure and 60 (46%) had conservation of an involved ovary. Fifty patients (24%) developed recurrences; fertility preservation (hazard ratio = 2.57; 95% confidence interval 1.1-6; p = 0.029) and advanced stage (hazard ratio = 4.15; 95% confidence interval 2.3-7.6; p < 0.001) were independently associated with recurrence on multivariate analysis. Eleven (5%) patients died of their disease. Fertility preservation was not associated with compromised survival. Borderline ovarian tumors carry a good prognosis overall. Fertility preservation is associated with a higher risk of disease relapse; however, as most relapses are localized and may be salvaged with surgical treatment, overall survival is not compromised. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience.

PubMed

Ambe, Chenwi M; Nguyen, Phuong; Centeno, Barbara A; Choi, Junsung; Strosberg, Jonathan; Kvols, Larry; Hodul, Pamela; Hoffe, Sarah; Malafa, Mokenge P

2017-01-01

Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

PubMed Central

Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

2014-01-01

To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the βA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

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

PubMed

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

2010-09-17

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

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

Characterization and Management of Borderline Ovarian Tumors - Results of a Retrospective, Single-center Study of Patients Treated at the Department of Gynecology and Obstetrics of the University Medicine Greifswald.

PubMed

Koensgen, Dominique; Weiss, Martin; Assmann, Kathrin; Brucker, Sara Y; Wallwiener, Diethelm; Stope, Matthias B; Mustea, Alexander

2018-03-01

Borderline ovarian tumors (BOT) are malignant epithelial ovarian tumors with a very low incidence, therefore lacking sufficient clinical experience in diagnostics and treatment. This study characterized the histology, clinical features, diagnostics and therapy of BOT including patients treated at the Department of Gynecology and Obstetrics of the University Medicine Greifswald. In this retrospective, single-center study, patients with BOT treated between 1990 and 2010 were analyzed according to their histological and clinical reports. A total of 54 patients were enrolled. The median age was 54.6 (range=23-83) years. Distribution of histological subtypes was: serous in 31 patients (57.4 %) and mucinous in 23 patients (42.6%). All patients underwent surgery. Eight patients (14.8%) were treated according to actual therapy recommendations during the initial surgery. Eight patients (14.8%) received adjuvant chemotherapy contrary to treatment recommendations. In the case of 36 patients (66.7%), a frozen section was taken intraoperatively, which matched the definitive histological result in 88.9%. During average follow-up of 70.3 months (range=0-231 months), two patients (3.7%) developed tumor recurrence after 9 and 29 months, respectively, two patients (3.7%) died of causes other than BOT. Our study critically demonstrated that until a few years ago, BOTs were not usually treated according to international therapy recommendations. Nevertheless, the rate of tumor recurrence was very low. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Comparison of plasma amino acid profile-based index and CA125 in the diagnosis of epithelial ovarian cancers and borderline malignant tumors.

PubMed

Miyagi, Etsuko; Maruyama, Yasuyo; Mogami, Tae; Numazaki, Reiko; Ikeda, Atsuko; Yamamoto, Hiroshi; Hirahara, Fumiki

2017-02-01

We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p < 0.05). At the API cutoff level of 6.0, API and CA125 had equal positive rates of detecting cancers and borderline malignancies (API, 0.71 vs. CA125, 0.74; p = 0.84) or cancers alone (API, 0.73 vs. CA125, 0.85; p = 0.12). However, API had a significantly lower detection rate of benign endometriotic cysts (0.35; 95 % CI, 0.21-0.52) compared with that of CA125 (0.65; 95 % CI, 0.48-0.79) (p < 0.05). API is an effective new tumor marker to detect ovarian cancers and borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.

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

PubMed

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

2017-03-01

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

Telomerase activity is a useful marker to distinguish malignant pancreatic cystic tumors from benign neoplasms and pseudocysts.

PubMed

Yeh, T S; Cheng, A J; Chen, T C; Jan, Y Y; Hwang, T L; Jeng, L B; Chen, M F; Wang, T C

1999-12-01

Pancreatic serous cystadenoma, mucinous cystic neoplasms, ductal adenocarcinoma with cystic change, and pseudocysts are a spectrum of pancreatic cystic lesions. Their management strategy and prognosis are extremely diverse. Imaging study, cytology, and analysis of the tumor markers of cyst fluid are not always reliable in differentiation of these disease entities. Fifteen patients with pancreatic cystic neoplasms (including six mucinous cystadenocarcinomas, two mucinous cystic neoplasms with borderline malignancy, two mucinous cystadenomas, and five serous cystadenomas), 4 patients with pancreatic ductal adenocarcinomas with cystic change, and 10 patients with pseudocysts were studied. Echo-guided or computed tomography-guided biopsies of pancreatic cystic lesions and their normal counterparts were conducted on all patients prior to operation or other management. The specimens were assayed for telomerase activity by using TRAP (telomere repeat amplification protocol). The level of telomerase activity in each specimen was semiquantitated as strong, moderate, weak, and none. The final diagnoses were made from histopathological examination of surgically resected or biopsied specimens. The efficacy of telomerase activity as a tumor marker to predict malignancy of pancreatic cystic lesions was evaluated. Three of the four pancreatic ductal adenocarcinomas with cystic change had strong or moderate telomerase activity; four of the six mucinous cystadenocarcinomas had moderate or weak telomerase activity; one of the two mucinous cystadenomas with borderline malignancy had weak telomerase activity; and none of their normal counterparts had detectable telomerase activity. In contrast, none of the two mucinous cystadenomas, five serous cystadenomas, and 10 pseudocysts had detectable telomerase activity. Based on these results, the sensitivity of telomerase activity for prediction of malignancy or premalignancy of pancreatic cystic lesions was 67%, the specificity was 100

ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer.

PubMed

Giannopoulou, Lydia; Mastoraki, Sophia; Buderath, Paul; Strati, Areti; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2018-05-25

Estrogen receptor, coded by the ESR1 gene, is highly expressed in epithelial ovarian cancer. ESR1 gene is frequently methylated in many types of gynecological malignancies. However, only a few studies attempted to investigate the role of ESR1 methylation and its clinical significance in ovarian cancer so far. The aim of our study was to examine ESR1 methylation status in primary tumors and corresponding circulating tumor DNA of patients with high-grade serous ovarian cancer (HGSC). ESR1 methylation was detected by a highly specific and sensitive real-time methylation-specific PCR assay. Two groups of HGSC samples were analyzed: group A (n = 66 primary tumors) and group B (n = 53 primary tumors and 50 corresponding plasma samples). ESR1 was found methylated in both groups of primary tumors: in 32/66 (48.5%) of group A and in 15/53 (28.3%) of group B. 19/50 (38.0%) corresponding plasma samples of group B were also methylated for ESR1. A significant agreement for ESR1 methylation was observed between primary tumors and paired plasma ctDNA samples (P = 0.004). Interestingly, the presence of ESR1 methylation in primary tumor samples of group B was significantly correlated with a better overall survival (P = 0.027) and progression-free survival (P = 0.041). We report for the first time the presence of ESR1 methylation in plasma ctDNA of patients with HGSC. The agreement between ESR1 methylation in primary tumors and paired ctDNA is statistically significant. Our results indicate a correlation between the presence of ESR1 methylation and a better clinical outcome in HGSC patients. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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

2000-12-15

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

IMP3 Expression in Borderline Tumors of the Ovary.

PubMed

El-Balat, Ahmed; Sänger, Nicole; Karn, Thomas; Becker, Sven; Holtrich, Uwe; Muallem, Zelal; Arsenic, Ruza

2017-02-01

Borderline ovarian tumors (BOTs) have a less aggressive behavior than invasive epithelial ovarian tumors. Still some patients relapse or succumb to disease. Molecular markers that reliably predict prognosis are lacking. Insulin-like growth factor II mRNA-binding protein (IMP3) has been suggested as a prognostic marker in colorectal, hepatocellular, and ovarian clear-cell carcinomas. We analyzed the expression of IMP3 by immunohistochemistry in a cohort of 140 BOT and its association with histopathological features. We found no association of IMP3 expression with patients' age, FIGO stage, microinvasion, and presence of implants. In contrast, IMP3 expression correlated to mucinous subtype of BOTs (42.2% vs. 9.5% among other subtypes) (p<0.001). IMP3 expression was found to be associated with the presence of in situ carcinoma in MBOT, but not in other subtypes (p=0.021). Expression of IMP3 in BOT is associated with the mucinous subtype and may serve as an early indicator for the development of malignant features. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

PubMed

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2017-03-28

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA

PubMed Central

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S.

2017-01-01

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients. PMID:28206954

Prediction of chemo-response in serous ovarian cancer.

PubMed

Gonzalez Bosquet, Jesus; Newtson, Andreea M; Chung, Rebecca K; Thiel, Kristina W; Ginader, Timothy; Goodheart, Michael J; Leslie, Kimberly K; Smith, Brian J

2016-10-19

Nearly one-third of serous ovarian cancer (OVCA) patients will not respond to initial treatment with surgery and chemotherapy and die within one year of diagnosis. If patients who are unlikely to respond to current standard therapy can be identified up front, enhanced tumor analyses and treatment regimens could potentially be offered. Using the Cancer Genome Atlas (TCGA) serous OVCA database, we previously identified a robust molecular signature of 422-genes associated with chemo-response. Our objective was to test whether this signature is an accurate and sensitive predictor of chemo-response in serous OVCA. We first constructed prediction models to predict chemo-response using our previously described 422-gene signature that was associated with response to treatment in serous OVCA. Performance of all prediction models were measured with area under the curves (AUCs, a measure of the model's accuracy) and their respective confidence intervals (CIs). To optimize the prediction process, we determined which elements of the signature most contributed to chemo-response prediction. All prediction models were replicated and validated using six publicly available independent gene expression datasets. The 422-gene signature prediction models predicted chemo-response with AUCs of ~70 %. Optimization of prediction models identified the 34 most important genes in chemo-response prediction. These 34-gene models had improved performance, with AUCs approaching 80 %. Both 422-gene and 34-gene prediction models were replicated and validated in six independent datasets. These prediction models serve as the foundation for the future development and implementation of a diagnostic tool to predict response to chemotherapy for serous OVCA patients.

Definition and Management of Borderline Resectable Pancreatic Cancer.

PubMed

Denbo, Jason W; Fleming, Jason B

2016-12-01

Patients with localized pancreatic ductal adenocarcinoma seek potentially curative treatment, but this group represents a spectrum of disease. Patients with borderline resectable primary tumors are a unique subset whose successful therapy requires a care team with expertise in medical care, imaging, surgery, medical oncology, and radiation oncology. This team must identify patients with borderline tumors then carefully prescribe and execute a combined treatment strategy with the highest possibility of cure. This article addresses the issues of clinical evaluation, imaging techniques, and criteria, as well as multidisciplinary treatment of patients with borderline resectable pancreatic ductal adenocarcinoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Mixed endometrial carcinomas with a "low-grade serous"-like component: a clinicopathologic, immunohistochemical, and molecular genetic study.

PubMed

Espinosa, Iñigo; D'Angelo, Emanuela; Corominas, Marina; Gonzalez, Alan; Prat, Jaime

2018-01-01

Recently, we reported 2 mixed endometrioid endometrial carcinomas with a "low-grade serous"-like component, which does not fit into any of the 4 molecular groups described by The Cancer Genome Atlas. To understand the nature of these tumors, we have done an immunohistochemical and molecular genetic study of these 2 cases and added a third case. Immunoreactivity for p53, ER, Ki67, WT1, MLH1, PMS2, MSH2, and MSH6 was assessed. Targeted next-generation sequencing for somatic mutations, including genes commonly implicated in carcinogenesis including TP53, KRAS, and PIK3CA, and Sanger sequencing for PTEN and POLE were also performed. All patients were nulliparous and had morbid obesity. Their tumors showed a micropapillary component that resembled that of ovarian low-grade serous carcinoma and merged with villoglandular endometrioid carcinoma. The invasive tumor glands exhibited a microcystic, elongated, or fragmented pattern and contained psammoma bodies. Two tumors showed aberrant p53 expression, and all 3 were positive for ER. All showed KRAS mutations, and TP53 mutations were found in 2 cases. One patient developed peritoneal carcinomatosis, one patient is alive with disease, and another died of a brain tumor. The third patient, whose tumor was confined to the uterus (stage IA), is alive without evidence of disease, but she has been followed for only 6 months. Mixed endometrial carcinomas with a "low-grade" serous-like component exhibit a morphologic spectrum of endometrioid and serous differentiation with microcystic, elongated, or fragmented features; ER expression; KRAS and TP53 mutations; and aggressive behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Does a p53 "Wild-type" Immunophenotype Exclude a Diagnosis of Endometrial Serous Carcinoma?

PubMed

Fadare, Oluwole; Roma, Andres A; Parkash, Vinita; Zheng, Wenxin; Walavalkar, Vighnesh

2018-01-01

An aberrant p53 immunophenotype may be identified in several histotypes of endometrial carcinoma, and is accordingly recognized to lack diagnostic specificity in and of itself. However, based on the high frequency with which p53 aberrations have historically been identified in endometrial serous carcinoma, a mutation-type immunophenotype is considered to be highly sensitive for the histotype. Using an illustrative case study and a review of the literature, we explore a relatively routine diagnostic question: whether the negative predictive value of a wild-type p53 immunophenotype for serous carcinoma is absolute, that is, whether a p53-wild type immunophenotype is absolutely incompatible with a diagnosis of serous carcinoma. The case is an advanced stage endometrial carcinoma that was reproducibly classified by pathologists from 3 institutions as serous carcinoma based on its morphologic features. By immunohistochemistry, the tumor was p53-wild type (DO-7 clone), diffusely positive for p16 (block positivity), and showed retained expression of PTEN, MSH2, MSH6, MLH1, and PMS2. Next generation sequencing showed that there indeed was an underlying mutation in TP53 (D393fs*78, R213*). The tumor was microsatellite stable, had a low mutational burden (4 mutations per MB), and displayed no mutations in the exonuclease domain of DNA polymerase epsilon (POLE) gene. Other genomic alterations included RB1 mutation (R46fs*19), amplifications in MYST3 and CRKL, and ARID1A deletion (splice site 5125-94_5138del108). A review of the recent literature identified 5 studies in which a total of 259 cases of serous carcinoma were whole-exome sequenced. The average TP53 mutational rate in endometrial serous carcinoma was only 75% (range, 60 to 88). A total of 12 (33%) of 36 immunohistochemical studies reported a p53-aberrant rate of <80% in endometrial serous carcinoma. We discuss in detail several potential explanations that may underlie the scenario of serous carcinoma-like morphology

Expression patterns of emmprin and monocarboxylate transporter-1 in ovarian epithelial tumors.

PubMed

Fukuoka, Miyoko; Hamasaki, Makoto; Koga, Kaori; Hayashi, Hiroyuki; Aoki, Mikiko; Kawarabayashi, Tatsuhiko; Miyamoto, Shingo; Nabeshima, Kazuki

2012-10-01

Emmprin is a transmembrane glycoprotein known as a matrix metalloproteinase inducer and is highly up-regulated in malignant cancer cells. The monocarboxylate transporters (MCTs) are responsible for H(+)-linked transport of monocarboxylates across the cell membrane. It was recently demonstrated that proper plasma membrane localization and activity of MCTs require the presence of emmprin as a chaperone and that MCT-1 also acts as chaperone for emmprin. The objectives of this study were to clarify emmprin and MCT-1 expression patterns in ovarian epithelial tumors and to elucidate the clinicopathological significance of co-localization of the two molecules. Immunohistochemical analysis of 205 epithelial tumors indicated that emmprin is always localized in cell membranes but its distribution differs according to tumor type: in lateral membranes in 89 % of adenomas, in lateral and basal membranes in 76 % of borderline tumors, and in membranes surrounding the entire cell in 98 % of carcinomas. Most carcinomas in situ also showed a lateral and basal expression pattern. In only 21 % of the carcinomas, the cells expressing membranous MCT-1 showed co-localized emmprin expression. Poor co-localization of the two molecules was more frequently found in serous carcinomas. However, the overall survival was not significantly different for the good and poor co-localization carcinoma groups. These findings indicate that the emmprin expression pattern might discriminate between invasive carcinomas and borderline tumors including carcinoma in situ. Moreover, there may be an as yet unidentified regulatory mechanism(s), for localization of MCT-1 and emmprin in cell membranes in vivo.

Coexistence of BRAF V600E and TERT Promoter Mutations in Low-grade Serous Carcinoma of Ovary Recurring as Carcinosarcoma in a Lymph Node: Report of a Case.

PubMed

Tavallaee, Mahkam; Steiner, David F; Zehnder, James L; Folkins, Ann K; Karam, Amer K

2018-04-03

Low-grade serous carcinomas only rarely coexist with or progress to high-grade tumors. We present a case of low-grade serous carcinoma with transformation to carcinosarcoma on recurrence in the lymph node. Identical BRAF V600E and telomerase reverse transcriptase promoter mutations were identified in both the original and recurrent tumor. Given that telomerase reverse transcriptase promotor mutations are thought to play a role in progression of other tumor types, the function of telomerase reverse transcriptase mutations in BRAF mutated low-grade serous carcinoma deserves investigation.

Primary peritoneal serous carcinoma presenting as inflammatory breast cancer.

PubMed

Khalifeh, Ibrahim; Deavers, Michael T; Cristofanilli, Massimo; Coleman, Robert L; Malpica, Anais; Gilcrease, Michael Z

2009-01-01

Metastasis to the breast from extramammary malignancies is rare. Nevertheless, its recognition is important because the prognosis and treatment differ from that of primary breast cancer. We report a unique case of primary peritoneal serous carcinoma that initially presented as inflammatory breast cancer. The patient received neoadjuvant chemotherapy for breast cancer and subsequently underwent bilateral total mastectomy and bilateral sentinel lymph node biopsy. She was found to have extensive intralymphatic carcinoma in both breasts, with only focal minimal breast parenchymal involvement, and residual metastatic carcinoma in bilateral sentinel lymph nodes. Further work-up revealed pelvic ascites and omental nodularities. The patient underwent laparoscopic bilateral salpingo-oophorectomy, which revealed high-grade serous carcinoma involving both ovaries and fallopian tubes. Molecular testing of tumor from the ovary and axillary lymph node showed an identical pattern of allelic loss, confirming a common origin for both tumors. To our knowledge, this is the first reported case of an extramammary primary malignancy that not only presented as inflammatory breast cancer but also was diagnosed and initially treated as such.

B7-H4 overexpression in ovarian tumors.

PubMed

Tringler, Barbara; Liu, Wenhui; Corral, Laura; Torkko, Kathleen C; Enomoto, Takayuki; Davidson, Susan; Lucia, M Scott; Heinz, David E; Papkoff, Jackie; Shroyer, Kenneth R

2006-01-01

Despite great advances in therapeutic management, the mortality rate for ovarian cancer has remained relatively stable over the past 50 years. This study was designed to evaluate the expression of B7-H4 protein, recently identified as a potential molecular marker of breast and ovarian cancer by quantitative PCR analysis, in benign tumors, tumors of low malignant potential and malignant tumors of the ovary. Archival formalin-fixed tissue blocks from serous, mucinous, endometrioid and clear cell ovarian tumors were evaluated by immunohistochemistry for the distribution of B7-H4 expression, and staining intensity was measured by automated image analysis. Univariate analyses were used to test for statistically significant relationships. B7-H4 cytoplasmic and membranous expression was detected in all primary serous (n = 32), endometrioid (n = 12), and clear cell carcinomas (n = 15), and in all metastatic serous (n = 23) and endometrioid (n = 7) ovarian carcinomas. By contrast, focal B7-H4 expression was detected in only 1/11 mucinous carcinomas. The proportion of positive cells and median staining intensity was greater in serous carcinomas than in serous cystadenomas or serous tumors of low malignant potential, and the differences were statistically significant (P < 0.0001 and P = 0.034, respectively). The median staining intensity was also significantly greater in endometrioid carcinomas than in endometriosis (P = 0.005). The consistent overexpression of B7-H4 in serous, endometrioid and clear cell ovarian carcinomas and the relative absence of expression in most normal somatic tissues indicates that B7-H4 should be further investigated as a potential diagnostic marker or therapeutic target for ovarian cancer.

Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study.

PubMed

Bodurka, Diane C; Deavers, Michael T; Tian, Chunqiao; Sun, Charlotte C; Malpica, Anais; Coleman, Robert L; Lu, Karen H; Sood, Anil K; Birrer, Michael J; Ozols, Robert; Baergen, Rebecca; Emerson, Robert E; Steinhoff, Margaret; Behmaram, Behnaz; Rasty, Golnar; Gershenson, David M

2012-06-15

A study was undertaken to use the 2-tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3-tier system and determine the progression-free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158. The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2-tier system. The association of tumor grade with PFS and OS was assessed. Of 241 cases, both systems demonstrated substantial agreement when combining FIGO grades 2 and 3 (overall agreement, 95%; kappa statistic, 0.68). By using the 2-tier system, patients with low-grade versus high-grade tumors had significantly longer PFS (45.0 vs 19.8 months, respectively; P = .01). By using FIGO criteria, median PFS for patients with grade 1, 2, and 3 tumors was 37.5, 19.8, and 20.1 months, respectively (P = .07). There was no difference in clinical outcome in patients with grade 2 or 3 tumors in multivariate analysis. Woman with high-grade versus low-grade tumors demonstrated significantly higher risk of death (hazard ratio, 2.43; 95% confidence interval, 1.17-5.04; P = .02). Women with high-grade versus low-grade serous carcinoma of the ovary are 2 distinct patient populations. Adoption of the 2-tier grading system provides a simple yet precise framework for predicting clinical outcomes. Copyright © 2011 American Cancer Society.

Risk for borderline ovarian tumours after exposure to fertility drugs: results of a population-based cohort study.

PubMed

Bjørnholt, Sarah Marie; Kjaer, Susanne Krüger; Nielsen, Thor Schütt Svane; Jensen, Allan

2015-01-01

Do fertility drugs increase the risk for borderline ovarian tumours, overall and according to histological subtype? The use of any fertility drug did not increase the overall risk for borderline ovarian tumours, but an increased risk for serous borderline ovarian tumours was observed after the use of progesterone. Many epidemiological studies have addressed the connection between fertility drugs use and risk for ovarian cancer; most have found no strong association. Fewer studies have assessed the association between use of fertility drugs and risk for borderline ovarian tumours, and the results are inconsistent. A retrospective case-cohort study was designed with data from a cohort of 96 545 Danish women with fertility problems referred to all Danish fertility clinics in the period 1963-2006. All women were followed for first occurrence of a borderline ovarian tumour from the initial date of infertility evaluation until a date of migration, date of death or 31 December 2006, whichever occurred first. The median length of follow-up was 11.3 years. Included in the analyses were 142 women with borderline ovarian tumours (cases) and 1328 randomly selected sub-cohort members identified in the cohort during the follow-up through 2006. Cases were identified by linkage to the Danish Cancer Register and the Danish Register of Pathology by use of personal identification numbers. To obtain information on use of fertility drugs, hospital files and medical records of infertility-associated visits to all Danish fertility clinics were collected and supplemented with information from the Danish IVF register. We used case-cohort techniques to calculate rate ratios (RRs) and corresponding 95% confidence intervals (CIs) for borderline ovarian tumours, overall and according to histological subtype, associated with the use of any fertility drug or five specific groups of fertility drugs: clomiphene citrate, gonadotrophins (human menopausal gonadotrophins and follicle

Unique presentation of giant metastatic microcystic serous adenocarcinoma of the pancreas.

PubMed

Philips, Cyriac Abby; Kalal, Chetan Ramesh; Bihari, Chhagan; Sahney, Amrish; Kumar, Kn Chandan; Rastogi, Archana

2014-01-01

Tumors of the pancreas that contain substantial cystic components include mainly mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, solid pseudopapillary tumor, and cystadenomas (which encompass microcystic, macrocystic/oligocystic, and rare solid serous adenomas). Microcystic adenoma of the pancreas is a tumor that is benign in nature. Malignant transformation in the tumor with metastases is rare and only about 26 cases have been reported so far. Here we present a giant microcystic adenoma of the pancreas, possibly the largest ever malignant type in this group ever reported in the literature with extensive metastases to the liver and causing extensive compression and encasement on surrounding structures.

Unique Presentation of Giant Metastatic Microcystic Serous Adenocarcinoma of the Pancreas

PubMed Central

Kalal, Chetan Ramesh; Bihari, Chhagan; Sahney, Amrish; Kumar, KN Chandan; Rastogi, Archana

2014-01-01

Tumors of the pancreas that contain substantial cystic components include mainly mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, solid pseudopapillary tumor, and cystadenomas (which encompass microcystic, macrocystic/oligocystic, and rare solid serous adenomas). Microcystic adenoma of the pancreas is a tumor that is benign in nature. Malignant transformation in the tumor with metastases is rare and only about 26 cases have been reported so far. Here we present a giant microcystic adenoma of the pancreas, possibly the largest ever malignant type in this group ever reported in the literature with extensive metastases to the liver and causing extensive compression and encasement on surrounding structures. PMID:24782930

Second primary cancers following borderline ovarian tumors.

PubMed

Sanci, Muzaffer; Gultekin, Emre; Cingillioglu, Basak; Gultekin, Ozge Elmastas; Ozvural, Seyfettin; Emirdar, Volkan; Yildirim, Yusuf

2011-06-01

Several studies have reported an increased risk of second primary cancers subsequent to invasive epithelial ovarian cancer. However, there is no adequate data regarding such risk in borderline ovarian tumors (BOTs). The aim of this study was to evaluate the risk of subsequent second primary cancers among women with BOTs. BOT patients treated in our center between December 1985 and April 2009 were retrospectively screened for developing second primary cancer during follow-up period. There were 96 women diagnosed with BOT. Mean age at the time of diagnosis was 47 ± 14.3, ranging from 19 to 79. Eighty-eight (91.6%) patients had stage I disease, two patients (2.1%) had stage II and six (6.2%) had stage III. Twenty-five (26.0%) patients received platinum-based adjuvant chemotherapy. Mean follow-up time was 96.5 ± 442 months (range: 9-280 months). There were ten (10.4%) recurrences. Only one patient developed second primary cancer. Second primary cancer observed in this case was basal cell carsinoma of the eyelid, which was diagnosed 2 years after primary disease. There were no patients with common women's cancers such as breast and colorectal cancers. These findings do not suggest increased risk of subsequent cancers in patients with BOT. However, population-based studies are needed for evaluating exact risk of developing second primary malignancies in women with BOTs.

Low-grade serous ovarian cancer: A review.

PubMed

Kaldawy, Anis; Segev, Yakir; Lavie, Ofer; Auslender, Ron; Sopik, Victoria; Narod, Steven A

2016-11-01

Epithelial ovarian cancers can be divided into the more common, aggressive type II cancers and the less common, slow-growing type I cancers. Under this model, serous ovarian carcinomas can be subdivided into high-grade (type II) and low-grade (type I) tumours. The two-tier system for grading serous ovarian carcinomas is superior to more detailed grading systems in terms of predicting survival. Low-grade serous carcinomas typically present in young women and have a relatively good prognosis, despite being resistant to chemotherapy. Low-grade serous cancers have a high prevalence of KRAS and BRAF mutations, but a low prevalence of TP53 mutations (which are characteristic of high-grade serous cancers). Among women with low-grade serous ovarian cancer, the presence of a KRAS/BRAF mutation is a favorable prognostic factor. Studies of the mitogen-activated protein kinase (MAPK) inhibitor in low-grade serous ovarian cancer suggest that identifying MAPK mutations might eventually be useful in guiding treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Uterine Serous Carcinomas Frequently Metastasize to the Fallopian Tube and Can Mimic Serous Tubal Intraepithelial Carcinoma.

PubMed

Kommoss, Friedrich; Faruqi, Asma; Gilks, C Blake; Lamshang Leen, Sarah; Singh, Naveena; Wilkinson, Nafisa; McCluggage, W Glenn

2017-02-01

We investigated the frequency, histopathologic, and immunohistochemical characteristics of tubal involvement in uterine serous carcinoma (USC) and aimed to clarify the relationship between "serous tubal intraepithelial carcinoma (STIC)" and USC in these cases. Cases of USC with complete tubal examination were prospectively collected and reviewed for the presence of tubal involvement. Immunohistochemical analysis for p53 and WT1 was performed on the endometrial and tubal tumor in cases with tubal involvement. Of 161 USC cases (pure USC or a component of a mixed carcinoma or a carcinosarcoma), 32 (20%) showed tubal involvement (unilateral: n=19; bilateral: n=13). The uterine tumors in cases with tubal involvement showed a trend toward increased likelihood of deep myometrial and lymphovascular invasion (LVI) compared with those without tubal involvement. The tubal fimbriae were involved in 15/32 cases. Tubal involvement was mucosal in 30/32 cases, mural in 14/32, serosal in 5/32, invasive in 22/32, and there was LVI in the tube in 13/32. STIC-like features were seen in 17/32 cases (7 as the only pattern of involvement, 9 with associated invasive carcinoma, and 5 with LVI). Immunostaining showed complete concordance of p53 and WT1 between the endometrial and tubal tumors in 26/32 cases, the majority being WT1 negative or only focally positive (19/26), and all exhibiting mutation-type p53 staining. On the basis of the histologic and immunohistochemical features, the tubal tumor was considered to represent metastatic USC in 26/32 cases, most likely metastatic USC in 2/32 cases, an independent tubal primary tumor in 3/32 cases, and to be of uncertain origin in the 1 remaining case. STIC-like lesions were considered to represent metastatic USC in 12/17 cases, most likely metastatic USC in 2/17 cases, an independent tubal primary in 2/17 cases, and of uncertain origin in the 1 remaining case. Tubal involvement, including STIC-like lesions, is seen in one fifth of USC when

A Case of Endometrioid Adenocarcinoma Originating from the Serous Surface of the Small Intestine.

PubMed

Makihara, Natsuko; Fujita, Ichiro; Soudaf, Hiroo; Yamamoto, Takahisa; Sashikata, Terumasa; Mukohara, Toru; Maeda, Tetsuo

2015-09-07

Malignant transformation of endometriosis has been extensively described in the literature. However, extragonadal endometrioid adenocarcinoma, either de novo or arising from malignant transformation of endometriosis, is rare. The present case report describes a patient with endometrioid adenocarcinoma on the serous surface of the small intestine. A 25-year-old female with no history of endometriosis was referred to our hospital with an intrapelvic tumor. An internal examination, ultrasound, and magnetic resonance imaging revealed a round mass approximately 80 mm in diameter; however, identification of the affected organ was difficult. Because we could not rule out malignancy based on the non-specific radiologic findings, laparotomy was performed. A mass with ileal adhesions was detected intraoperatively. In addition, the uterus and bilateral adnexa appeared normal. The tumor was resected with part of the ileum. Histopathology confirmed a diagnosis of endometrioid adenocarcinoma originating from the serous surface of the small intestine.

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

PubMed

Ramalingam, Preetha

2016-02-01

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

Risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors.

PubMed

Song, Taejong; Lee, Yoo-Young; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

2014-09-01

The aim of this study was to identify risk factors for progression to invasive carcinoma in patients with borderline ovarian tumors (BOTs). We performed a retrospective review of all patients treated and followed for BOTs between 1996 and 2011. Multivariate Cox proportional hazards model analysis was performed to identify independent risk factors for progression to invasive carcinoma. A total of 364 patients were identified. During the median follow-up of 53.8 months, 31 patients (8.5%) developed recurrent disease: 12 (3.3%) had recurrent disease with progression to invasive carcinoma, and 19 (5.2%) had recurrent disease with borderline histology. Disease-related deaths (7/364; 1.7%) were observed only in patients with progression to invasive carcinoma. The multivariate analysis showed that independent risk factors for progression to invasive carcinoma were advanced disease stage (hazard ratio [HR], 5.59; P = 0.005), age 65 years or older (HR, 5.13; P = 0.037), and the presence of microinvasion (HR, 3.71; P = 0.047). These 3 factors were also independently related to overall survival. Although patients with BOTs have an excellent prognosis, the risk of progression to invasive carcinoma and thereby death remains. Therefore, physicians should pay closer attention to BOT patients with these risk factors (ie, advanced disease stage, old age, and microinvasion), and more careful surveillance for progression to invasive carcinoma is needed.

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

PubMed

Pathiraja, P; Dhar, S; Haldar, K

2013-01-01

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

Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies

PubMed Central

Faber, Mette T.; Kjær, Susanne K.; Dehlendorff, Christian; Chang-Claude, Jenny; Andersen, Klaus K.; Høgdall, Estrid; Webb, Penelope M.; Jordan, Susan J.; Rossing, Mary Anne; Doherty, Jennifer A.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.; Goodman, Marc T.; Ness, Roberta B.; Modugnos, Francesmary; Edwards, Robert P.; Bunker, Clareann H.; Goode, Ellen L.; Fridley, Brooke L.; Vierkant, Robert A.; Larson, Melissa C.; Schildkraut, Joellen; Cramer, Daniel W.; Terry, Kathryn L.; Vitonis, Allison F.; Bandera, Elisa V.; Olson, Sara H.; King, Melony; Chandran, Urmila; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; van Altena, Anne M.; Vermeulen, Sita H.; Brinton, Louise; Wentzensen, Nicolas; Lissowska, Jolanta; Yang, Hannah P.; Moysich, Kirsten B.; Odunsi, Kunle; Kasza, Karin; Odunsi-Akanji, Oluwatosin; Song, Honglin; Pharaoh, Paul; Shah, Mitul; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Sutphen, Rebecca; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Pearce, Celeste Leigh; Wu, Anna H.; Pike, Malcolm C.; Risch, Harvey A.

2013-01-01

Purpose The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology. Methods We used data from 21 case–control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases). Study-specific odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio using a random effects model. Results Current cigarette smoking increased the risk of invasive mucinous (OR = 1.31; 95 % CI: 1.03–1.65) and borderline mucinous ovarian tumors (OR = 1.83; 95 % CI: 1.39–2.41), while former smoking increased the risk of borderline serous ovarian tumors (OR = 1.30; 95 % CI: 1.12–1.50). For these histological types, consistent dose– response associations were observed. No convincing associations between smoking and risk of invasive serous and endometrioid ovarian cancer were observed, while our results provided some evidence of a decreased risk of invasive clear cell ovarian cancer. Conclusions Our results revealed marked differences in the risk profiles of histological types of ovarian cancer with regard to cigarette smoking, although the magnitude of the observed associations was modest. Our findings, which may reflect different etiologies of the histological types, add to the fact that ovarian cancer is a heterogeneous disease. PMID:23456270

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

Application of X-Ray Fluorescence Analysis to Determine the Elemental Composition of Tissues from Different Ovarian Neoplasms

NASA Astrophysics Data System (ADS)

Motevich, I. G.; Strekal, N. D.; Papko, N. M.; Glebovich, M. I.; Shulha, A. V.; Maskevich, S. A.

2015-03-01

We present the results of x-ray fluorescence analysis of tissues from healthy ovaries and from ovaries with different pathologies: benign and borderline tumors, mucinous and endometrioid cancers, serous carcinomas. We determine the average copper, zinc, calcium, selenium, cadmium, lead, and mercury levels. We observed that in the benign ovarian tumors, we see a significant decrease in the cadmium, mercury, and lead levels compared with healthy tissues. In the borderline neoplasms, the copper level is reduced relative to zinc (Cu/Zn), cadmium, mercury, and lead, and also the zinc concentration is increased. In the ovarian carcinomas, we observed changes in the ratio of the chemical elements in the tumor tissues, depending on the histologic type. The results obtained can be used for differentiation, diagnosis, and adjustment of treatment for different ovarian neoplasms.

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

PubMed

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

2017-12-01

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

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer.

PubMed

Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M; Gehrig, Paola A; Zhou, Chunxiao; Bae-Jump, Victoria L

2016-06-28

Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women.

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

PubMed Central

Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M.; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M.; Gehrig, Paola A.; Zhou, Chunxiao; Bae-Jump, Victoria L.

2016-01-01

Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women. PMID:27074576

BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma.

PubMed

Pennington, Kathryn P; Walsh, Tom; Lee, Ming; Pennil, Christopher; Novetsky, Akiva P; Agnew, Kathy J; Thornton, Anne; Garcia, Rochelle; Mutch, David; King, Mary-Claire; Goodfellow, Paul; Swisher, Elizabeth M

2013-01-15

Uterine serous carcinoma (USC) is not recognized as part of any defined hereditary cancer syndrome, and its association with hereditary breast and ovarian carcinoma and Lynch syndrome are uncertain. Using targeted capture and massively parallel genomic sequencing, 151 subjects with USC were assessed for germline mutations in 30 tumor suppressor genes, including BRCA1 (breast cancer 1, early onset), BRCA2, the DNA mismatch repair genes (MLH1 [mutL homolog 1], MSH2 [mutS homolog 2], MSH6, PMS2 [postmeiotic segregation increased 2]), TP53 (tumor protein p53), and 10 other genes in the Fanconi anemia-BRCA pathway. Ten cases with < 10% serous histology were also assessed. Seven subjects (4.6%) carried germline loss-of-function mutations: 3 subjects (2.0%) with mutations in BRCA1, 2 subjects (1.3%) with mutations in TP53, and 2 subjects (1.3%) with mutations in CHEK2 (checkpoint kinase 2). One subject with < 10% serous histology had an MSH6 mutation. Subjects with MSH6 and TP53 mutations had neither personal nor family histories suggestive of Lynch or Li-Fraumeni syndromes. Of the 22 women with USC and a personal history of breast carcinoma, the frequency of BRCA1 mutations was 9%, compared to 0.9% in 119 women with no such history. Approximately 5% of women with USC have germline mutations in 3 different tumor suppressor genes: BRCA1, CHEK2, and TP53. Mutations in DNA mismatch repair genes that cause Lynch syndrome are rare in USC. The germline BRCA1 mutation rate in USC subjects of 2% is higher than expected in a nonfounder population, suggesting that USC is associated with hereditary breast and ovarian carcinoma in a small proportion of cases. Women with USC and breast cancer should be offered genetic testing for BRCA1 and BRCA2 mutations. Copyright © 2012 American Cancer Society.

Metastatic serous carcinoma presenting as inflammatory carcinoma over the breast-Report of two cases and literature review.

PubMed

Panse, Gauri; Bossuyt, Veerle; Ko, Christine J

2018-03-01

Non-mammary metastases involving breast are rare and most commonly involve the breast parenchyma. Infrequently, metastasis from an extramammary primary site presents as inflammatory carcinoma over the breast. Diagnosis of such lesions can be challenging, especially in patients with coexisting primary breast carcinoma. Few such cases have been described in literature; however, none of the previously reported cases had a prior history of primary breast carcinoma. We present 2 patients with history of breast carcinoma and serous carcinoma of ovarian/peritoneal origin that presented with inflammatory carcinoma over the breast. Biopsies from breast tissue showed atypical cells in the dermis forming cords and papillary structures. Histopathologic differential diagnosis included infiltrating ductal carcinoma of breast origin and metastatic serous carcinoma. Immunohistochemical studies showed that the tumor cells were positive for markers of ovarian origin such as PAX-8 and CA-125 and negative for breast markers such as GATA-3, thus supporting the diagnosis. In summary, we describe the unusual presentation of metastatic serous carcinoma as inflammatory carcinoma over breast and discuss the diagnostic challenges in patients with coexisting primary breast and ovarian malignancies. We also review the morphologic features of tumors of breast and ovarian origin and the immunohistochemical stains to differentiate these 2 entities. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of multiple novel protein biomarkers shed by human serous ovarian tumors into the blood of immunocompromised mice and verified in patient sera.

PubMed

Beer, Lynn A; Wang, Huan; Tang, Hsin-Yao; Cao, Zhijun; Chang-Wong, Tony; Tanyi, Janos L; Zhang, Rugang; Liu, Qin; Speicher, David W

2013-01-01

The most cancer-specific biomarkers in blood are likely to be proteins shed directly by the tumor rather than less specific inflammatory or other host responses. The use of xenograft mouse models together with in-depth proteome analysis for identification of human proteins in the mouse blood is an under-utilized strategy that can clearly identify proteins shed by the tumor. In the current study, 268 human proteins shed into mouse blood from human OVCAR-3 serous tumors were identified based upon human vs. mouse species differences using a four-dimensional plasma proteome fractionation strategy. A multi-step prioritization and verification strategy was subsequently developed to efficiently select some of the most promising biomarkers from this large number of candidates. A key step was parallel analysis of human proteins detected in the tumor supernatant, because substantially greater sequence coverage for many of the human proteins initially detected in the xenograft mouse plasma confirmed assignments as tumor-derived human proteins. Verification of candidate biomarkers in patient sera was facilitated by in-depth, label-free quantitative comparisons of serum pools from patients with ovarian cancer and benign ovarian tumors. The only proteins that advanced to multiple reaction monitoring (MRM) assay development were those that exhibited increases in ovarian cancer patients compared with benign tumor controls. MRM assays were facilely developed for all 11 novel biomarker candidates selected by this process and analysis of larger pools of patient sera suggested that all 11 proteins are promising candidate biomarkers that should be further evaluated on individual patient blood samples.

