Malpica, A; Wong, K-K
Molecular studies in ovarian serous borderline tumors (OSBTs) have been used to understand different aspects of this neoplasm. (i) Pathogenesis, Kras and Braf mutations represent very early events in the tumorigenesis of OSBT as both are detected in serous cystadenomas associated with OSBTs. In contrast, serous cystadenomas without OSBTs do not show Kras or Braf mutations. In OSBTs, Kras mutations range from 17% to 39.5%, while Braf mutations range from 23% to 48%. The former is comparable with the range of Kras mutations in ovarian low-grade serous carcinomas (OLGSCa), 19%-54.5%. In contrast, Braf mutations in OLGSCa range from 0% to 33%. Serous cystadenomas appear to progress to OSBT due to a Braf mutation, but this mutation is rarely involved in the progression to OLGSCa. OSBTs with Braf mutation are associated with cellular senescence and up-regulation of tumor suppressor genes. In contrast, OSBTs without a Braf mutation may progress to OLGSCa due to Kras mutation or some other genetic alterations. (ii) The relationship between OSBTs and the extraovarian disease, a monoclonal versus mutifocal origin? This is still matter of debate as studies using different techniques have failed to settle this controversy. (iii) Biological behavior, Braf mutations appear to have a protective role against the progression of OSBT to OLGSCa, while Kras mutations are commonly seen in cases of OSBT that recurred as LGSCa. Nevertheless, LGSCa as a recurrence of an OSBT can originate from OSBTs with or without detectable Kras mutations. Also, it appears to be an association between Kras G12v mutation and a more aggressive phenotype of OSBT that recurred as LGSCa. (iv) Actionable targets, currently there are limited data. It has been reported that cancer cell lines with Kras G12v mutation are more sensitive to selumetinib than cell lines with wild-type Kras.
Imamura, Hiroko; Ohishi, Yoshihiro; Aman, Murasaki; Shida, Kaai; Shinozaki, Tomoko; Yasutake, Nobuko; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao
Ovarian serous borderline tumors (SBTs) being a precursor of low-grade serous carcinomas are morphologically characterized by noninvasive growth and low-grade cytology. On the other hand, many pathologists regard cytologically high-grade, noninvasive (HG-noninv) ovarian serous tumors resembling SBTs in low magnification as conventional high-grade serous carcinomas (HGSCs) by personal experiences. Nonetheless, there are no established molecular characteristic of such tumors. In this study, therefore, we attempted to provide the molecular evidence. We selected 37 ovarian serous tumors that exhibited a cytologically HG-noninv growth pattern, including 36 tumors that coexisted with conventional invasive HGSC components (HG-inv) and a single tumor exclusively composed of pure HG-noninv. Histologically, all HG-noninv showed many mitotic figures, and serous tubal intraepithelial carcinomas were identified in 3 tumors with HG-noninv. Immunohistochemically, most HG-noninv showed aberrant p53 expression, frequent IMP3 positivity, p16 overexpression, a high MIB-1 labeling index, and infrequent PAX2. By molecular analysis, the pure HG-noninv and 13 HGSCs with HG-noninv showed TP53 mutations, but KRAS/BRAF mutations were not detected in any of them. In 1 tumor, we detected an identical TP53 mutation in both HG-noninv and HG-inv components by using laser capture microdissection. These immunohistochemical and molecular features of HG-noninv were similar to those of conventional invasive HGSCs but different from those of SBTs. In conclusion, our results showed that a cytologically HG-noninv growth pattern simulating an SBT is a morphological spectrum of HGSC, but not a true SBT.
Halperin, R; Zehavi, S; Dar, P; Habler, L; Hadas, E; Bukovsky, I; Schneider, D
The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.
Cruz-Galarza, Daniel; Pérez-Rodríguez, Omar; Laboy-Torres, Joaquín; Gutiérrez-Rivera, Silvia
Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.
Srinivasamurthy, Banushree C; Kulandai Velu, Ambedkar Raj; Krishnan, Nagarajan; Patil, Anand Shankar Rao
Serous borderline tumors (SBT) are defined by the World Health Organization (WHO) as serous neoplasms that show epithelial proliferation greater than that seen in serous cystadenomas, as evidenced by cellular stratification, cytologic atypicality, and epithelial tufting, but which exhibit no evidence of "destructive stromal" invasion and can show extra-ovarian implants. Characterization of invasive peritoneal implants from patients with noninvasive serous ovarian tumors has important prognostic and treatment implications. Peritoneal implants have been classified as either noninvasive or invasive based on their histopathologic appearance. Three criteria were applied for the diagnosis of "invasive" implants: Invasion of underlying normal tissue, micropapillary architecture, and solid epithelial nests surrounded by clefts. We encountered two cases of unilateral ovarian serous borderline tumors with non-invasive peritoneal implants in a 43-year-old female, and invasive peritoneal implants in 76-year-old female.
Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor
Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.
Ho, Ronnie S L; Chan, Godfrey C F; Ha, Shau Yin; Ip, Philip P C
Endometriosis in infancy is most unusual, and associated tumors in this age group are exceptionally rare. We report a case of a serous borderline tumor and endometrial stromal sarcoma arising in an ovarian endometriotic cyst. The patient was an infant of 18 months of age who presented with an incidental abdominal mass. The serum sex hormones were at prepubertal levels. There was no evidence of precocious puberty or any obvious genital anomaly. Intraoperative findings included a solitary solid and multicystic right ovarian mass without evidence of any extraovarian disease. On microscopic examination, the tumor was composed of an intimate mixture of florid papillary and stromal cell proliferation in the wall of an endometriotic cyst. The papillae showed hierarchical branching and had hyalinized and edematous cores with scattered psammoma bodies. The epithelial cells were mildly atypical and mitotically inactive. The underlying endometrial stromal cells were arranged in irregular tongues that permeated the thickened fibrous cyst wall. They were mitotically active and immunoreactive for CD10. There was no evidence of any primitive germ cell tumor. The patient received no adjuvant treatment and had an uneventful postoperative follow-up period of 30 months. To the best of our knowledge, endometriosis associated with this most unusual combination of ovarian tumors has never been reported in an infant.
Demirag, Guzin Gonullu; Kefeli, Mehmet; Kemal, Yasemin; Yucel, Idris
The present study aimed to analyze the clinical significance of epithelial membrane protein 1 (EMP1) expression in ovarian serous tumors. A total of 84 cases of ovarian serous tumor (50 patients with malignant ovarian serous tumors and 34 patients with borderline and benign serous tumors) were retrospectively analyzed. Differences in the expression levels of EMP1 between the malignant and non-malignant tumor groups were evaluated by immunohistochemical staining. In addition, the association between EMP1 expression and prognostic factors in malignant ovarian serous tumors was investigated. The expression levels of EMP1 were significantly reduced in all the 50 malignant ovarian serous tumors, compared with the 34 non-malignant ovarian serous tumors (P<0.000). Reduced expression of EMP1 was correlated with high grade (P=0.009) and stage (P<0.000) of malignant tumors. EMP1 expression was not observed to be correlated with any other investigated parameters, including surgery, type of operation and chemotherapy response (P>0.005). These results indicated that EMP1 may have a significant role as a negative regulator in ovarian serous tumors, and reduced EMP1 expression in serous tumors may be associated with increased disease severity.
Horn, Lars-Christian; Höhn, Anne K; Einenkel, Jens; Siebolts, Udo
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.
Wang, Min; Ma, Haifen
It has been suggested that Paired box gene (PAX)2 is activated by estradiol via estrogen receptor (ER)α in breast and endometrial cancer. The expression of PAX2 was restricted to ovarian serous tumors and only one case was positive in borderline mucinous tumor in our previous study. In the present study, immunohistochemistry was performed to assess the expression of ERα in 58 cases of ovarian serous tumors, including 30 serous cystadenomas, 16 borderline serous cystadenomas, 12 serous carcinomas and 67 cases of ovarian mucinous tumors, including 29 mucinous cystadenoma, 23 borderline mucinous cystadenoma and 15 mucinous carcinoma, which were the same specimens with detection of PAX2 expression. The results demonstrated that ERα was expressed in 10% (3/30) of serous cystadenomas, 62.5% (10/16) borderline serous cystadenomas and 66.7% (8/12) serous carcinomas. The expression of ERα in borderline serous cystadenomas and serous carcinomas were significantly higher compared with that in serous cystadenomas (P<0.01). ERα was detected in 3.4% (1/29) mucinous cystadenoma, 26.1% (6/23) borderline mucinous cystadenoma and only 6.7% (1/15) mucinous carcinoma. Furthermore, a scatter plot of the expression of PAX2 and ERα revealed a linear correlation between them in ovarian serous tumors (P<0.0001). With few positive results, no correlation was determined in ovarian mucinous tumors. It was demonstrated that PAX2 is associated with ERα in ovarian serous tumors, and this may become a potential theory basis for targeted therapy for ovarian serous tumors. Further research is required to determine how PAX2 and ERα work together, and the role of targeted therapy in ovarian serous tumors.
Mohammed, Rabab A A; Makboul, Rania; Elsers, Dalia A H; Elsaba, Tarek M A M; Thalab, Abeer M A B; Shaaban, Omar M
Amplification of HER-2 gene and overexpression of HER-2 receptor play a significant role in the progression of a number of malignancies such as breast cancer. Trastuzumab (anti-HER-2 therapeutic agent) has been used successfully in treatment of breast cancer. The aim of this study was to assess the pattern of HER-2 gene amplification and of HER-2 receptor expression in a spectrum of serous and mucinous ovarian tumors to determine whether HER-2 is altered in these neoplasms similar to that occurring in breast cancer. Formalin-fixed paraffin-embedded microarray tissue sections from 212 specimens were stained with HER-2 antibody using immunohistochemistry and with anti-HER-2 DNA probe using chromogenic in situ hybridization. Specimens consisted of 65 benign tumors (50 serous and 15 mucinous), 26 borderline (13 serous and 13 mucinous), 73 malignant (53 serous carcinoma and 20 mucinous carcinoma), 18 metastatic deposits (13 serous and 5 mucinous), in addition to 30 normal tissues (16 ovarian surface and 14 normal fallopian tube). HER-2 protein-positive expression was not detected in the normal or the benign tissues. Borderline neoplasms showed positive staining, but no overexpression. HER-2 overexpression was seen only in 4 carcinoma specimens: 1/53 (1.8%) primary serous carcinomas and 3/20 (15%) primary mucinous carcinomas. HER-2 gene amplification was seen in 4 specimens: 2 primary mucinous carcinomas and 2 malignant deposits of these 2 mucinous carcinomas. In conclusion, alteration of HER-2 was not detected in ovarian serous neoplasms; however, in mucinous carcinoma, HER-2 amplification and overexpression occur more frequently.
Incidence of serous tubal intraepithelial carcinoma (STIC) by algorithm classification in serous ovarian tumor associated with PAX8 expression in tubal epithelia: a study of single institution in Japan.
Munakata, Satoru; Yamamoto, Toshiya
Serous ovarian carcinoma is now hypothesized to originate from fallopian tube epithelium (FTE). We investigated the FTE abnormalities in the patients with epithelial ovarian tumors. Our study included 55 cases of serous tumors (24 carcinomas, 8 borderline tumors, and 23 adenomas), 14 mucinous carcinomas, 22 endometrioid carcinomas, 5 clear cell carcinomas, and 2 malignant Brenner tumors. FTE was diagnosed by the diagnostic algorithm, which combines the data of morphology, and p53, Ki-67 immunostaining, as serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive. Serous tubal intraepithelial carcinoma, serous tubal intraepithelial lesion, p53 signature, and normal/reactive were observed in 5, 3, 0, and 16 cases in serous carcinoma; 0, 3, 0, and 5 cases in serous borderline tumor; 0, 1, 1, and 21 cases in serous adenoma; 0, 0, 1, and 13 cases in mucinous carcinoma; 0, 0, 3, and 19 cases in endometrioid carcinoma; 0, 0, 0, and 5 cases in clear cell carcinoma; and 0, 1, 0, and 1 case in malignant Brenner tumor. Among tumors of serous histology and between carcinomas, FTE abnormalities differed significantly (P<0.05). Serous tubal intraepithelial carcinomas were only found in serous carcinoma. The incidence of secretory cell proliferation (SCP) was examined by PAX8 expression. The rate of SCP was extremely high in serous carcinoma (96%). Among tumors of serous histology and between carcinomas, an incidence of SCP differed significantly (P<0.05). Patients with SCP were significantly older (P<0.0001). Our observations were concordant with the hypothesis of serous ovarian carcinogenesis. The SCP has a meaningful association with serous ovarian cancer.
Khalid, Saifullah; Jamal, Faisal; Rafat, Dalia; Ahmed, Murad; Narayanasamy, Sabarish; Obaid, Amber; Shadan, Mariam
Hydatid disease (HD) is a commonly occurring zoonotic disease caused by tapeworms of the genus Echinococcus. It is endemic in many parts of the world and can involve almost any organ of the body. Although HD of the liver and lungs is quite common, ovarian involvement is rare. We present a case of a 24-year-old female patient who was diagnosed with multifocal hydatidosis involving the liver and bilateral ovaries on imaging. Postoperative histopathology confirmed the hydatid disease in the liver and one ovary. However, the cystic lesion in the other ovary turned out to be a borderline serous cystadenoma. This case highlights the limitation of imaging in differentiating between simple hydatid cysts and serous cystadenomas of the ovaries. Another point we learnt is that even in the presence of multifocal hydatidosis in endemic regions, serous cystadenoma needs to be considered in imaging differential diagnosis.