Identification of Multiple Novel Protein Biomarkers Shed by Human Serous Ovarian Tumors into the Blood of Immunocompromised Mice and Verified in Patient Sera

PubMed Central

Beer, Lynn A.; Wang, Huan; Tang, Hsin-Yao; Cao, Zhijun; Chang-Wong, Tony; Tanyi, Janos L.; Zhang, Rugang; Liu, Qin; Speicher, David W.

2013-01-01

The most cancer-specific biomarkers in blood are likely to be proteins shed directly by the tumor rather than less specific inflammatory or other host responses. The use of xenograft mouse models together with in-depth proteome analysis for identification of human proteins in the mouse blood is an under-utilized strategy that can clearly identify proteins shed by the tumor. In the current study, 268 human proteins shed into mouse blood from human OVCAR-3 serous tumors were identified based upon human vs. mouse species differences using a four-dimensional plasma proteome fractionation strategy. A multi-step prioritization and verification strategy was subsequently developed to efficiently select some of the most promising biomarkers from this large number of candidates. A key step was parallel analysis of human proteins detected in the tumor supernatant, because substantially greater sequence coverage for many of the human proteins initially detected in the xenograft mouse plasma confirmed assignments as tumor-derived human proteins. Verification of candidate biomarkers in patient sera was facilitated by in-depth, label-free quantitative comparisons of serum pools from patients with ovarian cancer and benign ovarian tumors. The only proteins that advanced to multiple reaction monitoring (MRM) assay development were those that exhibited increases in ovarian cancer patients compared with benign tumor controls. MRM assays were facilely developed for all 11 novel biomarker candidates selected by this process and analysis of larger pools of patient sera suggested that all 11 proteins are promising candidate biomarkers that should be further evaluated on individual patient blood samples. PMID:23544127

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

PubMed

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

2008-08-15

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

Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis

PubMed Central

Gedaly, Roberto; Jeon, Hoonbae; Johnston, Thomas D; McHugh, Patrick P; Rowland, Randall G; Ranjan, Dinesh

2008-01-01

Background Carcinoid tumors are characteristically low grade malignant neoplasms with neuroendocrine differentiation that arise in various body sites, most commonly the lung and gastrointestinal tract, but less frequently the kidneys, breasts, ovaries, testes, prostate and other locations. We report a case of a carcinoid of renal origin with synchronous single liver metastases on radiological studies. Case presentation A 45 year-old patient who presented with abdominal pain was found on CT scan to have lesions in the right ovary, right kidney, and left hepatic lobe. CA-125, CEA, and CA 19-9 were within normal limits, as were preoperative liver function tests and renal function. Biopsy of the liver mass demonstrated metastatic neuroendocrine tumor. At laparotomy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, radical right nephrectomy with lymphadenectomy, and left hepatectomy. Pathology evaluation reported a right ovarian borderline serous tumor, well-differentiated neuroendocrine carcinoma of the kidney (carcinoid) with 2 positive retroperitoneal lymph nodes, and a single liver metastasis. Immunohistochemistry revealed that this lesion was positive for synaptophysin and CD56, but negative for chromogranin as well as CD10, CD7, and CD20, consistent with a well-differentiated neuroendocrine tumor. She is doing well one year after her initial surgery, with no evidence of tumor recurrence. Conclusion Early surgical intervention, together with careful surveillance and follow-up, can achieve successful long-term outcomes in patients with this rare malignancy. PMID:18430248

Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.

PubMed

Blegen, H.; Einhorn, N.; Sjövall, K.; Roschke, A.; Ghadimi, B. M.; McShane, L. M.; Nilsson, B.; Shah, K.; Ried, T.; Auer, G.

2000-11-01

Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

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

PubMed

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

2018-01-01

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

Finasteride for chronic central serous chorioretinopathy.

PubMed

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

2011-04-01

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

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

PubMed

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

2016-09-26

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

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

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

PubMed

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

2011-01-01

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

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

PubMed

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

2012-06-01

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

FUNDUS AUTOFLUORESCENCE LIFETIMES AND CENTRAL SEROUS CHORIORETINOPATHY

PubMed Central

Dysli, Chantal; Berger, Lieselotte; Wolf, Sebastian

2017-01-01

Purpose: To quantify retinal fluorescence lifetimes in patients with central serous chorioretinopathy (CSC) and to identify disease specific lifetime characteristics over the course of disease. Methods: Forty-seven participants were included in this study. Patients with central serous chorioretinopathy were imaged with fundus photography, fundus autofluorescence, optical coherence tomography, and fluorescence lifetime imaging ophthalmoscopy (FLIO) and compared with age-matched controls. Retinal autofluorescence was excited using a 473-nm blue laser light and emitted fluorescence light was detected in 2 distinct wavelengths channels (498–560 nm and 560–720 nm). Clinical features, mean retinal autofluorescence lifetimes, autofluorescence intensity, and corresponding optical coherence tomography (OCT) images were further analyzed. Results: Thirty-five central serous chorioretinopathy patients with a mean visual acuity of 78 ETDRS letters (range, 50–90; mean Snellen equivalent: 20/32) and 12 age-matched controls were included. In the acute stage of central serous chorioretinopathy, retinal fluorescence lifetimes were shortened by 15% and 17% in the respective wavelength channels. Multiple linear regression analysis showed that fluorescence lifetimes were significantly influenced by the disease duration (P < 0.001) and accumulation of photoreceptor outer segments (P = 0.03) but independent of the presence or absence of subretinal fluid. Prolonged central macular autofluorescence lifetimes, particularly in eyes with retinal pigment epithelial atrophy, were associated with poor visual acuity. Conclusion: This study establishes that autofluorescence lifetime changes occurring in central serous chorioretinopathy exhibit explicit patterns which can be used to estimate perturbations of the outer retinal layers with a high degree of statistical significance. PMID:28099314

FUNDUS AUTOFLUORESCENCE LIFETIMES AND CENTRAL SEROUS CHORIORETINOPATHY.

PubMed

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

2017-11-01

To quantify retinal fluorescence lifetimes in patients with central serous chorioretinopathy (CSC) and to identify disease specific lifetime characteristics over the course of disease. Forty-seven participants were included in this study. Patients with central serous chorioretinopathy were imaged with fundus photography, fundus autofluorescence, optical coherence tomography, and fluorescence lifetime imaging ophthalmoscopy (FLIO) and compared with age-matched controls. Retinal autofluorescence was excited using a 473-nm blue laser light and emitted fluorescence light was detected in 2 distinct wavelengths channels (498-560 nm and 560-720 nm). Clinical features, mean retinal autofluorescence lifetimes, autofluorescence intensity, and corresponding optical coherence tomography (OCT) images were further analyzed. Thirty-five central serous chorioretinopathy patients with a mean visual acuity of 78 ETDRS letters (range, 50-90; mean Snellen equivalent: 20/32) and 12 age-matched controls were included. In the acute stage of central serous chorioretinopathy, retinal fluorescence lifetimes were shortened by 15% and 17% in the respective wavelength channels. Multiple linear regression analysis showed that fluorescence lifetimes were significantly influenced by the disease duration (P < 0.001) and accumulation of photoreceptor outer segments (P = 0.03) but independent of the presence or absence of subretinal fluid. Prolonged central macular autofluorescence lifetimes, particularly in eyes with retinal pigment epithelial atrophy, were associated with poor visual acuity. This study establishes that autofluorescence lifetime changes occurring in central serous chorioretinopathy exhibit explicit patterns which can be used to estimate perturbations of the outer retinal layers with a high degree of statistical significance.

Transconjunctival drainage of serous and hemorrhagic choroidal detachment.

PubMed

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

2012-02-01

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

Central serous choroidopathy in the Hallermann-Streiff Syndrome.

PubMed

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

1981-08-01

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

Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma.

PubMed

Hayes, Monica Prasad; Douglas, Wayne; Ellenson, Lora Hedrick

2009-06-01

Uterine serous carcinoma (USC) is an aggressive endometrial cancer associated with poor prognosis despite comprehensive surgical staging and adjuvant chemotherapy and radiation therapy. Biologic targets have yet to be fully explored in this disease and research on such targets could lead to clinical trials utilizing a new class of therapeutics. This study sought to evaluate primary USC tumors for molecular alterations in epidermal growth factor receptor (EGFR) and the recently characterized oncogene PIK3CA, which encodes the catalytic p110-alpha subunit of phosphatidylinositol 3-kinase (PI3K) and thus activates the AKT-mTOR oncogenic pathway. Paraffin-embedded archival tissue of 45 primary USC tumors was utilized in this study. Immunohistochemical analysis of EGFR was performed and cases given a score of 0 to 12 calculated as the product of staining intensity (0 to 3+) and the percentage of positively stained cells (0-4), with 1=1-25%, 2=26-50%, 3=51-75%, and 4=76-100%. For mutational analysis, neoplastic tissue was microdissected and DNA was extracted with phenol-chloroform. Exons 18 through 21 of EGFR and exons 9 and 20 of PIK3CA, the most commonly mutated exons of these genes, were amplified and directly sequenced. When EGFR was evaluated, moderate or strong EGFR membranous staining was observed in 25/45 (56%) USC cases. Thus, a mutational analysis was performed on 35 cases, including all cases with moderate and strong EGFR staining. No mutations were identified in EGFR. In contrast, PIK3CA mutations were confirmed in 5/34 (15%) of USC cases. Four cases were mutated in exon 20 and one case was mutated in exon 9. Since optimal treatment of uterine serous carcinoma remains unknown, novel therapeutic approaches need to be actively pursued. In the current study of primary USC tumors, oncogenic mutations of the PIK3CA gene were seen in 15% of USC cases. This represents the first report of this gene mutation in USC. In addition, EGFR stained positively in the majority

Phyllodes Tumor of the Breast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belkacemi, Yazid; University of Lille II, Lille; Bousquet, Guilhem

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 radiotherapymore » (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.« less

[Feasibility study of dynamic contrast enhanced magnetic resonance imaging qualitative diagnosis of musculoskeletal tumors].

PubMed

Zhang, J; Zuo, P L; Cheng, K B; Yu, A H; Cheng, X G

2016-04-18

To investigate the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in differentiating musculoskeletal tumors with different behaviours of pathological findings before therapy. A total of 34 subjects of musculoskeletal tumors were involved in this retrospective analysis. DCE-MRI was performed using a fat-saturated 3D VIBE (volumetric interpolated breath-hold exam) imaging sequence with following parameters: FA, 10 degree; TR/TE, 5.6/2.4 ms; slice thickness, 4.0 mm with no intersection gap; field of view, 310 mm×213 mm; matrix, 256×178; voxel size, 1.2 mm×1.2 mm×4.0 mm; parallel imaging acceleration factor. The actuation time for the DCE-MRI sequence was 255 s with a temporal resolution of 5 s and 40 image volumes. Using pathological results as a gold standard, tumors were divided into benign, borderline and malignant tumors. Toft's model was used for calculation of K(trans) (volume transfer constant), Ve (extravascular extracellular space distribute volume per unit tissue volume) and Kep (microvascular permeability reflux constant). Those parameters were compared between the lesions and the control tissues using paired t tests. The one-way analysis of variance was used to assess the difference among benign, borderline and malignant tumors. P values <0.05 difference was statistically significant. Based on the WHO Classification of Tumours of Soft Tissue and Bone(2012) criteria, 34 patients were divided into three groups: 11 for benign tumors, 12 for borderline tumors, and 11 for malignancies. Compared with control tissues, K(trans) and Kep showed no difference, but Ve was increased in benign tumors, Kep showed no difference, but K(trans) and Ve were increased in borderline tumors,K(trans), Kep and Ve were increased in malignant tumors. K(trans) (P<0.001) and Kep (P<0.01) were significantly higher in malignant tumors than in benign and borderline tumors, but did not show any difference between benign tumors and borderline

Comparison of risk of malignancy indices; RMI 1-4 in borderline ovarian tumor.

PubMed

Yenen, M C; Alanbay, I; Aktürk, E; Ercan, C M; Coksuer, H; Karaşahin, E; Ozan, H; Dede, M

2012-01-01

The aim of this study was to evaluate prognostic values of the risk of malignancy index (RMI)/1-4 in patients with borderline ovarian tumors (BOTs). The study consisted of 50 patients with BOT diagnosed and treated between 2005-2010 and 50 patients with benign adnexal massses between 2009-2010 as a control comparison group in the retropsective study. Preoperative serum CA125, U score, tumor size (S), and menopausal status were recorded. The RMI 1-3 was calculated according to the formula; UxMxCA125 and RMI4 formulation was; UxMxCA125xS. S equaled 1 for tumor size <7 cm and was 2 when size a 7 cm. The RMI 1-4 indices were calculated for all patients together with the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy (DA). The performances of RMI indices were evaluated by McNemar's test and determined the best score cutoff value by the receiver operating characteristic (ROC) curve. The mean age, median value of CA125, ultrasound score, menopausal status, median values of RMI 1-4 of BOTs were statistically higher than benign adnexal masses. The sensitivity of RMI 1-4 was 26, 36, 62, and 60% at cutoff 200 level, respectively. The areas under curve of RMI 1-4 were found to be 0.676, 0.665, 0.668 and 0.734, respectively. DA of RMI 1-4 was found to be 56, 59, 50, and 71, respectively. When RMI 1-4 indices were compared with each other RMI 4 was the best RMI for BOTs. RMI 4 was the best predictive RMI for preoperative discrimination of BOT at a cutoff level of 200.

Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancer.

PubMed

Castellvi, Josep; Garcia, Angel; Rojo, Federico; Ruiz-Marcellan, Carmen; Gil, Antonio; Baselga, Jose; Ramon y Cajal, Santiago

2006-10-15

Growth factor receptors and cell signaling factors play a crucial role in human carcinomas and have been studied in ovarian tumors with varying results. Cell signaling involves multiple pathways and a myriad of factors that can be mutated or amplified. Cell signaling is driven through the mammalian target of rapamycin (mTOR) and extracellular regulated kinase (ERK) pathways and by some downstream molecules, such as 4E binding protein 1 (4EBP1), eukaryotic initiation factor 4E, and p70 ribosomal protein S6 kinase (p70S6K). The objectives of this study were to analyze the real role that these pathways play in ovarian cancer, to correlate them with clinicopathologic characteristics, and to identify the factors that transmit individual proliferation signals and are associated with pathologic grade and prognosis, regardless specific oncogenic alterations upstream. One hundred twenty-nine ovarian epithelial tumors were studied, including 20 serous cystadenomas, 7 mucinous cystadenomas, 11 serous borderline tumors, 16 mucinous borderline tumors, 29 serous carcinomas, 16 endometrioid carcinomas, 15 clear cell carcinomas, and 15 mucinous carcinomas. Tissue microarrays were constructed, and immunohistochemistry for the receptors epidermal growth factor receptor (EGFR) and c-erb-B2 was performed and with phosphorylated antibodies for protein kinase B (AKT), 4EBP1, p70S6K, S6, and ERK. Among 129 ovarian neoplasms, 17.8% were positive for c-erb-B2, 9.3% were positive for EGFR, 47.3% were positive for phosphorylated AKT (p-AKT), 58.9% were positive for p-ERK, 41.1% were positive for p-4EBP1, 26.4% were positive for p70S6K, and 15.5% were positive for p-S6. Although EGFR, p-AKT, and p-ERK expression did not differ between benign, borderline, or malignant tumors, c-erb-B2, p-4EBP1, p-p70S6K, and p-S6 were expressed significantly more often in malignant tumors. Only p-4EBP1 expression demonstrated prognostic significance (P = .005), and only surgical stage and p-4EBP1 expression

Quantitative detection of RASSF1A DNA promoter methylation in tumors and serum of patients with serous epithelial ovarian cancer.

PubMed

Bondurant, Amy E; Huang, Zhiqing; Whitaker, Regina S; Simel, Lauren R; Berchuck, Andrew; Murphy, Susan K

2011-12-01

Detection of cell free tumor-specific DNA methylation has been proposed as a potentially useful noninvasive mechanism to detect malignancies, including ovarian cancer, and to monitor response to treatment. However, there are few easily implemented quantitative approaches available for DNA methylation analysis. Our objectives were to develop an absolute quantitative method for detection of DNA methylation using RASSF1A, a known target of promoter methylation in ovarian cancer, and test the ability to detect RASSF1A methylation in tumors and serum specimens of women with ovarian cancer. Bisulfite modified DNAs were subjected to real time PCR using nondiscriminatory PCR primers and a probe with sequence containing a single CpG site, theoretically able to capture the methylation status of that CpG for every allele within a given specimen. Input DNA was normalized to ACTB levels detected simultaneously by assay multiplexing. Methylation levels were established by comparison to results obtained from universally methylated DNA. The assay was able to detect one methylated RASSF1A allele in 100,000 unmethylated alleles. RASSF1A was methylated in 54 of 106 (51%) invasive serous ovarian cancers analyzed and methylation status was concordant in 20/20 matched preoperative serum-tumor pairs. Serial serum specimens taken over the course of treatment for 8 of 9 patients showed fluctuations in RASSF1A methylation concomitant with disease status. This novel assay provides a real-time PCR-based method for absolute quantitation of DNA methylation. Our results support feasibility of monitoring RASSF1A methylation from serum samples taken over the course of treatment from women with ovarian cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.

PubMed

Alici, Omer; Kefeli, Mehmet; Yildiz, Levent; Baris, Sancar; Karagoz, Filiz; Kandemir, Bedri

2014-12-01

The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors. Copyright © 2014 Elsevier GmbH. All rights reserved.

Claudin-18 overexpression in intestinal-type mucinous borderline tumour of the ovary.

PubMed

Halimi, Sultan Ahmad; Maeda, Daichi; Shinozaki-Ushiku, Aya; Koso, Takahiro; Matsusaka, Keisuke; Tanaka, Mariko; Arimoto, Takahide; Oda, Katsutoshi; Kawana, Kei; Yano, Tetsu; Fujii, Tomoyuki; Fukayama, Masashi

2013-10-01

Mucinous borderline tumours of the ovary are subclassified as intestinal-type (IMBT) and endocervical-like (EMBT), which differ in their clinicopathological features. In this study, we attempted to elucidate characteristics of the mucinous epithelium in each subtype. The expression of claudin-18, a marker of gastric differentiation, MUCs, CDX2, CK7, CK20, oestrogen receptor (ER), progesterone receptor (PgR), CA-125 and vimentin in IMBTs (n = 54), EMBTs (n = 25) and serous borderline tumours (SBTs) (n = 22) were compared by immunohistochemistry. Claudin-18 positivity was identified in 98% of the IMBTs, whereas only 4% of the EMBTs were claudin-18-positive. Expression of intestinal markers such as CDX2 and MUC2 was relatively infrequent in IMBTs (48% and 33%, respectively). Müllerian-lineage markers such as ER, PgR and vimentin were expressed rarely in IMBTs, while most EMBTs and SBTs were positive for these markers. Hierarchial clustering revealed a close association between EMBTs and SBTs, while IMBTs were clearly separate. Claudin-18 positivity is a specific phenotype that is characteristic of IMBTs. Frequent and diffuse expression of gastric markers, along with less frequent and usually focal expression of intestinal markers, suggests that IMBTs are essentially composed of gastrointestinal-type mucinous epithelium (gastric-type epithelium with a variable degree of intestinal differentiation). © 2013 John Wiley & Sons Ltd.

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

PubMed

Kannan, Kalpana; Coarfa, Cristian; Rajapakshe, Kimal; Hawkins, Shannon M; Matzuk, Martin M; Milosavljevic, Aleksandar; Yen, Laising

2014-03-01

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.

Prognostic value of GLUT-1 expression in ovarian surface epithelial tumors: a morphometric study.

PubMed

Ozcan, Ayhan; Deveci, Mehmet Salih; Oztas, Emin; Dede, Murat; Yenen, Mufit Cemal; Korgun, Emin Turkay; Gunhan, Omer

2005-08-01

To investigate the reported increase in the expression of the glucose transporter GLUT-1 in borderline and malignant ovarian epithelial tumors and its relationship to prognosis. In this study, areas in which immunohistochemical membranous staining with GLUT-1 were most evident were selected, and the proportions of GLUT-1 expression in 46 benign, 11 borderline and 42 malignant cases of ovarian epithelial tumors were determined quantitatively with a computer and Zeiss Vision KS 400 3.0 (Göttingen, Germany) for Windows (Microsoft, Redmond, Washington, U.S.A.) image analysis. GLUT-1 expression was determined in all borderline tumors (11 of 11) and in 97.6% of malignant tumors (41 of 42). No GLUT-1 expression was observed in benign tumors. The intensity of GLUT-1 staining was lower in borderline tumors than in malignant cases. This was statistically significant (p = 0.005). As differentiation in malignant tumors increased, proportions of GLUT-1 expression showed a relative increase, but this difference was not statistically significant (p = 0.68). When GLUT-1 expression in borderline and malignant ovarian epithelial tumors was analyzed against prognosis, no statistically significant difference was identified. Assessment of GLUT-1 expression using the image analysis program was more reliable, with higher reproducibility than in previous studies.

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

ClinicalTrials.gov

2016-10-20

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

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

PubMed

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

2015-10-01

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 coexpression may also be enriched for additional EOC risk associations. 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 coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). 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. We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. ©2015 American Association for Cancer Research.

Surgical management and perioperative morbidity of patients with primary borderline ovarian tumor (BOT).

PubMed

Trillsch, Fabian; Ruetzel, Jan David; Herwig, Uwe; Doerste, Ulrike; Woelber, Linn; Grimm, Donata; Choschzick, Matthias; Jaenicke, Fritz; Mahner, Sven

2013-07-09

Surgery is the cornerstone for clinical management of patients with borderline ovarian tumors (BOT). As these patients have an excellent overall prognosis, perioperative morbidity is the critical point for decision making when the treatment strategy is developed and the primary surgical approach is defined. Clinical and surgical parameters of patients undergoing surgery for primary BOT at our institutions between 1993 and 2008 were analyzed with regard to perioperative morbidity depending on the surgical approach (laparotomy vs. laparoscopy). A total of 105 patients were analyzed (44 with primary laparoscopy [42%], 61 with primary laparotomy [58%]). Complete surgical staging was achieved in 33 patients at primary surgical approach (31.4%) frequently leading to formal indication of re-staging procedures. Tumor rupture was significantly more frequent during laparoscopy compared to laparotomy (29.5% vs. 13.1%, p = 0.038) but no other intraoperative complications were seen in laparoscopic surgery in contrast to 7 of 61 laparotomies (0% vs. 11.5%, p = 0.020). Postoperative complication rates were similar in both groups (19.7% vs. 18.2%, p = 0.848). Irrespective of the surgical approach, surgical management of BOT has acceptable rates of perioperative complications and morbidity. Choice of initial surgical approach can therefore be made independent of complication-concerns. As the recently published large retrospective AGO ROBOT study observed similar oncologic outcome for both approaches, laparoscopy can be considered for staging of patients with BOT if this appears feasible. An algorithm for the surgical management of BOT patients has been developed.

Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors: Correlation with clinicopathological features.

PubMed

Ciepliński, Klaudiusz; Jóźwik, Maciej; Semczuk-Sikora, Anna; Gogacz, Marek; Lewkowicz, Dorota; Ignatov, Atanas; Semczuk, Andrzej

2018-02-01

The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms. The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs). The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients' age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα. For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinicopathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki-67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinicopathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001). We

The pain of being borderline: dysphoric states specific to borderline personality disorder.

PubMed

Zanarini, M C; Frankenburg, F R; DeLuca, C J; Hennen, J; Khera, G S; Gunderson, J G

1998-01-01

The objective of this study was to identify the dysphoric states that best characterize patients meeting criteria for borderline personality disorder and distinguish them from those in patients with other forms of personality disorder. One hundred forty-six patients with criteria-defined borderline personality disorder and 34 Axis II controls filled out the Dysphoric Affect Scale, a 50-item self-report measure that was designed for this purpose and has good internal consistency and test-retest reliability. Twenty-five dysphoric states (mostly affects) were found to be significantly more common among borderline patients than controls but nonspecific to borderline personality disorder. Twenty-five other dysphoric states (mostly cognitions) were found to be both significantly more common among borderline patients than controls and highly specific to borderline personality disorder. These states tended to fall into one of four clusters: (1) extreme feelings, (2) destructiveness or self-destructiveness, (3) fragmentation or "identitylessness," and (4) victimization. In addition, three of the 25 more-specific states (feeling betrayed, like hurting myself, and completely out of control), when occurring together, were particularly strongly associated with the borderline diagnosis. Equally important, overall mean Dysphoric Affect Scale scores correctly distinguished borderline personality disorder from other personality disorders in 84% of the subjects. Taken together, the results of this study suggest that the subjective pain of borderline patients may be both more pervasive and more multifaceted than previously recognized, and that the overall "amplitude" of this pain may be a particularly good marker for the borderline diagnosis.

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

PubMed

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

2018-05-07

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

Small Foci of Serous Component as a Predictor of Recurrence and Prognosis for Stage IA Endometrial Carcinomas.

PubMed

Miyamoto, Morikazu; Takano, Masashi; Tsuda, Hitoshi; Soyama, Hiroaki; Aoyama, Tadashi; Ishibashi, Hiroki; Kato, Kento; Iwahashi, Hideki; Matuura, Hiroko; Yoshikawa, Tomoyuki; Suzuki, Ayako; Hirata, Junko; Furuya, Kenichi

2017-01-01

Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1. © 2017 S. Karger AG, Basel.

Comparison of risk of malignancy index (RMI), CA125, CA 19-9, ultrasound score, and menopausal status in borderline ovarian tumor.

PubMed

Alanbay, Ibrahim; Akturk, Erhan; Coksuer, Hakan; Ercan, Mutlu; Karaşahin, Emre; Dede, Murat; Yenen, Mufit Cemal; Ozan, Hakan; Baser, Iskender

2012-06-01

The aim of this study was to assess the prognostic values of risk of malignancy index (RMI IV), ultrasound score, menopausal status, and serum CA125 and CA19-9 level in patients with borderline ovarian tumor (BOT). Fifty women having borderline ovarian tumor (BOT) and 5O individuals with benign adnexal mass were enrolled in this retrospective study. The sensitivity, specificity, positive predictive values, negative predictive values and diagnostic accuracy of preoperative serum levels of the CA125 and CA19-9, ultrasound findings and menopausal status, and RMI IV were calculated for prediction of discrimination between BOTs and benign adnexal masses and the results were compared. The RMI IV was the best method for discrimination between BOTs and benign adnexal masses and was more accurate than the other parameters. When Receiver Operator Characteristic area under the curves for menopausal status was analyzed, serum CA 125 and CA19-9 level, ultrasound score, RMI IV(CA125), and RMI IV(CA19-9) were, 0.580, 0.625, 0.548, 0.694, 0.734 and 0.711, respectively. The best RMI IV cut-off was found to be 200 for discrimination of benign and BOT lesions. In the RMI formulation, replacing CA125 with CA19-9 didn't affect RMI IV sensitivity and specificity for discrimination. Compared to ultrasound, menopausal status, CA-125, CA19-9, the RMI IV was found to be the best predictive method for differentiation of BOTs from benign adnexal masses. RMI IV cut-off value of 200 is suitable for differentiation of benign and BOT's.

The Ovary Is an Alternative Site of Origin for High-Grade Serous Ovarian Cancer in Mice

PubMed Central

Coffey, Donna M.; Ma, Lang; Matzuk, Martin M.

2015-01-01

Although named “ovarian cancer,” it has been unclear whether the cancer actually arises from the ovary, especially for high-grade serous carcinoma (HGSC), also known as high-grade serous ovarian cancer, the most common and deadliest ovarian cancer. In addition, the tumor suppressor p53 is the most frequently mutated gene in HGSC. However, whether mutated p53 can cause HGSC remains unknown. In this study, we bred a p53 mutation, p53R172H, into conditional Dicer-Pten double-knockout (DKO) mice, a mouse model duplicating human HGSC, to generate triple-mutant (TKO) mice. Like DKO mice, these TKO mice develop metastatic HGSCs originating from the fallopian tube. Unlike DKO mice, however, even after fallopian tubes are removed in TKO mice, ovaries alone can develop metastatic HGSCs, indicating that a p53 mutation can drive HGSC arising from the ovary. To confirm this, we generated p53R172H-Pten double-mutant mice, one of the genetic control lines for TKO mice. As anticipated, these double-mutant mice also develop metastatic HGSCs from the ovary, verifying the HGSC-forming ability of ovaries with a p53 mutation. Our study therefore shows that ovaries harboring a p53 mutation, as well as fallopian tubes, can be a distinct tissue source of high-grade serous ovarian cancer in mice. PMID:25815421

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

PubMed

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

2015-06-01

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

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

Keratin 5 overexpression is associated with serous ovarian cancer recurrence and chemotherapy resistance.

PubMed

Ricciardelli, Carmela; Lokman, Noor A; Pyragius, Carmen E; Ween, Miranda P; Macpherson, Anne M; Ruszkiewicz, Andrew; Hoffmann, Peter; Oehler, Martin K

2017-03-14

This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P < 0.0001) and overall survival (HR 1.28, P = 0.013) whilst high KRT6 mRNA was only associated with reduced progression-free survival (HR 1.2, P = 0.031). Both high K5/6 (≥ 10%, HR 1.78 95% CI; 1.03-2.65, P = 0.017) and high K5 (≥ 10%, HR 1.90, 95% CI; 1.12-3.19, P = 0.017) were associated with an increased risk of disease recurrence. KRT5 but not KRT6C mRNA expression was increased in chemotherapy resistant primary serous ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival.

Down-regulation of HECTD3 by HER2 inhibition makes serous ovarian cancer cells sensitive to platinum treatment.

PubMed

Shu, Tong; Li, Yi; Wu, Xiaowei; Li, Bin; Liu, Zhihua

2017-12-28

Resistance to platinum-based chemotherapy is a major cause of treatment failure in patients with epithelial ovarian cancer and predicts a poor prognosis. Previously, we found that HECTD3 confers cancer cell resistance to apoptosis. However, the significance of HECTD3 expression in ovarian cancer and its regulatory mechanisms were unknown. Here, we found that HECTD3 depletion promotes carboplatin-induced apoptosis in both an ovarian cancer cell model and a xenograft mouse model. Moreover, high HECTD3 expression is significantly associated with poor platinum response and prognosis in ovarian cancer patients. We further demonstrated that HER2 can up-regulate HECTD3 expression through activating STAT3. Furthermore, HER2 inhibitors, such as lapatinib, down-regulate HECTD3 expression and thus promote the chemosensitivity of ovarian cancer cells to carboplatin. Lapatinib combined with carboplatin also significantly inhibits serous ovarian carcinoma growth compared with each drug alone in a xenograft mouse model. HECTD3 may be considered a promising molecular predictor of platinum chemosensitivity and prognosis for serous ovarian cancer. Through decreasing HECTD3, lapatinib possesses significantly increased anti-tumor activity when combined with carboplatin compared with each agent alone, which provides an optional therapeutic regimen for serous ovarian cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of three new serous epithelial ovarian cancer cell lines

PubMed Central

Ouellet, Véronique; Zietarska, Magdalena; Portelance, Lise; Lafontaine, Julie; Madore, Jason; Puiffe, Marie-Line; Arcand, Suzanna L; Shen, Zhen; Hébert, Josée; Tonin, Patricia N; Provencher, Diane M; Mes-Masson, Anne-Marie

2008-01-01

Background Cell lines constitute a powerful model to study cancer, and here we describe three new epithelial ovarian cancer (EOC) cell lines derived from poorly differentiated serous solid tumors (TOV-1946, and TOV-2223G), as well as the matched ascites for one case (OV-1946). Methods In addition to growth parameters, the cell lines were characterized for anchorage independent growth, migration and invasion potential, ability to form spheroids and xenografts in SCID mice. Results While all cell lines were capable of anchorage independent growth, only the TOV-1946 and OV-1946 cell lines were able to form spheroid and produce tumors. Profiling of keratins, p53 and Her2 protein expression was assessed by immunohistochemistry and western blot analyses. Somatic TP53 mutations were found in all cell lines, with TOV-1946 and OV-1946 harboring the same mutation, and none harbored the commonly observed somatic mutations in BRAF, KRAS or germline BRCA1/2 mutations found to recur in the French Canadian population. Conventional cytogenetics and spectral karyotype (SKY) analyses revealed complex karyotypes often observed in ovarian disease. Conclusion This is the first report of the establishment of matched EOC cell lines derived from both solid tumor and ascites of the same patient. PMID:18507860

How to Differentiate Borderline Hepatic Nodules in Hepatocarcinogenesis: Emphasis on Imaging Diagnosis.

PubMed

Park, Hyun Jeong; Choi, Byung Ihn; Lee, Eun Sun; Park, Sung Bin; Lee, Jong Beum

2017-06-01

Rapid advances in liver imaging have improved the evaluation of hepatocarcinogenesis and early diagnosis and treatment of hepatocellular carcinoma (HCC). In this situation, detection of early-stage HCC in its development is important for the improvement of patient survival and optimal treatment strategies. Because early HCCs are considered precursors of progressed HCC, precise differentiation between a dysplastic nodule (DN), especially a high-grade DN, and early HCC is important. In clinical practice, these nodules are frequently called "borderline hepatic nodules." This article discusses radiological and pathological characteristics of these borderline hepatic nodules and offers an understanding of multistep hepatocarcinogenesis by focusing on the descriptions of the imaging changes in the progression of DN and early HCC. Detection and accurate diagnosis of borderline hepatic nodules are still a challenge with contrast enhanced ultrasonography, CT, and MRI with extracellular contrast agents. However, gadoxetic acid-enhanced MRI may be useful for improving the diagnosis of these borderline nodules. Since there is a net effect of incomplete neoangiogenesis and decreased portal venous flow in the early stage of hepatocarcinogenesis, borderline hepatic nodules commonly show iso- or hypovascularity. Therefore, precise differentiation of these nodules remains a challenging issue. In MRI using hepatobiliary contrast agents, signal intensity of HCCs on hepatobiliary phase (HBP) is regarded as a potential imaging biomarker. Borderline hepatic nodules are seen as nonhypervascular and hypointense nodules on the HBP, which is important for predicting tumor behavior and determining appropriate therapeutic strategies.

[Why and how should serous otitis media be treated?].

PubMed

François, M; Bonfils, P; Van Haver, K; Narcy, P

1992-10-01

Serous otitis media is an extremely commonplace condition in pediatric patients and tends to resolve spontaneously. Only some forms warrant treatment. Indications for treatment include frequent superinfections, lasting hearing impairment with adverse consequences on socialization, or debilitation of the tympanic membrane carrying a risk for the ear. Tympanostomy tubes are a palliative treatment for serous otitis which restores hearing within a few hours and eliminates unfixated retractions of the tympanic membrane within a few weeks. Tympanostomy tubes may lead to complications including otorrhea and perforation of the tympanic membrane and should therefore be used only in patients with severe otitis media. Etiologic treatment of serous otitis rests on restoration of satisfactory nasal ventilation (education to improve nose-blowing, adenoidectomy), improvement of eustachian tube patency (corticosteroids), and modification of the characteristics of middle ear secretions (mucolytic agents and mucomodifying agents).

Massive Bilateral Serous Retinal Detachment in a Case of Hypertensive Chorioretinopathy

PubMed Central

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

2014-01-01

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

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

PubMed

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

2017-10-17

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

Borderline personality disorder

MedlinePlus

... this page: //medlineplus.gov/ency/article/000935.htm Borderline personality disorder To use the sharing features on this page, please enable JavaScript. Borderline personality disorder (BPD) is a mental condition in which ...

[Borderline personality disorder and transsexualism].

PubMed

Seikowski, Kurt; Gollek, Sabine; Harth, Wolfgang; Reinhardt, Michaela

2008-04-01

The study addresses the question whether, as often assumed, the symptoms of borderline personality disorders occur more frequently in transsexuals or not. We examined 164 transsexuals. The subjects completed the following questionnaires: The Borderline-Personality Inventory (BPI), the Freiburg Personality Inventory (FPI) and the Questionnaire for Assessment of One's Own Body (FbeK). In 80 % of all the examined transsexuals, there was evidence of symptoms of neither a borderline personality disorder nor of other personality disorders. If borderline symptoms occurred, they were predictable from the variables depressivity, low composure, low sociability and lack of confidence in relation to the external appearance. The data obtained refute the often-assumed increased relationship between borderline personality disorders and transsexuality. It should be assumed that a borderline personality disorder is primarily a psychiatric illness, while transsexuality is a disorder of gender identity in which secondary borderline symptoms may arise in some cases.

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

PubMed

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

2015-01-01

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

Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue.

PubMed

Yang, Qiuyun; Zhao, Jinghe; Cui, Manhua; Gi, Shuting; Wang, Wei; Han, Xiaole

2015-12-01

Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. © 2015 Japan Society of Obstetrics and Gynecology.

Is Imprint Cytology Useful to Diagnose Malignancy for Brenner Tumors? A Case Series at a Single Institute.

PubMed

Minato, Junko; Tokunaga, Hideki; Okamoto, Satoshi; Shibuya, Yusuke; Niikura, Hitoshi; Yaegashi, Nobuo

2017-01-01

The aim of this study was to investigate cytological features of Brenner tumors according to tumor grade using imprint cytology. Between 2004 and 2015, intraoperative imprint cytology was performed on 8 patients with Brenner tumors suspected to be malignant neoplasmas on gross examination because of their large size and solid part. These consisted of 1 benign, 3 borderline, and 4 malignant tumors. In patients with benign and borderline tumors, naked nucleus-like stromal cells and tumor cells in a sheet-like arrangement were observed against a clear background. The nuclei were round to oval-shaped with finely granular chromatin patterns and small nucleoli. Papillary cell clusters and high nucleus-to-cytoplasm ratios were only observed in 1 borderline case. In cases with malignancy, the background was necrotic. The tumor cells occurred in large papillary clusters. The nuclei showed a high degree of nuclear atypia. Nuclear grooves were present in 6 of our 8 cases and they were scant in the malignant cases. Imprint cytology of Brenner tumors provided no characteristic findings to enable a definitive distinction of benign versus borderline tumors, but it enabled discrimination between malignant and other tumors. Imprint cytology can facilitate intraoperative diagnosis and aid in selecting the appropriate surgical procedure. © 2017 S. Karger AG, Basel.

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

Dark and white lesions observed in central serous chorioretinopathy on optical coherence tomography angiography.

PubMed

De Bats, Flore; Cornut, Pierre-Loïc; Wolff, Benjamin; Kodjikian, Laurent; Mauget-Faÿsse, Martine

2018-03-01

To describe abnormal dark (hyposignal) and white (hypersignal) lesions observed on optical coherence tomography angiography in central serous chorioretinopathy. Prospective, multicenter, and descriptive study including patients with active or quiescent central serous chorioretinopathy. All patients had undergone a complete ophthalmic examination. Abnormal dark lesions were detected as "dark spots" and "dark areas" on optical coherence tomography angiography. A "dark spot" could correspond to six different abnormalities: pigment epithelium detachment, subretinal deposit, "Lucency" within surrounding subretinal fibrin, choroidal cavitation, choroidal excavation, and choroidal fluid. A "dark area" could be related to a serous retinal detachment or choriocapillary compression. Abnormal white lesions were also detected: A "white spot" could correspond with the leaking point on fluorescein angiography or with hyper-reflective dots; A "white filamentous pattern" at the Brüch's membrane level corresponded to abnormal choroidal neovascular vessels. A semiology is described using optical coherence tomography angiography in central serous chorioretinopathy as abnormal dark and white lesions. Multimodal imaging is mandatory in addition to optical coherence tomography angiography to diagnose non-neovascular retinal and choroidal central serous chorioretinopathy lesions. However, optical coherence tomography angiography alone is helpful in detecting choroidal neovascular membrane in central serous chorioretinopathy.

Revisiting the role of radiation treatment for non-serous subtypes of epithelial ovarian cancer.

PubMed

Thomas, G

2013-01-01

Except for its palliative use, radiation has been largely abandoned in the management of ovarian cancers because of the recognized efficacy of chemotherapy agents. Whole abdominal irradiation (WAR), however, has been shown to be of adjuvant and curative value in ovarian cancer with microscopic or minimal residual disease in the pelvis, the so-called "intermediate risk group." Recent hypothesis generating data from the use of adjuvant radiation following adjuvant chemotherapy in ovarian cancer has shown an incremental survival benefit for the rarer non-serous ovarian subtypes including clear cell, endometrioid, and mucinous. No incremental benefit was observed for the more common serous subtype. A retrospective examination of early trials using WAR as the sole postoperative treatment in ovarian cancer has determined that the majority of patients in these studies and cured by radiation actually had the non-serous subtypes. The recognition that the non-serous subtypes differ from the serous cancers in their stage of presentation, their molecular characteristics, their response to classic chemotherapy, and their outcomes suggest the non-serous subtypes should be treated as rare and different cancers. In addition to specific targeting therapies that may be developed, radiation should be reconsidered as part of the treatment armamentarium for these diseases.

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

Borderline resectable pancreatic cancer: Definitions and management

PubMed Central

Lopez, Nicole E; Prendergast, Cristina; Lowy, Andrew M

2014-01-01

Pancreatic cancer is the fourth leading cause of cancer death in the United States. While surgical resection remains the only curative option, more than 80% of patients present with unresectable disease. Unfortunately, even among those who undergo resection, the reported median survival is 15-23 mo, with a 5-year survival of approximately 20%. Disappointingly, over the past several decades, despite improvements in diagnostic imaging, surgical technique and chemotherapeutic options, only modest improvements in survival have been realized. Nevertheless, it remains clear that surgical resection is a prerequisite for achieving long-term survival and cure. There is now emerging consensus that a subgroup of patients, previously considered poor candidates for resection because of the relationship of their primary tumor to surrounding vasculature, may benefit from resection, particularly when preceded by neoadjuvant therapy. This stage of disease, termed borderline resectable pancreatic cancer, has become of increasing interest and is now the focus of a multi-institutional clinical trial. Here we outline the history, progress, current treatment recommendations, and future directions for research in borderline resectable pancreatic cancer. PMID:25152577

Polycystic Ovary Syndrome, Oligomenorrhea, and Risk of Ovarian Cancer Histotypes: Evidence from the Ovarian Cancer Association Consortium.

PubMed

Harris, Holly R; Babic, Ana; Webb, Penelope M; Nagle, Christina M; Jordan, Susan J; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Moysich, Kirsten B; Kjær, Susanne K; Høgdall, Estrid; Jensen, Allan; Schildkraut, Joellen M; Berchuck, Andrew; Cramer, Daniel W; Bandera, Elisa V; Wentzensen, Nicolas; Kotsopoulos, Joanne; Narod, Steven A; Phelan, Catherine M; McLaughlin, John R; Anton-Culver, Hoda; Ziogas, Argyrios; Pearce, Celeste L; Wu, Anna H; Terry, Kathryn L

2018-02-01

Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies. Methods: We analyzed data from 14 case-control studies including 16,594 women with invasive ovarian cancer ( n = 13,719) or borderline ovarian disease ( n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression. Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58-0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with women with regular cycles (OR = 0.83; 95% CI = 0.76-0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR = 0.87; 95% CI = 0.65-1.15). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors ( P heterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors ( P heterogeneity < 0.0001). Conclusions: Our results suggest that menstrual cycle characteristics influence ovarian cancer risk differentially based on histotype. Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174-82. ©2017 AACR . ©2017 American

Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer.

PubMed

Goode, Ellen L; Block, Matthew S; Kalli, Kimberly R; Vierkant, Robert A; Chen, Wenqian; Fogarty, Zachary C; Gentry-Maharaj, Aleksandra; Tołoczko, Aleksandra; Hein, Alexander; Bouligny, Aliecia L; Jensen, Allan; Osorio, Ana; Hartkopf, Andreas; Ryan, Andy; Chudecka-Głaz, Anita; Magliocco, Anthony M; Hartmann, Arndt; Jung, Audrey Y; Gao, Bo; Hernandez, Brenda Y; Fridley, Brooke L; McCauley, Bryan M; Kennedy, Catherine J; Wang, Chen; Karpinskyj, Chloe; de Sousa, Christiani B; Tiezzi, Daniel G; Wachter, David L; Herpel, Esther; Taran, Florin Andrei; Modugno, Francesmary; Nelson, Gregg; Lubiński, Jan; Menkiszak, Janusz; Alsop, Jennifer; Lester, Jenny; García-Donas, Jesús; Nation, Jill; Hung, Jillian; Palacios, José; Rothstein, Joseph H; Kelley, Joseph L; de Andrade, Jurandyr M; Robles-Díaz, Luis; Intermaggio, Maria P; Widschwendter, Martin; Beckmann, Matthias W; Ruebner, Matthias; Jimenez-Linan, Mercedes; Singh, Naveena; Oszurek, Oleg; Harnett, Paul R; Rambau, Peter F; Sinn, Peter; Wagner, Philipp; Ghatage, Prafull; Sharma, Raghwa; Edwards, Robert P; Ness, Roberta B; Orsulic, Sandra; Brucker, Sara Y; Johnatty, Sharon E; Longacre, Teri A; Ursula, Eilber; McGuire, Valerie; Sieh, Weiva; Natanzon, Yanina; Li, Zheng; Whittemore, Alice S; Anna, deFazio; Staebler, Annette; Karlan, Beth Y; Gilks, Blake; Bowtell, David D; Høgdall, Estrid; Candido dos Reis, Francisco J; Steed, Helen; Campbell, Ian G; Gronwald, Jacek; Benítez, Javier; Koziak, Jennifer M; Chang-Claude, Jenny; Moysich, Kirsten B; Kelemen, Linda E; Cook, Linda S; Goodman, Marc T; García, María José; Fasching, Peter A; Kommoss, Stefan; Deen, Suha; Kjaer, Susanne K; Menon, Usha; Brenton, James D; Pharoah, Paul DP; Chenevix-Trench, Georgia; Huntsman, David G; Winham, Stacey J; Köbel, Martin; Ramus, Susan J

2017-12-01

Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium. More than 5500 patients, including 3196 with high-grade serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650 person-years. Following immunohistochemical analysis, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1-2), moderate (3-19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Overall survival time. The final sample included 5577 women; mean age at diagnosis was 58.4 years (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (P value for trend = 4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near-log-linear functional form. This study

Borderline resectable pancreatic cancer: conceptual evolution and current approach to image-based classification.

PubMed

Gilbert, J W; Wolpin, B; Clancy, T; Wang, J; Mamon, H; Shinagare, A B; Jagannathan, J; Rosenthal, M

2017-09-01

Diagnostic imaging plays a critical role in the initial diagnosis and therapeutic monitoring of pancreatic adenocarcinoma. Over the past decade, the concept of 'borderline resectable' pancreatic cancer has emerged to describe a distinct subset of patients existing along the spectrum from resectable to locally advanced disease for whom a microscopically margin-positive (R1) resection is considered relatively more likely, primarily due to the relationship of the primary tumor with surrounding vasculature. This review traces the conceptual evolution of borderline resectability from a radiological perspective, including the debates over the key imaging criteria that define the thresholds between resectable, borderline resectable, and locally advanced or metastatic disease. This review also addresses the data supporting neoadjuvant therapy in this population and discusses current imaging practices before and during treatment. A growing body of evidence suggests that the borderline resectable group of patients may particularly benefit from neoadjuvant therapy to increase the likelihood of an ultimately margin-negative (R0) resection. Unfortunately, anatomic and imaging criteria to define borderline resectability are not yet universally agreed upon, with several classification systems proposed in the literature and considerable variance in institution-by-institution practice. As a result of this lack of consensus, as well as overall small patient numbers and lack of established clinical trials dedicated to borderline resectable patients, accurate evidence-based diagnostic categorization and treatment selection for this subset of patients remains a significant challenge. Clinicians and radiologists alike should be cognizant of evolving imaging criteria for borderline resectability given their profound implications for treatment strategy, follow-up recommendations, and prognosis. © The Author 2017. Published by Oxford University Press on behalf of the European Society for

Seven-Year Course of Borderline Personality Disorder Features: Borderline Pathology Is as Unstable as Depression during Adolescence.

PubMed

Conway, Christopher C; Hipwell, Alison E; Stepp, Stephanie D

2017-07-01

Borderline personality disorder (PD) historically is construed as an unremitting condition with poor prognosis. The present study takes a new approach to examining stability and change in borderline PD by explaining symptom expression in terms of an unchanging foundation-termed borderline proneness-on one hand, and transitory influences on the other. We monitored borderline PD symptoms annually in a large sample of high-risk adolescent girls ( N = 2,450) from ages 14 to 20. Trait-state-occasion modeling revealed that just over half (52-57%) of borderline PD symptom variation was attributable to fixed borderline proneness, whereas the remainder was subject to change across yearly measurement occasions. This degree of stability was no larger than the corresponding estimate for depression, a condition known for its variable course. Our results indicate that, contrary to its reputation, borderline pathology is not set in stone, and it fluctuates in response to situational influences.

Neuropeptides degranulate serous cells of ferret tracheal glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gashi, A.A.; Borson, D.B.; Finkbeiner, W.E.

1986-08-01

To determine whether serous or mucous cells in tracheal submucosal glands respond to the neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP). The authors studied the peptide-induced changes in gland cell morphology accompanying release of TVSO4-labeled macromolecules from tracheal explants of ferrets. Explants were labeled for 1 h in medium containing TVSO4 and washed for 3.5 additional hours. Base-line secretion in the absence of drugs declined between 1.5 and 3.5 h after the pulse. Between 2.5 and 3.5 h, the average percent change in counts per minute recovered per sample period was not significantly different from zero. Substance Pmore » and VIP added 4 h after labeling each increased greatly the release of TVSO4-labeled macromolecules above base line. Bethanechol, a muscarinic-cholinergic agonist, increased secretion by an average of 142% above base line. Light and electron microscopy of the control tissues showed glands with narrow lumens and numerous secretory granules. Glands treated with SP or VIP had enlarged lumens and the serous cells were markedly degranulated. These phenomena were documented by morphometry and suggest that SP and VIP cause secretion from glands at least partially by stimulating exocytosis from serous cells.« less

Reliability of criteria for borderline personality disorder: a comparison of DSM-III and the Diagnostic Interview for Borderline Patients.

PubMed

Frances, A; Clarkin, J F; Gilmore, M; Hurt, S W; Brown, R

1984-09-01

The authors compared the reliability of two methods of distinguishing borderline personality disorder--DSM-III and the Diagnostic Interview for Borderline Patients. The reference group, outpatients with other personality disorders and without major axis I pathology, was more difficult to distinguish from the patients with borderline personality disorder than such groups used in previous samples. The sensitivity and specificity of the Diagnostic Interview for Borderline Patients were calculated, with DSM-III used as a criterion. The findings confirm considerable overlap between borderline and schizotypal personality disorders, more impairment in functioning in borderline patients than in those with other personality disorders, and the high reliability with which borderline personality disorder can be diagnosed.

Neoadjuvant imatinib for borderline resectable GIST.

PubMed

Koontz, M Zach; Visser, Brendan M; Kunz, Pamela L

2012-12-01

A 36-year-old woman presented to the emergency department with black stools and syncope. Her hemoglobin was 7.0 and her red blood cells were microcytic. Upper endoscopy did not identify a clear source of bleeding, but a bulge in the third portion of the duodenum was noted. A CT scan showed a large extraintestinal mass, and follow-up esophagogastroduodenoscopy/endoscopic ultrasound with biopsy revealed a spindle cell neoplasm, consistent with gastrointestinal stromal tumor (GIST). Because of the size of the lesion and association with the superior mesenteric vein and common bile duct, she was referred to medical oncology for consideration of neoadjuvant imatinib. Neoadjuvant tyrosine kinase inhibitor therapy for GISTs is emerging as a viable treatment strategy for borderline resectable tumors, although the dose, duration, and optimal imaging modalities have not been clearly established. Recent pathologic and radiographic data have provided insight into the mechanism and kinetics of this approach. This case report presents a patient for whom surgery was facilitated using neoadjuvant imatinib.

GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens.

PubMed

Shield, Paul W; Papadimos, David J; Walsh, Michael D

2014-04-01

The usefulness of GATA3 (GATA-binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial, and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from the breast (30 specimens), female genital tract (13 specimens), gastrointestinal tract (7 specimens), lung adenocarcinoma (9 specimens), pancreas (1 specimen), kidney (1 specimen), and bladder (1 specimen). The breast carcinoma cases included 15 ductal carcinomas and 8 lobular carcinomas; the histology subtype was not available for 7 specimens. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and gross cystic disease fluid protein of 15 kilodaltons (GCDFP-15) to compare their sensitivity with GATA3. Positive nuclear staining for GATA3 was found to be present in 90% of metastatic breast carcinoma specimens (27 of 30 specimens). All nonbreast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases demonstrated weak positivity of benign lymphoid cells. Staining results were unambiguous because all positive cases demonstrated intense nuclear staining in > 50% of tumor cells. Mammaglobin (57% staining; 17 of 30 cases) and GCDFP-15 (33% staining; 10 of 30 cases) were found to be less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only 1 additional case compared with those stained with GATA3. GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

ClinicalTrials.gov

2018-06-27

Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma

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

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

CONCOMITANT MACULAR HOLE AND CENTRAL SEROUS CHORIORETINOPATHY AFTER BLUNT EYE TRAUMA.

PubMed

Tekin, Kemal; Citirik, Mehmet; Atalay, Muhammed; Teke, Mehmet Yasin

2018-01-01

To report concomitant macular hole and central serous chorioretinopathy after blunt trauma. Case presentation. A 31-year-old man presented with a complaint of a reduction in visual acuity and blurred vision in the right eye after blunt eye trauma. The patient did not have a history of any systemic disorders and drug administration. On ocular examination, best corrected visual acuity was 2/20 in the right eye and 20/20 in the left eye. His intraocular pressures were 14 mmHg right eye and 13 mmHg left eye by applanation tonometry. Dilated fundus examination of the right eye showed macular hole and serous macular detachment, whereas the left eye was completely normal. Optical coherence tomography confirmed the full-thickness macular hole and subretinal fluid in the right eye, and ink-blot leakage pattern was determined in fundus fluorescein angiography. The patient was followed up without systemic therapy. Three months later, the vision was 10/20 in the right eye with completely closed macular hole and complete resolution of subretinal fluid. This is the first case which describes concomitant macular hole and central serous chorioretinopathy after blunt eye trauma. This presentation demonstrates that macular hole and central serous chorioretinopathy can be developed after blunt trauma. Both pathology may result with spontaneous closure of macular hole and spontaneous resolution of subretinal fluid within 3 months.

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

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.

Integrated proteogenomic characterization of human high grade serous ovarian cancer

PubMed Central

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

2016-01-01

SUMMARY 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 (HGSC). 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, as well as 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. PMID:27372738

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Ovarian tumor antigens.

PubMed

Bhattacharya, M; Barlow, J J

1978-09-01

Evidence has been reported for at least two common tumor-associated antigens, or antigenic determinants, in human cystadenocarcinomas of the ovary that are apparently absent in tissues of normal reproductive organs. These antigenic determinants are immunologically distinct from carcinoembryonic antigen, alpha-fetoprotein, ferritins and histocompatibility antigens. One of these two ovarian cystadenocarcinoma-associated antigens (OCAA) is not detectable in any ovarian carcinomas except serous or mucinous types, other gynecologic or nongynecologic malignancies thus far tested, while the second antigen is present in about 90% of all gynecologic tumors and occasionally in breast and colon tumors. OCAA has been purified and partially characterized. It is a high molecular weight glycoprotein which carries the unique ovarian tumor-specific antigenic determinant along with some normal cross-reacting determinants. High levels of this glycoprotein antigen have been detected in the sera of ovarian cancer patients with advanced disease by the radioimmunoassay inhibition technique. The serial determination of circulating OCAA appeared to correlate with tumor volume as well as the clinical status of the patients.

Maternal Psychological Control, Maternal Borderline Personality Disorder, and Adolescent Borderline Features.

PubMed

Mahan, Rebecca M; Kors, Stephanie B; Simmons, Meredith L; Macfie, Jenny

2017-12-14

Linehan (1993) theorized that the experience of invalidating parenting interacts with emotional vulnerability in the development of borderline personality disorder (BPD). Parental psychological control is a type of invalidating parenting, defined as manipulation by parents of their offspring's psychological and emotional expression and experience (Barber, 1996). In a normative sample of adolescent females, adolescent-reported maternal psychological control was related to maternal borderline symptoms (Zalewski et al., 2014). The current study expanded on these findings to sample mothers with a diagnosis of BPD (n = 28) and normative comparisons (n = 28) with male and female adolescents aged 14-18. We assessed maternal and adolescent self-reported borderline features (affective instability, negative relationships, identity disturbance, and self-harm) and coded maternal psychological control from filmed problem-solving interactions. Controlling for current major depressive disorder and family income, mothers with BPD used more total psychological control with their adolescents in comparison with normative mothers. Further, maternal psychological control was positively associated with all mothers' borderline features and with adolescent affective instability. Finally, we found a significant indirect effect for maternal affective instability between maternal total psychological control and adolescent affective instability. We discuss adolescents' risk of developing BPD themselves and prevention and treatment implications. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The Families of Borderline Patients

PubMed Central

2009-01-01

We examine the families of patients with borderline personality disorder. According to existing data, the family members of individuals with borderline personality disorder have higher-than-expected levels of psychopathology, particularly with regard to mood, impulse, substance use, and Axis II disorders. Likewise, in the empirical literature, patients with borderline personality disorder seem to consistently portray parents in a very negative light. Collectively, this information suggests that there may be considerable levels of psychopathology in the families of patients with borderline personality disorder. In terms of family treatment, there is very little available information. Reported strategies seem to focus on psychoeducation, in addition to skills training and problem solving, and there are a number of educational resources for families on the web. Overall, this area is clearly in need of further research. PMID:19724744

Biometric characteristics of eyes with central serous chorioretinopathy.

PubMed

Oh, Jong-Hyun; Oh, Jaeryung; Togloom, Ariunaa; Kim, Seong-Woo; Huh, Kuhl

2014-03-13

To investigate the biometric characteristics of eyes with idiopathic central serous chorioretinopathy (CSC). Medical records of 52 consecutive patients with unilateral CSC were reviewed. Central serous chorioretinopathy was diagnosed using spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography. Data collected for comparison with fellow eyes were refractive error, biometric measurements using partial coherence interferometry, and SD-OCT parameters. Mean time from subjective symptom onset to initial visit was 8.3 ± 12.29 weeks. Mean axial length (AL) was shorter in CSC eyes than in fellow eyes by 0.24 ± 0.379 mm (P < 0.001), and mean anterior chamber depth (ACD) was shallower in CSC eyes than in fellow eyes by 0.03 ± 0.088 mm (P = 0.021). Central serous chorioretinopathy eyes also had thicker subfoveal choroidal thickness (CT) than fellow eyes by 34.0 ± 45.93 μm (P < 0.001). Differences in spherical equivalents between CSC and fellow eyes correlated with AL differences (r = -0.690, P < 0.001) and CT differences (r = 0.473, P = 0.001). On multiple linear regression analysis, the differences in ACD between CSC and fellow eyes were significantly correlated with AL differences (P = 0.032) and symptom duration (P = 0.019). Biometric characteristics such as AL and ACD were different between eyes with CSC and fellow eyes. Variations in biometry, which correlated with CT differences, might be related to differences in refractive errors between eyes.

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…

Histochemical and Immunohistochemical Study of α-SMA, Collagen, and PCNA in Epithelial Ovarian Neoplasm

PubMed

Anggorowati, Nungki; Ratna Kurniasari, Chatarina; Damayanti, Karina; Cahyanti, Titik; Widodo, Irianiwati; Ghozali, Ahmad; Romi, Muhammad Mansyur; Sari, Dwi Cahyani Ratna; Arfian, Nur

2017-03-01

Background: Alpha-smooth muscle actin (α-SMA) is an isoform of actin, positive in myofibroblasts and is an epithelial to mesenchymal transition (EMT) marker. EMT is a process by which tumor cells develop to be more hostile and able to metastasize. Progression of tumor cells is always followed by cell composition and extracellular matrix component alteration. Increased α-SMA expression and collagen alteration may predict the progressivity of ovarian neoplasms. Objective: The aim of this research was to analyse the characteristic of α-SMA and collagen in tumor cells and stroma of ovarian neoplasms. In this study, PCNA (proliferating cell nuclear antigen) expression was also investigated. Methods: Thirty samples were collected including serous, mucinous, endometrioid, and clear cell subtypes. The expression of α-SMA and PCNA were calculated in cells and stroma of ovarian tumors. Collagen was detected using Sirius Red staining and presented as area fraction. Results: The overexpressions of α-SMA in tumor cells were only detected in serous and clear cell ovarian carcinoma. The histoscore of α-SMA was higher in malignant than in benign or borderline ovarian epithelial neoplasms (105.3±129.9 vs. 17.3±17.1, P=0.011; mean±SD). Oppositely, stromal α-SMA and collagen area fractions were higher in benign than in malignant tumors (27.2±6.6 vs 20.5±8.4, P=0.028; 31.0±5.6 vs. 23.7±6.4, P=0.04). The percentages of epithelial and stromal PCNA expressions were not significantly different between benign and malignant tumors. Conclusion: Tumor cells of serous and clear cell ovarian carcinoma exhibit mesenchymal characteristic as shown by α-SMA positive expression. This expression might indicate that these subtypes were more aggressive. This research showed that collagen and α-SMA area fractions in stroma were higher in benign than in malignant neoplasms. 10.22034/APJCP.2017.18.3.667

Cystic pancreatic tumors (CPT): predictors of malignant behavior.

PubMed

Javle, Milind; Shah, Pankaj; Yu, Jihnhee; Bhagat, Vishal; Litwin, Alan; Iyer, Renuka; Gibbs, John

2007-03-01

Due to widespread use of imaging studies, increasing cystic pancreatic tumor (CPT) cases are being detected. The diagnosis of malignancy in CPT cases requires pancreatectomy. Clinical and laboratory characteristics of CPT may predict underlying malignancy. CPT cases treated between 1994 and 2004 at our institution were included. Pseudocysts were excluded. Serous cystadenoma (SCA), mucinous cystadenoma (MCA), intrapapillary mucinous tumor, cystic endocrine tumor, and lymphoepithelial cysts were classified as benign or pre-malignant. Serous cystadenocarcinoma (SCACA), mucinous cystadenocarcinoma (MCACA), and adenocarcinoma (ACA) were classified as malignant. Thirty-five patients had histological confirmation. Median age was 65 years. Male/female ratio was higher in malignant group (P = 0.0284). Weight loss and abdominal mass were more prevalent in malignant group (P = 0.042 and 0.028, respectively). Malignant lesions were larger, associated with local invasion (superior mesenteric artery (SMA), superior mesenteric vein (SMV), portal vein (PV) complex or celiac encasement) and CA 19-9 elevation. On univariate analyses, local invasion (P = 0.0029), negative surgical intervention (P = 0.0010), presence of ACA (P = 0.0044), or malignant CPT (P = 0.0018) were associated with shorter survival. On a multivariate analysis, local invasion was associated with shorter survival [Hazard ratio (HR) = 4.322, P = 0.0218], while surgical intervention was associated with improved survival (HR = 0.179, P = 0.0124). Male sex, abdominal mass, weight loss, larger tumor size, local invasion, and elevated CA 19-9 were associated with malignant CPT.

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

Aspects of depression associated with borderline personality disorder.

PubMed

Rogers, J H; Widiger, T A; Krupp, A

1995-02-01

Shared symptoms between borderline personality disorder and depression have resulted in inherent difficulties in evaluating the relationship between these disorders. Some theorists have argued that depression in patients with borderline personality disorder is qualitatively distinct from depression in nonborderline patients. The purpose of this study was to empirically identify aspects of depression most associated with borderline personality disorder. Through interview and self-report measures, the authors studied depression in 50 inpatients, 21 of whom had borderline personality disorder. The aspects of depression most associated with borderline personality disorder were self-condemnation, emptiness, abandonment fears, self-destructiveness, and hopelessness; boredom and somatic complaints exhibited no association. Depression associated with borderline pathology appears to be in some respects unique, as well as distinct from nonborderline depression. The study's implications delineate the importance of considering the phenomenological aspects of depression in borderline personality disorder.

Facial emotion recognition and borderline personality pathology.

PubMed

Meehan, Kevin B; De Panfilis, Chiara; Cain, Nicole M; Antonucci, Camilla; Soliani, Antonio; Clarkin, John F; Sambataro, Fabio

2017-09-01

The impact of borderline personality pathology on facial emotion recognition has been in dispute; with impaired, comparable, and enhanced accuracy found in high borderline personality groups. Discrepancies are likely driven by variations in facial emotion recognition tasks across studies (stimuli type/intensity) and heterogeneity in borderline personality pathology. This study evaluates facial emotion recognition for neutral and negative emotions (fear/sadness/disgust/anger) presented at varying intensities. Effortful control was evaluated as a moderator of facial emotion recognition in borderline personality. Non-clinical multicultural undergraduates (n = 132) completed a morphed facial emotion recognition task of neutral and negative emotional expressions across different intensities (100% Neutral; 25%/50%/75% Emotion) and self-reported borderline personality features and effortful control. Greater borderline personality features related to decreased accuracy in detecting neutral faces, but increased accuracy in detecting negative emotion faces, particularly at low-intensity thresholds. This pattern was moderated by effortful control; for individuals with low but not high effortful control, greater borderline personality features related to misattributions of emotion to neutral expressions, and enhanced detection of low-intensity emotional expressions. Individuals with high borderline personality features may therefore exhibit a bias toward detecting negative emotions that are not or barely present; however, good self-regulatory skills may protect against this potential social-cognitive vulnerability. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

[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.

BILATERAL SEROUS MACULAR DETACHMENT IN A PATIENT WITH NEPHROTIC SYNDROME.

PubMed

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

2018-01-01

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

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

Neurochemical alterations associated with borderline personality disorder.

PubMed

Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi

2015-01-01

In neuroimaging on borderline personality disorder, prior studies focused on the hippocampus and amygdala, as mentioned above. However, no study investigated whether there were neurochemical changes in the patients with borderline personality disorder. Therefore, in the present study, we aimed to investigate neurochemical change of patients diagnosed with borderline disorder and hypothesized that neurochemicals would change in the hippocampus region of these patients. Seventeen patients and the same number of healthy control subjects were analyzed by using a 1.5 Tesla GE Signa Imaging System. N-acetylaspartate (NAA), choline compounds (CHO), and creatine (CRE) values of hippocampal region were measured. The mean NAA/CRE ratio in the hippocampus region was significantly reduced in the patients with borderline personality disorder compared to that of healthy control subjects, In addition, NAA/CHO ratio of the patients with borderline personality disorder was also significantly reduced when compared to that of healthy subjects. There was no difference in the ratio of CHO/CRE. In summary, we present evidence for reduced NAA in the patients with borderline personality disorder. © 2015, The Author(s).

CPTAC Releases Largest-Ever Ovarian Cancer Proteome Dataset from Previously Genome Characterized Tumors | Office of Cancer Clinical Proteomics Research

Cancer.gov

National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) scientists have just released a comprehensive dataset of the proteomic analysis of high grade serous ovarian tumor samples, previously genomically analyzed by The Cancer Genome Atlas (TCGA).  This is one of the largest public datasets covering the proteome, phosphoproteome and glycoproteome with complementary deep genomic sequencing data on the same tumor.

A Mouse Model to Investigate Postmenopausal Biology as an Etiology of Ovarian Cancer Risk

DTIC Science & Technology

2007-11-01

1 mucinous adenocarcinomas 3 clear-cell carcinomas 1 malignant mixed mesodermal tumor 3 metastatic ovarian carcinomas 5 undifferentiated carcinomas 2...serous LMP tumors 2 mucinous LMP tumors 1 benign serous cystadenoma Ovarian tumor blocks 38 18 serous adenocarcinomas 5 mucinous adenocarcinomas 2...endometrioid adenocarcinomas 3 clear cell carcinomas 6 serous LMP 3 mucinous LMP 1 benign fibrous cystadenoma MMPs IN EARLY OVARIAN CANCER DEVELOPMENT

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

PubMed

Liu, Changmei; Yang, Fangmei

2015-09-01

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

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

PubMed

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

to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC). The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test. The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (p<0.01); when comparing the same patient groups, that of SCO was 3.4 times higher (p<0.05). The immunohistochemical characteristics of the investigated lesions (in scores) were as follows: PAX2 was expressed in the intact epithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), β-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (p<0.05) for: 1) PAX2 between the intact epithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO

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

PubMed

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

2017-05-01

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

Central serous chorioretinopathy due to tadalafil use.

PubMed

Türkcü, Fatih Mehmet; Yüksel, Harun; Şahin, Alparslan; Murat, Mehmet; Bozkurt, Yaşar; Çaça, Ihsan

2013-04-01

Phosphodiesterase-5 (PDE5) inhibitors are commonly used in the treatment of erectile dysfunction. There are a small number of case reports that associate this agent with central serous chorioretinopathy (CSCR). Our report presents the treatment approach to a 42-year-old patient who described blurred vision and metamorphopsia and was diagnosed with CSCR following the use of tadalafil, a PDE5 inhibitor.

BENIGN TUMORS AND TUMOR-LIKE LESIONS OF THE PANCREAS

PubMed Central

Basturk, Olca; Askan, Gokce

2017-01-01

Synopsis The pancreas is a complex organ that may give rise to large number of neoplasms and non-neoplastic lesions. This article will focus on benign neoplasms such as serous neoplasms as well as tumor-like (pseudotumoral) lesions that may be mistaken for neoplasm not only by clinicians and radiologists, but also by pathologists. The family of pancreatic pseudotumors, by a loosely defined conception of that term, includes a variety of lesions including heterotopia, hamartoma, and lipomatous pseudohypertrophy. Autoimmue pancreatitis (covered in chronic pancreatitis chapter) and paraduodenal (“groove”) pancreatitis may also lead to pseudotumor formation. Knowledge of these entities will help in making an accurate diagnosis. PMID:27926363

Ultrasonographic markers and preoperative CA-125 to distinguish between borderline ovarian tumors and stage I ovarian cancer.

PubMed

Zacharakis, Dimitrios; Thomakos, Nikolaos; Biliatis, Ioannis; Rodolakis, Alexandros; Simou, Maria; Daskalakis, Georgios; Bamias, Aris; Antsaklis, Aris

2013-03-01

Preoperative evaluation of ovarian masses has become increasingly important for optimal planning of treatment. The aim of this study was to assess the role of preoperative serum cancer antigen 125 (CA-125) levels in correlation with ultrasonographic features in order to distinguish between borderline ovarian tumors (BOTs) and stage I epithelial ovarian carcinoma (EOC). Retrospective study. Tertiary University Hospital. We reviewed all women with BOTs and stage I EOC from January 2000 to December 2010. Data from 165 women (66 BOTs and 99 stage I EOC) were analyzed. Multivariable logistic regression with stepwise selection of variables was used to determine which clinical variables, ultrasound features and CA-125 level were independently associated with invasiveness. Utility of ultrasonographic markers and CA-125 in the preoperative differential diagnosis between BOTs and stage I EOC. Women with CA-125 > 100 IU mL(-1) had almost three times greater likelihood of belonging in the EOC group [odds ratio (OR) 3.02; confidence interval (CI) 95%: 1.13-8.12]. Furthermore, the presence of large solid component (≥20% of the tumor comprised of solid components) was associated with 4.25 times greater odds of it to representing ovarian cancer rather than a BOT (OR 4.25; 95% CI: 2.05-8.82). In contrast, the presence of papillary projections was associated with a 73% lower likelihood of EOC (OR 0.27; 95% CI: 0.13-0.58). Preoperative CA-125 > 100 IU mL(-1) combined with the presence of a large solid component and the absence of papillary projections seems to improve the discriminative ability in favor of stage I EOC. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Affective Disorders among Patients with Borderline Personality Disorder

PubMed Central

Sjåstad, Hege Nordem; Gråwe, Rolf W.; Egeland, Jens

2012-01-01

Background The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. Methods In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. Results More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. Conclusions The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar

Borderline Personality and Externalized Aggression

PubMed Central

Sansone, Lori A.

2012-01-01

Individuals with borderline personality disorder are diagnostically and clinically characterized by self-harm behavior, as indicated by the criterion in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, “recurrent suicidal behavior, gestures, or threats, or self-mutilating behavior.” However, individuals with borderline personality disorder can display externalized aggressive behavior, as well. In an area characterized by considerably less research, empirical evidence indicates that individuals with borderline personality disorder may exhibit physical violence toward partners, physical violence toward known but nonintimate individuals, criminal behaviors that embody externalized violence (e.g., property damage), and, on very rare occasion, murderous behavior (either of family members or anonymous others through serial killing). Given this under-researched area, there are probably other types of externalized aggressive behaviors that have not been empirically revealed. However, externalized aggressive behaviors in individuals with borderline personality disorder clearly exist and need to be assessed in both psychiatric and primary care settings in an effort to promote safety of medical personnel and effective patient management. PMID:22567607

Emotional Hypochondriasis, Hyperbole, and the Borderline Patient

PubMed Central

ZANARINI, MARY C.; FRANKENBURG, FRANCES R.

1994-01-01

The authors define a new defense mechanism, emotional hypochondriasis, that is hypothesized to be central to borderline psychopathology. The behavioral manifestation of this defense—the hyperbolic stance of the borderline patient—is also defined and related to the complex phenomenology of borderline personality disorder. Borderline patients are seen as making an active attempt to maintain a tolerable, if tenuous, adaptation in the face of tremendous subjective emotional pain that has been shaped in large measure by traumatic childhood events that have never been validated. Twelve treatment implications and three expectable, if overlapping, stages of treatment stemming from the use of this defense and its behavioral sequelae are detailed. PMID:22700171

ALK-FISH borderline cases in non-small cell lung cancer: Implications for diagnostics and clinical decision making.

PubMed

von Laffert, Maximilian; Stenzinger, Albrecht; Hummel, Michael; Weichert, Wilko; Lenze, Dido; Warth, Arne; Penzel, Roland; Herbst, Hermann; Kellner, Udo; Jurmeister, Philipp; Schirmacher, Peter; Dietel, Manfred; Klauschen, Frederick

2015-12-01

Fluorescence in-situ hybridization (FISH) for the detection of ALK-rearrangements in non-small cell lung cancer (NSCLC) is based on at first sight clear cut-off criteria (≥15% of tumor cells) for split signals (SS) and single red signals (SRS). However, NSCLC with SS-counts around the cut-off may cause interpretation problems. Tissue microarrays containing 753 surgically resected NSCLCs were independently tested for ALK-alterations by FISH and immunohistochemistry (IHC). Our analysis focused on samples with SS/SRS in the range between 10% and 20% (ALK-FISH borderline group). To better understand the role of these samples in routine diagnostics, we performed statistical analyses to systematically estimate the probability of ALK-FISH-misclassification (false negative or positive) for different numbers of evaluated tumor cell nuclei (30, 50, 100, and 200). 94.3% (710/753) of the cases were classified as unequivocally (<10% or ≥20%) ALK-FISH-negative (93%; 700/753) or positive (1.3%; 10/753) and showed concordant IHC results. 5.7% (43/753) of the samples showed SS/SRS between 10% and 20% of the tumor cells. Out of these, 7% (3/43; ALK-FISH: 14%, 18% and 20%) were positive by ALK-IHC, while 93% (40/43) had no detectable expression of the ALK-protein. Statistical analysis showed that ALK-FISH misclassifications occur frequently for samples with rearrangements between 10% and 20% if ALK-characterization is based on a sharp cut-off point (15%). If results in this interval are defined as equivocal (borderline), statistical sampling-related ALK-FISH misclassifications will occur in less than 1% of the cases if 100 tumor cells are evaluated. While ALK status can be determined robustly for the majority of NSCLC by FISH our analysis showed that ∼6% of the cases belong to a borderline group for which ALK-FISH evaluation has only limited reliability due to statistical sampling effects. These cases should be considered equivocal and therapy decisions should include

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

PubMed

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

2006-05-01

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

Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors.

PubMed

Larson, Allison R; Dresser, Karen A; Zhan, Qian; Lezcano, Cecilia; Woda, Bruce A; Yosufi, Benafsha; Thompson, John F; Scolyer, Richard A; Mihm, Martin C; Shi, Yujiang G; Murphy, George F; Lian, Christine Guo

2014-07-01

DNA methylation is the most well-studied epigenetic modification in cancer biology. 5-hydroxymethylcytosine is an epigenetic mark that can be converted from 5-methylcytosine by the ten-eleven translocation gene family. We recently reported the loss of 5-hydroxymethylcytosine in melanoma compared with benign nevi and suggested that loss of this epigenetic marker is correlated with tumor virulence based on its association with a worse prognosis. In this study, we further characterize the immunoreactivity patterns of 5-hydroxymethylcytosine in the full spectrum of melanocytic lesions to further validate the potential practical application of this epigenetic marker. One hundred and seventy-five cases were evaluated: 18 benign nevi, 20 dysplastic nevi (10 low-grade and 10 high-grade lesions), 10 atypical Spitz nevi, 20 borderline tumors, 5 melanomas arising within nevi, and 102 primary melanomas. Progressive loss of 5-hydroxymethylcytosine from benign dermal nevi to high-grade dysplastic nevi to borderline melanocytic neoplasms to melanoma was observed. In addition, an analysis of the relationship of nuclear diameter with 5-hydroxymethylcytosine staining intensity within lesional cells revealed a significant correlation between larger nuclear diameter and decreased levels of 5-hydroxymethylcytosine. Furthermore, borderline lesions uniquely exhibited a diverse spectrum of staining of each individual case. This study further substantiates the association of 5-hydroxymethylcytosine loss with dysplastic cytomorphologic features and tumor progression and supports the classification of borderline lesions as a biologically distinct category of melanocytic lesions.

Loss of 5-hydroxymethylcytosine correlates with increasing morphologic dysplasia in melanocytic tumors

PubMed Central

Larson, Allison R.; Dresser, Karen; Zhan, Qian; Lezcano, Cecilia; Woda, Bruce A.; Yosufi, Benafsha; Thompson, John F.; Scolyer, Richard A.; Mihm, Martin C.; Shi, Yujiang G.; Murphy, George F.; Lian, Christine Guo

2013-01-01

DNA methylation is the most well studied epigenetic modification in cancer biology. 5-hydroxymethylcytosine is an epigenetic mark that can be converted from 5-methylcytosine by the ten-eleven translocation gene family. We recently reported the loss of 5-hydroxymethylcytosine in melanoma compared to benign nevi and suggested that loss of this epigenetic marker is correlated with tumor virulence based on its association with a worse prognosis. In this study we further characterize the immunoreactivity patterns of 5-hydroxymethylcytosine in the full spectrum of melanocytic lesions to further validate the potential practical application of this epigenetic marker. 175 cases were evaluated: 18 benign nevi, 20 dysplastic nevi (10 low-grade and 10 high-grade lesions), 10 atypical Spitz nevi, 20 borderline tumors, 5 melanomas arising within nevi, and 102 primary melanomas. Progressive loss of 5-hydroxymethylcytosine from benign dermal nevi to high-grade dysplastic nevi to borderline melanocytic neoplasms to melanoma was observed. In addition, an analysis of the relationship of nuclear diameter to 5-hydroxymethylcytosine staining intensity within lesional cells revealed a significant correlation between larger nuclear diameter and decreased levels of 5-hydroxymethylcytosine. Furthermore, borderline lesions uniquely exhibited a diverse spectrum of staining of each individual case. This study further substantiates the association of 5-hydroxymethylcytosine loss with dysplastic cytomorphologic features and tumor progression and supports the classification of borderline lesions as a biologically distinct category of melanocytic lesions. PMID:24390216

Clinical Impact of Detectable Antithyroglobulin Antibodies Below the Reference Limit (Borderline) in Patients with Papillary Thyroid Carcinoma with Undetectable Serum Thyroglobulin and Normal Neck Ultrasonography After Ablation: A Prospective Study.