Wong, Kwong-Kwok; Gershenson, David
The role of serous tumors of low malignant potential (LMP) in the development of invasive epithelial cancer of the ovary is debatable. This review summarizes the current clinical, genetic, and genomic evidence for the existence of a continuum comprising both LMP serous tumors and low-grade serous ovarian carcinomas. PMID:18057521
Grimaldi, Luciano; Danzi, Michele; Reggio, Stefano; Pannullo, Mario; Danzi, Roberta; Lauria, Rossella
Psammocarcinoma is a rare variant of serous carcinoma arising either from ovary or peritoneum, characterized by massive psammoma body formation, low-grade of cytologic differentiation and invasiveness. Its clinical behavior is similar to the serous borderline tumors, whose prognosis is significantly better compared to invasive forms, with a 5-year survival in stage I greater than 95%. A typical feature of borderline ovary tumors is the presence, in more than 30% of cases, of borderline peritoneal implants similar to primary ovarian cancer or of invasive forms. We report a case of a 44-years-old woman who referred to our clinic for mesosigmoid mass , accidentally discovered by ultrasonography. Sigmoidectomy with fertility sparing surgery was performed in september 2010. The mass was hystologically characterized by many psammoma bodies and low grade cytological features with diagnosis of psammocarcinoma of mesosigma. One year after the primary surgery, the patient showed with left adnexial mass; optimal debulking surgery was performed including omentectomy, total abdominal hysterectomy, bilateral adnexectomy and appendicectomy. The patient did not receive any adjuvant chemotherapy and to date she is alive and with no evidence of disease. The conclusion is that psammocarcinoma is a very rare tumor that behaves less aggressively than typical serous carcinoma, the mainstay of treatment is surgical debulking , with fertility sparing surgery as possible option in young patients with ovaries macroscopically free of disease.
Kuo, Kuan-Ting; Guan, Bin; Feng, Yuanjian; Mao, Tsui-Lien; Chen, Xu; Jinawath, Natini; Wang, Yue; Kurman, Robert J.; Shih, Ie-Ming; Wang, Tian-Li
Ovarian serous carcinoma, the most common and lethal type of ovarian cancer, was thought to develop from two distinct molecular pathways. High-grade (HG) serous carcinomas contain frequent TP53 mutations while low-grade (LG) carcinomas arise from serous borderline tumors (SBT) and harbor mutations in KRAS/BRAF/ERBB2 pathway. However, the molecular alterations involved in the progression from SBT to LG carcinoma remain largely unknown. As well, the extent of deletion of tumor suppressors in ovarian serous carcinomas has not been well-studied. To further address these two issues, we assessed DNA copy number changes among affinity-purified tumor cells from 37 ovarian serous neoplasms including SBT, LG and HG tumors using high density 250K SNP arrays. Chromosomal instability index as measured by changes in DNA copy number was significantly higher in HG than in LG serous carcinomas. Hemizygous ch1p36 deletion was common in LG serous carcinomas but was rarely seen in SBT. This region contains several candidate tumor suppressors including miR-34a. In contrast, in HG serous carcinomas, significant numbers of amplifications and deletions including homozygous deletions were identified. Among homozygous deletions, loci containing Rb1, CDKN2A/B, CSMD1, and DOCK4 were most common, being present in 10.6%, 6.4%, 6.4% and 4.3%, respectively, in independent 47 affinity-purified HG serous carcinomas. Except the CDKN2A/B region, these homozygous deletions were not present in either SBT or LG tumors. Our study provides a genome-wide homozygous deletion profiles in HG serous carcinomas, serving as a molecular foundation to study tumor suppressors in ovarian cancer. PMID:19383911
Chambers, J. T.
Borderline ovarian tumors have an excellent prognosis. In stage I disease, no therapy in addition to surgery is needed, and conservation of ovarian tissue for future childbearing may be appropriate. In advanced stages, the use of adjuvant therapy has not consistently led to cures, and complications have been reported. A randomized study of no adjuvant therapy versus adjuvant treatment with long-term follow-up will be necessary to determine the efficacy of additional treatment. PMID:2556863
el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.
BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284
Park, Jee Soo; Choi, Soo Beom; Chung, Jai Won; Kim, Sung Woo; Kim, Deok Won
Ovarian cancer, the most fatal of reproductive cancers, is the fifth leading cause of death in women in the United States. Serous borderline ovarian tumors (SBOTs) are considered to be earlier or less malignant forms of serous ovarian carcinomas (SOCs). SBOTs are asymptomatic and progression to advanced stages is common. Using DNA microarray technology, we designed multicategory classification models to discriminate ovarian cancer subclasses. To develop multicategory classification models with optimal parameters and features, we systematically evaluated three machine learning algorithms and three feature selection methods using five-fold cross validation and a grid search. The study included 22 subjects with normal ovarian surface epithelial cells, 12 with SBOTs, and 79 with SOCs according to microarray data with 54,675 probe sets obtained from the National Center for Biotechnology Information gene expression omnibus repository. Application of the optimal model of support vector machines one-versus-rest with signal-to-noise as a feature selection method gave an accuracy of 97.3%, relative classifier information of 0.916, and a kappa index of 0.941. In addition, 5 features, including the expression of putative biomarkers SNTN and AOX1, were selected to differentiate between normal, SBOT, and SOC groups. An accurate diagnosis of ovarian tumor subclasses by application of multicategory machine learning would be cost-effective and simple to perform, and would ensure more effective subclass-targeted therapy.