PubMed

Côrtes, Marina Carvalho Souza; Rosario, Pedro Weslley; Oliveira, Luís Fernando Faria; Calsolari, Maria Regina

2018-02-01

Interference of antithyroglobulin antibodies (TgAb) with serum thyroglobulin (Tg) can occur even at detectable TgAb concentrations below the reference limit (borderline TgAb). Thus, borderline TgAb is considered as TgAb positivity in patients with thyroid cancer. This prospective study evaluated patients with papillary thyroid carcinoma with undetectable Tg and normal neck ultrasonography (US) after total thyroidectomy and ablation with 131 I, and compared tumor persistence/recurrence and long-term Tg and TgAb behavior in those with borderline versus undetectable TgAb. A total of 576 patients were evaluated, divided into two groups: group A with undetectable TgAb (n = 420), and group B with borderline TgAb (n = 156). Groups A and B were similar in terms of patient and tumor characteristics. The time of follow-up ranged from 24 to 120 months. During follow-up, 11 (2.6%) patients in group A and 5 (3.2%) in group B developed a recurrence (p = 0.77). In group A, recurrences occurred in 9/390 patients who continued to have undetectable TgAb and in 1/9 patients who progressed to borderline TgAb. In group B, recurrences were detected in 1/84 patients who progressed to have undetectable TgAb, in 1/45 who still had borderline TgAb, and in 3/12 who developed elevated TgAb. In the presence of Tg levels <0.2 ng/mL, recurrences were detected in 2/486 patients with undetectable TgAb, in 0/67 with borderline TgAb, and in 3/12 with elevated TgAb. The results of post-therapy whole-body scanning (RxWBS) of 216 patients with Tg ≤0.2 ng/mL and normal US at the time of ablation were also analyzed. In low-risk patients, none of the 40 patients with borderline TgAb and none of the 94 with undetectable TgAb exhibited ectopic uptake on RxWBS. In intermediate-risk patients, lymph node metastases were detected by RxWBS in 1/25 (4%) with borderline TgAb and in 2/57 (3.5%) with undetectable TgAb. The results suggest that among low- or intermediate-risk patients with

Finasteride for Chronic Central Serous Chorioretinopathy

PubMed Central

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

2010-01-01

Purpose To evaluate the safety and efficacy of finasteride, an inhibitor of dihyroxytestosterone (DHT) synthesis, in the treatment of chronic central serous chorioretinopathy (CSC). Methods Five patients with chronic CSC were prospectively enrolled in this pilot study. Patients were administered finasteride (5mg) daily for 3 months, following which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity (BCVA), center-subfield macular thickness and subretinal fluid volume as assessed by optical coherence tomography (OCT). Serum DHT, serum testosterone, and urinary cortisol were also measured. Results There was no change in mean BCVA. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months, and rose to levels that were below baseline by 6 months. The changes in both OCT parameters paralleled changes in serum DHT level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased following discontinuation of finasteride. In the remaining patient, both OCT parameters normalized with finasteride and remained stable when the study medication was discontinued. Conclusion Finasteride may represent a novel medical treatment for chronic CSC. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of CSC. Summary Pilot study to evaluate finasteride for treatment of chronic central serous chorioretinopathy suggests efficacy and tolerability. PMID:21273946

Evolution of platinum resistance in high-grade serous ovarian cancer.

PubMed

Cooke, Susanna L; Brenton, James D

2011-11-01

High-grade serous ovarian cancers account for most ovarian-cancer mortality. Although this disease initially responds well to platinum-based chemotherapy, relapse and progression to chemotherapy resistance are frequently seen. Time to relapse after first-line therapy is a predictor of response to secondary platinum treatment: more than 12 months is associated with high chance of a secondary response, whereas relapses within 6 months generally indicate platinum resistance. In this Personal View we discuss whether patterns of response, relapse, and the development of drug resistance in high-grade serous ovarian cancers are related to distinct underlying molecular and cellular biological characteristics. In particular, we propose that rapid relapse with platinum-resistant disease is due to minor subpopulations of intrinsically resistant cancer cells at presentation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Utility of DWI with quantitative ADC values in ovarian tumors: a meta-analysis of diagnostic test performance.

PubMed

Pi, Shan; Cao, Rong; Qiang, Jin Wei; Guo, Yan Hui

2018-01-01

Background Diffusion-weighted imaging (DWI) and quantitative apparent diffusion coefficient (ADC) values are widely used in the differential diagnosis of ovarian tumors. Purpose To assess the diagnostic performance of quantitative ADC values in ovarian tumors. Material and Methods PubMed, Embase, the Cochrane Library, and local databases were searched for studies assessing ovarian tumors using quantitative ADC values. We quantitatively analyzed the diagnostic performances for two clinical problems: benign vs. malignant tumors and borderline vs. malignant tumors. We evaluated diagnostic performances by the pooled sensitivity and specificity values and by summary receiver operating characteristic (SROC) curves. Subgroup analyses were used to analyze study heterogeneity. Results From the 742 studies identified in the search results, 16 studies met our inclusion criteria. A total of ten studies evaluated malignant vs. benign ovarian tumors and six studies assessed malignant vs. borderline ovarian tumors. Regarding the diagnostic accuracy of quantitative ADC values for distinguishing between malignant and benign ovarian tumors, the pooled sensitivity and specificity values were 0.91 and 0.91, respectively. The area under the SROC curve (AUC) was 0.96. For differentiating borderline from malignant tumors, the pooled sensitivity and specificity values were 0.89 and 0.79, and the AUC was 0.91. The methodological quality of the included studies was moderate. Conclusion Quantitative ADC values could serve as useful preoperative markers for predicting the nature of ovarian tumors. Nevertheless, prospective trials focused on standardized imaging parameters are needed to evaluate the clinical value of quantitative ADC values in ovarian tumors.

Unblending Borderline Personality and Bipolar Disorders.

PubMed

di Giacomo, Ester; Aspesi, Flora; Fotiadou, Maria; Arntz, Arnoud; Aguglia, Eugenio; Barone, Lavinia; Bellino, Silvio; Carpiniello, Bernardo; Colmegna, Fabrizia; Lazzari, Marina; Lorettu, Liliana; Pinna, Federica; Sicaro, Aldo; Signorelli, Maria Salvina; Clerici, Massimo

2017-08-01

Borderline Personality (BPD) and Bipolar (BP) disorders stimulate an academic debate between their distinction and the inclusion of Borderline in the Bipolar spectrum. Opponents to this inclusion attribute the important differences and possible diagnostic incomprehension to overlapping symptoms. We tested 248 Borderline and 113 Bipolar patients, consecutively admitted to the Psychiatric Unit, through DSM-IV Axis I and II Disorders (SCID-I/II), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS) and Borderline Personality Disorder Severity Index-IV (BPDSI-IV). All the tests statistically discriminated the disorders (p < 0.0001). Overlapping symptoms resulted significantly different (impulsivity = 5.32 in BPD vs 1.55 in BP, p < 0.0001; emotional instability = 7.11 in BPD vs 0.55 in BP, p < 0.0001) and the range of their scores gives the opportunity for an even more precise discrimination. Distinctive traits (e.g. irritability or sexual arousal) are also discussed in order to try to qualify the core of these disorders to a higher degree. Comorbidity proves to be extremely small (3.6%). However, Borderline patients with manic features offer a privileged point of view for a deeper analysis. This allows for the possibility of a more precise examination of the nature and load of each symptom. Borderline Personality and Bipolar Disorders can be distinguished with high precision using common and time-sparing tests. The importance of discriminating these clinical features may benefit from this evidence. Copyright © 2017. Published by Elsevier Ltd.

Features of central serous chorioretinopathy presenting at a tertiary care hospital in Lahore.

PubMed

Jamil, Ahmad Zeeshan; Mirza, Khurram Azam; Qazi, Zaheer Uddin Aqil; Iqbal, Wasim; Khaliq, Javed; Fawad-ur-Rahman; Ahmed, Arslan

2013-04-01

To evaluate the clinical, angiographic and optical coherence tomographic features of central serous chorioretinopathy in patients presenting at a tertiary care centre in Lahore. The observational study was conducted at the Layton Rehmatulla Benevolent Trust Eye and Cancer Hospital Lahore from July 15, 2010 to December 15, 2011. Patients who had received prior treatment for the condition and allergy to fluorescein were excluded. There were 86 eyes of 64 adult patients with central serous chorioretinopathy. The following data was recorded: history, signs and symptoms, best corrected visual acuity, fundus fluorescein angiography, and central macular thickness measurement with optical coherence tomography. Data was analyzed using SPSS 17. Mean age of patients who presented during the study duration was 39.52 +/- 8.85 years.There were 53 (82.8%) males and 11(17.2%) females. Of the total, 42 (65.6%) cases had unilateral and 22 (34.4%) cases had bilateral involvement. Chronic central serous chorioretinopathy was seen in 27 (42.2%) cases while 37 (57.8%) cases were acute presentations. Retinal pigment epithelial detachment was observed in 29 (45.3%) cases. On fundus fluorescein angiography, there were 62 (72.1%) eyes that showed ink blot pattern. Median visual acuity at presentation was 0.25. Median central macular thickness at presentation was 550.5micro. Central serous chorioretinopathy in the study sample was associated with pigment epithelial detachment, bilateral involvement, and presence of systemic diseases.

The prevalence of borderline personality symptoms in adolescents.

PubMed

Mohammadi, Mohammad Reza; Shamohammadi, Morteza; Salmanian, Maryam

2014-07-01

This study aimed to assess the prevalence of borderline personality symptoms in 16-18 year old adolescents. In this cross sectional - descriptive study, 422 high school students (211 boys, 211 girls) aged 16-18 were selected by cluster random sampling and simple random sampling in 2011-2012. The participants were assessed using the revised diagnostic interview for borderline questionnaire (DIB-R) and demographic questionnaire. Data were analyzed using Pearson correlation coefficient and Spearman correlation coefficient. Of the participants, 0/9% (0/22 % of the 16 year olds, 0.45 % of the 17 year olds and 0/22% of the 18 year olds) were diagnosed with borderline personality symptoms. Also, the prevalence of borderline personality symptoms in boys was 0/45 % of the total sample and it was 0/45 % of the total sample in girls. With respect to the relationship between demographic variables (age, sex, location, parents' occupation, parents' kinship, parents' education and birth order) and borderline personality symptoms, only parents' kinship showed a weak correlation with borderline personality symptoms. In the view of the prevalence of 0.9% of the borderline personality symptoms in adolescents, attention should be paid to the diagnosis and treatment of this disorder. Furthermore, works need to be done to improve the mental health and quality of life of adolescents.

Adverse perinatal outcomes in borderline amniotic fluid index.

PubMed

Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh

2016-11-01

Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10 th percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10 th percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI.

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…

High-risk borderline ovarian tumors: analysis of clinicopathological features and prognostic impact of different follow-up strategies.

PubMed

Lorusso, Domenica; Ratti, Martina; Ditto, Antonino; Raspagliesi, Francesco

2014-01-01

Borderline ovarian tumors (BOTs) represent 10-20% of all epithelial ovarian malignancies. Most of them are comparable to benign cysts but a high-risk group has been recognized. The aim of the study was to analyze different follow-up strategies in high-risk patients. Patients with BOT treated at our institution from 1992 to 2011 were retrospectively reviewed. Clinicopathological features influencing prognosis were analyzed and two different follow-up strategies compared [6-month laparoscopic look (LPS-look): group A vs. ultrasound/CA-125 evaluation: group B]. 70 patients with high-risk BOTs were identified. After a median progression-free survival (PFS) of 43 months, 27% of patients experienced recurrences. Six months after diagnosis, 26 high-risk patients were submitted to LPS-look: at surgery, 6 out of 10 patients presenting evidence of disease were optimally debulked while in the remaining 4, only biopsies were performed. No difference in PFS was registered between group A and B patients, nevertheless a significant increase in PFS was registered among completely versus incompletely debulked patients with evidence of disease at laparoscopy. Clinical follow-up remains the gold standard for BOTs. These very preliminary data seem to suggest that LPS-look may have an impact on the secondary PFS in a subgroup of high-risk patients. © 2014 S. Karger AG, Basel.

Proteomic Analysis of Matched Formalin-Fixed, Paraffin-Embedded Specimens in Patients with Advanced Serous Ovarian Carcinoma

PubMed Central

Smith, Ashlee L.; Sun, Mai; Bhargava, Rohit; Stewart, Nicolas A.; Flint, Melanie S.; Bigbee, William L.; Krivak, Thomas C.; Strange, Mary A.; Cooper, Kristine L.; Zorn, Kristin K.

2013-01-01

Objective: The biology of high grade serous ovarian carcinoma (HGSOC) is poorly understood. Little has been reported on intratumoral homogeneity or heterogeneity of primary HGSOC tumors and their metastases. We evaluated the global protein expression profiles of paired primary and metastatic HGSOC from formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: After IRB approval, six patients with advanced HGSOC were identified with tumor in both ovaries at initial surgery. Laser capture microdissection (LCM) was used to extract tumor for protein digestion. Peptides were extracted and analyzed by reversed-phase liquid chromatography coupled to a linear ion trap mass spectrometer. Tandem mass spectra were searched against the UniProt human protein database. Differences in protein abundance between samples were assessed and analyzed by Ingenuity Pathway Analysis software. Immunohistochemistry (IHC) for select proteins from the original and an additional validation set of five patients was performed. Results: Unsupervised clustering of the abundance profiles placed the paired specimens adjacent to each other. IHC H-score analysis of the validation set revealed a strong correlation between paired samples for all proteins. For the similarly expressed proteins, the estimated correlation coefficients in two of three experimental samples and all validation samples were statistically significant (p < 0.05). The estimated correlation coefficients in the experimental sample proteins classified as differentially expressed were not statistically significant. Conclusion: A global proteomic screen of primary HGSOC tumors and their metastatic lesions identifies tumoral homogeneity and heterogeneity and provides preliminary insight into these protein profiles and the cellular pathways they constitute. PMID:28250404

Granular cutaneous glands in the frog Physalaemus biligonigerus (Anura, Leptodactylidae): comparison between ordinary serous and 'inguinal' glands.

PubMed

Delfino, G; Brizzi, R; Alvarez, B B; Gentili, M

1999-12-01

Beside the ordinary granular (or serous) glands, the skin of the leptodactylid frog Physalaemus biligonigerus possesses peculiar clusters of large granular units, the 'inguinal' glands, located in the dorsolateral areas of the pelvic girdle. Both gland types store their specific products within the syncytial cytoplasm of the secretory unit. These secretory materials consist of spheroidal or ellipsoidal bodies (granules) with a repeating substructure. The subcellular features of the immature products of the ordinary serous and inguinal glands are identical. However, these products undergo divergent maturative processes, leading to fluidation on the one hand and condensation on the other. Secretory release into the small gland lumen was observed in both cases, involving merocrine mechanisms. On the basis of the analysis of cutaneous serous gland polymorphism in anurans, the inguinal units in P. biligonigerus do not appear to be an independent line. Rather, these large units belong to the ordinary serous type and represent a gland population specialized in the storage of remarkable amounts of product used in chemical defence of the skin.

Inhibition of gamma-secretase activity impedes uterine serous carcinoma growth in a human xenograft model.

PubMed

Groeneweg, Jolijn W; Hall, Tracilyn R; Zhang, Ling; Kim, Minji; Byron, Virginia F; Tambouret, Rosemary; Sathayanrayanan, Sriram; Foster, Rosemary; Rueda, Bo R; Growdon, Whitfield B

2014-06-01

Uterine serous carcinoma (USC) represents an aggressive subtype of endometrial cancer. We sought to understand Notch pathway activity in USC and determine if pathway inhibition has anti-tumor activity. Patient USC tissue blocks were obtained and used to correlate clinical outcomes with Notch1 expression. Three established USC cell lines were treated with gamma-secretase inhibitor (GSI) in vitro. Mice harboring cell line derived or patient derived USC xenografts (PDXs) were treated with vehicle, GSI, paclitaxel and carboplatin (P/C), or combination GSI and P/C. Levels of cleaved Notch1 protein and Hes1 mRNA were determined in GSI treated samples. Statistical analysis was performed using the Wilcoxon rank sum and Kaplan-Meier methods. High nuclear Notch1 protein expression was observed in 58% of USC samples with no correlation with overall survival. GSI induced dose-dependent reductions in cell number and decreased levels of cleaved Notch1 protein and Hes1 mRNA in vitro. Treatment of mice with GSI led to decreased Hes1 mRNA expression in USC xenografts. In addition, GSI impeded tumor growth of cell line xenografts as well as UT1 USC PDXs. When GSI and P/C were combined, synergistic anti-tumor activity was observed in UT1 xenografts. Notch1 is expressed in a large subset of USC. GSI-mediated Notch pathway inhibition led to both reduced cell numbers in vitro and decreased tumor growth of USC some xenograft models. When combined with conventional chemotherapy, GSI augmented anti-tumor activity in one USC PDX line suggesting that targeting of the Notch signaling pathway is a potential therapeutic strategy for future investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Myelin Oligodendrocyte Glycoprotein-IgG-positive Recurrent Bilateral Optic Papillitis with Serous Retinal Detachment: A Case Report.

PubMed

Kon, Tomoya; Hikichi, Hiroki; Ueno, Tatsuya; Suzuki, Chieko; Nunomura, Jinichi; Kaneko, Kimihiko; Takahashi, Toshiyuki; Nakashima, Ichiro; Tomiyama, Masahiko

2018-05-18

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been detected in inflammatory demyelinating central nervous system diseases. A 30-year-old woman had blurred vision, marked optic nerve disc swelling, serous retinal detachment at the macular on optic coherence tomography, and MOG-IgG seropositivity. The patient was thought to have optic papillitis associated with MOG-IgG. Her symptoms rapidly improved after high-dose methylprednisolone therapy. We hypothesize that serous retinal detachment was secondary, arising from optic papillitis. This is the first report of the concurrence of optic papillitis with MOG-IgG and serous retinal detachment. MOG-IgG should be tested in patients with marked optic disc swelling.

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells.

PubMed

Testa, Ugo; Petrucci, Eleonora; Pasquini, Luca; Castelli, Germana; Pelosi, Elvira

2018-02-01

Four main histological subtypes of ovarian cancer exist: serous (the most frequent), endometrioid, mucinous and clear cell; in each subtype, low and high grade. The large majority of ovarian cancers are diagnosed as high-grade serous ovarian cancers (HGS-OvCas). TP53 is the most frequently mutated gene in HGS-OvCas; about 50% of these tumors displayed defective homologous recombination due to germline and somatic BRCA mutations, epigenetic inactivation of BRCA and abnormalities of DNA repair genes; somatic copy number alterations are frequent in these tumors and some of them are associated with prognosis; defective NOTCH, RAS/MEK, PI3K and FOXM1 pathway signaling is frequent. Other histological subtypes were characterized by a different mutational spectrum: LGS-OvCas have increased frequency of BRAF and RAS mutations; mucinous cancers have mutation in ARID1A , PIK3CA , PTEN , CTNNB1 and RAS . Intensive research was focused to characterize ovarian cancer stem cells, based on positivity for some markers, including CD133, CD44, CD117, CD24, EpCAM, LY6A, ALDH1. Ovarian cancer cells have an intrinsic plasticity, thus explaining that in a single tumor more than one cell subpopulation, may exhibit tumor-initiating capacity. The improvements in our understanding of the molecular and cellular basis of ovarian cancers should lead to more efficacious treatments.

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

PubMed Central

Castelli, Germana; Pelosi, Elvira

2018-01-01

Four main histological subtypes of ovarian cancer exist: serous (the most frequent), endometrioid, mucinous and clear cell; in each subtype, low and high grade. The large majority of ovarian cancers are diagnosed as high-grade serous ovarian cancers (HGS-OvCas). TP53 is the most frequently mutated gene in HGS-OvCas; about 50% of these tumors displayed defective homologous recombination due to germline and somatic BRCA mutations, epigenetic inactivation of BRCA and abnormalities of DNA repair genes; somatic copy number alterations are frequent in these tumors and some of them are associated with prognosis; defective NOTCH, RAS/MEK, PI3K and FOXM1 pathway signaling is frequent. Other histological subtypes were characterized by a different mutational spectrum: LGS-OvCas have increased frequency of BRAF and RAS mutations; mucinous cancers have mutation in ARID1A, PIK3CA, PTEN, CTNNB1 and RAS. Intensive research was focused to characterize ovarian cancer stem cells, based on positivity for some markers, including CD133, CD44, CD117, CD24, EpCAM, LY6A, ALDH1. Ovarian cancer cells have an intrinsic plasticity, thus explaining that in a single tumor more than one cell subpopulation, may exhibit tumor-initiating capacity. The improvements in our understanding of the molecular and cellular basis of ovarian cancers should lead to more efficacious treatments. PMID:29389895

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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

GRAFT-VERSUS-HOST DISEASE PANUVEITIS AND BILATERAL SEROUS DETACHMENTS: MULTIMODAL IMAGING ANALYSIS.

PubMed

Jung, Jesse J; Chen, Michael H; Rofagha, Soraya; Lee, Scott S

2017-01-01

To report the multimodal imaging findings and follow-up of a case of graft-versus-host disease-induced bilateral panuveitis and serous retinal detachments after allogenic bone marrow transplant for acute myeloid leukemia. A 75-year-old black man presented with acute decreased vision in both eyes for 1 week. Clinical examination and multimodal imaging, including spectral domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and swept-source optical coherence tomography angiography (Investigational Device; Carl Zeiss Meditec Inc) were performed. Clinical examination of the patient revealed anterior and posterior inflammation and bilateral serous retinal detachments. Ultra-widefield fundus autofluorescence demonstrated hyperautofluorescence secondary to subretinal fluid; and fluorescein angiography revealed multiple areas of punctate hyperfluorescence, leakage, and staining of the optic discs. Spectral domain and enhanced depth imaging optical coherence tomography demonstrated subretinal fluid, a thickened, undulating retinal pigment epithelium layer, and a thickened choroid in both eyes. En-face swept-source optical coherence tomography angiography did not show any retinal vascular abnormalities but did demonstrate patchy areas of decreased choriocapillaris flow. An extensive systemic infectious and malignancy workup was negative and the patient was treated with high-dose oral prednisone immunosuppression. Subsequent 6-month follow-up demonstrated complete resolution of the inflammation and bilateral serous detachments after completion of the prednisone taper over a 3-month period. Graft-versus-host disease panuveitis and bilateral serous retinal detachments are rare complications of allogenic bone marrow transplant for acute myeloid leukemia and can be diagnosed with clinical and multimodal imaging analysis. This form of autoimmune inflammation may occur after the recovery of T-cell activity within the donor graft targeting the host

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

PubMed

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

2018-02-01

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

Giant serous cystadenoma arising from an accessory ovary in a morbidly obese 11-year-old girl: a case report.

PubMed

Sharatz, Steven M; Treviño, Taína A; Rodriguez, Luís; West, Jared H

2008-01-18

Ectopic ovarian tissue is an unusual entity, especially if it is an isolated finding thought to be of embryological origin. An 11-year-old, morbidly obese female presented with left flank pain, nausea, and irregular menses. Various diagnostic procedures suggested a large ovarian cyst, and surgical resection was performed. Histologically, the resected mass was not of tubal origin as suspected, but a serous cystadenoma arising from ovarian tissue. The patient's two normal, eutopic ovaries were completely uninvolved and unaffected. A tumor arising from ectopic ovarian tissue of embryological origin seems the most likely explanation. We suggest refining the descriptive nomenclature so as to more precisely characterize the various presentations of ovarian ectopia.

Borderline Personality Disorder: Ontogeny of a Diagnosis

PubMed Central

Gunderson, John G.

2011-01-01

Objective The purpose of this article is to describe the development of the borderline personality disorder diagnosis, highlighting both the obstacles encountered and the associated achievements. Method On the basis of a review of the literature, the author provides a chronological account of the borderline construct in psychiatry, summarizing progress in decade-long intervals. Results Borderline personality disorder has moved from being a psychoanalytic colloquialism for untreatable neurotics to becoming a valid diagnosis with significant heritability and with specific and effective psychotherapeutic treatments. Nonetheless, patients with this disorder pose a major public health problem while they themselves remain highly stigmatized and largely neglected. Conclusions Despite remarkable changes in our knowledge about borderline personality disorder, increased awareness involving much more education and research is still needed. Psychiatric institutions, professional organizations, public policies, and reimbursement agencies need to prioritize this need. PMID:19411380

INTEGRATIVE BORDERLINE ADOLESCENT FAMILY THERAPY: MEETING THE CHALLENGES OF TREATING ADOLESCENTS WITH BORDERLINE PERSONALITY DISORDER

PubMed Central

SANTISTEBAN, DANIEL A.; MUIR, JOAN A.; MENA, MAITE P.; MITRANI, VICTORIA B.

2014-01-01

With the growing acceptance of the borderline personality disorder diagnosis for adolescents has come a need for specialized treatments for this challenging population. Further, because of the prominence of the family system during early and later adolescence, family treatments are particularly needed. The purpose of this article is to present the integrative borderline adolescent family therapy (I-BAFT) model that emerged from a National Institute on Drug Abuse–funded (Stage 1) treatment development and enhancement effort. I-BAFT integrates (a) key interventions from the family treatment of adolescent drug abuse (D. A. Santisteban et al., 2003; J. Szapocznik & W. Kurtines, 1989), (b) skills training shown effective with adults with borderline personality disorder (M. Linehan, 1993a) and adapted for adolescents, and (c) individual treatment interventions that promote motivation for treatment and enhance the integration of the 3 treatment components. PMID:25663719

Inhibition of the Receptor Tyrosine Kinase AXL Restores Paclitaxel Chemosensitivity in Uterine Serous Cancer.

PubMed

Palisoul, Marguerite L; Quinn, Jeanne M; Schepers, Emily; Hagemann, Ian S; Guo, Lei; Reger, Kelsey; Hagemann, Andrea R; McCourt, Carolyn K; Thaker, Premal H; Powell, Matthew A; Mutch, David G; Fuh, Katherine C

2017-12-01

Uterine serous cancer (USC) is aggressive, and the majority of recurrent cases are chemoresistant. Because the receptor tyrosine kinase AXL promotes invasion and metastasis of USC and is implicated in chemoresistance in other cancers, we assessed the role of AXL in paclitaxel resistance in USC, determined the mechanism of action, and sought to restore chemosensitivity by inhibiting AXL in vitro and in vivo We used short hairpin RNAs and BGB324 to knock down and inhibit AXL. We assessed sensitivity of USC cell lines to paclitaxel and measured paclitaxel intracellular accumulation in vitro in the presence or absence of AXL. We also examined the role of the epithelial-mesenchymal transition (EMT) in AXL-mediated paclitaxel resistance. Finally, we treated USC xenografts with paclitaxel, BGB324, or paclitaxel plus BGB324 and monitored tumor burden. AXL expression was higher in chemoresistant USC patient tumors and cell lines than in chemosensitive tumors and cell lines. Knockdown or inhibition of AXL increased sensitivity of USC cell lines to paclitaxel in vitro and increased cellular accumulation of paclitaxel. AXL promoted chemoresistance even in cells that underwent the EMT in vitro Finally, in vivo studies of combination treatment with BGB324 and paclitaxel showed a greater than 51% decrease in tumor volume after 2 weeks of treatment when compared with no treatment or single-agent treatments ( P < 0.001). Our results show that AXL expression mediates chemoresistance independent of EMT and prevents accumulation of paclitaxel. This study supports the continued investigation of AXL as a clinical target, particularly in chemoresistant USC. Mol Cancer Ther; 16(12); 2881-91. ©2017 AACR . ©2017 American Association for Cancer Research.

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.

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.

Clinical status of comorbid bipolar disorder and borderline personality disorder.

PubMed

Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine

2016-09-01

The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hui; Liu, Tao; Zhang, Zhen

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

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

PubMed

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

2017-01-01

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

Problematizing the concept of the "borderline" group in performance assessments.

PubMed

Homer, Matt; Pell, Godfrey; Fuller, Richard

2017-05-01

Many standard setting procedures focus on the performance of the "borderline" group, defined through expert judgments by assessors. In performance assessments such as Objective Structured Clinical Examinations (OSCEs), these judgments usually apply at the station level. Using largely descriptive approaches, we analyze the assessment profile of OSCE candidates at the end of a five year undergraduate medical degree program to investigate the consistency of the borderline group across stations. We look specifically at those candidates who are borderline in individual stations, and in the overall assessment. While the borderline group can be clearly defined at the individual station level, our key finding is that the membership of this group varies considerably across stations. These findings pose challenges for some standard setting methods, particularly the borderline group and objective borderline methods. They also suggest that institutions should ensure appropriate conjunctive rules to limit compensation in performance between stations to maximize "diagnostic accuracy". In addition, this work highlights a key benefit of sequential testing formats in OSCEs. In comparison with a traditional, single-test format, sequential models allow assessment of "borderline" candidates across a wider range of content areas with concomitant improvements in pass/fail decision-making.

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.

Treatment of borderline personality disorder and co-occurring anxiety disorders

PubMed Central

Valenstein, Helen R.

2013-01-01

Anxiety disorders are highly prevalent among individuals with borderline personality disorder, with comorbidity rates of up to 90%. Anxiety disorders have been found to reduce the likelihood of achieving remission from borderline personality disorder over time and to increase the risk of suicide and self-injury in this population. Evidence-based treatments for borderline personality disorder have not sufficiently focused on targeting anxiety disorders, and their effects on these disorders are either limited or unknown. Conversely, evidence-based treatments for anxiety disorders typically exclude suicidal, self-injuring, and seriously comorbid patients, thereby limiting their generalizability to individuals with borderline personality disorder. To address these limitations, recent research has begun to emerge focused on developing and evaluating treatments for individuals with co-occurring borderline personality disorder and anxiety disorders, specifically posttraumatic stress disorder (PTSD), with promising initial results. However, there is a need for additional research in this area, particularly studies evaluating the treatment of anxiety disorders among high-risk and complex borderline personality disorder patients. PMID:23710329

Characterizing somatization, hypochondriasis, and hysteria in the borderline personality disorder.

PubMed

Snyder, S; Pitts, W M

1986-03-01

Somatization, hypochondriasis, and hysteria have often been considered as associated features of the borderline personality disorder. This study was designed to characterize these three syndromes in the borderline patient. Inpatients with DSM-III borderline personality disorder were compared with controls with dysthymic disorder. Scales and items from standardized rating instruments which measured the three syndromes were scored and compared between groups. Although the hysteria-obvious and hypochondriasis scales of the MMPI and the Hamilton Depression Scale item measuring hypochondriasis were elevated in the borderline group, there were no significant differences between groups. Scores of dysthymic patients significantly exceeded those of borderline patients on four of five MMPI codetypes measuring the three syndromes. Findings are discussed in light of previous psychodynamic, empirical, and research literature.

Pathways to Genome-targeted Therapies in Serous Ovarian Cancer.

PubMed

Axelrod, Joshua; Delaney, Joe

2017-07-01

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

Impact of the Ovarian Microenvironment on Serous Cancer

DTIC Science & Technology

2016-10-01

Collagen is a well-established matrix utilized by serous cancer cells, of unknown origin, to seed metastatic sites, such as the mesothelium. An RNAseq...analysis will be performed between human TEC adhered to collagen matrix compared to tissue culture plastic and used to identify gene expression...changes responsible for adhesion on collagen . Ovarian conditioned medium (OCM) with and without H2O2 treatment will be added to normal and our series of

Dose-Response Relationship of CD8+ Tumor Infiltrating Lymphocytes and Survival Time in High-Grade Serous Ovarian Cancer

PubMed Central

Goode, Ellen L; Block, Matthew S; Kalli, Kimberly R; Vierkant, Robert A; Chen, Wenqian; Fogarty, Zachary C; Gentry-Maharaj, Aleksandra; Tołoczko, Aleksandra; Hein, Alexander; Bouligny, Aliecia L; Jensen, Allan; Osorio, Ana; Hartkopf, Andreas D; Ryan, Andy; Chudecka-Głaz, Anita; Magliocco, Anthony M; Hartmann, Arndt; Jung, Audrey Y; Gao, Bo; Hernandez, Brenda Y; Fridley, Brooke L; McCauley, Bryan M; Kennedy, Catherine J; Wang, Chen; Karpinskyj, Chloe; de Sousa, Christiani B; Tiezzi, Daniel G; Wachter, David L; Herpel, Esther; Taran, Florin Andrei; Modugno, Francesmary; Nelson, Gregg; Lubiński, Jan; Menkiszak, Janusz; Alsop, Jennifer; Lester, Jenny; García-Donas, Jesús; Nation, Jill; Hung, Jillian; Palacios, José; Rothstein, Joseph H; Kelley, Joseph L; de Andrade, Jurandyr M; Robles-Díaz, Luis; Intermaggio, Maria P; Widschwendter, Martin; Beckmann, Matthias W; Ruebner, Matthias; Jimenez-Linan, Mercedes; Singh, Naveena; Oszurek, Oleg; Harnett, Paul R; Rambau, Peter F; Sinn, Peter; Wagner, Philipp; Ghatage, Prafull; Sharma, Raghwa; Edwards, Robert P; Ness, Roberta B; Orsulic, Sandra; Brucker, Sara Y; Johnatty, Sharon E; Longacre, Teri A; Eilber, Ursula; McGuire, Valerie; Sieh, Weiva; Natanzon, Yanina; Li, Zheng; Whittemore, Alice S; deFazio, Anna; Staebler, Annette; Karlan, Beth Y; Gilks, Blake; Bowtell, David D; Høgdall, Estrid; Candido dos Reis, Francisco J; Steed, Helen; Campbell, Ian G; Gronwald, Jacek; Benítez, Javier; Koziak, Jennifer M; Chang-Claude, Jenny; Moysich, Kirsten B; Kelemen, Linda E; Cook, Linda S; Goodman, Marc T; García, María José; Fasching, Peter A; Kommoss, Stefan; Deen, Suha; Kjaer, Susanne K; Menon, Usha; Brenton, James D; Pharoah, Paul DP; Chenevix-Trench, Georgia; Huntsman, David G; Winham, Stacey J; Köbel, Martin; Ramus, Susan J

2017-01-01

Importance Cytotoxic CD8+ T lymphocytes (TILs) participate in immune control of ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design Prospective survival cohort. Setting Multi-center observational. Participants Over 5,500 patients, including 3,196 high-grade serous ovarian carcinomas (HGSOCs), followed prospectively for over 24,650 person-years. Exposure(s) Following immunohistochemistry, CD8+ TILs were identified within the epithelial components of tumor islets. Patients were grouped based on the estimated number of CD8+ TILs per high-powered field: negative (none), low (1–2), moderate (3–19), and high (≥20). CD8+ TILs in a subset of patients were also assessed in a quantitative, uncategorized manner, and the functional form of associations with survival was assessed using penalized B-splines. Main Outcome Measure(s) Overall survival time. Results Among the five major invasive histotypes, HGSOCs showed the most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer overall survival; median survival was 2.8 years for patients with no CD8+ TILs and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high levels of CD8+ TILs, respectively (p-trend=4.2 × 10−16). A survival benefit was also observed among women with endometrioid and mucinous carcinomas, but not the other histotypes. Among HGSOCs, CD8+ TILs were favorable regardless of extent of residual disease following cytoreduction, known standard treatment, and germline BRCA1 pathogenic mutation, but were not prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL counts showed a near linear functional form. Conclusions and Relevance This study demonstrates the histotype-specific nature of immune infiltration and provides definitive evidence for a dose-response relationship

Giant ovarian serous cystadenoma in a postmenopausal woman: a case report

PubMed Central

Babu, Sunkavalli Chinna

2009-01-01

A case of 66-year-old South Indian post menopausal woman presenting a giant ovarian serous cyst adenoma weighing 23 kg is reported here. A 66-year-old woman was referred to our clinic from a local medical center. When she was seen first at our outpatient clinic, she had gross abdominal distension since 2 years and she was unable to walk. On abdominal ultrasound, a giant cyst was found which encompassed the whole abdomen. At laparotomy, a giant, totally cystic, vascularized and smooth mass attached to the right ovary was encountered. Staging laparotomy was performed. On the postoperative tenth day, she was discharged without any problem. Her pathology report disclosed a 60×47×30 cm serous cyst adenoma weighing 23 kg. This is the largest ovarian cyst that ever reported from our hospital and one of the largest among the reported cases in the literature. PMID:19830023

Gene-Environment Studies and Borderline Personality Disorder: A Review

PubMed Central

Carpenter, Ryan W.; Tomko, Rachel L.; Boomsma, Dorret I.

2014-01-01

We review recent gene-environment studies relevant to borderline personality disorder, including those focusing on impulsivity, emotion sensitivity, suicidal behavior, aggression and anger, and the borderline personality phenotype itself. Almost all the studies reviewed suffered from a number of methodological and statistical problems, limiting the conclusions that currently can be drawn. The best evidence to date supports a gene-environment correlation (rGE) model for borderline personality traits and a range of adverse life events, indicating that those at risk for BPD are also at increased risk for exposure to environments that may trigger BPD. We provide suggestions regarding future research on GxE interaction and rGE effects in borderline personality. PMID:23250817

[Expressions of Ras and Sos1 in epithelial ovarian cancer tissues and their clinical significance].

PubMed

Xiao, Zheng-Hua; Linghu, Hua; Liu, Qian-Fen

2016-11-20

To detect the expressions of Ras and Sos1 proteins in human epithelial ovarian cancer (EOC) tissues and explore their correlation with the clinicopathological features of the patients. The expressions of Ras and Sos1 proteins were detected immunohistochemically in 62 EOC tissues, 5 borderline ovarian cancer tissues, 15 benign epithelial ovarian neoplasm tissues, and 18 normal ovarian tissues. The EOC tissues showed significantly higher expression levels of both Ras and Sos1 than the other tissues tested (P<0.05). In EOC tissues, Ras and Sos1 proteins were expressed mostly on the cell membrane and in the cytoplasm. The expression level of Ras was correlated with pathological types of the tumor (P<0.05) and was the highest in serous cystadenomcarcinoma; Sos1 expression did not show significant correlation with the clinicopathological indexes of the patients. High expressions of both Ras and Sos1 proteins were associated with shorter progression-free survival of the patients, but this association was not statistically significant. Ras and Sos1 protein may participate in in the occurrence and development of EOC. The tissue-specific variation of Ras expression can lend support to a specific diagnosis of ovarian serous adenocarcinoma. The association of Ras and Sos1 protein expression with the tumor-free survival time of the patients awaits further investigation with a larger sample size.

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

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

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

Gratz, Kim L; Tull, Matthew T; Reynolds, Elizabeth K; Bagge, Courtney L; Latzman, Robert D; Daughters, Stacey B; Lejuez, C W

2009-01-01

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.

Borderline personality symptoms and work performance: a population-based survey.

PubMed

Juurlink, Trees T; Ten Have, Margreet; Lamers, Femke; van Marle, Hein J F; Anema, Johannes R; de Graaf, Ron; Beekman, Aartjan T F

2018-06-19

This study aims to elucidate the interplay between borderline personality symptoms and working conditions as a pathway for impaired work performance among workers in the general population. Cross-sectional data from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2) were used, including 3672 workers. Borderline personality symptoms were measured with the International Personality Disorder Examination (IPDE) questionnaire. Working conditions (decision latitude, psychological job demands, job security and co-worker support) were assessed with the Job Content Questionnaire (JCQ). Impaired work performance was assessed as total work loss days per month, defined as the sum of days of three types of impaired work performance (inability to work, cut-down to work, and diminished quality at work). These were assessed with the WHO Disability Assessment Schedule (WHO-DAS). Common mental disorders (CMD) were assessed with the Composite International Diagnostic Interview (CIDI). Number of borderline personality symptoms was consistently associated with impaired work performance, even after controlling for type or number of adverse working conditions and co-occurrence of CMD. Borderline personality symptoms were associated with low decision latitude, job insecurity and low co-worker support. The relationship between borderline personality symptoms and work performance diminished slightly after controlling for type or number of working conditions. The current study shows that having borderline personality symptoms is a unique determinant of work performance. This association seems partially explained through the impact of borderline personality symptoms on working conditions. Future studies are warranted to study causality and should aim at diminishing borderline personality symptoms and coping with working conditions.

Defining borderline patients: an overview.

PubMed

Gunderson, J G; Singer, M T

1975-01-01

This review of the descriptive literature on borderline patients indicates that accounts of such patients vary depending upon who is describing them, in what context, how the samples are selected, and what data are collected. The authors identify six features that provide a rational means for diagnosing borderline patients during an initial interview: the presence of intense affect, usually depressive or hostile; a history of impulsive behavior; a certain social adaptiveness; brief psychotic experiences; loose thinking in unstructured situations; and relationships that vacillate between transient superficiality and intense dependency. Reliable identification of these patients will permit better treatment planning and clinical research.

Bilateral exudative retinal detachment associated with central serous chorioretinopathy in a patient treated with corticosteroids.

PubMed

Rueda-Rueda, T; Sánchez-Vicente, J L; Llerena-Manzorro, L; Medina-Tapia, A; González-García, L; Alfaro-Juárez, A; Vital-Berral, C; López-Herrero, F; Muñoz-Morales, A; Ortega, L S; Herrador-Montiel, Á

2017-10-01

The case is presented on a 54-year-old woman with a central serous chorioretinopathy, misdiagnosed as Vogt-Koyanagi-Harada disease, and treated with systemic corticosteroids. The patient presented with a bilateral bullous exudative retinal detachment. Discontinuation of corticosteroid therapy, surgical drainage of subretinal fluid, and photodynamic therapy, led to anatomical and functional improvement. The recognition of an atypical presentation of central serous chorioretinopathy may avoid complications of the inappropriate treatment with corticosteroids. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

ALK ambiguous-positive non-small cell lung cancers are tumors challenged by diagnostic and therapeutic issues.

PubMed

Uguen, Arnaud; Andrieu-Key, Sophie; Vergne, Florence; Descourt, Renaud; Quéré, Gilles; Quintin-Roué, Isabelle; Key, Stéphane; Guéguen, Paul; Talagas, Matthieu; De Braekeleer, Marc; Marcorelles, Pascale

2016-09-01

Searching for ALK rearrangements using the approved fluorescent in situ hybridization (FISH) test and complementary immunohistochemistry (IHC) has become the rule to treat patients with advanced non‑small cell lung cancer (NSCLC) with anti‑ALK targeted therapy. The concordance between the two techniques is reported to be strong but imperfect. We report our experience with cases of ALK‑rearranged lung adenocarcinomas pointing out particularly ambiguous cases. FISH and IHC data on ALK but also c‑MET IHC as well as EGFR and KRAS mutation screening are considered, together with response to crizotinib treatment. We classified the 55 FISH ALK‑rearranged tumors into two groups according to the FISH and IHC results: a concordant FISH+IHC+ group (31 tumors) and an ambiguous group (24 tumors). These tumors were considered as 'ambiguous' ALK‑positive due to negative (21 tumors) or non‑contributive (3 tumors) IHC. In addition, the percentage of FISH-positive nuclei was between 15 and 20% in 17 tumors belonging to one or the other group (now called borderline tumors). We discuss the accuracy of the different tests with intent to determine whether ambiguous and borderline tumors are real positive ALK‑rearranged tumors. To conclude, ambiguous ALK‑positive lung cancers are challenging tumors with diagnosis and therapeutic issues that can justify parallel FISH, IHC and molecular screening strategy.

[Bilateral abnormalities in central serous chorioretinopathy seen in optical coherence tomography, ultra-widefield fluorescein angiography and microperimetry--case report].

PubMed

Tylus, Magdalena; Święch-Zubilewicz, Anna; Dolar-Szczasny, Joanna; Mackiewicz, Jerzy

2015-01-01

Central serous chorioretinopathy is a common retinopathy, which is manifested by the idiopathic detachment of the neurosensory retina in the posterior pole, secondary to fluid leakage from choroidal vessels at the level of retinal pigment epithelium. The disease is typically unilateral and affects young men. We present a case of a 48-year old man, admitted to the Department of Vitreo-Retinal Surgery, Medical University in Lublin, reporting vision impairment in his right eye. The bilateral ocular exam followed by optical coherence tomography, ultra-widefield fluorescein angiography and microperimetry revealed bilateral central serous chorioretinopathy. This case presents a bilateral manifestation of central serous chorioretinopathy and emphasizes the role of advanced diagnostic imaging techniques in analyzing retinal function and disease management.

Food consumption as affect modulation in borderline personality.

PubMed

Ambwani, Suman; Morey, Leslie C

2015-04-01

The present study examined relationships among negative affect, borderline personality features, and eating behavior through the experimental manipulation of mood. Undergraduate women (N = 307) completed a baseline mood assessment, viewed a 39-minute sad film either with or without concurrent food presentation, then completed a second mood assessment and questionnaires assessing personality and eating attitudes/behaviors. Women reporting more borderline personality features exhibited greater negative affect across time and were more reactive to the sad film. Food presentation appeared to have a small ameliorative effect on sadness and general negative affect. However, quantity of food consumption was associated with improvements in mood only for women reporting higher levels of borderline personality features. These data suggest that women with borderline personality characteristics may be at elevated risk for developing problems with binge eating, because consuming larger quantities of food appeared to have a tempering effect on their negative mood and feelings of sadness.

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.

Outcomes of borderline rheumatic heart disease: A prospective cohort study.

PubMed

Bertaina, Geneviève; Rouchon, Bernard; Huon, Bertrand; Guillot, Nina; Robillard, Corinne; Noël, Baptiste; Nadra, Marie; Tribouilloy, Christophe; Marijon, Eloi; Jouven, Xavier; Mirabel, Mariana

2017-02-01

The advent of systematic screening for rheumatic heart disease (RHD) by echocardiography in endemic regions has led to a new entity: borderline RHD. The pathogenicity and natural history of borderline RHD needs to be addressed. The aim of this study was to assess the outcomes of children detected by echocardiography as having borderline RHD. Schoolchildren in 4th grade (i.e., aged 9-10years) who were prospectively echo-screened for RHD (2012-2014) in Nouméa, New Caledonia, were asked to participate. Children with borderline RHD according to consistent independent review by two cardiologists were included and followed-up in 2015. Among the 8684 schoolchildren screened, 49 were diagnosed with borderline RHD according to the Cardiologist clinically involved in the child's management plan. After independent review by two cardiologists, 25 children were consistently diagnosed with borderline RHD and included in the follow-up study. Overall, inter-observer agreement was moderate with diagnostic kappa values of 0.63 (95% CI 0.45-0.78). After a median follow-up of 23months (IQR (20.5-33.0), 15 children (60.0%) had stability of valvular lesions, 8 (32.0%) had normal findings according to the WHF criteria. Two children (8.0%) had definite RHD on the follow-up echocardiogram, but no clinical events or audible pathological murmur during the study period. No factor could be identified as prognostic of either stability or progression. Borderline RHD diagnosed by systematic screening in high-risk populations remains mostly unchanged at 2years follow-up. Diagnosis of borderline RHD may require two reviewers for consistency. Copyright © 2016. Published by Elsevier Ireland Ltd.

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

PubMed

Goldhagen, Brian E; Goldhardt, Raquel

2017-06-01

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

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…

Histone deacetylase (HDAC)-1, -2, -4 and -6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.

PubMed

Giaginis, Constantinos; Damaskos, Christos; Koutsounas, Ioannis; Zizi-Serbetzoglou, Adamantia; Tsoukalas, Nicolaos; Patsouris, Efstratios; Kouraklis, Gregorios; Theocharis, Stamatios

2015-10-26

Histone deacetylases (HDACs) have been associated with malignant tumor development and progression in humans. HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, -2, -4 and -6 protein expression in pancreatic adenocarcinoma. HDAC-1, -2, -4 and -6 protein expression was assessed immunohistochemically on 70 pancreatic adenocarcinoma tissue specimens and was statistically analyzed with clinicopathological characteristics and patients' survival. Enhanced HDAC-1 expression was significantly associated with increased tumor proliferative capacity (p = 0.0238) and borderline with the absence of lymph node metastases (p = 0.0632). Elevated HDAC-4 expression was significantly associated with the absence of organ metastases (p = 0.0453) and borderline with the absence of lymph node metastases (p = 0.0571) and tumor proliferative capacity (p = 0.0576). Enhanced HDAC-6 expression was significantly associated with earlier histopathological stage (p = 0.0115) and borderline with smaller tumor size (p = 0.0864). Pancreatic adenocarcinoma patients with enhanced HDAC-1 and -6 expression showed significantly longer survival times compared to those with low expression (p = 0.0022 and p = 0.0113, respectively), while a borderline association concerning HDAC-2 expression was noted (p = 0.0634). The present study suggested that HDACs may be implicated in pancreatic malignant disease progression, being considered of clinical utility with potential use as therapeutic targets.

Mental state decoding impairment in major depression and borderline personality disorder: meta-analysis.

PubMed

Richman, Mara J; Unoka, Zsolt

2015-12-01

Patients with major depression and borderline personality disorder are characterised by a distorted perception of other people's intentions. Deficits in mental state decoding are thought to be the underlying cause of this clinical feature. To examine, using meta-analysis, whether mental state decoding abilities in patients with major depression and borderline personality disorder differ from those of healthy controls. A systematic review of 13 cross-sectional studies comparing Reading in the Mind of the Eyes Test (RMET) accuracy performance of patients with major depression or borderline personality disorder and healthy age-matched controls (n = 976). Valence scores, where reported, were also assessed. Large significant deficits were seen for global RMET performance in patients with major depression (d = -0.751). The positive RMET valence scores of patients with depression were significantly worse; patients with borderline personality disorder had worse neutral scores. Both groups were worse than controls. Moderator analysis revealed that individuals with comorbid borderline personality disorder and major depression did better than those with borderline personality disorder alone on accuracy. Those with comorbid borderline personality disorder and any cluster B or C personality disorder did worse than borderline personality disorder alone. Individuals with both borderline personality disorder and major depression performed better then those with borderline personality disorder without major depression for positive valence. These findings highlight the relevance of RMET performance in patients with borderline personality disorder and major depression, and the importance of considering comorbidity in future analysis. © The Royal College of Psychiatrists 2015.

Adrenal Metastasis from Uterine Papillary Serous Carcinoma.

PubMed

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

2016-04-27

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. 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. 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.

Accurately Diagnosing and Treating Borderline Personality Disorder

PubMed Central

Gentile, Julie P.; Correll, Terry L.

2010-01-01

The high prevalence of comorbid bipolar and borderline personality disorders and some diagnostic criteria similar to both conditions present both diagnostic and therapeutic challenges. This article delineates certain symptoms which, by careful history taking, may be attributed more closely to one of these two disorders. Making the correct primary diagnosis along with comorbid psychiatric conditions and choosing the appropriate type of psychotherapy and pharmacotherapy are critical steps to a patient's recovery. In this article, we will use a case example to illustrate some of the challenges the psychiatrist may face in diagnosing and treating borderline personality disorder. In addition, we will explore treatment strategies, including various types of therapy modalities and medication classes, which may prove effective in stabilizing or reducing a broad range of symptomotology associated with borderline personality disorder. PMID:20508805

Perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios.

PubMed

Sahin, Erdem; Madendag, Yusuf; Tayyar, Ahter Tanay; Sahin, Mefkure Eraslan; Col Madendag, Ilknur; Acmaz, Gokhan; Unsal, Deniz; Senol, Vesile

2017-08-16

The purpose of this study is to determine the adverse perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios. A total of 430 pregnant women with an uncomplicated singleton pregnancy at a gestational age of 34 + 0-36 + 6 weeks were included. Borderline oligohydramnios was defined as an amniotic fluid index (AFI) of 5.1-8 cm, which was measured using the four-quadrant technique. Adverse perinatal outcomes were compared between the borderline and normal AFI groups. Approximately 107 of the 430 pregnant women were borderline AFI, and 323 were normal AFI. The demographic and obstetric characteristics were similar in both groups. Delivery <37 weeks, cesarean delivery for non-reassuring fetal heart-rate testing, meconium-stained amniotic fluid, Apgar 5 min <7, transient tachypnea of the newborn, respiratory distress syndrome, neonatal intensive care unit, and hyperbilirubinemia were not statistically different between the groups (p = .054, p = .134, p = .749, p = 0.858, p = .703, p = .320, p = .185, and p = .996, respectively). Although gestational age was full-term, induction of labor rates were significantly higher in the borderline AFI group (p = .040). In addition, fetal renal artery pulsatility index pulsatility index (PI) was significantly lower in the borderline AFI group than in the normal AFI group (p = .014). Our results indicated that borderline AFI was not a risk for adverse perinatal outcomes in uncomplicated, late preterm pregnancies.

Ultrastructural Evidence of Serous Gland Polymorphism in the Skin of the Tungara Frog Engystomops pustulosus (Anura Leptodactylidae).

PubMed

Delfino, Giovanni; Giachi, Filippo; Malentacchi, Cecilia; Nosi, Daniele

2015-09-01

Three types of serous products were detected in the syncytial cutaneous glands of the leptodactylid tungara frog, Engystomops pustulosus: type Ia, granules with wide halos and variable density cores; type Ib, high density granules without halos; and type II, vesicles containing a finely dispersed product. Ultrastructural evidence revealed that these products were manufactured by different serous gland types and excluded that they represented different steps in the secretory cycle of a single gland type. Indeed, secretory maturation affecting the products released by the Golgi apparatus proceeded through different mechanisms: confluence (vesicles), interactions between syncytium and secretory product (type Ib granules), and a combination of both processes (type Ia granules). In conclusion, this investigation of secretory maturation was shown to be a suitable approach for the identification of serous gland polymorphism and demonstrated that the tungara frog belongs to the minority of anuran species characterized by this peculiar morpho-functional trait. © 2015 Wiley Periodicals, Inc.

[Pancreatic serous cystadenoma associated with pancreatic heterotopia].

PubMed

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

2016-01-01

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

CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

PubMed

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

2017-01-01

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

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

Pooled clustering of high-grade serous ovarian cancer gene expression leads to novel consensus subtypes associated with survival and surgical outcomes

PubMed Central

Wang, Chen; Armasu, Sebastian M.; Kalli, Kimberly R.; Maurer, Matthew J.; Heinzen, Ethan P.; Keeney, Gary L.; Cliby, William A.; Oberg, Ann L.; Kaufmann, Scott H.; Goode, Ellen L.

2017-01-01

Purpose Here we assess whether molecular subtyping identifies biological features of tumors that correlate with survival and surgical outcomes of high-grade serous ovarian cancer (HGSOC). Experimental Design Consensus clustering of pooled mRNA expression data from over 2,000 HGSOC cases was used to define molecular subtypes of HGSOCs. This de novo classification scheme was then applied to 381 Mayo Clinic HGSOC patients with detailed survival and surgical outcome information. Results Five molecular subtypes of HGSOC were identified. In the pooled dataset, three subtypes were largely concordant with prior studies describing proliferative, mesenchymal, and immunoreactive tumors (concordance > 70%), and the group of tumors previously described as differentiated type was segregated into two new types, one of which (anti-mesenchymal) had down-regulation of genes that were typically upregulated in the mesenchymal subtype. Molecular subtypes were significantly associated with overall survival (p<0.001) and with rate of optimal surgical debulking (≤1 cm, p=1.9E-4) in the pooled dataset. Among stage III-C or IV Mayo Clinic patients, molecular subtypes were also significantly associated with overall survival (p=0.001), as well as rate of complete surgical debulking (no residual disease; 16% in mesenchymal tumors comparing to >28% in other subtypes; p=0.02). Conclusions HGSOC tumors may be categorized into five molecular subtypes that associate with overall survival and the extent of residual disease following debulking surgery. Because mesenchymal tumors may have features that were associated with less favorable surgical outcome, molecular subtyping may have future utility in guiding neoadjuvant treatment decisions for women with HGSOC. PMID:28280090

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

Prognostic Effect and Longitudinal Hemodynamic Assessment of Borderline Pulmonary Hypertension.

PubMed

Assad, Tufik R; Maron, Bradley A; Robbins, Ivan M; Xu, Meng; Huang, Shi; Harrell, Frank E; Farber-Eger, Eric H; Wells, Quinn S; Choudhary, Gaurav; Hemnes, Anna R; Brittain, Evan L

2017-12-01

Pulmonary hypertension (PH) is diagnosed by a mean pulmonary arterial pressure (mPAP) value of at least 25 mm Hg during right heart catheterization (RHC). While several studies have demonstrated increased mortality in patients with mPAP less than that threshold, little is known about the natural history of borderline PH. To test the hypothesis that patients with borderline PH have decreased survival compared with patients with lower mPAP and frequently develop overt PH and to identify clinical correlates of borderline PH. Retrospective cohort study from 1998 to 2014 at Vanderbilt University Medical Center, comprising all patients undergoing routine RHC for clinical indication. We extracted demographics, clinical data, invasive hemodynamics, echocardiography, and vital status for all patients. Patients with mPAP values of 18 mm Hg or less, 19 to 24 mm Hg, and at least 25 mm Hg were classified as reference, borderline PH, and PH, respectively. Mean pulmonary arterial pressure. Our primary outcome was all-cause mortality after adjusting for clinically relevant covariates in a Cox proportional hazards model. Our secondary outcome was the diagnosis of overt PH in patients initially diagnosed with borderline PH. Both outcomes were determined prior to data analysis. We identified 4343 patients (mean [SD] age, 59 [15] years, 51% women, and 86% white) among whom the prevalence of PH and borderline PH was 62% and 18%, respectively. Advanced age, features of the metabolic syndrome, and chronic heart and lung disease were independently associated with a higher likelihood of borderline PH compared with reference patients in a logistic regression model. After adjusting for 34 covariates in a Cox proportional hazards model, borderline PH was associated with increased mortality compared with reference patients (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = .001). The hazard of death increased incrementally with higher mPAP, without an observed threshold. In the 70 patients with

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

DTIC Science & Technology

2015-10-01

journals including J Pathol (PMID: 23378270), Am J Surg Pathol (PMID: 22892598) and Mod Pathology (PMID: 25216223). Task 2d. Telomere FISH on STICs...STICs have shorter telomere length and lower degree of centrosome amplification than the adjacent high- grade serous carcinomas (HGSC). Therefore, our

Shame and implicit self-concept in women with borderline personality disorder.

PubMed

Rüsch, Nicolas; Lieb, Klaus; Göttler, Ines; Hermann, Christiane; Schramm, Elisabeth; Richter, Harald; Jacob, Gitta A; Corrigan, Patrick W; Bohus, Martin

2007-03-01

Shame is considered to be a central emotion in borderline personality disorder and to be related to self-injurious behavior, chronic suicidality, and anger-hostility. However, its level and impact on people with borderline personality disorder are largely unknown. The authors examined levels of self-reported shame, guilt, anxiety, and implicit shame-related self-concept in women with borderline personality disorder and assessed the association of shame with self-esteem, quality of life, and anger-hostility. Sixty women with borderline personality disorder completed self-report measures of shame- and guilt-proneness, state shame, anxiety, depression, self-esteem, quality of life, and clinical symptoms. Comparison groups consisted of 30 women with social phobia and 60 healthy women. Implicit shame-related self-concept (relative to anxiety) was assessed by the Implicit Association Test. Women with borderline personality disorder reported higher levels of shame- and guilt-proneness, state shame, and anxiety than women with social phobia and healthy comparison subjects. The implicit self-concept in women with borderline personality disorder was more shame-prone (relative to anxiety-prone) than in women in the comparison groups. After depression was controlled for, shame-proneness was negatively correlated with self-esteem and quality of life and positively correlated with anger-hostility. Shame, an emotion that is prominent in women with borderline personality disorder, is associated with the implicit self-concept as well as with poorer quality of life and self-esteem and greater anger-hostility. Psychotherapeutic approaches to borderline personality disorder need to address explicit and implicit aspects of shame.

[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. © Georg Thieme Verlag KG Stuttgart · New York.

Concomitant endometriosis in malignant and borderline ovarian tumours.

PubMed

Oral, Engin; Aydin, Ovgu; Kumbak, Banu Aygun; İlvan, Sennur; Yilmaz, Handan; Tustas, Esra; Bese, Tugan; Demirkiran, Fuat; Arvas, Macit

2018-06-08

The aim of the study was to reveal the prevalence of concomitant endometriosis in malignant and borderline ovarian tumours. A retrospective analysis was performed of 530 patients with malignant ovarian tumours and 131 with borderline ovarian tumours, who underwent surgery in our hospital between 1995 and 2011. Forty-eight (7.3%) of 661 patients with malignant and borderline ovarian tumours were associated with endometriosis. Of the 48 endometriosis cases, 73% of those were atypical. Infertility was noted in 38% of patients with endometriosis-associated ovarian tumours. The most frequently endometriosis-associated subtypes were endometrioid (33%) and clear cell (18%) histologies. Of endometriosis-associated endometrioid and clear cell ovarian tumours, 70% were early stage and 60% were premenopausal. The prevalence of concomitant endometriosis in borderline tumours (12%) was found to be significantly higher than that found in the malignant ones (6%; p = .02). Of 32 endometriosis-associated malignant ovarian tumours, 69% were FIGO stages I and II. In conclusion, ovarian endometriosis is seen with both malignant and borderline ovarian tumours, the association being significant with borderline tumours. Fortunately, the endometriosis-associated malignant ovarian tumours are mostly early stage. Impact statement What is already known on this subject? Epidemiologic data suggest that endometriosis has malignant potential. However, a subgroup of women with endometriosis at a high risk for ovarian cancer is yet to be clarified. Currently, endometriosis and ovarian cancer association does not seem to have a clinical implication. What do the results of this study add? The findings of this study revealed that nearly 75% of endometriosis-associated ovarian tumours were of atypical endometriosis. Half of endometriosis-associated ovarian tumour cases were of endometrioid/clear cell histology and 70% were early-stage. Endometriosis was significantly associated with borderline

Missed diagnosis: The emerging crisis of borderline personality disorder in older people.

PubMed

Beatson, Josephine; Broadbear, Jillian Helen; Sivakumaran, Hemalatha; George, Kuruvilla; Kotler, Eli; Moss, Francine; Rao, Sathya

2016-12-01

Clinical experience suggests a growing prevalence of borderline personality disorder in aged residential care and psychiatric facilities with attendant difficulties in their management. This paper reviews the literature concerning the prevalence, phenomenology and diagnosis of borderline personality disorder in old age. The aim is to elucidate the phenomenological differences in old age and thus improve identification of the disorder. A systematic search was conducted using MEDLINE, PubMed, EMBASE and PsycINFO databases, employing the search terms including 'personality disorder', 'borderline personality disorder', 'aged care', 'gerontology', 'geriatric psychiatry' and 'life span'. The search included articles in English involving participants 65+ years. Long-term prospective studies of borderline personality disorder, long-term follow-up studies and studies involving older adults from 50+ years were also examined. There is a paucity of literature on borderline personality disorder in the elderly. No diagnostic or rating instruments have been developed for borderline personality disorder in the elderly. The phenomenology of borderline personality disorder in the aged population differs in several respects from that seen in younger adults, causing some of the difficulties in reaching a diagnosis. Escalations of symptoms and maladaptive behaviours usually occur when the diagnosis of borderline personality disorder is either not made or delayed. Improved identification of borderline personality disorder in older patients, together with staff education concerning the phenomenology, aetiology and management of these patients, is urgently needed. Diagnostic instruments for borderline personality disorder in the elderly need to be developed. In the interim, suggestions are offered concerning patient symptoms and behaviours that could trigger psychiatric assessment and advice concerning management. A screening tool is proposed to assist in the timely diagnosis of

The continuum between Bipolar Disorder and Borderline Personality Disorder.

PubMed

Elisei, Sandro; Anastasi, Serena; Verdolini, Norma

2012-09-01

Several studies have been carried out regarding the possible overlap between Bipolar Disorder and borderline personality disorder. Up to now, it is not possible to provide a definitive picture. In fact, there is currently significant debate about the relationship between Borderline Personality Disorder and Bipolar Disorder. MEDLINE searches were performed to identify the latest studies of these disorders, considering psychodynamic aspects. Bipolar disorder and borderline personality disorder share common clinical features, namely affective instability and impulsivity which however differ in quality. Consequently, to better understand these aspects, it is necessary to trace the stages of childhood psychological development. It has been claimed that Bipolar Disorder Type II can be divided into two subtypes: one stable and functional between episodes and one unstable between episodes which is related to Borderline Personality Disorder. However, better diagnostic theories, psychiatrist's empathy and patience remain the essential tool to understand and to face human suffering.

The properties of borderlines in discontinuous conservative systems

NASA Astrophysics Data System (ADS)

Wang, X.-M.; Fang, Z.-J.

2006-02-01

The properties of the set of borderline images in discontinuous conservative systems are commonly investigated. The invertible system in which a stochastic web was found in 1999 is re-discussed here. The result shows that the set of images of the borderline actually forms the same stochastic web. The web has two typical local fine structures. Firstly, in some parts of the web the borderline crosses the manifold of hyperbolic points so that the chaotic diffusion is damped greatly; secondly, in other parts of phase space many holes and elliptic islands appear in the stochastic layer. This local structure shows infinite self-similarity. The noninvertible system in which the so-called chaotic quasi-attractor was found in [X.-M. Wang et al., Eur. Phys. J. D 19, 119 (2002)] is also studied here. The numerical investigation shows that such a chaotic quasi-attractor is confined by the preceding lower order images of the borderline. The mechanism of this confinement is revealed: a forbidden zone exists that any orbit can not visit, which is the sub-phase space of one side of the first image of the borderline. Each order of the images of the forbidden zone can be qualitatively divided into two sub-phase regions: one is the so-called escaping region that provides the orbit with an escaping channel, the other is the so-called dissipative region where the contraction of phase space occurs.

Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) - a study of the TOC Consortium.

PubMed

Braicu, Elena Ioana; Van Gorp, Toon; Nassir, Mani; Richter, Rolf; Chekerov, Radoslav; Gasimli, Khayal; Timmerman, Dirk; Vergote, Ignace; Sehouli, Jalid

2014-01-01

Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.

[Mentalization based treatment and borderline personality disorder].

PubMed

De Oliveira, C; Rahioui, H; Smadja, M; Gorsane, M A; Louppe, F

2017-08-01

The borderline personality disorder is a complex psychiatric disorder that represents a high number of patients in a psychiatric adult service. Even if some therapies have shown to be effective in the therapeutic care of the borderline personality disorder they only target certain symptoms (e.g. anxiety, sadness, self-mutilation). The aim of this paper is to introduce a therapeutic model little known in France: the mentalization based therapy (MBT) developed in 2004 by Bateman and Fonagy. This therapeutic model apprehends the borderline personality disorder in all its complexity and is based on two main concepts: Bowlby's attachment theory and the concept of mentalization. The MBT is based on the hypothesis that a deficit of mentalization leads to the development of borderline disorder. The capacity of mentalization, also known as reflexive function, is acquired in infancy through interpersonal relationships, in particular those of attachment, and is the ability to understand the mental state (emotions, needs, thoughts, etc.) of oneself and others which underlies explicit behaviour. This reflexive capacity is of a better quality when the person has a secure attachment style. Indeed, borderline patients have, mainly, a deficit of mentalization capacity associated with an insecure attachment style. Thus, the main objective of the Bateman and Fonagy approach is to develop and reinforce the mentalization capacity through a therapeutic relationship as a secure base, a group therapy and the concept of insight. Classically, MBT is structured over a period of 18 months divided into 3 distinct phases distributed in two therapeutic axes: group and individual therapy. The initial phase aims to engage the patient in the therapy by evaluating attachment style, mentalization's ability, interpersonal functioning; providing psychoeducation about borderline disorder and establishing a therapeutic contract. To evaluate attachment style, the authors strongly recommend the use of the

Psychodrama and the Treatment of Narcissistic and Borderline Patients.

PubMed

Olsson, Peter A

2018-01-01

Psychiatric clinicians are faced with the challenge of remaining flexible and psychotherapeutically relevant to the broadening scope of patients with severe narcissistic and borderline personality disorders. Diagnostic sophistication among mental health professionals, increased availability of psychotherapy services, and economic pressures combine to cause the public to expect cost-effective, successful, and shorter duration of treatments. These treatment challenges are particularly poignant with the treatment of those narcissistic and borderline patients who have meager capacity for insight and limited verbal skills. This article describes the use of psychodynamically oriented and informed psychodrama for the treatment of narcissistic and borderline patients.

Reported childhood onset of self-mutilation among borderline patients.

PubMed

Zanarini, Mary C; Frankenburg, Frances R; Ridolfi, Maria E; Jager-Hyman, Shari; Hennen, John; Gunderson, John G

2006-02-01

The purpose of this study was to determine the percentage of borderline patients who first engaged in self-mutilation as children and to compare the parameters of their self-harm to those of borderline patients who first harmed themselves at an older age. Two hundred and ninety inpatients meeting both Revised Diagnostic Interview for Borderlines (DIB-R; Zanarini, Gunderson, Frankenburg, & Chauncey, 1989) and Diagnostic and Statistical Manual of Mental Disorders (3rd ed. ref.) (DSM-III-R; APA, 1987) criteria for borderline personality disorder were interviewed about their history of self-mutilation. Of the 91% with a history of self mutilation, 32.8% reported first harming themselves as children (12 years of age or younger), 30.2% as adolescents (13-17 years of age), and 37% as adults (18 or older). Using logistic regression analyses and controlling for baseline age, it was found that those with a childhood onset reported more episodes of self-harm, a longer duration of self-harm, and a greater number of methods of self-harm than either those with an adolescent or adult onset to their self-mutilation. The results of this study suggest that a sizable minority of borderline patients first engage in self-harm as children and that the course of their self-mutilation may be particularly malignant.

Chromosome 3 Anomalies Investigated by Genome Wide SNP Analysis of Benign, Low Malignant Potential and Low Grade Ovarian Serous Tumours

PubMed Central

Birch, Ashley H.; Arcand, Suzanna L.; Oros, Kathleen K.; Rahimi, Kurosh; Watters, A. Kevin; Provencher, Diane; Greenwood, Celia M.; Mes-Masson, Anne-Marie; Tonin, Patricia N.

2011-01-01

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive

Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low malignant potential and low grade ovarian serous tumours.

PubMed

Birch, Ashley H; Arcand, Suzanna L; Oros, Kathleen K; Rahimi, Kurosh; Watters, A Kevin; Provencher, Diane; Greenwood, Celia M; Mes-Masson, Anne-Marie; Tonin, Patricia N

2011-01-01

Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive

[Serous cysts of the spleen treated by laparoscopic surgery].

PubMed

Alecu, L; Deacu, Adriana; Costan, I; Viţalariu, Adriana; Gulinescu, L

2002-01-01

The authors present two case of a 25 years and 32 years old male patients with serous cysts of spleen that were detected on an random abdominal ultrasonography. Abdominal pain in the left hypocondrium was only symptom of this patients. The patients was operated by laparoscopic method, with Ultra-Shears and intraoperative ultrasonography examination. This kind of techniques give us the opportunity to performed the ablation of the cysts with preservation of the spleen with fast full recovery.

Borderline Personality Features, Anger, and Intimate Partner Violence: An Experimental Manipulation of Rejection.

PubMed

Armenti, Nicholas A; Babcock, Julia C

2018-04-01

Individuals with borderline personality features may be susceptible to react to situational stressors with negative and interpersonally maladaptive emotionality (e.g., anger) and aggression. The current study attempted to test two moderated mediation models to investigate dispositional risk factors associated with borderline personality features and intimate partner violence (IPV). Results from an experimental rejection induction paradigm were examined using moderated regression to observe contextual reactions to imagined romantic rejection from a current romantic partner among individuals with borderline personality features. An ethnically diverse sample of 218 undergraduates at a large public university in the southwestern United States was recruited. Participants responded to demographic questions and self-report measures, and engaged in an experimental rejection induction paradigm. Borderline personality features was positively associated with rejection sensitivity, physical assault, and psychological aggression. Contrary to initial hypotheses, rejection sensitivity did not serve as a mediator of the relations between borderline personality features and physical assault and psychological aggression. However, trait anger mediated the relation between borderline personality features and psychological aggression. As such, trait anger may be an important explanatory variable in the relation between borderline personality features and psychological aggression specifically. Results of the rejection induction paradigm indicated that, for individuals who were asked to imagine an ambiguous rejection, the relation between borderline personality features and state anger post-rejection was strengthened. For individuals who imagined a critical rejection, there was no significant relation between borderline personality features and state anger post-rejection. Findings suggest that trait anger may be an important dispositional factor in the link between borderline personality

Dual HER2 targeting impedes growth of HER2 gene-amplified uterine serous carcinoma xenografts.

PubMed

Groeneweg, Jolijn W; Hernandez, Silvia F; Byron, Virginia F; DiGloria, Celeste M; Lopez, Hector; Scialabba, Vanessa; Kim, Minji; Zhang, Ling; Borger, Darrell R; Tambouret, Rosemary; Foster, Rosemary; Rueda, Bo R; Growdon, Whitfield B

2014-12-15

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that commonly harbors HER2 gene amplification. We investigated the effectiveness of HER2 inhibition using lapatinib and trastuzumab in vitro and in xenografts derived from USC cell lines and USC patient-derived xenografts. Immunohistochemistry and FISH were performed to assess HER2 expression in 42 primary USC specimens. ARK1, ARK2, and SPEC2 cell lines were treated with trastuzumab or lapatinib. Cohorts of mice harboring xenografts derived from ARK2 and SPEC2 cell lines and EnCa1 and EnCa2 primary human USC samples were treated with either vehicle, trastuzumab, lapatinib, or the combination of trastuzumab and lapatinib. Acute and chronic posttreatment tumor samples were assessed for downstream signaling alterations and examined for apoptosis and proliferation. HER2 gene amplification (24%) correlated significantly with HER2 protein overexpression (55%). All models were impervious to single-agent trastuzumab treatment. Lapatinib decreased in vitro proliferation of all cell lines and in vivo growth of HER2-amplified xenografts (ARK2, EnCa1). In addition, dual therapy with trastuzumab and lapatinib resulted in significant antitumor activity only in ARK2 and EnCa1 tumors. Dual HER2 therapy induced on target alteration of downstream MAPK and PI3K pathway mediators only in HER2-amplified models, and was associated with increased apoptosis and decreased proliferation. Although trastuzumab alone did not impact USC growth, dual anti-HER2 therapy with lapatinib led to improved inhibition of tumor growth in HER2-amplified USC and may be a promising avenue for future investigation. ©2014 American Association for Cancer Research.

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,…

Morphological three-dimensional analysis of papillary muscles in borderline left ventricles.

PubMed

Velasco Forte, Mari N; Nassar, Mohamed; Byrne, Nick; Silva Vieira, Miguel; Pérez, Israel V; Ruijsink, Bram; Simpson, John; Hussain, Tarique

2017-09-01

Mitral valve anatomy has a significant impact on potential surgical options for patients with hypoplastic or borderline left ventricle. Papillary muscle morphology is a major component regarding this aspect. The purpose of this study was to use cardiac magnetic resonance to describe the differences in papillary muscle anatomy between normal, borderline, and hypoplastic left ventricles. We carried out a retrospective, observational cardiac magnetic resonance study of children (median age 5.36 years) with normal (n=30), borderline (n=22), or hypoplastic (n=13) left ventricles. Borderline and hypoplastic cases had undergone an initial hybrid procedure. Morphological features of the papillary muscles, location, and arrangement were analysed and compared across groups. All normal ventricles had two papillary muscles with narrow pedicles; however, 18% of borderline and 46% of hypoplastic cases had a single papillary muscle, usually the inferomedial type. In addition, in borderline or hypoplastic ventricles, the supporting pedicle occasionally displayed a wide insertion along the ventricular wall. The length ratio of the superolateral support was significantly different between groups (normal: 0.46±0.08; borderline: 0.39±0.07; hypoplastic: 0.36±0.1; p=0.009). No significant difference, however, was found when analysing the inferomedial type (0.42±0.09; 0.38±0.07; 0.39±0.22, p=0.39). The angle subtended between supports was also similar among groups (113°±17°; 111°±51° and 114°±57°; p=0.99). A total of eight children with borderline left ventricle underwent biventricular repair. There were no significant differentiating features for papillary muscle morphology in this subgroup. The superolateral support can be shorter or absent in borderline or hypoplastic left ventricle cases. The papillary muscle pedicles in these patients often show a broad insertion. These changes have important implications on surgical options and should be described routinely.

MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer

ClinicalTrials.gov

2018-04-27

Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Serous Tumor; Ovarian Seromucinous Carcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Is research on borderline personality disorder underfunded by the National Institute of Health?

PubMed

Zimmerman, Mark; Gazarian, Doug

2014-12-30

The relationship between bipolar disorder and borderline personality disorder has generated intense interest. Similar to patients with bipolar disorder, patients with borderline personality disorder are frequently hospitalized, are chronically unemployed, abuse substances, attempt and commit suicide. However, one significant difference between the two disorders is that patients with borderline personality disorder are often viewed negatively by mental health professionals. In the present paper we examined whether this negative bias against borderline personality disorder might be reflected in the level of research funding on the disorder. We searched the National Institute of Health (NIH) Research Portfolio Online Portfolio Reporting Tool (RePORT) for the past 25 years and compared the number of grants funded and the total amount of funding for borderline personality disorder and bipolar disorder. The yearly mean number of grants receiving funding was significantly higher for bipolar disorder than for borderline personality disorder. Results were the same when focusing on newly funded grants. For every year since 1990 more grants were funded for bipolar disorder than borderline personality disorder. Summed across all 25 years, the level of funding for bipolar disorder was more than 10 times greater than the level of funding for borderline personality disorder ($622 million vs. $55 million). These findings suggest that the level of NIH research funding for borderline personality disorder is not commensurate with the level of psychosocial morbidity, mortality, and health expenditures associated with the disorder.

[Emotional and impulsive dimensions in bipolar disorder and borderline personality disorder].

PubMed

Leblanc, A; Jarroir, M; Vorspan, F; Bellivier, F; Leveillee, S; Romo, L

2017-05-01

Studies have shown that patients with borderline personality disorder are often misdiagnosed to have bipolar disorder and conversely. Indeed, a number of characteristics common to both disorders could explain this problem: emotional instability as well as impulsivity represent confounding factors and contribute to the risk of misdiagnosis. However, it appears that these characteristics manifest themselves in different ways according to the pathology. The aim of the study is to show differences between affective lability, emotional intensity and impulsivity dimensions. The clinical aim is to refine bipolar disorder and borderline personality disorder diagnosis, to improve psychological care for these patients in the long-term. We compared the emotional and impulsive dimensions in two groups of patients: a group of 21 patients with bipolar disorder and a group of 19 patients with borderline personality disorder. Tools: ALS, a self-report questionnaire to evaluate affective lability, AIM, a self-report questionnaire to see affective intensity, and UPPS, a self-report questionnaire to measure impulsivity according to several dimensions. The results indicate that borderline patients scored significantly higher than bipolar patients at the ALS and AIM scales. Regarding the UPPS, borderline patients scored significantly higher than bipolar patients for the dimensions "lack of premeditation" and "lack of perseverance"; however, bipolar patients had significantly higher scores than borderline patients for the dimension "negative emergency". This study shows that bipolar disorder and borderline personality can be differentiated thanks to emotional dimensions as well as different dimensions of impulsivity: borderline patients appear to have an affective lability and intensity more important than bipolar patients; it also appears that impulsivity manifests itself differently according to the disorder. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All

Prognostic factors in breast phyllodes tumors: a nomogram based on a retrospective cohort study of 404 patients.

PubMed

Zhou, Zhi-Rui; Wang, Chen-Chen; Sun, Xiang-Jie; Yang, Zhao-Zhi; Chen, Xing-Xing; Shao, Zhi-Ming; Yu, Xiao-Li; Guo, Xiao-Mao

2018-04-01

The aim of this study was to explore the independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low-risk group, while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence-free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence-free survival at 1, 3, and 5 years. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis.

PubMed

Wong, Kwong-Kwok; Lu, Karen H; Malpica, Anais; Bodurka, Diane C; Shvartsman, Hyun S; Schmandt, Rosemarie E; Thornton, Angela D; Deavers, Michael T; Silva, Elvio G; Gershenson, David M

2007-10-01

A 2-tier system that classifies ovarian serous carcinoma (OSC) as low grade or high grade is gaining acceptance. Women with low-grade OSC generally have higher 5-year survival rates than do women with high-grade OSC. We examined the expression of various markers to further understand the molecular differences between low-grade and high-grade OSCs: the potential therapeutic targets or prognostic markers Her-2/neu, estrogen receptor, and progesterone receptor (PR); the metastasis-associated markers cyclin D1 (BCL1), E-cadherin, matrix metalloproteinase (MMP) 2, and MMP-9; and the cell proliferation-associated markers BCL1, Ki-67 antigen (Ki-67), and p53. For this immunohistochemical analysis, we used paraffin-embedded specimens from 47 patients with advanced-stage low-grade OSC and from 49 patients with advanced-stage high-grade OSC. Our results showed that low-grade tumors expressed significantly higher levels of estrogen receptor, PR, and E-cadherin than did high-grade tumors, suggesting the involvement of gonadal steroid hormones, especially in the pathogenesis of low-grade OSC; the PR positivity was also observed in the stromal component of these low-grade tumors. On the other hand, high-grade tumors trended toward increased expression of MMP-9, BCL1, p53, and Ki-67, and robust MMP-9 positivity was observed in the stromal component of these high-grade tumors. These differences may lead to the development of different therapeutic strategies for women with either the low-grade or the high-grade form of OSC.

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

A quantum probability perspective on borderline vagueness.

PubMed

Blutner, Reinhard; Pothos, Emmanuel M; Bruza, Peter

2013-10-01

The term "vagueness" describes a property of natural concepts, which normally have fuzzy boundaries, admit borderline cases, and are susceptible to Zeno's sorites paradox. We will discuss the psychology of vagueness, especially experiments investigating the judgment of borderline cases and contradictions. In the theoretical part, we will propose a probabilistic model that describes the quantitative characteristics of the experimental finding and extends Alxatib's and Pelletier's () theoretical analysis. The model is based on a Hopfield network for predicting truth values. Powerful as this classical perspective is, we show that it falls short of providing an adequate coverage of the relevant empirical results. In the final part, we will argue that a substantial modification of the analysis put forward by Alxatib and Pelletier and its probabilistic pendant is needed. The proposed modification replaces the standard notion of probabilities by quantum probabilities. The crucial phenomenon of borderline contradictions can be explained then as a quantum interference phenomenon. © 2013 Cognitive Science Society, Inc.

Prognostic factors of phyllodes tumor of the breast.

PubMed

Roa, Juan Carlos; Tapia, Oscar; Carrasco, Paula; Contreras, Enrique; Araya, Juan Carlos; Muñoz, Sergio; Roa, Iván

2006-06-01

The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior.

Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer.

PubMed

Jackson, Amanda L; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M; Gilliam, Timothy P; Zhou, Chunxiao; Bae-Jump, Victoria L

2017-11-21

Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease.

Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer

PubMed Central

Jackson, Amanda L.; Sun, Wenchuan; Kilgore, Joshua; Guo, Hui; Fang, Ziwei; Yin, Yajie; Jones, Hannah M.; Gilliam, Timothy P.; Zhou, Chunxiao; Bae-Jump, Victoria L.

2017-01-01

Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin. Thus, our goal was to evaluate the effect of phenformin on established OC cell lines, primary cultures of human OC cells and in an orthotopic mouse model of high grade serous OC. In three OC cell lines, phenformin significantly inhibited cellular proliferation, induced cell cycle G1 arrest and apoptosis, caused cellular stress, inhibited adhesion and invasion, and activation of AMPK and inhibition of the mTOR pathway. Phenformin also exerted anti-proliferative effects in seven primary cell cultures of human OC. Lastly, phenformin inhibited tumor growth in an orthotopic mouse model of serous OC, coincident with decreased Ki-67 staining and phosphorylated-S6 expression and increased expression of caspase 3 and phosphorylated-AMPK. Our findings demonstrate that phenformin has anti-tumorigenic effects in OC as previously demonstrated by metformin but it is yet to be determined if it is superior to metformin for the potential treatment of this disease. PMID:29245964

Serum and peritoneal fluid concentrations of soluble human leukocyte antigen, tumor necrosis factor alpha and interleukin 10 in patients with selected ovarian pathologies.

PubMed

Sipak-Szmigiel, Olimpia; Włodarski, Piotr; Ronin-Walknowska, Elżbieta; Niedzielski, Andrzej; Karakiewicz, Beata; Słuczanowska-Głąbowska, Sylwia; Laszczyńska, Maria; Malinowski, Witold

2017-04-04

Although immune system plays a key role in the pathogenesis of both endometriosis and ovarian cancer, its function is different. Therefore, we hypothesized, that selected immune parameters can serve as diagnostic markers of these two conditions. The aim of this study was to compare serum and peritoneal fluid concentrations of sHLA-G, IL-10 and TNF-alpha in women with selected ovarian pathologies: benign serous cysts, endometrioma and malignant tumors. Clinical significance of using them for diagnostic purposes in women with serous ovarian cysts, endometriosis, and ovarian cancer, which in the future may improve the early diagnosis of ovarian diseases. The study included women treated surgically for benign serous ovarian cysts, ovarian endometrioma and serous ovarian adenocarcinomas. Peripheral blood and peritoneal fluid samples were obtained intraoperatively. Patients with benign serous cysts, endometrioma and ovarian malignancies did not differ significantly in terms of their serum and peritoneal fluid concentrations of sHLA-G. Ovarian cancer patients presented with significantly higher median serum concentrations of IL-10 and TNF-alpha than other study subjects. Median concentrations of IL-10 and TNF-alpha in peritoneal fluid turned out to be the highest in ovarian cancer patients, followed by women with endometrioma and subjects with benign serous cysts. All these intergroup differences were statistically significant. Irrespective of the group, median concentrations of sHLA-G, IL-10 and TNF-alpha in peritoneal fluid were higher than serum levels of these markers. Elevated serum and peritoneal fluid concentrations of IL-10 and TNF-alpha distinguish ovarian malignancies and endometriomas from benign serous ovarian cysts. In contrast to endometriosis, ovarian malignancies are characterized by elevated peritoneal fluid concentrations of IL-10 and TNF-alpha, elevated serum concentrations of IL-10 and low serum levels of TNF-alpha. Serum and peritoneal fluid

A unique case of ovarian psammocarcinoma with mediastinal, pulmonary, subcutaneous, and omental metastases.

PubMed

Chase, Daniel M; Sparks, Dorothy A; Gener, Melissa; Smith, James

2009-08-01

Psammocarcinoma is a rare form of serous ovarian and peritoneal carcinoma, characterized by abundant psammoma bodies, invasiveness, and low-grade cytological features. Many of the cases which have been reported had extraovarian spread and peritoneal seeding at the time of presentation. We present a case of 45-year-old woman with ovarian psammocarcinoma who initially presented with a metastatic subcutaneous nodule, and was found to have pulmonary and mediastinal metastases. We believe this to be the first report of a psammocarcinoma with these metastases. Ovarian and peritoneal psammocarcinomas are quite rare, and because of this, knowledge of their behavior is limited. Although most seem to follow an indolent course similar to that of borderline lesions of the ovary, this case demonstrates that some of these tumors may be clinically aggressive with distant metastases.

Elesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

ClinicalTrials.gov

2017-05-02

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Tumor; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Borderline personality disorder and polycystic ovary syndrome: A review of the literature.

PubMed

Tan, Raelene Ym; Grigg, Jasmin; Kulkarni, Jayashri

2018-02-01

This review examines the existing evidence for the relationship between borderline personality disorder and polycystic ovary syndrome, and to identify commonalities in etiological mechanisms of borderline personality disorder and polycystic ovary syndrome that might explain the relationship between these seemingly disparate disorders. A search of Medline, EMBASE and Cochrane Central was undertaken on 5 December 2016 to identify studies investigating women with borderline personality disorder and polycystic ovary syndrome (or symptoms and markers specific to polycystic ovary syndrome). Nine studies were identified, including three cross-sectional studies investigating symptoms of polycystic ovary syndrome in women with borderline personality disorder, two cross-sectional and one cohort study examining the prevalence of psychiatric diagnoses in women with polycystic ovary syndrome and three case reports of comorbid borderline personality disorder and polycystic ovary syndrome. Overall, the literature shows women with borderline personality disorder to have higher than expected serum androgen levels and incidence of polycystic ovaries, which can be key features of polycystic ovary syndrome. However, this research is still in its infancy, which limits our understanding of this potential comorbid phenomenon. Given the emerging anecdotal and empirical evidence to date, a theoretical discussion of the potential psychoneuroendocrinological mechanism underlying the borderline personality disorder and polycystic ovary syndrome comorbidity is provided. Further rigorous studies using standardized diagnostic criteria for polycystic ovary syndrome are warranted. Specifically, the use of prospective controlled cohort studies may be able to determine the causality and temporality of observed comorbid borderline personality disorder and polycystic ovary syndrome.

Borderline Personality Disorder: Bipolarity, Mood Stabilizers and Atypical Antipsychotics in Treatment

PubMed Central

Belli, Hasan; Ural, Cenk; Akbudak, Mahir

2012-01-01

In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders. In this context, common phenomenology between borderline personality and bipolar disorders and differential features of clinical diagnosis will be reviewed in line with the literature. Both disorders can demonstrate common features in the diagnostic aspect, and can overlap phenomenologically. Concomitance rate of both disorders is quite high. In order to differentiate these two disorders from each other, quality of mood fluctuations, impulsivity types and linear progression of disorders should be carefully considered. There are various studies in mood stabilizer use, like lithium, carbamazepine, oxcarbazepine, sodium valproate and lamotrigine, in the treatment of borderline personality disorder. Moreover, there are also studies, which have revealed efficacies of risperidone, olanzapine and quetiapine as atypical antipsychotics. It is not easy to differentiate borderline personality disorder from the bipolar disorders. An intensively careful evaluation should be performed. This differentiation may be helpful also for the treatment. There are many studies about efficacy of valproate and lamotrigine in treatment of borderline personality disorder. However, findings related to other mood stabilizers are inadequate. Olanzapine and quetiapine are reported to be more effective among atypical antipsychotics. No drug is approved for the treatment of borderline personality disorder by the entitled authorities, yet. Psychotherapeutic approaches have preserved their significant places in treatment of borderline personality disorder. Moreover, symptom based approach is recommended in use of mood stabilizers and atypical antipsychotics. PMID:23024731

[Childhood traumatization, dissociation and nonsuicidal self-injurious behavior in borderline personality disorder].

PubMed

Merza, Katalin; Harmatta, János; Papp, Gábor; Kuritárné Szabó, Ildikó

2017-05-01

Childhood traumatization plays a significant role in the etiology of borderline personality disorder. Studies found a significant association between childhood traumatization, dissociation, and nonsuicidal self-injurious behavior. The aim of our study was to assess dissociation and nonsuicidal self-injury among borderline inpatients and to reveal the association between childhood traumatization, dissociation, and self-injurious behavior. The sample consisted of 80 borderline inpatients and 73 depressed control patients. Childhood traumatization, dissociation and self-injurious behavior were assessed by questionnaires. Borderline patients reported severe and multiplex childhood traumatization. Cumulative trauma score and sexual abuse were the strongest predictors of dissociation. Furthermore, we have found that cumulative trauma score and dissociation were highly predictive of self-injurious behavior. Our results suggest that self-injurious behavior and dissociation in borderline patients can be regarded as indicators of childhood traumatization. Orv Hetil. 2017; 158(19): 740-747.

Second neoplasms after invasive and borderline ovarian cancer.

PubMed

Levi, Fabio; Randimbison, Lalao; Blanc-Moya, Rafael; La Vecchia, Carlo

2009-06-01

Excess risk of subsequent cancers has been documented in women diagnosed with ovarian cancer. We updated to 2006 data on second cancers in women diagnosed with invasive and borderline ovarian cancer in the Swiss canton of Vaud. Between 1974 and 2006, 304 borderline and 1530 invasive first ovarian tumours were abstracted from the Vaud Cancer Registry database and followed up till the end of 2006. Calculation of expected numbers of tumours in the cohorts was based on site-specific, age-specific and calendar-year-specific incidence rates. We computed the standardized incidence ratios (SIRs) of second cancers, and the corresponding 95% confidence intervals (CI). There was no change in the incidence of malignant cancers, but that of borderline tumours increased over more recent years. Overall, 110 second neoplasms were observed versus 49.7 expected after invasive ovarian cancer (SIR 2.21; 95% CI: 1.82-2.67). Significant excess risks were observed for cancers of the breast, corpus uteri and leukaemias. When synchronous cancers were excluded, the overall SIR for all sites declined to 1.05. Thirty-one second neoplasms were observed after borderline tumours compared with 21.1 expected (SIR=1.47; 95% CI: 1.00-2.09). SIRs were above unity for ovary, colorectum and uterus. After exclusion of synchronous neoplasms, SIR for all neoplasms declined to 1.09, and remained significant only for second ovarian cancers (SIR=4.93). The present record linkage cohort study shows an excess risk for selected synchronous neoplasms in women diagnosed with both borderline and invasive ovarian cancer, likely because of shared genetic and perhaps environmental factors.

Somatostatin receptors in differentiated ovarian tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reubi, J.C.; Horisberger, U.; Klijn, J.G.

1991-05-01

The presence of somatostatin receptors was investigated in 57 primary human ovarian tumors using in vitro receptor autoradiography with three different somatostatin radioligands, {sup 125}I-(Tyr11)-somatostatin-14, {sup 125}I-(Leu8, D-Trp22, Tyr25)-somatostatin-28, or {sup 125}I-(Tyr3)-SMS 201-995. Three cases, all belonging to epithelial tumors, were receptor positive; specifically 1 of 42 adenocarcinomas, 1 of 3 borderline malignancies, and 1 of 2 cystadenomas. Four other epithelial tumors (3 fibroadenomas, 1 Brenner tumor), 4 sex cord-stromal tumors (2 fibrothecomas, 2 granulosa cell tumors), and 2 germ cell tumors (1 dysgerminoma, 1 teratoma) were receptor negative. In the positive cases, the somatostatin receptors were localized on epithelialmore » cells exclusively, were of high affinity (KD = 4.6 nmol/l (nanomolar)), and specific for somatostatin analogs. These receptors bound somatostatin-14 and somatostatin-28 radioligands with a higher affinity than the octapeptide (Tyr3)-SMS 201-995. Healthy ovarian tissue had no somatostatin receptors. A subpopulation of relatively well-differentiated ovarian tumors, therefore, was identified pathobiochemically on the basis of its somatostatin receptor content. This small group of somatostatin receptor-positive tumors may be a target for in vivo diagnostic imaging with somatostatin ligands.« less

Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer.

PubMed

Liang, Haihai; Zhao, Xiaoguang; Wang, Chengyu; Sun, Jian; Chen, Yingzhun; Wang, Guoyuan; Fang, Lei; Yang, Rui; Yu, Mengxue; Gu, Yunyan; Shan, Hongli

2018-06-21

A deeper mechanistic understanding of epithelial-to-mesenchymal transition (EMT) regulation is needed to improve current anti-metastasis strategies in ovarian cancer (OvCa). This study was designed to investigate the role of lncRNAs in EMT regulation during process of invasion-metastasis in serous OvCa to improve current anti-metastasis strategies for OvCa. We systematically analyzes high-throughput gene expression profiles of both lncRNAs and protein-coding genes in OvCa samples with integrated epithelial (iE) subtype and integrated mesenchymal (iM) subtype labels. Mouse models, cytobiology, molecular biology assays and clinical samples were performed to elucidate the function and underlying mechanisms of lncRNA PTAF-mediated promotion of EMT and invasion-metastasis in serous OvCa. We constructed a lncRNA-mediated competing endogenous RNA (ceRNA) regulatory network that affects the expression of many EMT-related protein-coding genes in mesenchymal OvCa. Using a combination of in vitro and in vivo studies, we provided evidence that the lncRNA PTAF-miR-25-SNAI2 axis controlled EMT in OvCa. Our results revealed that up-regulated PTAF induced elevated SNAI2 expression by competitively binding to miR-25, which in turn promoted OvCa cell EMT and invasion. Moreover, we found that silencing of PTAF inhibited tumor progression and metastasis in an orthotopic mouse model of OvCa. We then observed a significant correlation between PTAF expression and EMT markers in OvCa patients. The lncRNA PTAF, a mediator of TGF-β signaling, can predispose OvCa patients to metastases and may serve as a potential target for anti-metastatic therapies for mesenchymal OvCa patients.

False memories and memory confidence in borderline patients.

PubMed

Schilling, Lisa; Wingenfeld, Katja; Spitzer, Carsten; Nagel, Matthias; Moritz, Steffen

2013-12-01

Mixed results have been obtained regarding memory in patients with borderline personality disorder (BPD). Prior reports and anecdotal evidence suggests that patients with BPD are prone to false memories but this assumption has to been put to firm empirical test, yet. Memory accuracy and confidence was assessed in 20 BPD patients and 22 healthy controls using a visual variant of the false memory (Deese-Roediger-McDermott) paradigm which involved a negative and a positive-valenced picture. Groups did not differ regarding veridical item recognition. Importantly, patients did not display more false memories than controls. At trend level, borderline patients rated more items as new with high confidence compared to healthy controls. The results tentatively suggest that borderline patients show uncompromised visual memory functions and display no increased susceptibility for distorted memories. Copyright © 2013 Elsevier Ltd. All rights reserved.

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…

Immigrants and borderline personality disorder at a psychiatric emergency service.

PubMed

Pascual, J C; Malagón, A; Córcoles, D; Ginés, J M; Soler, J; García-Ribera, C; Pérez, V; Bulbena, A

2008-12-01

Several studies have suggested that immigrants have higher rates of psychiatric emergency service use and a higher risk of mental disorders such as schizophrenia than indigenous populations. To compare the likelihood that immigrants (immigrant group) v. indigenous population (indigenous group) will be diagnosed with borderline personality disorder in a psychiatric emergency service and to determine differences according to area of origin. A total of 11 578 consecutive admissions over a 4-year period at a tertiary psychiatric emergency service were reviewed. The collected data included socio-demographic and clinical variables and the Severity of Psychiatric Illness rating score. Psychiatric diagnosis was limited to information available in the emergency room given that a structured interview is not usually feasible in this setting. The diagnosis of borderline personality disorder was based on DSM-IV criteria. Immigrants were divided into five groups according to region of origin: North Africa, sub-Saharan Africa, South America, Asia and Western countries. Multivariate statistical logistic regression analysis showed that all subgroups of immigrants had a lower likelihood of being diagnosed with borderline personality disorder than the indigenous population independently of age and gender. Furthermore, the rates of borderline personality disorder diagnosis were considerably lower in Asian and sub-Saharan subgroups than in South American, North African, Western or native subgroups. Our results showed that in the psychiatric emergency service borderline personality disorder was diagnosed less frequently in the immigrant group v. the indigenous group. Our results do not support the concept of migration as a risk factor for borderline personality disorder.

Immune cells in the normal ovary and spontaneous ovarian tumors in the laying hen (Gallus domesticus) model of human ovarian cancer.

PubMed

Bradaric, Michael J; Penumatsa, Krishna; Barua, Animesh; Edassery, Seby L; Yu, Yi; Abramowicz, Jacques S; Bahr, Janice M; Luborsky, Judith L

2013-01-01

Spontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically. The goal was to determine if there are differences in lymphocyte content between normal ovaries and ovarian tumors in chickens as a basis for further studies to understand the role of immunity in human ovarian cancer progression. Hens were selected using grey scale and color Doppler ultrasound to determine if they had normal or tumor morphology. Cells were isolated from ovaries (n = 6 hens) and lymphocyte numbers were determined by flow cytometry using antibodies to avian CD4 and CD8 T and B (Bu1a) cells. Ovarian sections from another set of hens (n = 26) were assessed to verify tumor type and stage and to count CD4, CD8 and Bu1a immunostained cells by morphometric analysis. T and B cells were more numerous in ovarian tumors than in normal ovaries by flow cytometry and immunohistochemistry. There were less CD4+ cells than CD8+ and Bu1a+ cells in normal ovaries or ovarian tumors. CD8+ cells were the dominant T cell sub-type in both ovarian stroma and in ovarian follicles compared to CD4+ cells. Bu1a+ cells were consistently found in the stroma of normal ovaries and ovarian tumors but were not associated with follicles. The number of immune cells was highest in late stage serous tumors compared to endometrioid and mucinous tumors. The results suggest that similar to human ovarian cancer there are comparatively more immune cells in chicken ovarian tumors than in normal ovaries, and the highest immune cell content occurs in serous tumors. Thus, this study establishes a foundation for further study of tumor immune responses in a spontaneous model of ovarian cancer which will facilitate studies of the role of immunity in early ovarian cancer progression and use of the hen in pre-clinical vaccine trials.

Immune Cells in the Normal Ovary and Spontaneous Ovarian Tumors in the Laying Hen (Gallus domesticus) Model of Human Ovarian Cancer

PubMed Central

Bradaric, Michael J.; Penumatsa, Krishna; Barua, Animesh; Edassery, Seby L.; Yu, Yi; Abramowicz, Jacques S.; Bahr, Janice M.; Luborsky, Judith L.

2013-01-01

Background Spontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically. The goal was to determine if there are differences in lymphocyte content between normal ovaries and ovarian tumors in chickens as a basis for further studies to understand the role of immunity in human ovarian cancer progression. Methods Hens were selected using grey scale and color Doppler ultrasound to determine if they had normal or tumor morphology. Cells were isolated from ovaries (n = 6 hens) and lymphocyte numbers were determined by flow cytometry using antibodies to avian CD4 and CD8 T and B (Bu1a) cells. Ovarian sections from another set of hens (n = 26) were assessed to verify tumor type and stage and to count CD4, CD8 and Bu1a immunostained cells by morphometric analysis. Results T and B cells were more numerous in ovarian tumors than in normal ovaries by flow cytometry and immunohistochemistry. There were less CD4+ cells than CD8+ and Bu1a+ cells in normal ovaries or ovarian tumors. CD8+ cells were the dominant T cell sub-type in both ovarian stroma and in ovarian follicles compared to CD4+ cells. Bu1a+ cells were consistently found in the stroma of normal ovaries and ovarian tumors but were not associated with follicles. The number of immune cells was highest in late stage serous tumors compared to endometrioid and mucinous tumors. Conclusions The results suggest that similar to human ovarian cancer there are comparatively more immune cells in chicken ovarian tumors than in normal ovaries, and the highest immune cell content occurs in serous tumors. Thus, this study establishes a foundation for further study of tumor immune responses in a spontaneous model of ovarian cancer which will facilitate studies of the role of immunity in early ovarian cancer progression and use of the hen in pre-clinical vaccine trials. PMID:24040191

Is a More Comprehensive Surgery Necessary in Patients With Uterine Serous Carcinoma?

PubMed

Touhami, Omar; Trinh, Xuan-Bich; Gregoire, Jean; Sebastianelli, Alexandra; Renaud, Marie-Claude; Grondin, Katherine; Plante, Marie

2015-09-01

Uterine serous carcinoma (USC) is an aggressive histologic subtype of endometrial cancer that shares similarities to serous ovarian cancer, with a propensity for spread to the upper abdomen, a high recurrence rate, and a poor prognosis. The aim of this study was to determine whether the traditional surgical staging procedure for endometrial cancer was adequate for USC or whether a more extensive surgery, similar to the staging procedure for ovarian cancer, needs to be performed. Specifically, the roles of omentectomy and sentinel lymph node (SLN) mapping were evaluated. We retrospectively identified cases of presumed clinical stage I USC at our institution from April 2005 to March 2014. Medical records were reviewed for the following information: age at diagnosis, preoperative imaging, operative findings, surgical procedure, and final histology with definitive International Federation of Gynecology and Obstetrics stage. A total of 39 patients with presumed clinical stage I USC were identified. According to the final pathology report, the surgical stage was as follows: 17 stage IA (44%), 8 stage IB (20%), 3 stage II (8%), 2 stage IIIA (5%), 6 stage IIIC1 (15%), 1 IIIC2 (3%), and 2 stage IVB (5%). Therefore, 14 patients (36%) were surgically upstaged, but none of the patients had their clinical disease upstaged by virtue of finding microscopic metastatic disease in an otherwise normal-looking omentum. Sentinel lymph node mapping was performed in 19 patients (42%). Sensitivity and negative predictive value of SLN mapping were 100% when at least 1 SLN was identified. The detection of microscopic disease in radiologically and clinically normal-appearing omentum seems to be rare in USC. Sentinel lymph node mapping seems to be valuable in the serous subtype of endometrial cancer. A less extensive surgery may be possible in patients with USC as it seems to provide the same information as a more extensive surgery.

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

Etiological features of borderline personality related characteristics in a birth cohort of 12-year-old children.

PubMed

Belsky, Daniel W; Caspi, Avshalom; Arseneault, Louise; Bleidorn, Wiebke; Fonagy, Peter; Goodman, Marianne; Houts, Renate; Moffitt, Terrie E

2012-02-01

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.

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

PubMed

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

1997-05-01

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

Epinephrine stimulation of anion secretion in the Calu-3 serous cell model

PubMed Central

Banga, Amiraj; Flaig, Stephanie; Lewis, Shanta; Winfree, Seth

2014-01-01

Calu-3 is a well-differentiated human bronchial cell line with the characteristics of the serous cells of airway submucosal glands. The submucosal glands play a major role in mucociliary clearance because they secrete electrolytes that facilitate airway hydration. Given the significance of both long- and short-term β-adrenergic receptor agonists in the treatment of respiratory diseases, it is important to determine the role of these receptors and their ligands in normal physiological function. The present studies were designed to characterize the effect of epinephrine, the naturally occurring β-adrenergic receptor agonist, on electrolyte transport of the airway serous cells. Interestingly, epinephrine stimulated two anion secretory channels, the cystic fibrosis transmembrane conductance regulator and a Ca2+-activated Cl− channel, with the characteristics of transmembrane protein 16A, thereby potentially altering mucociliary clearance via multiple channels. Consistent with the dual channel activation, epinephrine treatment resulted in increases in both intracellular cAMP and Ca2+. Furthermore, the present results extend previous reports indicating that the two anion channels are functionally linked. PMID:24705724

Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT).

PubMed

Karlsen, Nikoline Marie Schou; Karlsen, Mona Aarenstrup; Høgdall, Estrid; Nedergaard, Lotte; Christensen, Ib Jarle; Høgdall, Claus

2016-07-01

The aim of the study was to evaluate the rate of relapse as well as disease-free, overall, and disease-specific survival in women with borderline ovarian tumour (BOT). Furthermore, the study aims to identify the clinical parameters correlated to relapse. National clinical data of women diagnosed with BOT from January 2005 to January 2013 constituted the basis for our study population. The prognostic influence of clinical variables was evaluated using univariate and multivariate analyses. A total of 1143 women were eligible for analysis, with 87.9% in FIGO stage I and 12.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. A general favourable prognosis in women with BOT was confirmed in our study. Our findings indicate that systematic, long-term follow-up does not seem necessary in women treated for FIGO stage IA BOT with no residual disease or microinvasion. Copyright © 2016 Elsevier Inc. All rights reserved.

Association between history of abuse and borderline personality disorder for hospitalized adolescent girls.

PubMed

Atlas, J A

1995-12-01

Records of 38 hospitalized female adolescents were analyzed to evaluate the relationship between a history of earlier physical and/or sexual abuse and borderline personality. Those with histories of abuse were significantly more likely to score as Borderline Personality Disorder when assessed by the Diagnostic Interview for Borderlines--Revised.

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

PubMed Central

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

2018-01-01

Purpose A major challenge in platinum-based cancer therapy is the clinical management of chemoresistant tumors, which have a largely unknown pathogenesis at the level of epigenetic regulation. Experimental Design We evaluated the potential of using global loss of 5-hydroxymethylcytosine (5-hmC) levels as a novel diagnostic and prognostic epigenetic marker to better assess platinum-based chemotherapy response and clinical outcome in high-grade serous tumors (HGSOC), the most common and deadliest subtype of ovarian cancer. Furthermore, we identified a targetable pathway to reverse these epigenetic changes, both genetically and pharmacologically. Results This study shows that decreased 5-hmC levels are an epigenetic hallmark for malignancy and tumor progression in HGSOC. In addition, global 5-hmC loss is associated with a decreased response to platinum-based chemotherapy, shorter time to relapse, and poor overall survival in patients newly diagnosed with HGSOC. Interestingly, the rescue of 5-hmC loss restores sensitivity to platinum chemotherapy in vitro and in vivo, decreases the percentage of tumor cells with cancer stem cell markers, and increases overall survival in an aggressive animal model of platinum-resistant disease. Conclusions Consequently, a global analysis of patient 5-hmC levels should be included in future clinical trials, which use pretreatment with epigenetic adjuvants to elevate 5-hmC levels and improve the efficacy of current chemotherapies. Identifying prognostic epigenetic markers and altering chemotherapeutic regimens to incorporate DNMTi pretreatment in tumors with low 5-hmC levels could have important clinical implications for newly diagnosed HGSOC disease. PMID:29263182

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

PIK3CA missense mutation is associated with unfavorable outcome in grade 3 endometrioid carcinoma but not in serous endometrial carcinoma.

PubMed

McIntyre, John B; Nelson, Gregg S; Ghatage, Prafull; Morris, Don; Duggan, Máire A; Lee, Cheng-Han; Doll, Corinne M; Köbel, Martin

2014-01-01

To evaluate the outcome association of PIK3CA mutational status within histological types of rigorously classified high-grade endometrial carcinomas. We assessed PIK3CA mutational status in exon 9 and exon 20 hot spots by Sanger sequencing of DNA derived from formalin fixed paraffin embedded tissue of 57 grade 3 endometrioid, 26 serous, 11 clear cell and 5 dedifferentiated carcinomas. We correlated PIK3CA mutation status with clinicopathological and other molecular parameters. Univariate and multivariate disease specific survival analysis was performed using Kaplan-Meier and Cox regression analyses. PIK3CA exon 9 or exon 20 missense mutations were identified in 20 of 99 (20%) high-grade endometrial carcinomas without significant difference across histological types (p=0.22). Presence of PIK3CA exon 9 or exon 20 missense mutations was associated with shorter disease specific survival within grade 3 endometrioid (p=0.0029) but not endometrial serous (p=0.57) carcinoma based on univariate analysis. Within grade 3 endometrioid carcinoma, PIK3CA exon 9 or exon 20 missense mutations were more commonly observed in cases that were deficient for mismatch repair protein expression (p=0.0058) and showed loss of ARID1A expression (p=0.037). PIK3CA exon 9 or exon 20 missense mutations are present across all histological types of high-grade endometrial carcinomas but a significant outcome association is only seen in grade 3 endometrioid carcinoma, suggesting a greater biological importance in this tumor type. Copyright © 2013 Elsevier Inc. All rights reserved.

YKL-40 in Serum Samples From Patients With Newly Diagnosed Stage III-IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer Receiving Chemotherapy

ClinicalTrials.gov

2018-05-21

Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Mixed Epithelial Tumor; Malignant Ovarian Mucinous Tumor; Malignant Ovarian Neoplasm; Malignant Ovarian Serous Tumor; Malignant Ovarian Transitional Cell Tumor; Ovarian Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

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…

Borderline amniotic fluid index and perinatal outcomes in the uncomplicated term pregnancy.

PubMed

Choi, Soo Ran

2016-01-01

To determine perinatal outcomes in uncomplicated term pregnancies with a borderline amniotic fluid index (AFI). A retrospective review was conducted of uncomplicated singleton pregnancies at term (>37 weeks). Borderline and normal AFI were defined as 5.1 ≤ AFI ≤ 8.0 cm and 8.1 ≤ AFI ≤ 24 cm, respectively. Adverse perinatal outcomes, cesarean delivery for non-reassuring fetal heart rate testing, meconium-stained amniotic fluid, a 5-min Apgar score of <7, admission to the neonatal intensive care unit (NICU), and whether the neonate was small for gestational age were compared between the borderline and normal AFI groups. Borderline AFI was not significantly associated with cesarean delivery for non-reassuring fetal heart rate testing (p = 0.513), meconium-stained amniotic fluid (p = 0.641), admission to the NICU (p = 0.368), or a 5-min Apgar score of <7 (p = 1.00). However, the number of neonates who were small for gestational age (p = 0.021) and rates of induction of labor (p < 0.001) were significantly higher in the borderline group. Multiple logistic regression analysis showed that borderline AFI was not associated with cesarean delivery for non-reassuring fetal heart rate testing (odds ratio [OR] = 0.72, 95% confidence interval [CI] 0.27-1.91, p = 0.52). In uncomplicated term pregnancies, a borderline AFI does not increase the risk of adverse perinatal outcomes.

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

PubMed

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

2017-03-01

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

Phyllodes tumors with and without fibroadenoma-like areas display distinct genomic features and may evolve through distinct pathways.

PubMed

Pareja, Fresia; Geyer, Felipe C; Kumar, Rahul; Selenica, Pier; Piscuoglio, Salvatore; Ng, Charlotte K Y; Burke, Kathleen A; Edelweiss, Marcia; Murray, Melissa P; Brogi, Edi; Weigelt, Britta; Reis-Filho, Jorge S

2017-01-01

Breast fibroepithelial lesions (fibroadenomas and phyllodes tumors) are underpinned by recurrent MED12 exon 2 mutations, which are more common in fibroadenomas and benign phyllodes tumors. TERT promoter hotspot mutations have been documented in phyllodes tumors, and found to be more frequent in borderline and malignant lesions. Several lines of evidence suggest that a subset of phyllodes tumors might arise from fibroadenomas. Here we sought to investigate the genetic differences between phyllodes tumors with fibroadenoma-like areas vs. those without. We retrieved data for 16 borderline/ malignant phyllodes tumors, including seven phyllodes tumors with fibroadenoma-like areas and nine phyllodes tumors without fibroadenoma-like areas, which had been previously subjected to targeted capture massively parallel sequencing. Whilst MED12 exon 2 mutations were significantly more frequent in tumors with fibroadenoma-like areas (71 vs. 11%), an enrichment in genetic alterations targeting bona fide cancer genes was found in those without fibroadenoma-like areas, in particular in EGFR mutations and amplifications (78 vs. 14%). No significant difference in the frequency of TERT genetic alterations was observed (71% in cases with fibroadenoma-like areas vs 56% in those without fibroadenoma-like areas). Our data suggest that the development of phyllodes tumors might follow two different evolutionary pathways: a MED12 -mutant pathway that involves the progression from a fibroadenoma to a malignant phyllodes tumor; and a MED12 -wild-type pathway, where malignant phyllodes tumors arise de novo through the acquisition of genetic alterations targeting cancer genes. Additional studies are warranted to confirm our observations and define whether the outcome differs between both pathways.

Borderline personality pathology in young people at ultra high risk of developing a psychotic disorder.

PubMed

Ryan, Jaymee; Graham, Anne; Nelson, Barnaby; Yung, Alison

2017-06-01

The association between borderline personality disorder and the ultra high risk (UHR) for psychosis state is unclear. The following study aimed to investigate the type of attenuated psychotic symptoms and prevalence of borderline personality pathology in a sample of UHR young people. Additionally, the study aimed to explore whether borderline personality pathology influenced the transition rate to psychosis. Medical records from Orygen Youth Health between 2007 and 2009 were examined. There were 180 patients who met UHR criteria and were included for analysis. Most patients were females (62.8%) and age ranged from 15 to 24 years. A quarter (25.2%) of UHR patients endorsed items consistent with borderline personality pathology. UHR patients with borderline personality pathology experienced a range of attenuated psychotic symptoms and could not be statistically differentiated from UHR patients with less significant or without borderline personality pathology. Borderline personality pathology did not increase or decrease the risk of developing a psychotic disorder. The absence of depression was the only predictor of psychosis. Many UHR patients present with concurrent borderline personality features. The psychotic experiences reported by UHR patients with borderline personality features were not limited to paranoid ideation, supporting the idea that borderline personality disorder may include a wider range of psychotic symptoms than previously thought. It is further possible that the psychotic symptoms experienced in this group could also be indicative of an emerging psychotic disorder. © 2015 Wiley Publishing Asia Pty Ltd.

Association Between Borderline Personality Features and Temporal Summation of Second Pain: A Cross-Sectional Study.

PubMed

You, Dokyoung S; Meagher, Mary W

2017-01-01

Individuals with greater borderline personality features may be vulnerable to chronic pain. Because pain is an unpleasant sensory and emotional experience, affect dysregulation as the core personality feature may be linked to pain hypersensitivity. Studies have found that greater borderline features are associated with increased intensity in clinical and experimental pain, and that depression mediates this increase. The current study further examined the association between borderline features and heat pain sensitivity, the contribution of affect dysregulation and the other borderline personality factors (identity problems, negative relationships, self-harming/impulsivity) to the association, and depression as a mediator. Additionally, we examined whether blunted sympathetic responses mediate the association between borderline features and temporal summation of second pain (TSSP). Thermal pain threshold, thermal TSSP and aftersensations pain were assessed in 79 healthy individuals with varying degrees of borderline features. TSSP is a proxy measure for central sensitization and refers to the gradual increase in pain to repeated nociceptive stimuli. A regression analysis showed that greater borderline features predicted greater TSSP (β = .22, p = .050, R 2 = .05). Borderline features were unrelated to pain threshold and TSSP decay. A stepwise regression showed greater TSSP in individuals with greater borderline features was accounted for by the negative relationships factor rather than the affect dysregulation factor. The results of mediational analyses showed depression and blunted sympathetic skin conductance responses mediated the positive association between TSSP and borderline features.

The five-factor model of personality and borderline personality disorder: a genetic analysis of comorbidity.

PubMed

Distel, Marijn A; Trull, Timothy J; Willemsen, Gonneke; Vink, Jacqueline M; Derom, Catherine A; Lynskey, Michael; Martin, Nicholas G; Boomsma, Dorret I

2009-12-15

Recently, the nature of personality disorders and their relationship with normal personality traits has received extensive attention. The five-factor model (FFM) of personality, consisting of the personality traits neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness, is one of the proposed models to conceptualize personality disorders as maladaptive variants of continuously distributed personality traits. The present study examined the phenotypic and genetic association between borderline personality and FFM personality traits. Data were available for 4403 monozygotic twins, 4425 dizygotic twins, and 1661 siblings from 6140 Dutch, Belgian, and Australian families. Broad-sense heritability estimates for neuroticism, agreeableness, conscientiousness, extraversion, openness to experience, and borderline personality were 43%, 36%, 43%, 47%, 54%, and 45%, respectively. Phenotypic correlations between borderline personality and the FFM personality traits ranged from .06 for openness to experience to .68 for neuroticism. Multiple regression analyses showed that a combination of high neuroticism and low agreeableness best predicted borderline personality. Multivariate genetic analyses showed the genetic factors that influence individual differences in neuroticism, agreeableness, conscientiousness, and extraversion account for all genetic liability to borderline personality. Unique environmental effects on borderline personality, however, were not completely shared with those for the FFM traits (33% is unique to borderline personality). Borderline personality shares all genetic variation with neuroticism, agreeableness, conscientiousness, and extraversion. The unique environmental influences specific to borderline personality may cause individuals with a specific pattern of personality traits to cross a threshold and develop borderline personality.

[Dialectical Behavioral Therapy for Male Adolescents with Borderline Symptomatology].

PubMed

Heider, Jens; Fleck, Anna; Peteler, Christina; Anker, Sabine; Lieb, Susanne; Behrens, Michael; Schröder, Annette; In-Albon, Tina; Brünger, Michael

2017-02-01

Dialectical Behavioral Therapy for Male Adolescents with Borderline Symptomatology The efficacy of Dialectical Behavior Therapy for adolescents (DBT-A) in patients with borderline symptomatology has mainly been shown in female adolescents. However, male adolescents with borderline symptoms are characterized by more aggressive, disruptive, and antisocial behavior. Therefore, the efficacy of the DBT-A has to be investigated in male adolescents. The DBT-A manual was adopted for male adolescents in an inpatient setting. The program has been investigated using a pre-post design in seven male adolescents (on average 14 years of age) with an average of five borderline symptoms according to DSM-IV. Criteria for outcome are symptoms of psychopathology, emotion regulation, aggressive, and self-injurious behavior. After treatment a reduction in aggressive behavior (pre-post effect size d = 1.18) and an improvement in adaptive emotion regulation (d = 0.65) were shown. No improvement could be shown in general symptoms of psychopathology (d = 0.02). The results of these case studies of DBT-A in male adolescents are promising. However, further RCTs with larger sample sizes and a control group will be required.

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

The effects of oxytocin on social cognition in borderline personality disorder.

PubMed

Servan, A; Brunelin, J; Poulet, E

2018-02-01

Deficits in social cognition and interpersonal difficulties are key features in borderline personality disorder. Social cognition refers to the function of perceiving and adequately dealing with social signals, leading to the establishment and maintenance of healthy and positive social relationships. Evidence suggests that oxytocin (OT) may improve social cognition and human social behavior. Recently, several studies have highlighted the beneficial effects of oxytocin in several psychiatric conditions involving social cognition deficits such as schizophrenia, autism or social phobia. However, despite growing interest, the effects of oxytocin in patients with borderline personality disorder are far from being clearly demonstrated. The objective of this work was to review and discuss studies investigating the interest of oxytocin in alleviating social cognition deficits in patients with borderline personality disorder (recognition of emotion, trust and cooperation, affective and cognitive empathy, emotional expression and social problem-solving). A systematic review of the literature was conducted up to September 31, 2016 on the Pubmed, Science direct, Medline and Scopus databases using "borderline personality disorder" and "oxytocin" as keywords. To be included, studies were to include patients with borderline personality disorder; to investigate social cognition and to investigate the effect of oxytocin on social cognition in patients with TPB. The initial search yielded 52 articles. Among them, 11 studies were selected according to the PRISMA criteria. The effect of oxytocin on social cognition in patients with borderline personality disorder was mainly investigated in relation to recognition of emotions and trust and cooperation. We did not find any studies investigating the effect of oxytocin on affective and cognitive empathy, emotional expression or social problem-solving abilities. In patients with borderline personality disorder, oxytocin had a beneficial

No. 347-Obstetric Management at Borderline Viability.

PubMed

Ladhani, Noor Niyar N; Chari, Radha S; Dunn, Michael S; Jones, Griffith; Shah, Prakesh; Barrett, Jon F R

2017-09-01

The primary objective of this guideline was to develop consensus statements to guide clinical practice and recommendations for obstetric management of a pregnancy at borderline viability, currently defined as prior to 25+6 weeks. Clinicians involved in the obstetric management of women whose fetus is at the borderline of viability. Women presenting for possible birth at borderline viability. This document presents a summary of the literature and a general consensus on the management of pregnancies at borderline viability, including maternal transfer and consultation, administration of antenatal corticosteroids and magnesium sulfate, fetal heart rate monitoring, and considerations in mode of delivery. Medline, EMBASE, and Cochrane databases were searched using the following keywords: extreme prematurity, borderline viability, preterm, pregnancy, antenatal corticosteroids, mode of delivery. The results were then studied, and relevant articles were reviewed. The references of the reviewed studies were also searched, as were documents citing pertinent studies. The evidence was then presented at a consensus meeting, and statements were developed. The content and recommendations were developed by the consensus group from the fields of Maternal-Fetal Medicine, Neonatology, Perinatal Nursing, Patient Advocacy, and Ethics. The quality of evidence was rated using criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework (reference 1). The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations, Assessment, Development, and Evaluation methodology framework. The interpretation of strong and weak recommendations is described later. The Summary of Findings is available upon request. A multidisciplinary approach should be used in counselling women and families at borderline

[The relevance of sexuality in the treatment of borderline personality disorder].