Hacker, Kari E; Uppal, Shitanshu; Johnston, Carolyn
Borderline ovarian tumors (BOTs) are less common than epithelial ovarian cancers (EOCs). Low-grade EOCs (LG-EOCs) occur even less frequently than BOTs. After primary therapy, recurrence rates of BOTs and LG-EOCs are significantly lower and the stage-adjusted survival is higher than for high-grade EOCs. Thus, determining the best management in terms of traditional ovarian cancer staging and debulking procedures is more challenging and has been recently brought to question. This article reviews the particulars of BOTs and LG-EOCs, their similarities and differences, and how they are best managed and treated, and emphasizes the major role of surgery and the controversial role of chemotherapy. Because these tumors disproportionately affect younger women, this review addresses ovarian preservation in circumstances when fertility or hormonal preservation is desired.
Mun, Semih; Uysal, Fatma; Öztekin, Murat; Büyüktosun, Cem; Şehirali1, Salim; Başoğul, Ömer; Taner, Cüneyt E.
Aim of the study The purpose of the study was to evaluate patients with borderline ovarian tumors. Material and methods Clinical features, treatment and survival status of 100 patients with borderline ovarian tumors were retrospectively evaluated between 1998 and 2007. Results Patients’ mean age was 37.75 years (range: 15–72); 22 of them were postmenopausal. Histopathological diagnoses were serous, mucinous, endometrioid and clear cell in 54%, 41%, 2% and 3% of the patients, respectively; 70 patients had stage IA disease, 8 were at stage IB, 16 at stage IC, 2 at stage IIIA, 3 at stage IIIB and 1 at stage IIIC. Restaging laparotomies were performed on 19 patients; fertility-sparing surgery was performed on 52 patients; 2 patients received chemotherapy because of advanced-stage disease. All patients are currently alive. The 5-year disease-free survival rate for 71 cases was 100%. Conclusions Borderline ovarian tumors have excellent prognoses, and fertility-conserving surgery can be performed in young patients with early-stage disease. PMID:24596520
Vitiazeva, Varvara; Kattla, Jayesh J.; Flowers, Sarah A.; Lindén, Sara K.; Premaratne, Pushpa; Weijdegård, Birgitta; Sundfeldt, Karin; Karlsson, Niclas G.
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
Buas, Matthew F.; Gu, Haiwei; Djukovic, Danijel; Zhu, Jiangjiang; Drescher, Charles W.; Urban, Nicole; Raftery, Daniel; Li, Christopher I.
OBJECTIVE Serous ovarian carcinoma (OC) represents a leading cause of cancer-related death among U.S. women. Non-invasive tools have recently emerged for discriminating benign from malignant ovarian masses, but evaluation remains ongoing, without widespread implementation. In the last decade, metabolomics has matured into a new avenue for cancer biomarker development. Here, we sought to identify novel plasma metabolite biomarkers to distinguish serous ovarian carcinoma and benign ovarian tumor. METHODS Using liquid chromatography-mass spectrometry, we conducted global and targeted metabolite profiling of plasma isolated at the time of surgery from 50 serous OC cases and 50 serous benign controls. RESULTS Global lipidomics analysis identified 34 metabolites (of 372 assessed) differing significantly (P<0.05) between cases and controls in both training and testing sets, with 17 candidates satisfying FDR q<0.05, and two reaching Bonferroni significance. Targeted profiling of ~150 aqueous metabolites identified a single amino acid, alanine, as differentially abundant (P<0.05). A multivariate classification model built using the top four lipid metabolites achieved an estimated AUC of 0.85 (SD=0.07) based on Monte Carlo cross validation. Evaluation of a hybrid model incorporating both CA125 and lipid metabolites was suggestive of increased classification accuracy (AUC=0.91, SD=0.05) relative to CA125 alone (AUC=0.87, SD=0.07), particularly at high fixed levels of sensitivity, without reaching significance. CONCLUSIONS Our results provide insight into metabolic changes potentially correlated with the presence of serous OC versus benign ovarian tumor and suggest that plasma metabolites may help differentiate these two conditions. PMID:26521694
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
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
Kharma, Budiman; Baba, Tsukasa; Matsumura, Noriomi; Kang, Hyun Sook; Hamanishi, Junzo; Murakami, Ryusuke; McConechy, Melissa M; Leung, Samuel; Yamaguchi, Ken; Hosoe, Yuko; Yoshioka, Yumiko; Murphy, Susan K; Mandai, Masaki; Hunstman, David G; Konishi, Ikuo
Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a "SPEC signature" as a molecular definition of its malignant features and poor prognosis. Specifically, we found that STAT1 regulated MYC as well as ICAM1, PD-L1, and SMAD7, as well as the capacity for proliferation, adhesion, migration, invasion, and in vivo tumorigenecity in cells with a high SPEC signature. Together, our results define STAT1 as a driver oncogene in SPEC that modulates disease progression. We propose that STAT1 functions as a prosurvival gene in SPEC, in a manner important to tumor progression, and that STAT1 may be a novel target for molecular therapy in this disease.
Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin
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.
El-Gendi, Saba; Abdelzaher, Eman; Mostafa, Mohamed Farouk; Sheasha, Ghada Abu
Fibroblast growth factor 18 (FGF18) has been suggested to play important roles in promoting progression of ovarian high-grade serous carcinoma. Our aim was to investigate FGF18 expression in the whole spectrum of serous and mucinous ovarian tumors, highlighting differences in expression within the adenoma-carcinoma sequence and differences between type I and type II tumors. We also aimed to test the prognostic significance of this expression and its relation to microvessel density (MVD). We evaluated the immunohistochemical expression of FGF18 and CD31 in 103 ovarian tumors and statistically analyzed their association with clinicopathological variables and patients' outcome. FGF18 score increased significantly within the adenoma-carcinoma sequence for serous and mucinous tumors. MVD increased significantly only among serous tumors. FGF18 and MVD correlated significantly (overall and among serous tumors only) and were significantly higher in type II than type I tumors. Cox regression models were built. Independent predictors could not be determined due to multicollinearity between the predictors. However, the combination of International Federation of Gynecology and Obstetrics (FIGO) stage, ovarian carcinoma type, and/or FGF18 score achieved the highest predictability of poor prognosis. FGF18 could play a role within the adenoma-carcinoma sequence in type I tumors and might modulate angiogenesis among serous tumors. Our findings further augment the differences between type I and type II tumors. The combination of FIGO stage, ovarian carcinoma type, and/or FGF18 score could predict poor prognosis among ovarian carcinoma patients. Our work identifies FGF18 in ovarian neoplasia as a promising field of research, although evaluation of the performance of the developed models is still needed.
Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun
Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation.
Gao, Weiwei; Zhang, Qin; Wang, Yan; Wang, Jiandong; Zhang, Shu
Eph (Erythropoietin-producing human hepatocellular carcinoma cell) is the largest subfamily of receptor tyrosine kinases. Eph receptors and their ephrin ligands are involved in embryonic development and physiological processes. Aberrant expression of Eph/ephrin may contribute to a variety of diseases including cancer. EphB3 is a member of Eph receptors and has been found to play roles in carcinogenesis of some types of human cancer. But, its expression and clinical significance in ovarian serous carcinoma have not been well investigated and are unknown. In this study, a set of ovarian tissues including normal fallopian tube, serous borderline tumor, and serous carcinoma were subjected to immunohistochemistry using a specific polyclonal antibody for EphB3. The relationship between EphB3 expression and clinicopathological parameters was statistically analyzed. EphB3 was strongly expressed in all fallopian tube specimens (19/19, 100%). EphB3 was negatively or weekly expressed in 1 of 17 (5.8%) in borderline tumors and 26 of 50 (52.0%) in serous carcinomas, moderately expressed in 7 of 17 (41.2%) in borderline tumors and 14 of 50 (28%) in serous carcinomas, and strongly expressed in 9 17 (52.9%) in borderline tumors and 10 of 50 (20%) in serous carcinomas. EphB3 expression is significantly reduced in serous carcinomas compared with normal fallopian tubes and borderline tumors (p < 0.001). EphB3 expression is negatively associated with histological grade (p < 0.001, rs = -0.613) and FIGO stage (p = 0.001, rs = -0.464) of serous carcinomas. Our results show EphB3 protein lost in ovarian serous carcinoma and is associated with tumor grade and FIGO stage, which indicate EphB3 protein may play a role in carcinogenesis of ovarian serous carcinoma and may be used as a molecular marker for prognosis.
Buttarelli, Marianna; Martinelli, Enrica; Mascilini, Floriana; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Gallo, Daniela
Only recently low-grade serous carcinoma (LGSOC) of the ovary has been recognized as a disease entity distinct from the more common high-grade serous carcinoma (HGSOC), with significant differences in pathogenesis and clinical and pathologic features. The present study aimed at evaluating whether the different natural histories and patterns of response to therapy demonstrated for LGSOC and HGSOC, along with a diverse genomic landscape, may also reside in the supporting tumor stroma, specifically in the state of differentiation and activation of tumor associated macrophages (TAMs). TAMs play complex roles in tumorigenesis since they are believed to possess both tumor rejecting (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we showed that, when compared to HGSOC (n = 55), LGSOC patients (n = 25) exhibited lower density of tumor-infiltrating CD68+ macrophage, along with an attenuated M2-skewed (CD163+) phenotype. Accordingly, assessment of intratumoral vascularization and of matrix metalloproteinase 9 expression (a key protein involved in tumor invasion and metastasis) revealed lower expression in LGSOC compared to HGSOC patients, in line with emerging evidence supporting a role for TAMs in all aspects of tumor initiation, growth, and development. In conclusion, results from the present study demonstrate that microenvironmental factors contribute greatly to determine clinical and pathological features that differentiate low and high grade serous ovarian carcinomas. This understanding may increase possibilities and opportunities to improve disease control and design new therapeutic strategies. PMID:27462782
Uğraş, Nesrin; Tolunay, Şahsine; Öz Atalay, Fatma; Gökgöz, Şehsuvar
Phyllodes tumors are uncommon biphasic fibroepithelial neoplasms of breast, comprising less than 1% of all breast neoplasms. We therefore aimed to present the case with its microscopic findings. In this article, we report a 59-year-old female admitted to the general surgery department with a rapidly, enlarging, palpable mass in right breast. After histopathological examination, it was diagnosed as borderline phyllodes tumor with extensive squamous metaplasia. Metaplastic changes are infrequent in the stromal and epithelial component of these tumors. Extensive squamous metaplasia within phyllodes tumor is rare and may occur in benign, borderline and malign subtypes.
Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep
Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682
Yong, W H; Southern, J F; Pins, M R; Warshaw, A L; Compton, C C; Lewandrowski, K B
Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous tumors, some of which are malignant. Preoperative clinical and radiological parameters are unreliable and may result in incorrect diagnosis and inappropriate treatment. Cyst fluid analysis for cytology, viscosity, carcino-embryonic antigen, CA 72-4, and CA 15-3 will distinguish mucinous from nonmucinous lesions and usually help in determining malignancy. Currently, there is no reliable method to differentiate inflammatory pseudocysts from serous cystadenomas. This distinction is important because the treatment of these two lesions is different; pseudocysts are either observed or drained, whereas serous tumors are usually resected. The tumor marker NB/70K was measured in aspirated cyst fluid from 13 inflammatory pseudocysts and 11 serous cystadenomas by a commercial immunoassay. Leukocyte esterase was measured using Chemstrip SG urine test strips and amylase and lipase on a routine chemistry analyzer. The cyst fluid NB/70K concentration was significantly higher in pseudocysts (mean, 555 U/ml; range, 42-1,926 U/ml) than in serous cystadenomas (mean, 12 U/ml; range 0-130 U/ml) and this difference was significant (p < 0.0002). Leukocyte esterase was detected in 7 of 11 pseudocysts but was absent in 10 of 10 serous tumors (p = 0.002). Amylase and lipase values were generally higher in pseudocysts but these markers were unreliable due to marked outliers. Cyst fluid NB/70K and leukocyte esterase are promising markers to help differentiate pseudocysts from serous tumors on percutaneous aspirates. When combined with previously reported cyst fluid parameters (amylase, lipase, cytology, and amylase isoenzymes), these two cystic lesions can be reliably distinguished.
Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G; Meier, Samuel M; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar
The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.
Auer, Katharina; Bachmayr-Heyda, Anna; Sukhbaatar, Nyamdelger; Aust, Stefanie; Schmetterer, Klaus G.; Meier, Samuel M.; Gerner, Christopher; Grimm, Christoph; Horvat, Reinhard; Pils, Dietmar
The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors. PMID:27665539
Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kaku, Tsunehisa; Kato, Kiyoko; Oda, Yoshinao
"Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs.
Heinrich, J K R; Böttcher-Luiz, F; Andrade, L L A; Davidson, S; Bonds, L; Stephens, J; Varella-Garcia, M
The study determined the expression of cancer antigen (CA) 125 and HER-2 in 45 borderline ovarian tumors (BOTs) and investigated the correlation of these biologic markers with histologic type, clinical stage, and outcome. The level of CA 125 protein was assessed using DAKO's M-11 clone antibody in immunohistochemistry (IHC) assays (Carpinteria, CA). The HER-2 protein expression was assessed in IHC assays using the HercepTest (DAKO), and the HER-2 gene copy number per cell was investigated through fluorescence in situ hybridization (FISH) assays using VYSIS' PathVysion DNA Probe (Downers Grove, IL). Expression of the CA 125 protein was detected in 49% of the samples (22 out of 45 tumors) and significantly associated with the serous histologic type. However, CA 125 expression did not associate with clinical stage or outcome. Protein overexpression or gene amplification of HER-2 was not found. However, abnormal FISH results were detected in 16% (seven out of 45 patients) of specimens comprising extranumerary copies of HER-2 and/or chromosome 17 per cell. Abnormal FISH results were found to be independent of CA 125 expression and histologic type whereas they positively associate with advanced clinical stage. Our data show that HER-2 is not altered in BOTs, and the presence of aneusomy for chromosome 17 and HER-2 may predict tumor progression.