PubMed

Neeleman, A J F

2007-01-01

Although many articles about borderline personality disorder have been published over the last 25 years, sexuality has not received much attention. Sexual functioning may however be relevant for the treatment of this disorder. To find out from research reports, the literature and clinical practice whether they contain evidence of varying degrees of problematical sexuality in borderline patients, and if so, to make an inventory of the evidence. A literature search was conducted via PubMed and Psycinfo using the search terms 'borderline personality disorder', 'sexuality' and 'research'. In addition, the literature was searched manually. Only six empirical studies about the sexual functioning of patients with borderline personality disorder were found. The research findings provided information about patients' problems with regard to intimate and sexual relations. These problems related to heightened sexual impulsivity, reduced satisfaction, increased sexual boredom, greater preoccupation with sex, avoidance of sex and a range of other sexual complaints. In addition, there is evidence that homosexuality and vulnerability regarding gender identity occur more frequently in these patients. Helping to integrate love and sexuality with a suitable partner seems to be an important developmental assignment for persons assisting borderline patients.

Childhood maltreatment and its link to borderline personality disorder features in children: A systematic review approach.

PubMed

Ibrahim, Jeyda; Cosgrave, Nicola; Woolgar, Matthew

2018-01-01

Borderline personality disorder has repeatedly been associated with a history of maltreatment in childhood; however, research on maltreatment and its link to borderline features in children is limited. The aim of this review is to synthesise the existing data on the association between maltreatment and borderline features in childhood. In total, 10 studies were included in this systematic review. Studies indicated that children with borderline features were more likely to have a history of maltreatment, and that children who had been maltreated were more likely to present with borderline features. Other risk factors such as cognitive and executive functioning deficits, parental dysfunction and genetic vulnerability were also identified across studies. This review adds to the literature by highlighting maltreatment as a risk factor for borderline features in childhood. Longitudinal research is required to establish the link between childhood borderline features and adult borderline features. Implications for early identification, prevention and intervention services are discussed.

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

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

2015-01-01

Idiopathic central serous chorioretinopathy (CSCR) is a relatively common ophthalmic disorder characterized by the development of a serous detachment of the sensory retina. Psychophysiological factors may trigger or maintain CSCR, though, surprisingly, the association between CSCR and anxiety has yet to be studied. The aims of the present study were threefold: to determine whether 1) Iranian patients with CSCR have higher scores for anxiety, 2) anxiety is lower, if CSCR has been experienced twice, and whether 3) anxiety scores differ between sexes. A total of 30 patients with CSCR and 30 healthy age-and sex-matched controls took part in the study. A brief face-to-face interview was conducted covering demographic variables and history and occurrence of CSCR and assessing anxiety. Compared to healthy controls, anxiety was significantly higher in both first-time and second-time CSCR patients. In CSCR patients, anxiety scores did not differ between sexes. Higher anxiety scores were observed in Iranian patients with CSCR, irrespective of whether this was the first or second occurrence of CSCR. This suggests there is no psychological adaptation in terms of reduced anxiety among patients with repeated CSCR.

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

Prognostic value of estrogen receptor and progesterone receptor tumor expression in Danish ovarian cancer patients: from the 'MALOVA' ovarian cancer study.

PubMed

Høgdall, Estrid V S; Christensen, Lise; Høgdall, Claus K; Blaakaer, Jan; Gayther, Simon; Jacobs, Ian J; Christensen, Ib Jarle; Kjaer, Susanne K

2007-11-01

Estrogen and progesterone are important hormones secreted by the ovary acting through specific receptors. Tumor tissue expression profiles of these have demonstrated prognostic value in malignancies such as breast, uterine and prostate cancer. In this study, including tissue samples from 773 Danish patients with an ovarian tumor, we evaluated whether estrogen receptor (ER) and progesterone receptor (PR) expression correlated with clinico-pathological parameters, and a possible prognostic impact on ovarian cancer (OC) patients was investigated. Using tissue array and immunohistochemistry, we analyzed the ER and PR expression levels in tissues from 582 women with OC and 191 women with low malignancy potential (LMP) ovarian tumors. Our results demonstrated that ER was expressed in 30 of the 191 LMP tumors (16%) and in 207 of the 582 OC (36%). PR was expressed in 38 LMP tumors (20%) and in 115 OC (20%). For both tumor types an excess of positive tumors was found in the serous compared to the mucinous subtype (p< or =0.00001). The frequency of ER expression-positive OC increased with increasing FIGO stage (p=0.0003), and the frequency of PR-positive tumors increased with increasing histological grade (p=0.0006). In a Cox survival analysis, a tissue ER and PR expression 10% or higher was found to imply an independent significant advantageous course of patient disease-specific survival (ER: hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.63-0.99; PR: HR, 0.69; 95% CI, 0.51-0.94) together with FIGO stage, residual tumor after primary surgery, age at diagnosis and other histological types vs. serous adenocarcinoma. The histological grade of tumor was found to have no independent prognostic value. The prognostic value of ER and PR was found additive with a HR for patients with high ER and PR expression of 0.48 (95% CI, 0.31-0.74) compared to patients with <10% expression for both receptors. In conclusion, our results predict that an elevated expression of ER and PR

[Pharmacotherapy in the treatment of borderline personality disorder].

PubMed

Alliani, Daniela; Tarantelli, Silvia

2009-01-01

The aim of this study is to bring together the previous studies on pharmacotherapy of borderline disorder from the oldest to the recent ones, mainly focusing on atypical antipsychotic, whose success has been underlined in recent medical literature with peculiar reference to olanzapine. Since the '80 the pharmacotherapy in borderline personality disorder has been playing an increasing role in the interest of scientific community and in the medical practice as indicated by APA guidelines (2000). Nowadays the pharmacological approach, supported by some experimental outcomes, follow a so called "dimensional" standard. The targets of this standard drug approach are specific psychopathological "dimensions" of the disorder and related neurotransmitters' changes in particular linked to serotoninergic and dopaminergic systems, both supported by experimental outcomes. The psychopathological dimensions to which pharmacological approach is more suitable are: impulsiveness and emotional dysregulation. During the last past years, effectiveness of atypical antipsychotic drugs became of major interest in medical treatment of borderline disorder, mainly related to their action toward the serotoninergic and dopaminergic systems.

[Endometrial carcinomas and precursor lesions--new aspects].

PubMed

Schmidt, D

2009-07-01

Endometrial carcinomas can be separated into two groups which are designated as type I and type II carcinomas today. Both groups of tumors are clearly different with regard to conventional light microscopy, immunohistochemistry, molecular pathology and clinical features. Only type I carcinomas are associated with hyperestrogenism. The group of type I carcinomas consists of endometrioid carcinoma and its variants, and mucinous carcinoma. The prototypes of type II carcinomas are serous and clear cell carcinoma. Not all carcinomas, however, can be assigned to one of the two groups, because there are hybrid tumors and mixed carcinomas, e.g. endometrioid carcinoma with a serous component. The precursor lesions of the endometrioid carcinoma and the serous carcinoma are well characterized morphologically and by molecular pathology. Atypical hyperplasia is the precursor lesion of endometrioid carcinoma, whereas endometrial intraepithelial carcinoma (EIC) is the precursor lesion of serous carcinoma. No precursor lesion has as yet been identified for clear cell carcinoma. Immunohistochemical markers for endometrial carcinoma are CK7 and vimentin, for serous carcinoma markers are p53 and p16. Correct typing is of essential prognostic necessity in endometrial carcinoma. Of utmost importance is the detection of a serous component, because serous carcinoma leads to early tumor spread with the necessity of radical surgery, chemotherapy and radiotherapy.

Olaparib and Cediranib Maleate in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2018-06-18

Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Optimal management for surgically Stage 1 serous cancer of the uterus.

PubMed

Elit, L; Kwon, J; Bentley, J; Trim, K; Ackerman, I; Carey, M

2004-01-01

To describe the outcomes of patients who have undergone well-conducted surgery and found to have Stage 1 serous uterine cancer. This retrospective cohort study includes women who have been treated for Stage 1 serous cancer of the uterus from 1985 to 2001. Cases were included from the regional cancer centers in Hamilton, London, Sunnybrook Toronto and Cancer Care Manitoba. Forty-three women met the inclusion criteria: Complete surgical staging (n = 27), surgery followed by pelvic radiation therapy (n = 4), surgery followed by whole abdominal radiation therapy (n = 6), surgery followed by adjuvant chemotherapy (n = 6). Patient age or depth of invasion did not influence survival. Progression free interval was 22 months (SD = 14.29). Recurrence rate was highest for adjuvant chemotherapy (66%). Survival was assessed by treatment modality and a statistically significant poorer survival was seen in the adjuvant chemotherapy group (OR 17.5; 95% CI 1.3-227.6). No comment can be made on a superior treatment regimen given the small numbers in each treatment strata. This study supports the findings of others in the literature. In a group of patients where surgical staging shows limited disease (i.e., surgically Stage 1 disease), then surgery alone appears to be adequate treatment.

A Computer-Aided Distinction Method of Borderline Grades of Oral Cancer

NASA Astrophysics Data System (ADS)

Sami, Mustafa M.; Saito, Masahisa; Muramatsu, Shogo; Kikuchi, Hisakazu; Saku, Takashi

We have developed a new computer-aided diagnostic system for differentiating oral borderline malignancies in hematoxylin-eosin stained microscopic images. Epithelial dysplasia and carcinoma in-situ (CIS) of oral mucosa are two different borderline grades similar to each other, and it is difficult to distinguish between them. A new image processing and analysis method has been applied to a variety of histopathological features and shows the possibility for differentiating the oral cancer borderline grades automatically. The method is based on comparing the drop-shape similarity level in a particular manually selected pair of neighboring rete ridges. It was found that the considered similarity level in dysplasia was higher than those in epithelial CIS, of which pathological diagnoses were conventionally made by pathologists. The developed image processing method showed a good promise for the computer-aided pathological assessment of oral borderline malignancy differentiation in clinical practice.

Sexual Orientation and Borderline Personality Disorder Features in a Community Sample of Adolescents.

PubMed

Reuter, Tyson R; Sharp, Carla; Kalpakci, Allison H; Choi, Hye J; Temple, Jeff R

2016-10-01

Empirical literature demonstrates that sexual minorities are at an increased risk of developing psychopathology, including borderline personality disorder (BPD). The specific link between sexual orientation and BPD has received significantly less attention in youth, and it remains unclear what drives this relation. Given that there are higher rates of psychopathology in both sexual minorities and individuals with BPD, the present study aimed to determine if sexual orientation uniquely contributes to borderline personality pathology, controlling for other psychopathology. An ethnically diverse sample of 835 adolescents completed self-report measures of borderline features, depression, anxiety, and sexual orientation. Sexual minorities scored higher on borderline features compared to heterosexual adolescents. When controlling for depression and anxiety, sexual orientation remained significantly associated with borderline features. The relation between sexual orientation and BPD cannot fully be explained by other psychopathology. Future research is necessary to understand potential mechanisms underlying this relation.

The borderline range of toxicological methods: Quantification and implications for evaluating precision.

PubMed

Leontaridou, Maria; Urbisch, Daniel; Kolle, Susanne N; Ott, Katharina; Mulliner, Denis S; Gabbert, Silke; Landsiedel, Robert

2017-01-01

Test methods to assess the skin sensitization potential of a substance usually use threshold criteria to dichotomize continuous experimental read-outs into yes/no conclusions. The threshold criteria are prescribed in the respective OECD test guidelines and the conclusion is used for regulatory hazard assessment, i.e., classification and labelling of the substance. We can identify a borderline range (BR) around the classification threshold within which test results are inconclusive due to a test method's biological and technical variability. We quantified BRs in the prediction models of the non-animal test methods DPRA, LuSens and h-CLAT, and of the animal test LLNA, respectively. Depending on the size of the BR, we found that between 6% and 28% of the substances in the sets tested with these methods were considered borderline. When the results of individual non-animal test methods were combined into integrated testing strategies (ITS), borderline test results of individual tests also affected the overall assessment of the skin sensitization potential of the testing strategy. This was analyzed for the 2-out-of-3 ITS: Four out of 40 substances (10%) were considered borderline. Based on our findings we propose expanding the standard binary classification of substances into "positive"/"negative" or "hazardous"/"non-hazardous" by adding a "borderline" or "inconclusive" alert for cases where test results fall within the borderline range.

Borderline Personality Disorder in the perinatal period: early infant and maternal outcomes.

PubMed

Blankley, Gaynor; Galbally, Megan; Snellen, Martien; Power, Josephine; Lewis, Andrew J

2015-12-01

This study examines pregnancy and early infant outcomes of pregnant women with a clinical diagnosis of Borderline Personality Disorder presenting for obstetric services to a major metropolitan maternity hospital in Victoria, Australia. A retrospective case review of pregnancy and early infant outcomes on 42 women who had been diagnosed with Borderline Personality Disorder via psychiatric assessment using DSM-IV-R criteria was undertaken. Outcomes were compared with a control group of 14,313 consisting of women and infants of non-affected women from the same hospital over the same period of time. Women presenting for obstetric services with a clinical diagnosis of Borderline Personality Disorder experienced considerable psychosocial impairment. They anticipated birth as traumatic and frequently requested early delivery. High comorbidity with substance abuse was found and high rates of referral to child protective services. Mothers with Borderline Personality Disorder were significantly more likely to have negative birth outcomes such as lowered Apgar scores, prematurity and special care nursery referral when compared with controls. These findings offer preliminary evidence to be considered by clinicians in developing treatments and services for the perinatal care of women with Borderline Personality Disorder and their infants. Further research is required in order to develop evidence informed clinical guidelines for the management of women with Borderline Personality Disorder and their infants. © The Royal Australian and New Zealand College of Psychiatrists 2015.

APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma

PubMed Central

Leonard, Brandon; Hart, Steven N.; Burns, Michael B.; Carpenter, Michael A.; Temiz, Nuri A.; Rathore, Anurag; Vogel, Rachel Isaksson; Nikas, Jason B.; Law, Emily K.; Brown, William L.; Li, Ying; Zhang, Yuji; Maurer, Matthew J.; Oberg, Ann L.; Cunningham, Julie M.; Shridhar, Viji; Bell, Debra A.; April, Craig; Bentley, David; Bibikova, Marina; Cheetham, R. Keira; Fan, Jian-Bing; Grocock, Russell; Humphray, Sean; Kingsbury, Zoya; Peden, John; Chien, Jeremy; Swisher, Elizabeth M.; Hartmann, Lynn C.; Kalli, Kimberly R.; Goode, Ellen L.; Sicotte, Hugues; Kaufmann, Scott H.; Harris, Reuben S.

2013-01-01

Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here we report wide variation in expression of the DNA cytosine deaminase APOBEC3B, with elevated expression in a majority of ovarian cancer cell lines (3 standard deviations above the mean of normal ovarian surface epithelial cells) and high grade primary ovarian cancers. APOBEC3B is active in the nucleus of several ovarian cancer cell lines and elicits a biochemical preference for deamination of cytosines in 5′TC dinucleotides. Importantly, examination of whole-genome sequence from 16 ovarian cancers reveals that APOBEC3B expression correlates with total mutation load as well as elevated levels of transversion mutations. In particular, high APOBEC3B expression correlates with C-to-A and C-to-G transversion mutations within 5′TC dinucleotide motifs in early-stage high grade serous ovarian cancer genomes, suggesting that APOBEC3B-catalyzed genomic uracil lesions are further processed by downstream DNA ‘repair’ enzymes including error-prone translesion polymerases. These data identify a potential role for APOBEC3B in serous ovarian cancer genomic instability. PMID:24154874

Association among self-compassion, childhood invalidation, and borderline personality disorder symptomatology in a Singaporean sample.

PubMed

Keng, Shian-Ling; Wong, Yun Yi

2017-01-01

Linehan's biosocial theory posits that parental invalidation during childhood plays a role in the development of borderline personality disorder symptoms later in life. However, little research has examined components of the biosocial model in an Asian context, and variables that may influence the relationship between childhood invalidation and borderline symptoms. Self-compassion is increasingly regarded as an adaptive way to regulate one's emotions and to relate to oneself, and may serve to moderate the association between invalidation and borderline symptoms. The present study investigated the association among childhood invalidation, self-compassion, and borderline personality disorder symptoms in a sample of Singaporean undergraduate students. Two hundred and ninety undergraduate students from a large Singaporean university were recruited and completed measures assessing childhood invalidation, self-compassion, and borderline personality disorder symptoms. Analyses using multiple regression indicated that both childhood invalidation and self-compassion significantly predicted borderline personality disorder symptomatology. Results from moderation analyses indicated that relationship between childhood invalidation and borderline personality disorder symptomatology did not vary as a function of self-compassion. This study provides evidence in support of aspects of the biosocial model in an Asian context, and demonstrates a strong association between self-compassion and borderline personality disorder symptoms, independent of one's history of parental invalidation during childhood.

A Non-linear Predictive Model of Borderline Personality Disorder Based on Multilayer Perceptron.

PubMed

Maldonato, Nelson M; Sperandeo, Raffaele; Moretto, Enrico; Dell'Orco, Silvia

2018-01-01

Borderline Personality Disorder is a serious mental disease, classified in Cluster B of DSM IV-TR personality disorders. People with this syndrome presents an anamnesis of traumatic experiences and shows dissociative symptoms. Since not all subjects who have been victims of trauma develop a Borderline Personality Disorder, the emergence of this serious disease seems to have the fragility of character as a predisposing condition. Infect, numerous studies show that subjects positive for diagnosis of Borderline Personality Disorder had scores extremely high or extremely low to some temperamental dimensions (harm Avoidance and reward dependence) and character dimensions (cooperativeness and self directedness). In a sample of 602 subjects, who have had consecutive access to an Outpatient Mental Health Service, it was evaluated the presence of Borderline Personality Disorder using the semi-structured interview for the DSM IV-TR personality disorders. In this population we assessed the presence of dissociative symptoms with the Dissociative Experiences Scale and the personality traits with the Temperament and Character Inventory developed by Cloninger. To assess the weight and the predictive value of these psychopathological dimensions in relation to the Borderline Personality Disorder diagnosis, a neural network statistical model called "multilayer perceptron," was implemented. This model was developed with a dichotomous dependent variable, consisting in the presence or absence of the diagnosis of borderline personality disorder and with five covariates. The first one is the taxonomic subscale of dissociative experience scale, the others are temperamental and characterial traits: Novelty-Seeking, Harm-Avoidance, Self-Directedness and Cooperativeness. The statistical model, that results satisfactory, showed a significance capacity (89%) to predict the presence of borderline personality disorder. Furthermore, the dissociative symptoms seem to have a greater influence than

Evaluation of changes in prescription medication use after a residential treatment programme for borderline personality disorder.

PubMed

Broadbear, Jillian H; Nesci, Julian; Thomas, Rosemary; Thompson, Katherine; Beatson, Josephine; Rao, Sathya

2016-12-01

Residential patients diagnosed with borderline personality disorder were evaluated to determine whether borderline personality disorder-focused psychotherapy reduced prescribing, personality disorder and co-morbid symptom severity. Psychotropic prescriptions were measured at admission, discharge and 1 year later in 74 female participants with one or more personality disorder diagnosis and co-morbid mood disorders. Changes in pharmacotherapy were examined in the context of improvements in borderline personality disorder and/or co-morbid disorder symptom severity. Residential treatment included individual and group psychotherapy for borderline personality disorder. The Structured Clinical Interview for DSM-IV was used to confirm the borderline personality disorder diagnosis and associated co-morbid conditions. The Beck Depression Inventory was completed at each time point. A significant reduction in the incidence and severity of self-rated depression as well as clinician assessed personality disorder, including borderline personality disorder, was accompanied by a reduction in prescription of psychoactive medications. Three to six months of intensive borderline personality disorder-specific psychotherapy showed lasting benefit with regard to symptom severity of personality disorders (borderline personality disorder in particular) as well as depressive symptoms. This improvement corresponded with a reduction in prescriptions for psychoactive medications, which is consistent with current thinking regarding treatment for borderline personality disorder. © The Royal Australian and New Zealand College of Psychiatrists 2016.

[Anorexia and borderline personality disorder : bonds pathology].

PubMed

Cayn, Delphine; Pham-Scottez, Alexandra

Comorbidity with a borderline personality disorder is far from rare in patients suffering from eating disorders. Clinically, this presents as chronic instability in many areas: interpersonal relationships, self-image, emotions, mood and acting out. Treatment is mainly based on a containing and reassuring therapeutic framework. A care plan may be put in place that incorporates reducing impulsive harmful, eating and self-harming behaviours. Dialectical behaviour therapy is intended in particular to prevent suicide risk in borderline personality disorder patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

Impulsivity, Rejection Sensitivity, and Reactions to Stressors in Borderline Personality Disorder

PubMed Central

Berenson, Kathy R.; Gregory, Wesley Ellen; Glaser, Erin; Romirowsky, Aliza; Rafaeli, Eshkol; Yang, Xiao; Downey, Geraldine

2016-01-01

This research investigated baseline impulsivity, rejection sensitivity, and reactions to stressors in individuals with borderline personality disorder compared to healthy individuals and those with avoidant personality disorder. The borderline group showed greater impulsivity than the avoidant and healthy groups both in a delay-discounting task with real monetary rewards and in self-reported reactions to stressors; moreover, these findings could not be explained by co-occurring substance use disorders. Distress reactions to stressors were equally elevated in both personality disorder groups (relative to the healthy group). The borderline and avoidant groups also reported more maladaptive reactions to a stressor of an interpersonal vs. non-interpersonal nature, whereas the healthy group did not. Finally, self-reported impulsive reactions to stressors were associated with baseline impulsivity in the delay-discounting task, and greater self-reported reactivity to interpersonal than non-interpersonal stressors was associated with rejection sensitivity. This research highlights distinct vulnerabilities contributing to impulsive behavior in borderline personality disorder. PMID:27616800

[Psychological Treatments for Borderline Personality Disorder: A Review of Cognitive-Behavioral Oriented Therapies].

PubMed

Marques, Sofia; Barrocas, Daniel; Rijo, Daniel

2017-04-28

Borderline personality disorder is the most common personality disorder, with a global prevalence rate between 1.6% and 6%. It is characterized by affective disturbance and impulsivity, which lead to a high number of self-harm behaviors and great amount of health services use. International guidelines recommend psychotherapy as the primary treatment for borderline personality disorder. This paper reviews evidence about the effects and efficacy of cognitive-behavioral oriented psychological treatments for borderline personality disorder. A literature review was conducted in Medline and PubMed databases, using the following keywords: borderline personality disorder, cognitive-behavioral psychotherapy and efficacy. Sixteen randomized clinical trials were evaluate in this review, which analyzed the effects of several cognitive-behavioral oriented psychotherapeutic interventions, namely dialectical behavioral therapy, cognitive behavioral therapy, schema-focused therapy and manual-assisted cognitive therapy. All above stated treatments showed clinical beneficial effects, by reducing borderline personality disorder core pathology and associated general psychopathology, as well as by reducing the severity and frequency of self-harm behaviors, and by improving the overall social, interpersonal and global adjustment. Dialectical behavioral therapy and schema-focused therapy also caused a soaring remission rate of diagnostic borderline personality disorder criteria of 57% and 94%, respectively. Although there were differences between the psychotherapeutic interventions analysed in this review, all showed clinical benefits in the treatment of borderline personality disorder. Dialectical behavioral therapy and schema-focused therapy presented the strongest scientific data documenting their efficacy, but both interventions are integrative cognitive-behavioral therapies which deviate from the traditional cognitive-behavioral model. In summary, the available studies support

Incision and stress regulation in borderline personality disorder: neurobiological mechanisms of self-injurious behaviour.

PubMed

Reitz, Sarah; Kluetsch, Rosemarie; Niedtfeld, Inga; Knorz, Teresa; Lis, Stefanie; Paret, Christian; Kirsch, Peter; Meyer-Lindenberg, Andreas; Treede, Rolf-Detlef; Baumgärtner, Ulf; Bohus, Martin; Schmahl, Christian

2015-08-01

Patients with borderline personality disorder frequently show non-suicidal self-injury (NSSI). In these patients, NSSI often serves to reduce high levels of stress. Investigation of neurobiological mechanisms of NSSI in borderline personality disorder. In total, 21 women with borderline personality disorder and 17 healthy controls underwent a stress induction, followed by either an incision into the forearm or a sham treatment. Afterwards participants underwent resting-state functional magnetic resonance imaging while aversive tension, heart rate and heart rate variability were assessed. We found a significant influence of incision on subjective and objective stress levels with a stronger decrease of aversive tension in the borderline personality disorder group following incision than sham. Amygdala activity decreased more and functional connectivity with superior frontal gyrus normalised after incision in the borderline personality disorder group. Decreased stress levels and amygdala activity after incision support the assumption of an influence of NSSI on emotion regulation in individuals with borderline personality disorder and aids in understanding why these patients use self-inflicted pain to reduce inner tension. © The Royal College of Psychiatrists 2015.

Cystic pancreatic neoplasms evaluation by CT and magnetic resonance cholangiopancreatography.

PubMed

Sahani, Dushyant; Prasad, Srinivasa; Saini, Sanjay; Mueller, Peter

2002-10-01

CT provides limited assistance in the differentiation between serous and mucinous neoplasms. Because of the variability in the radiographic appearance of serous cystadenomas and overlap in CT characteristics with mucinous neoplasms, most serous neoplasms still require ancillary testing such as biopsy to reach a definitive diagnosis. MRCP is useful in differentiating benign and malignant mucinous tumors including IPMT of the pancreas. The presence of mural nodules is suggestive of malignancy; however, the absence of mural nodules does not indicate that the tumor is benign. A maximum main pancreatic duct diameter of greater than 15 mm and diffuse dilatation of the main pancreatic duct are suggestive of malignancy in main duct-type tumors. Among branch duct-type tumors, malignant tumors tend to be larger than benign tumors; however, this finding is variable. The presence of main pancreatic duct dilatation may be helpful in determining malignancy of branch duct-type tumors.

Association of Helicobacter pylori with central serous chorioretinopathy: hypotheses regarding pathogenesis.

PubMed

Giusti, Cristiano

2004-01-01

Central serous chorioretinopathy (CSC) is a serous macular detachment that usually affects young people and leads fortunately to a spontaneous resolution and a good visual prognosis in most patients. Nevertheless, although in a small percentage of subjects only, it may also develop a chronic or progressive disease with widespread decompensation of the retinal pigment epithelium (RPE) and severe vision loss. The aetiopathogenesis of the disease is still not completely understood and no effective treatment is available at this time. However, an interesting association has been recently highlighted between CSC and the Helicobacter pylori infection. In particular, in a first case report recurrences of the disease were always associated with HP-positivity whereas improvements of both retinal findings and visual acuity were significantly correlated with a successful eradication of the bacterium using the conventional antimicrobial triple-therapy. In a second study, the prevalence of HP infection was found to be significantly higher in CSC-affected subjects compared to age- and sex-matched controls from the same country. Much speculation surrounds the role potentially played by HP in determining CSC. In particular, CSC seems not to be more a merely RPE disease but the final result of a general involvement of the choroidal microcirculation. In fact, several vascular abnormalities, such as localized vasoconstriction and impaired fibrinolysis, have been demonstrated during CSC whose "end-points" might be a focal occlusion of the choriocapillaries with decreased foveal choroidal blood flow, secondary RPE defects and serous macular detachment. Moreover, a HP-dependent immune mechanism, based on a "molecular mimicry" between pathogenic antigens expressed on the bacterium and homologous host proteins (e.g., those of the endothelial vascular wall), might also be involved in the pathophysiology of CSC. In this case, a genetically determined susceptibility of the subject could be

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

PubMed

Yashpal, Madhu; Mittal, Ajay Kumar

2014-02-01

Serous goblet cells in the oral epithelium of Rita rita are characterized by the presence of distinct eosinophilic granules occupying large parts of the cytoplasm. In R. rita, a range of histochemical results reveal that these cells are involved in proteinaceous secretions, and thus likely contribute to various functions analogous to those of mammalian saliva. The secretions of these cells have also been associated with specific functions and are discussed in relation to their physiological importance with special reference to their roles in lubrication, alteration in viscosity, various functions of mucus such as handling, maneuvering and driving of food items toward the esophagus, maintaining taste sensitivity and protection of the oral epithelium. In addition, the serous goblet cells may also be considered as the primary defensive cell of the oral epithelium of R. rita. The results significantly add to very limited set of literature on the serous goblet cells and provide noteworthy information on the mucous secretions in the oral cavity of fish. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Vitrectomy and gas-fluid exchange for the treatment of serous macular detachment due to optic disc pit: long-term evaluation].

PubMed

Moreira Neto, Carlos Augusto; Moreira Junior, Carlos Augusto

2013-01-01

To evaluate 5 patients with serous macular detachment due to optic disc pit that were submitted to pars plana vitrectomy and were followed for at least 7 years. Patients were submitted to pars plana vitrectomy, posterior hyaloid removal, autologous serum injection and gas-fluid exchange, without laser photocoagulation, and were evaluated pre and post-operatively with visual acuity and Amsler grid testing, retinography, and recently, with autofluorescence imaging and high resolution OCT. All 5 eyes improved visual acuity significantly following the surgical procedure maintaining good vision throughout the follow-up period. Mean pre-operative visual acuity was 20/400 and final visual acuity was 20/27 with a mean follow-up time of 13.6 years. No recurrences of serous detachments were observed. OCT examinations demonstrated an attached retina up to the margin of the pit. Serous macular detachments due to optic disc pits were adequately treated with pars plana vitrectomy and gas fluid exchange, without the need for laser photocoagulation, maintaining excellent visual results for a long period of time.

[Affective mentalizing in Addictive Borderline Personality: A literature review].

PubMed

Lecointe, P; Bernoussi, A; Masson, J; Schauder, S

2016-10-01

This literature review concerns affective mentalizing in borderline addictive personality. This concept postulates the group between addictions and borderline personalities may correspond to Personality Disorders (PDs). First, we will present conceptualizations and evaluations of affective mentalizing. The latter refers to one dimension of mentalization, a process by which an individual interprets his/her mental states and those of others. Lecours and Bouchard proposed a hierarchic model: the Élaboration verbale de l'affect (EVA). They also developed an empiric methodology: the Grille de l'élaboration verbale de l'affect (GEVA). The methodological approach of Lecours fulfils the requirements made by Cho-Kain, Gunderson and Luyten, involving a narrower operationalization of the mentalization concept through the evaluation of its dimensions. Conceptualizations and evaluations enabled focus on mentalization psychopathology. Fonagy and Bateman studied this latter in the subjects with PDs, particularly in Borderline Personality Disorders (BPD). We describe mentalization failure, its etiology and consequences in the BPD. Several forms of mentalization psychopathology are identified. Its etiology is largely environmental. Fonagy and Bateman developed the optimum developmental model of mentalization and referred to it to explain etiology of mentalization failure in BPD. Consequences of mentalization failure explicate its functioning. Mentalization may be considered as essential in their comprehension and their care. Research about mentalization of PDs does not integrate addiction as one comorbidity factor. However, Allen, Fonagy and Bateman describe a bidirectional interaction between mentalization failure and addiction. We propose to examine the mentalization of Borderline Addictive Personality. This concept groups addictions and borderline personalities in just one clinical entity other than their links of co-morbidities. Copyright © 2016 L'Encéphale, Paris

MAINTENANCE OF GOOD VISUAL ACUITY IN BEST DISEASE ASSOCIATED WITH CHRONIC BILATERAL SEROUS MACULAR DETACHMENT.

PubMed

Gattoussi, Sarra; Boon, Camiel J F; Freund, K Bailey

2017-08-10

We describe the long-term follow-up of a patient with multifocal Best disease with chronic bilateral serous macular detachment and unusual peripheral findings associated with a novel mutation in the BEST1 gene. Case report. A 59-year-old white woman was referred for an evaluation of her macular findings in 1992. There was a family history of Best disease in the patient's mother and a male sibling. Her medical history was unremarkable. Best-corrected visual acuity was 20/20 in her right eye and 20/25 in her left eye. The anterior segment examination was normal in both eyes. Funduscopic examination showed multifocal hyperautofluorescent vitelliform deposits with areas of subretinal fibrosis in both eyes. An electrooculogram showed Arden ratios of 1.32 in the right eye and 1.97 in the left eye. Ultra-widefield color and fundus autofluorescence imaging showed degenerative retinal changes in areas throughout the entire fundus in both eyes. Optical coherence tomography, including annual eye-tracked scans from 2005 to 2016, showed persistent bilateral serous macular detachments. Despite chronic foveal detachment, visual acuity was 20/25 in her right eye and 20/40 in her left eye, 24 years after initial presentation. Genetic testing showed a novel c.238T>A (p.Phe80Ile) missense mutation in the BEST1 gene. Some patients with Best disease associated with chronic serous macular detachment can maintain good visual acuity over an extended follow-up. To our knowledge, this is the first report of Best disease associated with this mutation in the BEST1 gene.

Early Intervention for Borderline Personality Disorder: Psychodynamic Therapy in Adolescents.

PubMed

Salzer, Simone; Cropp, Carola; Streeck-Fischer, Annette

2014-01-01

Borderline personality disorder (BPD) should be understood as a disorder of development (Streeck-Fischer 2008, 2013) that has its first manifestation in late childhood and adolescence. There are only few treatment studies of adolescents meeting the diagnostic criteria of borderline personality disorder, although early interventions for these patients are urgently needed (see Chanen & McCutcheon 2013). We examined the effectiveness of an inpatient psychodynamic therapy (PDT). Twenty-eight adolescents fulfilling the DSM-IV diagnostic criteria of borderline personality disorder were treated with psychodynamic therapy. The mean duration of treatment was 29.87 weeks (SD = 15.88). Outcomes were remission rates, GAF, GSI, SDQ, IIP and BPI scores. Assessments were made at admission and after treatment. Pre-post comparisons and comparisons with normative data were conducted. At the end of treatment 39.29% of the patients were remitted. We found significant improvements for the GAF, GSI, SDQ, IIP (all p0.001) and the BPI (p = 0.006). These clinically relevant improvements demonstrate the effectiveness of psychodynamic therapy in adolescents with borderline personality disorder and stress the usefulness of an early intervention for these patients.

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.

Sustained unemployment in psychiatric outpatients with bipolar depression compared to major depressive disorder with comorbid borderline personality disorder.

PubMed

Zimmerman, Mark; Martinez, Jennifer H; Young, Diane; Chelminski, Iwona; Dalrymple, Kristy

2012-12-01

The morbidity associated with bipolar disorder is, in part, responsible for repeated calls for improved detection and recognition. No such clinical commentary exists for improved detection of borderline personality disorder in depressed patients. Clinical experience suggests that borderline personality disorder is as disabling as bipolar disorder; however, no studies have directly compared the two disorders. For this reason we undertook the current analysis from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project comparing unemployment and disability rates in patients with bipolar disorder and borderline personality disorder. Patients were interviewed with semi-structured interviews. We compared three non-overlapping groups of depressed patients: (i) 181 patients with DSM-IV major depressive disorder and borderline personality disorder, (ii) 1068 patients with major depressive disorder without borderline personality disorder, and (iii) 84 patients with bipolar depression without borderline personality disorder. Compared to depressed patients without borderline personality disorder, depressed patients with borderline personality disorder were significantly more likely to have been persistently unemployed. A similar difference was found between patients with bipolar depression and major depressive disorder without borderline personality disorder. No differences were found between patients with bipolar depression and depression with borderline personality disorder. Both bipolar disorder and borderline personality disorder were associated with impaired occupational functioning and thus carry a significant public health burden. Efforts to improve detection of borderline personality disorder in depressed patients might be as important as the recognition of bipolar disorder. © 2012 John Wiley and Sons A/S.

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…

Examining the relationship between childhood sexual abuse and borderline personality disorder: does social support matter?

PubMed

Elzy, Meredith B

2011-05-01

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 social support source in a sample of 290 female undergraduate students enrolled at a major southeastern university. Consistent with previous research, retrospective self-reports of childhood sexual abuse and low social support were both positively correlated with current borderline personality features. It was hypothesized that the presence of a supportive relationship at the time the childhood sexual abuse occurred would moderate the relationship between childhood sexual abuse and borderline personality features. This moderation hypothesis was not supported in the current study, but post-hoc analyses reveal the need to further examine how we define social support following childhood sexual abuse. This research is a stepping stone toward the prevention of borderline personality disorder following childhood sexual abuse.

Aloneness and borderline psychopathology: the possible relevance of child development issues.

PubMed

Adler, G; Buie, D H

1979-01-01

The experience of intense painful aloneness is a common event in the lives of borderline patients, especially those closer to the psychotic spectrum. This experience is defined as an intrinsic aspect of the borderline personality defect and consists of a relative or total inability to remember positive images or fantasies of sustaining people in the patient's present or past life, or being overwhelmed by negative memories and images of these people. The development of borderline aloneness is related to a possible developmental failure, defined by Piaget, Fraiberg, and A.-M. Sandler. These workers describe the child's development of object permanence and evocative memory capacity (Piaget's sensori-motor stage VI). We postulate that a major borderline vulnerability is the tenuous achievement of the capacity for affective object permanence and its regressive loss to recognition memory or earlier when under specific stresses. We relate our hypotheses to possible empathic parental failures during the substages of separation-individuation, especially the rapprochement sub-phase. The treatment implications of our formulations are discussed, with an emphasis on the clarification of the need for the therapist's availability and the use of transitional objects during times of the patient's loss of his affective cognitive capacities. These regressive experiences often emerge as a core transference manifestation during psychoanalytic therapy with borderline patients, and often become the basis of significant therapeutic work.

Borderline personality disorder and the emerging field of developmental neuroscience.

PubMed

Crowell, Sheila E; Kaufman, Erin A

2016-10-01

Over the past 2 decades there has been a dramatic shift in understanding of personality disorders, such as borderline personality disorder (BPD). What was historically viewed as an entrenched pattern of antagonistic, interpersonally dependent, and uncorrectable conduct is now seen as the outcome of complex-yet modifiable-developmental processes. The borderline label, which once inspired such harsh opprobrium in clinical communities that early diagnosis was considered taboo, is now increasingly applied to adolescents who are receiving effective treatment and desisting from a borderline trajectory. Research examining the developmental origins and early manifestations of BPD is increasing rapidly, making it an appropriate time to take stock of current developmental research and articulate an agenda for the future. We identify 4 challenges that continue to impede innovative research on borderline personality development: (a) inadequate attention to continuity and discontinuity across development, (b) medical and diagnostic systems that localize personality pathology within the individual, (c) the lingering belief that biological research is antithetical to contextual/interpersonal understandings of psychopathology (and vice versa), and (d) reluctance to reach across disciplinary and developmental boundaries to identify creative paradigms and foster innovative discovery. In order to overcome these challenges, we propose an approach to future research on adolescent borderline pathology that integrates developmental psychopathology, social and affective neuroscience, and personality theory perspectives. This intersection-the developmental neuroscience of personality pathology-offers theoretical and methodological advantages over disciplinary isolation and is fertile ground for generating novel hypotheses on the development and prevention of BPD. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Staff countertransference reactions in the hospital treatment of borderline patients.

PubMed

Brown, L J

1980-11-01

The aim of this paper is to elucidate a systematic framework for understanding the nature of the borderline patient's reactions to the hospital milieu and for comprehending the responses of hospital staff to such patients. The theory and principles of the therapeutic milieu or milieu therapy are not the focus of this paper; rather, the unique ways in which borderline patients create their own reality and interact with that reality are examined. The borderline patients considered here constitute a group who present severe character pathology, including pronounced distortions in reality testing, marked paranoid trends, minimal distinction between self and others, and multiple hospitalizations that have proven ineffectual. Overall, these patients are functioning at a level more regressed than most borderline patients and their histories often reveal many psychotic episodes. Because of their severe psychopathology, long-term intensive treatment in a hospital setting, termed "reconstructive hospital treatment" by Zee (1975), is indicated. The goal of such treatment is to augment the patient's failing ego functioning, to help the patient develop constructive alternatives for dealing with conflict, and to aid the patient develop constructive alternatives for dealing with conflict, and to aid the patient in embarking upon a psychoanalytically oriented exploration of his highly conflicted object relations. Without the use of the hospital as a treatment modality these patients tend to continue in a downward spiral of destructive relationships. These remarks, therefore, are addressed to the effect severely ill borderline patients have upon the hospital milieu and to the impact of the milieu upon them.

Metformin Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2017-01-24

Ovarian Papillary Serous Carcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer

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

Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating its Early Changes

DTIC Science & Technology

We will determine the early molecular changes in STIC and their biological significance in developing high-grade serous carcinoma. marker selection...and sample preparation will begin in the next coming months. Project 2 We will evaluate whether the presence of a STIC is associated with different...clinical manifestations and/or outcome compare to those patients in whom a STIC was not identified. Molecular profiling will be initiated after quality

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

PubMed

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

2017-07-01

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

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

PubMed

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

2017-03-14

High-grade serous ovarian carcinoma (HGSOC) originates mainly from the fallopian tube (FT) epithelium and always carries early TP53 mutations. We previously reported that tumors initiate in the FT fimbria epithelium because of apoptotic failure and the expansion of cells with DNA double-strand breaks (DSB) caused by bathing of the FT epithelial cells in reactive oxygen species (ROSs) and hemoglobin-rich follicular fluid (FF) after ovulation. Because ovulation is frequent and HGSOC is rare, we hypothesized that luteal-phase progesterone (P4) could eliminate p53-defective FT cells. Here we show that P4, via P4 receptors (PRs), induces necroptosis in Trp53 -/- mouse oviduct epithelium and in immortalized human p53-defective fimbrial epithelium through the TNF-α/RIPK1/RIPK3/MLKL pathway. Necroptosis occurs specifically at diestrus, recovers at the proestrus phase of the estrus cycle, and can be augmented with P4 supplementation. These results reveal the mechanism of the well-known ability of progesterone to prevent ovarian cancer. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Robotic enucleation of benign pancreatic tumors

PubMed Central

Ore, Ana Sofia; Barrows, Courtney E.; Solis-Velasco, Monica; Shaker, Jessica

2017-01-01

Robot-assisted enucleation provides the dual benefits of a minimally-invasive technique and pancreatic parenchymal conservation to selected patients with functional pancreatic neuroendocrine tumors (F-pNETs) and serous cystadenomas. Insulinomas, the most common F-pNETs, are ideal candidates for enucleation when <2 cm given the 80% probability of being benign. Current evidence suggests enucleation for the following: benign, isolated lesions with a distance between tumor and main pancreatic duct ≥3 mm (no focal stricture or dilation), insulinomas, gastrinomas <2 cm, and nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) <1–2 cm and low Ki67 mitotic index. Minimally-invasive enucleation is an imaging-dependent procedure that requires recognizable anatomic landmarks for successful completion, including tumor proximity to the pancreatic duct as well as localization relative to major structures such as the gastroduodenal artery, bile duct, and portal vein. Tumor localization often mandates intraoperative ultrasound aided by duplex studies of intratumoral blood flow and frozen section confirmation. Five patients have undergone robot-assisted enucleation at Beth Israel Deaconess Medical Center between January 2014 and January 2017 with median tumor diameter of 1.3 cm (0.9–1.7 cm) located in the pancreatic head [2] and tail [3]. Surgical indications included insulinoma [2] and NF-pNETs [3]. Median operative time was 204 min (range, 137–347 min) and estimated blood loss of 50 mL. There were no conversions to open or transfusions. Robotic enucleation is a safe and feasible technique that allows parenchymal conservation in a minimally-invasive setting, reducing operative time and length of stay with equivalent pathological outcomes compared to open surgery. PMID:29302427

KLF1 gene and borderline hemoglobin A2 in Saudi population.

PubMed

Borgio, J Francis; AbdulAzeez, Sayed; Al-Muslami, Ahmed M; Naserullah, Zaki A; Al-Jarrash, Sana; Al-Suliman, Ahmed M; Al-Madan, Mohammed S; Al-Ali, Amein K

2018-01-01

Elevated HbA 2 (hemoglobin A 2 ) level is considered the most reliable hematological parameter for the detection of β-thalassemia carriers. However, some carriers are difficult to recognize because the level of HbA 2 is not in the distinctive carrier range, i.e. 4.0-6.0%; instead, some carriers have HbA 2 levels between normal and carrier levels, i.e. borderline HbA 2 (HbA 2 = 3.1-3.9%). Studies have shown that variations in the erythroid Krüppel-like factor ( KLF1 ) gene lead to borderline HbA 2 in β-thalassemia carriers from various populations. The incidence of borderline HbA 2 in Saudis is high. To confirm the influence of variations in KLF1 , HBA1 , HBA2 and HBB genes for the reduction of the level of HbA 2 in Saudi β-thalassemia carriers, we performed a direct sequence analysis of KLF1 , HBA1 , HBA2 and HBB genes from 212 healthy Saudis (88 subjects: HbA 2 < 3; 72 subjects: HbA 2 = 3.1 to 3.9; 52 subjects HbA 2 > 4.3). The presence of the borderline HbA 2 level is not specific to any type of β-thalassemia variation or β + -thalassemia variations in Saudis. Two exonic (c.304T>C and c.544T>C) and two 3' untranslated region (3'UTR) (c.*296G>A and c.*277C>G) variations have been identified in the KLF1 gene for the first time from an Arab population. None of these four variations in KLF1 genes are significantly associated with the Saudis with borderline HbA 2 . α Globin genotype, -α 2 3.7 /α 1 α 2 , is found to be the most frequent (55.55%) among healthy Saudis with borderline HbA 2 compared with the other groups (HbA 2 < 3 = 20.45%; HbA 2 > 4.3 = 13.51%). Further studies are necessary to determine the influence of other factors on the presence of borderline HbA 2 in 41.67% of Saudis.

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

PubMed

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

2018-01-17

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

The psychodynamics of borderline psychopathology.

PubMed

Corradi, Richard B

2015-01-01

The concept of borderline personality disorder (BPD) remains problematic despite psychiatrists' general familiarity with its DSM diagnostic criteria. The diagnosis of BPD is frequently based simply on the DSM checklist of traits and symptoms without knowledge of their origins or significance. Misdiagnosis is common, as is lack of recognition of the full complexity of this severe personality disorder and the nature of the vulnerabilities that underlie its myriad forms of pathology. The stresses of ordinary life are often too much for people with BPD. Knowledge of the nature and origins of their stress points, such as their great fear of loss or rejection, is necessary for adequate diagnosis and treatment. The author addresses how signature features of the disorder relate to psychosocial development, how they correlate with failed developmental milestones, and how they can be understood psychodynamically. This is essential knowledge for psychotherapists because the pathological interpersonal relationships of the borderline patient will be repeated and acted out in the transference, whatever the modality or intensity of treatment.

Significance of aggressive surgery for an invasive carcinoma derived from an intraductal papillary mucinous neoplasm diagnosed preoperatively as borderline resectable.

PubMed

Aimoto, Takayuki; Mizutani, Satoshi; Kawano, Youichi; Suzuki, Hideyuki; Uchida, Eiji

2013-01-01

We investigated the clinicopathological features of borderline resectable invasive carcinomas (BRICs) derived from intraductal papillary mucinous neoplasms (IPMNs) and examined the significance of the aggressive "surgery first" approach compared with the treatment of conventional borderline resectable pancreatic ductal adenocarcinomas (BRPDAs). We retrospectively studied 7 patients with BRICs derived from IPMNs and 14 patients with conventional BRPDAs. Several factors were reviewed: initial symptoms, preoperative imaging, serum level of CA19-9, perioperative factors, pathological findings, adjuvant chemotherapy, and outcome. All BRICs derived from IPMN were huge tumors (more than 3 cm in diameter) suspected to involve <180° of the circumference of the vessel. Five patients (71%) underwent a modified Whipple procedure, and 2 (29%) underwent distal pancreatectomy. Only 3 patients (43%) required vascular resection. Curative resection was achieved in all 7 patients, who are alive with no evidence of recurrence. There were no severe postoperative complications. With regards to the pathological IPMN subtype, 2 tumors (29%) were gastric and 5 (71%) were intestinal. Only 2 patients (29%) had lymph node metastasis. The final stage was II in 4 (57%) cases and IVa in 3 cases (43%). The 3-year survival rate was 100%. Tumors of BRICs derived from IPMNs were larger than those of conventional BRPDAs (p<0.05). The BRICs derived from IPMN less frequently metastasized to lymph nodes (p<0.05) and were of an earlier stage (p<0.05) than were conventional BRPDAs. The 3-year survival rate was significantly higher for BRICs derived from IPMNs (100%) than for conventional BRPDAs (19%, p<0.001). The BRICs derived from an intestinal or gastric IPMN are less aggressive than conventional BRPDAs and have a more favorable prognosis. In addition, aggressive "surgery first" approach may contribute to this better prognosis.

The Emerging Genomic Landscape of Endometrial Cancer

PubMed Central

Le Gallo, Matthieu; Bell, Daphne W.

2014-01-01

BACKGROUND Endometrial cancer is responsible for ~74,000 deaths amongst women worldwide each year. It is a heterogeneous disease that consists of multiple different histological subtypes. In the United States, the majority of deaths from endometrial carcinoma are attributed to the serous and endometrioid subtypes. An understanding of the fundamental genomic alterations that drive serous and endometrioid endometrial carcinomas lays the foundation for the identification of molecular markers that could improve the clinical management of patients presenting with these tumors. CONTENT Herein we review the current state of knowledge of the somatic genomic alterations that are present in serous and endometrioid endometrial tumors. We present this knowledge in a historical context – reviewing the genomic alterations that have been identified over the past two decades or more, from studies of individual genes and proteins, followed by a review of very recent studies that have conducted comprehensive, systematic surveys of genomic, exomic, transcriptomic, epigenomic, and proteomic alterations in serous and endometrioid endometrial carcinomas. SUMMARY The recent mapping of the genomic landscape of serous and endometrioid endometrial carcinomas has resulted in the first comprehensive molecular classification of these tumors and has distinguished four molecular subgroups: a POLE ultramutated subgroup, a hypermutated/microsatellite unstable subgroup, a copy number low/microsatellite stable subgroup, and a copy number high subgroup. This molecular classification may ultimately serve to refine the diagnosis and treatment of women with endometrioid and serous endometrial tumors. PMID:24170611

Relationship between borderline personality symptoms and Internet addiction: The mediating effects of mental health problems.

PubMed

Lu, Wei-Hsin; Lee, Kun-Hua; Ko, Chih-Hung; Hsiao, Ray C; Hu, Huei-Fan; Yen, Cheng-Fang

2017-09-01

Aim To examine the relationship between borderline personality symptoms and Internet addiction as well as the mediating role of mental health problems between them. Methods A total of 500 college students from Taiwan were recruited and assessed for symptoms of Internet addiction using the Chen Internet Addiction Scale, borderline personality symptoms using the Taiwanese version of the Borderline Symptom List and mental health problems using four subscales from the Symptom Checklist-90-Revised Scale (interpersonal sensitivity, depression, anxiety, and hostility). Structural equation modeling (SEM) was used to test our hypothesis that borderline personality symptoms are associated with the severity of Internet addiction directly and also through the mediation of mental health problems. Results SEM analysis revealed that all paths in the hypothesized model were significant, indicating that borderline personality symptoms were directly related to the severity of Internet addiction as well as indirectly related to the severity of Internet addiction by increasing the severity of mental health problems. Conclusion Borderline personality symptoms and mental health problems should be taken into consideration when designing intervention programs for Internet addiction.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

First evidence of a prospective relation between avoidance of internal states and borderline personality disorder features in adolescents.

PubMed

Sharp, Carla; Kalpakci, Allison; Mellick, William; Venta, Amanda; Temple, Jeff R

2015-03-01

At least two leading developmental models of borderline personality disorder (BPD) emphasize the role of accurate reflection and understanding of internal states as significant to the development of BPD features (Fonagy, Int J Psycho-Anal 72:639-656, 1991; Linehan, Cognitive-behavioral treatment of borderline personality disorder, 1993). The current study used the construct of experiential avoidance (EA) to operationalize avoidance of internal states and sought to examine (1) the concurrent relations between EA and borderline features in a large and diverse community sample; and (2) the prospective relation between EA and borderline features over a 1-year follow-up, controlling for baseline levels of borderline features. N = 881 adolescents recruited from public schools in a large metropolitan area participated in baseline assessments and N = 730 completed follow-up assessments. Two main findings were reported. First, EA was associated with borderline features, depressive, and anxiety symptoms at the bivariate level, but when all variables were considered together, depression and anxiety no longer remained significantly associated with borderline features, suggesting that the relations among these symptom clusters may be accounted for by EA as a cross-cutting underlying psychological process. Second, EA predicted levels of borderline symptoms at 1-year follow-up, controlling for baseline levels of borderline symptoms, and symptoms of anxiety and depression. Results are interpreted against the background of developmental theories of borderline personality disorder.

Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary.

PubMed

Ahmed, Ahmed Ashour; Etemadmoghadam, Dariush; Temple, Jillian; Lynch, Andy G; Riad, Mohamed; Sharma, Raghwa; Stewart, Colin; Fereday, Sian; Caldas, Carlos; Defazio, Anna; Bowtell, David; Brenton, James D

2010-05-01

Numerous studies have tested the association between TP53 mutations in ovarian cancer and prognosis but these have been consistently confounded by limitations in study design, methodology, and/or heterogeneity in the sample cohort. High-grade serous (HGS) carcinoma is the most clinically important histological subtype of ovarian cancer. As these tumours may arise from the ovary, Fallopian tube or peritoneum, they are collectively referred to as high-grade pelvic serous carcinoma (HGPSC). To identify the true prevalence of TP53 mutations in HGPSC, we sequenced exons 2-11 and intron-exon boundaries in tumour DNA from 145 patients. HGPSC cases were defined as having histological grade 2 or 3 and FIGO stage III or IV. Surprisingly, pathogenic TP53 mutations were identified in 96.7% (n = 119/123) of HGPSC cases. Molecular and pathological review of mutation-negative cases showed evidence of p53 dysfunction associated with copy number gain of MDM2 or MDM4, or indicated the exclusion of samples as being low-grade serous tumours or carcinoma of uncertain primary site. Overall, p53 dysfunction rate approached 100% of confirmed HGPSCs. No association between TP53 mutation and progression-free or overall survival was found. From this first comprehensive mapping of TP53 mutation rate in a homogeneous group of HGPSC patients, we conclude that mutant TP53 is a driver mutation in the pathogenesis of HGPSC cancers. Because TP53 mutation is almost invariably present in HGPSC, it is not of substantial prognostic or predictive significance. Copyright (c) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Borderline personality disorder in the primary care setting.

PubMed

Dubovsky, Amelia N; Kiefer, Meghan M

2014-09-01

Borderline personality disorder is estimated to be present in approximately 6% of outpatient primary care settings. However, the time and energy spent on this population can greatly exceed what primary care doctors are able to spend. This article gives an overview of borderline personality disorder, including the clinical characteristics, epidemiology, and comorbidities, as well as pharmacologic and most important behavioral management. It is our hope that, with improved understanding of the disorder and skills for managing this population, caring for patients with the disorder can be more satisfying and less taxing for both primary care doctors and their patients. Copyright © 2014 Elsevier Inc. All rights reserved.

[Comparison of paired box genes 8 and 2 expression in epithelium tissues and the related tumors].

PubMed

Song, Y; Huang, X; Shen, G H; Liu, X Y; Zhang, X

2017-06-23

Objective: To explore the expressional differences between paired box genes 2(Pax2) and 8 (Pax8) protein in different kinds of epitheliums and tumors, and to investigate the clinicopathologic significance. Methods: Expression levels of Pax2 and Pax8 protein were detected in 75 cases of different human epithelium tissues and 255 cases of different tumors on tissue microarray by immunohistochemistry. Results: Pax2 and Pax8 selectively expressed in different tissues. The positive rates of Pax8 protein expressed in the normal epithelium of the thyroid, urinary system and female reproductive system were 100% (2/2), 60.0% (3/5) and 76.9% (10/13), respectively. The positive rates of Pax2 expressed in the epithelium tissues of urinary system and the female reproductive system were 40.0% (2/5) and 38.5% (5/13) respectively. However, the expression of Pax2 protein was not detected in the normal thyroid epithelium. The positive rate of Pax8 protein expressing in the epithelium of reproductive system was significantly higher than that of Pax2 protein ( P <0.05). The tumors derived from different tissues also expressed different levels of protein Pax2 and Pax8. The positive rates of Pax8 in renal cell carcinoma, thyroid carcinoma and endometrial adenocarcinoma were 65.2% (15/23), 66.7% (10/15) and 80.0% (4/5), respectively. The positive rates of Pax2 in renal cell carcinoma, thyroid carcinoma and endometrial adenocarcinoma were 34.8% (8/23), 13.3% (2/15) and 20.0% (1/5), respectively. The positive rates of Pax8 protein expressed in renal cell carcinoma, thyroid carcinoma and endometrial adenocarcinoma were significantly higher than those of Pax2 protein ( P <0.05). The positive rates of Pax8 in ovarian serous carcinoma, endometrial carcinoma and clear cell carcinoma were 92.9% (26/28), 81.8% (9/11) and 82.4% (14/17), respectively. The positive rates of Pax2 in ovarian serous carcinoma, endometrial carcinoma and clear cell carcinoma were 28.6% (8/28), 9.1% (1/11) and 17.6% (3

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…

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.…

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…

Is self disturbance the core of borderline personality disorder? An outcome study of borderline personality factors.

PubMed

Meares, Russell; Gerull, Friederike; Stevenson, Janine; Korner, Anthony

2011-03-01

To determine which constellation of clinical features constitutes the core of borderline personality disorder (BPD). The criterion of endurance was used to identify the constellation of features which are most basic, or core, in borderline personality disorder. Two sets of constellations of DSM-III features were tested, each consisting of three groupings. The first set of constellations was constructed according to Clarkin's factor analysis; the second was theoretically derived. Broadly speaking, the three groupings concerned 'self', 'emotional regulation', and 'impulse'. Changes of these constellations were charted over one year in a comparison of the effect of treatment by the Conversational Model (n = 29) with treatment as usual (n = 31). In addition, measures of typical depression (Zung) were scored before and after the treatment period. The changes in the constellations were considered in relation to authoritative opinion. The changes in the two sets of constellations were similar. In the treatment as usual (TAU) group, 'self' endured unchanged, while 'emotional regulation' and 'impulse' improved. In the Conversational Model cohort, 'self' improved, 'emotional regulation' improved more greatly than the TAU group, while 'impulse' improved but not more than the treatment as usual group. Depression scores were not particularly associated with any grouping. A group of features including self/identity disturbance, emptiness and fear of abandonment may be at the core of BPD. Correlations between the three groupings and Zung scores favoured the view that the core affect is not typical depression. Rather, the central state may be 'painful incoherence'. It is suggested that the findings have implications for the refinement and elaboration of treatment methods in borderline personality disorder.

Longitudinal transmission pathways of borderline personality disorder symptoms: from mother to child?

PubMed

Reinelt, Eva; Stopsack, Malte; Aldinger, Maren; Ulrich, Ines; Grabe, Hans Jörgen; Barnow, Sven

2014-01-01

There is evidence that the borderline symptomatology of the mother longitudinally predicts the number of borderline criteria met by the children. However, possible underlying mechanisms have rarely been examined. In line with transactional models of borderline personality disorder (BPD), we analyzed a broad concept of maladaptive mother-child interactions of mothers with BPD symptoms towards their children, including insensitive parenting and mother-child discrepancies, in reporting the child's psychopathological behavior. SAMPLING/METHODS: The sample was drawn from the population-based Greifswald Family Study and consisted of 295 children and their biological mothers. Both were examined at two points in time, first when the children were about 15 years old (T0) and again 5 years later (T1), using path analyses. Maladaptive mother-child interactions (especially an overprotective and rejecting parenting style and high discrepancies regarding internalizing problems) mediate the longitudinal transmission of borderline symptoms from mother to child. Furthermore, our data revealed that this result is consistent for various youth symptoms which are associated with BPD such as impulsivity or dissociation. The data of the current study imply that the transmission of borderline symptoms from mother to child is mediated by maladaptive mother-child interactions. For this reason early and professional support may be useful to prevent these children from developing severe psychopathology. Copyright © 2012 S. Karger AG, Basel.

Childhood adversity and borderline personality disorder: a focus on adolescence.

PubMed

Newnham, Elizabeth A; Janca, Aleksandar

2014-01-01

This article explores recent research in the field of childhood exposure to trauma and the development of borderline personality disorder in adolescence. Adolescence is a critical period of development. Exposure to trauma, specifically sexual abuse, prior to and during puberty has specific implications for personality development and heightens risk for borderline personality disorder. Elevated symptom levels in adolescence are likely to decline across adulthood, but social and vocational impairments remain. Impulsivity, difficulties in emotion regulation, and suicidality may characterize adolescent expression of borderline personality disorder, whereas negative affect and functional impairment are more stable features of the disorder. Preliminary findings in treatment models for adults have potential for benefit among adolescence. Further research is required to examine treatment effectiveness and efficiency. Greater attention to low-income and middle-income nations, which are disproportionately affected by adversity, is needed to determine cross-cultural validity and the impact of trauma in adolescent populations.

Impact of Banff borderline acute rejection among renal allograft recipients.

PubMed

Matoza, J R A; Danguilan, R A; Chicano, S

2008-09-01

This study was performed to determine the incidence, treatment, and outcomes of Banff borderline acute rejection (AR) among renal transplant recipients. We reviewed the courses of adult kidney transplant recipients with borderline AR on clinically indicated biopsies performed at our center from January 2003 to July 2006. Patients with complete transplant records and serum creatinine values at 6 and 12 months were included in this study. The primary outcome measures were serum creatinine values at 1 to 2 weeks after treatment, and at 6 and 12 months after graft biopsy. Among 428 renal graft biopsies, borderline AR was observed in 100 cases (23%). Patients were maintained on the same immunosuppression. The 86 who had complete data were included in the study. Seventy-eight percent of the patients received treatment with 3 days of methylprednisolone, while 22% were untreated. Mean serum creatinine values in the treated group were 2.9 +/- 1.0, 2.6 +/- 2.5, and 3.0 +/- 2.9 mg/dL at the time of biopsy, and at 6 and 12 months thereafter, respectively. In the untreated group, mean serum creatinine values were 2.2 +/- 1.0, 1.9 +/- 0.8, and 2.3 +/- 1.2 mg/dL during biopsy, and at 6 and 12 months thereafter, respectively. There was no significant difference in the serum creatinine at any of the measured time points between the 2 groups. Twelve patients had repeat renal graft biopsies which showed AR (6%), chronic allograft nephropathy (2.4%), and borderline changes (3.8%). Nine of the patients in the treated group eventually developed graft loss. Patients with borderline AR showed a progressive increase in serum creatinine over time. They should be followed closely; immunosuppression may need to be intensified.

Prevalence of High-Grade Cartilage Defects in Patients With Borderline Dysplasia With Femoroacetabular Impingement: A Comparative Cohort Study.

PubMed

Bolia, Ioanna K; Briggs, Karen K; Locks, Renato; Chahla, Jorge; Utsunomiya, Hajime; Philippon, Marc J

2018-05-02

To compare the prevalence, size, and location of Outerbridge grade III and IV cartilage defects on the femoral head and acetabulum between patients with borderline acetabular dysplasia and patients with non-borderline dysplasia who underwent hip arthroscopy for femoroacetabular impingement (FAI). Patients aged 18 years or older who underwent primary hip arthroscopy for correction of FAI and labral repair from November 2005 to April 2016 were included. We excluded patients with previous hip surgery, a radiographic hip joint space of 2 mm or less, and/or a lateral center-edge angle (LCEA) of less than 20° or greater than 40°. The study patients were divided into 2 groups based on the LCEA on the anteroposterior pelvic radiograph: Patients with an LCEA between 20° and 25° were included in the borderline group, and patients with an LCEA between 25° and 40° were included in the non-borderline group. The prevalence, size, and location of Outerbridge grade III and IV chondral lesions on the femoral head and acetabulum were recorded intraoperatively. Comparisons between groups were performed with the Mann-Whitney U test for nonparametric testing and the t test for data that were normally distributed. Data were analyzed to calculate odds ratios associated with the various factors. In total, 2,429 patients (1,114 women and 1,315 men) met the inclusion criteria. The borderline group consisted of 305 patients (150 men and 155 women), whereas the non-borderline dysplasia group comprised 2,124 patients (1,165 men and 959 women). Outerbridge grade III and IV chondral lesions were found on the femoral head in 118 patients with borderline dysplasia (39%) and 127 patients with non-borderline dysplasia (6%) and on the acetabulum in 132 patients with borderline dysplasia (43%) and 874 patients with non-borderline dysplasia (41%). Patients with borderline dysplasia were 10 times more likely (95% confidence interval, 7.3-13.4; P < .001) to have a grade III or IV cartilage

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

PubMed

Giovansili, Iama; Belange, Georeges; Affortit, Aude

2013-01-01

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

Cancer-testis antigen expression is shared between epithelial ovarian cancer tumors.

PubMed

Garcia-Soto, Arlene E; Schreiber, Taylor; Strbo, Natasa; Ganjei-Azar, Parvin; Miao, Feng; Koru-Sengul, Tulay; Simpkins, Fiona; Nieves-Neira, Wilberto; Lucci, Joseph; Podack, Eckhard R

2017-06-01

Cancer-testis (CT) antigens have been proposed as potential targets for cancer immunotherapy. Our objective was to evaluate the expression of a panel of CT antigens in epithelial ovarian cancer (EOC) tumor specimens, and to determine if antigen sharing occurs between tumors. RNA was isolated from EOC tumor specimens, EOC cell lines and benign ovarian tissue specimens. Real time-PCR analysis was performed to determine the expression level of 20 CT antigens. A total of 62 EOC specimens, 8 ovarian cancer cell lines and 3 benign ovarian tissues were evaluated for CT antigen expression. The majority of the specimens were: high grade (62%), serous (68%) and advanced stage (74%). 58 (95%) of the EOC tumors analyzed expressed at least one of the CT antigens evaluated. The mean number of CT antigen expressed was 4.5 (0-17). The most frequently expressed CT antigen was MAGE A4 (65%). Antigen sharing analysis showed the following: 9 tumors shared only one antigen with 62% of the evaluated specimens, while 37 tumors shared 4 or more antigens with 82%. 5 tumors expressed over 10 CT antigens, which were shared with 90% of the tumor panel. CT antigens are expressed in 95% of EOC tumor specimens. However, not a single antigen was universally expressed across all samples. The degree of antigen sharing between tumors increased with the total number of antigens expressed. These data suggest a multi-epitope approach for development of immunotherapy for ovarian cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

A proteomic signature of ovarian cancer tumor fluid identified by highthroughput and verified by targeted proteomics.

PubMed

Poersch, Aline; Grassi, Mariana Lopes; Carvalho, Vinícius Pereira de; Lanfredi, Guilherme Pauperio; Palma, Camila de Souza; Greene, Lewis Joel; de Sousa, Christiani Bisinoto; Carrara, Hélio Humberto Angotti; Candido Dos Reis, Francisco José; Faça, Vitor Marcel

2016-08-11

Tumor fluid samples have emerged as a rich source for the identification of ovarian cancer in the context of proteomics studies. To uncover differences among benign and malignant ovarian samples, we performed a quantitative proteomic study consisting of albumin immunodepletion, isotope labeling with acrylamide and in-depth proteomic profiling by LC-MS/MS in a pool of 10 samples of each histological type. 1135 proteins were identified, corresponding to 505 gene products. 223 proteins presented associated quantification and the comparative analysis of histological types revealed 75 differentially abundant proteins. Based on this, we developed a panel for targeted proteomic analysis using the multiple reaction monitoring (MRM) method for validation of 51 proteins in individual samples of high-grade serous ovarian tumor fluids (malignant) and benign serous cystadenoma tumor fluids. This analysis showed concordant results in terms of average amounts of proteins, and APOE, SERPINF2, SERPING1, ADAM17, CD44 and OVGP1 were statistically significant between benign and malignant group. The results observed in the MRM for APOE were confirmed by western blotting, where APOE was more abundant in malignant samples. This molecular signature can contribute to improve tumor stratification and shall be investigated in combination with current biomarkers in larger cohorts to improve ovarian cancer diagnosis. Despite advances in cancer research, ovarian cancer has a high mortality and remains a major challenge due to a number of particularities of the disease, especially late diagnosis caused by vague clinical symptoms, the cellular and molecular heterogeneity of tumors, and the lack of effective treatment. Thus, efforts are directed to better understand this neoplasia, its origin, development and, particularly the identification and validation of biomarkers for early detection of the disease in asymptomatic stage. In the present work, we confirmed by MRM method in individual ovarian

Borderline histories: psychoanalysis inside and out.

PubMed

Lunbeck, Elizabeth

2006-03-01

Sociologists and historians have long favored externalist over internalist accounts of practices in the clinical disciplines. This has been particularly true in the case of the so-called new patient or borderline personality, which a range of commentators have located in culturally resonant narratives of decline. I argue here that these narratives, while pleasing, do not hold up as history; most problematic is their assumption that the appearance of the borderline portends the emergence of altogether novel forms of modal personhood. Internalist accounts of the category's consolidation are equally problematic in asserting a coherence and a stable referent that repeatedly proves elusive. In the end, I suggest that a complex account of disciplinary practice that attends to knowledge production in the clinical encounter supports the conclusion that the new patient was new to psychoanalysis. Whether or not he was altogether new cannot be established, undermining the critics' certitude and prophecies of decline.

Integrated Analyses of microRNAs Demonstrate Their Widespread Influence on Gene Expression in High-Grade Serous Ovarian Carcinoma

PubMed Central

Levine, Douglas A.; Mankoo, Parminder; Schultz, Nikolaus; Du, Ying; Zhang, Yiqun; Larsson, Erik; Sheridan, Robert; Xiao, Weimin; Spellman, Paul T.; Getz, Gad; Wheeler, David A.; Perou, Charles M.; Gibbs, Richard A.; Sander, Chris; Hayes, D. Neil; Gunaratne, Preethi H.

2012-01-01

Background The Cancer Genome Atlas (TCGA) Network recently comprehensively catalogued the molecular aberrations in 487 high-grade serous ovarian cancers, with much remaining to be elucidated regarding the microRNAs (miRNAs). Here, using TCGA ovarian data, we surveyed the miRNAs, in the context of their predicted gene targets. Methods and Results Integration of miRNA and gene patterns yielded evidence that proximal pairs of miRNAs are processed from polycistronic primary transcripts, and that intronic miRNAs and their host gene mRNAs derive from common transcripts. Patterns of miRNA expression revealed multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression across tumors showed a higher frequency of in silico predicted target sites in the mRNA 3′-untranslated region (with less frequency observed for coding sequence and 5′-untranslated regions). The miR-29 family and predicted target genes were among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR-29a in vitro repressed several anti-correlated genes (including DNMT3A and DNMT3B) and substantially decreased ovarian cancer cell viability. Conclusions This study establishes miRNAs as having a widespread impact on gene expression programs in ovarian cancer, further strengthening our understanding of miRNA biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit high diversity reflecting the genomic heterogeneity within a clinically homogeneous disease population. Putative miRNA:mRNA interactions, as identified using integrative analysis, can be validated. TCGA data are a valuable resource for the identification of novel tumor suppressive miRNAs in ovarian as well as other cancers. PMID:22479643

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

PubMed

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

2012-01-01

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

A single-center experience and review of the literature: 64 cases of phyllodes tumors to better understand risk factors and disease management.

PubMed

Lightner, Amy L; Shurell, Elizabeth; Dawson, Nicole; Omidvar, Yasaman; Foster, Nova

2015-03-01

Phyllodes tumors of the breast are rare fibroepithelial tumors that are characterized as benign, borderline, or malignant based on cellular characteristics such as stromal overgrowth and number of mitoses. Currently, there is a lack of consensus on risk factors and management of patients with phyllodes tumors, which has led to variation in treatment patterns as well as patient outcomes across many institutions. This study seeks to understand the clinicopathologic features, risk factors for local and metastatic recurrence, and clinical outcomes of patients with phyllodes tumors to better define optimal treatment patterns.

Assessing suicidal youth with antisocial, borderline, or narcissistic personality disorder.

PubMed

Links, Paul S; Gould, Brent; Ratnayake, Ruwan

2003-06-01

This paper has 3 objectives. First, we review the epidemiologic evidence for the association between suicidal behaviour and suicide in individuals diagnosed with antisocial, borderline, or narcissistic personality disorder. Second, we examine whether any potentially modifiable risk factors are associated with these diagnoses, based on existing empirical evidence. Last, we discuss clinical approaches to assessing youth with antisocial, borderline, or narcissistic personality disorder presenting at risk for suicide. We reviewed the English-language literature for the last 12 years (from January 1, 1991, to December 31, 2002), using as search terms the names of the 3 disorders, as well as the key words suicide, suicidal behaviour, youth, and adolescents. Patients with antisocial or borderline personality disorder are likely to be at increased risk for suicidal behaviour when they demonstrate such comorbid disorders as major depressive episodes or substance abuse disorders, when they experience recent negative life events, or when they have a history of childhood sexual abuse. For patients with antisocial personality disorder, the risk of violence has to be judged in addition to the risk of suicide or self-harm. For patients with borderline personality disorder, interventions are determined by differentiating acute-on-chronic from chronic risk of suicidal behaviour. Finally, patients with narcissistic personality disorder can be at high risk for suicide during periods when they are not suffering from clinical depression. These episodes can seem to be unpredictable.

The Neural Correlates of Anomalous Habituation to Negative Emotional Pictures in Borderline and Avoidant Personality Disorder Patients

PubMed Central

Koenigsberg, Harold W.; Denny, Bryan T.; Fan, Jin; Liu, Xun; Guerreri, Stephanie; Jo Mayson, Sarah; Rimsky, Liza; New, Antonia S.; Goodman, Marianne; Siever, Larry J

2013-01-01

Objective Extreme emotional reactivity is a defining feature of borderline personality disorder, yet the neural-behavioral mechanisms underlying this affective instability are poorly understood. One possible contributor would be diminished ability to engage the mechanism of emotional habituation. We tested this hypothesis by examining behavioral and neural correlates of habituation in borderline patients, healthy controls, and a psychopathological control group of avoidant personality disorder patients. Method During fMRI scan acquisition, borderline patients, healthy controls and avoidant personality disorder patients viewed novel and repeated pictures, providing valence ratings at each presentation. Statistical parametric maps of the contrasts of activation during repeat versus novel negative picture viewing were compared between groups. Psychophysiological interaction analysis was employed to examine functional connectivity differences between groups. Results Unlike healthy controls, neither borderline nor avoidant personality disorder participants showed increased activity in dorsal anterior cingulate cortex when viewing repeat versus novel pictures. This failure to increase dorsal anterior cingulate activity was associated with greater affective instability in borderline participants. In addition, borderline and avoidant participants showed smaller insula-amygdala connectivity increases than healthy participants and did not show habituation in ratings of the emotional intensity of the images as did healthy participants. Borderline patients differed from avoidant patients in insula-ventral anterior cingulate connectivity during habituation. Conclusions Borderline patients fail to habituate to negative pictures as do healthy participants and differ from both healthy controls and avoidant patients in neural activity during habituation. A failure to effectively engage emotional habituation processes may contribute to affective instability in borderline patients

[Symptoms of DSM IV borderline personality disorder in a nonclinical population of adolescents: study of a series of 35 patients].

PubMed

Chabrol, H; Chouicha, K; Montovany, A; Callahan, S

2001-01-01

1,363 high school students were solicited to complete a personality disorder questionnaire and were encouraged to continue in the study by signing up for interviews with Master's level psychology students. 107 students (7.8%, 34 males, 73 females, mean age = 16.7 +/- 1.8) manifested themselves for the interview and were assessed by using structured diagnostic interviews for borderline personality disorder and major depressive disorder (DIB-R, Revised Diagnostic Interview for Borderlines; MINI, Mini International Neuropsychiatric Interview). The interviews were audiotaped. Interrater reliability was determined by independent ratings of 12 borderline subjects and 12 non-borderline subjects (kappa: 0.795). The distribution of the 107 subjects based on the number of DSM IV borderline personality disorder criteria indicated a gradual dispersion suggesting a continuum from normality to borderline personality disorder: 8% of the subjects met none of the criteria; 16% met one criterion; 17% met two; 12.5%, three; 13.7%, four; 8.4%, five; 5.6%, six; 9.3%, seven; 4.6%, eight; 4.6%, nine. Thirty-five of these 107 subjects (32.7%, 6 males, 29 females, mean age = 16.7 +/- 1.7) received a diagnosis of borderline personality disorder according to DSM IV criteria. The most frequent symptoms were paranoid ideation or dissociative symptoms (97.1%), affective instability (88.6%), inappropriate, intense anger (85.6%), suicidal gestures or automutilation (82.9%), followed by frantic efforts to avoid abandonment (77%), impulsivity (65.7%), unstable and intense relationships (62.9%), identity disturbance (60%), and emptiness (57.1%). The comparison between borderline and non-borderline subjects showed that all borderline personality disorder criteria discriminated significantly between the two groups. The high incidence of paranoid ideation (97.1%) and dissociative experiences (65.7%) in the borderline group suggests the pertinence of criterion 9 in the diagnosis of borderline

The role of defense mechanisms in borderline and antisocial personalities.

PubMed

Presniak, Michelle D; Olson, Trevor R; Macgregor, Michael Wm

2010-03-01

We examined whether borderline personality disorder (BPD) and antisocial personality disorder (APD) could be differentiated based on defense mechanisms as measured by observer (Defense-Q; MacGregor, Olson, Presniak, & Davidson, 2008) and self-report (Defense Style Questionnaire; Andrews, Singh, & Bond, 1993) measures. We conducted 2 studies whereby nonclinical participants were divided into borderline and antisocial groups based on scores from the Personality Assessment Inventory (Morey, 1991). Multivariate analysis of variance results revealed significant overall group differences in defense use. Univariate analyses further showed group differences on several individual defenses (e.g., acting out, denial, and turning against self). Together, the findings suggest that in BPD, the defenses may emphasize interpersonal dependency and a tendency to direct aggression toward the self; whereas in APD, the defenses may emphasize egocentricity, interpersonal exploitation, and a tendency to direct aggression toward others. Overall, this study demonstrates important differences in defense use between borderline and antisocial personality groups across both observer and self-report measures.

HCO3(-) secretion by murine nasal submucosal gland serous acinar cells during Ca2+-stimulated fluid secretion.

PubMed

Lee, Robert J; Harlow, Janice M; Limberis, Maria P; Wilson, James M; Foskett, J Kevin

2008-07-01

Airway submucosal glands contribute to airway surface liquid (ASL) composition and volume, both important for lung mucociliary clearance. Serous acini generate most of the fluid secreted by glands, but the molecular mechanisms remain poorly characterized. We previously described cholinergic-regulated fluid secretion driven by Ca(2+)-activated Cl(-) secretion in primary murine serous acinar cells revealed by simultaneous differential interference contrast (DIC) and fluorescence microscopy. Here, we evaluated whether Ca(2+)-activated Cl(-) secretion was accompanied by secretion of HCO(3)(-), possibly a critical ASL component, by simultaneous measurements of intracellular pH (pH(i)) and cell volume. Resting pH(i) was 7.17 +/- 0.01 in physiological medium (5% CO(2)-25 mM HCO(3)(-)). During carbachol (CCh) stimulation, pH(i) fell transiently by 0.08 +/- 0.01 U concomitantly with a fall in Cl(-) content revealed by cell shrinkage, reflecting Cl(-) secretion. A subsequent alkalinization elevated pH(i) to above resting levels until agonist removal, whereupon it returned to prestimulation values. In nominally CO(2)-HCO(3)(-)-free media, the CCh-induced acidification was reduced, whereas the alkalinization remained intact. Elimination of driving forces for conductive HCO(3)(-) efflux by ion substitution or exposure to the Cl(-) channel inhibitor niflumic acid (100 microM) strongly inhibited agonist-induced acidification by >80% and >70%, respectively. The Na(+)/H(+) exchanger (NHE) inhibitor dimethylamiloride (DMA) increased the magnitude (greater than twofold) and duration of the CCh-induced acidification. Gene expression profiling suggested that serous cells express NHE isoforms 1-4 and 6-9, but pharmacological sensitivities demonstrated that alkalinization observed during both CCh stimulation and pH(i) recovery from agonist-induced acidification was primarily due to NHE1, localized to the basolateral membrane. These results suggest that serous acinar cells secrete HCO(3

Clinical management of borderline tumours of the ovary - experience from the "Berlin online tumour conference for gynaecological malignancies".

PubMed

Sehouli, Jalid; Oskay-Oezcelik, Guelten; Pietzner, Klaus; Chen, Frank; Coumbos, Alexandra; Darb-Esfahani, Silvia; Schuback, Beatrix; Heinrich, Georg; Kronenberger, Christel; Lorsbach, Michael; Lichtenegger, Werner; Chekerov, Radoslav

2010-05-01

Borderline ovarian tumour (BOT) represents a rare and special tumour entity. Despite a generally favourable prognosis for patients with BOT, the presence of invasive peritoneal implants decreases the survival rate to 30-50%. In contrast to ovarian cancer, only few data exist concerning the current clinical management of patients with BOT. For this reason, the present analyses were performed for patients with BOT who were admitted into our online tumor conference for patients with gynaecological malignancies. Based on the results discussed in this article, the current aspects and problems regarding the diagnostic, surgical and conservative treatment and aftercare management of patients with BOT are considered.

The Effect of Attending Good Psychiatric Management (GPM) Workshops on Attitudes Toward Patients With Borderline Personality Disorder.