Śniadecki, Marcin; Bianek-Bodzak, Agnieszka; Liro, Marcin; Szurowska, Edyta
Borderline ovarian tumors represent about 10% of all epithelial ovarian cancers, but in contrast to epithelial ovarian cancers, they constitute a group of tumors with a much better prognosis. An assessment of clinical presentation, physical examination, radiological and biochemical findings is necessary to tailor management strategies for patients with ovarian tumors. The article, which is based on a case report, describes different approaches for preoperative diagnosis as well as discusses approaches that might bring some insights on tumor histology. Furthermore, it raises a question about which imaging techniques should be proposed for a reliable diagnosis of borderline ovarian tumors to ensure safe surgery planning. PMID:28138412
Le Gallo, Matthieu; O'Hara, Andrea J; Rudd, Meghan L; Urick, Mary Ellen; Hansen, Nancy F; O'Neil, Nigel J; Price, Jessica C; Zhang, Suiyuan; England, Bryant M; Godwin, Andrew K; Sgroi, Dennis C; Hieter, Philip; Mullikin, James C; Merino, Maria J; Bell, Daphne W
Endometrial cancer is the sixth most commonly diagnosed cancer in women worldwide, causing ~74,000 deaths annually. Serous endometrial cancers are a clinically aggressive subtype with a poorly defined genetic etiology. We used whole-exome sequencing to comprehensively search for somatic mutations within ~22,000 protein-encoding genes in 13 primary serous endometrial tumors. We subsequently resequenced 18 genes, which were mutated in more than 1 tumor and/or were components of an enriched functional grouping, from 40 additional serous tumors. We identified high frequencies of somatic mutations in CHD4 (17%), EP300 (8%), ARID1A (6%), TSPYL2 (6%), FBXW7 (29%), SPOP (8%), MAP3K4 (6%) and ABCC9 (6%). Overall, 36.5% of serous tumors had a mutated chromatin-remodeling gene, and 35% had a mutated ubiquitin ligase complex gene, implicating frequent mutational disruption of these processes in the molecular pathogenesis of one of the deadliest forms of endometrial cancer.
Mitra, Anirban; Davis, David A.; Tomar, Sunil; Roy, Lynn; Gurler, Hilal; Xie, Jia; Lantvit, Daniel D.; Cardenas, Horacio; Fang, Fang; Liu, Yueying; Loughran, Elizabeth; Yang, Jing; Stack, M. Sharon; Emerson, Robert E; Cowden Dahl, Karen D.; Barbolina, Maria; Nephew, Kenneth P.; Matei, Daniela; Burdette, Joanna E.
Objective Genomic studies of ovarian cancer (OC) cell lines frequently used in research revealed that these cells do not fully represent high-grade serous ovarian cancer (HGSOC), the most common OC histologic type. However, OC lines that appear to genomically resemble HGSOC have not been extensively used and their growth characteristics in murine xenografts are essentially unknown. Methods To better understand growth patterns and characteristics of HGSOC cell lines in vivo, CAOV3, COV362, KURAMOCHI, NIH-OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVSAHO, OVKATE, SNU119, UWB1.289 cells were assessed for tumor formation in nude mice. Cells were injected intraperitoneally (i.p.) or subcutaneously (s.c.) in female athymic nude mice and allowed to grow (maximum of 90 days) and tumor formation was analyzed. All tumors were sectioned and assessed using H&E staining and immunohistochemistry for p53, PAX8 and WT1 expression. Results Six lines (OVCAR3, OVCAR4, OVCAR5, OVCAR8, CAOV3, and OVSAHO) formed i.p xenografts with HGSOC histology. OVKATE and COV362 formed s.c. tumors only. Rapid tumor formation was observed for OVCAR3, OVCAR5 and OVCAR8, but only OVCAR8 reliably formed ascites. Tumors derived from OVCAR3, OVCAR4, and OVKATE displayed papillary features. Of the 11 lines examined, three (Kuramochi, SNU119 and UWB1.289) were non-tumorigenic. Conclusions Our findings help further define which HGSOC cell models reliably generate tumors and/or ascites, critical information for preclinical drug development, validating in vitro findings, imaging and prevention studies by the OC research community. PMID:26050922
Bachmayr-Heyda, Anna; Auer, Katharina; Sukhbaatar, Nyamdelger; Aust, Stefanie; Deycmar, Simon; Reiner, Agnes T.; Polterauer, Stephan; Dekan, Sabine; Pils, Dietmar
High grade serous ovarian cancer (HGSOC) is among the most deadly malignancies in women, frequently involving peritoneal tumor spread. Understanding molecular mechanisms of peritoneal metastasis is essential to develop urgently needed targeted therapies. We described two peritoneal tumor spread types in HGSOC apparent during surgery: miliary (numerous millet-sized implants) and non-miliary (few big, bulky implants). The former one is defined by a more epithelial-like tumor cell characteristic with less immune cell reactivity and with significant worse prognosis, even if corrected for typical clinicopathologic factors. 23 HGSOC patients were enrolled in this study. Isolated tumor cells from fresh tumor tissues of ovarian and peritoneal origin and from ascites were used for ribosomal RNA depleted RNA and small RNA sequencing. RT-qPCR was used to validate results and an independent cohort of 32 patients to validate the impact on survival. Large and small RNA sequencing data were integrated and a new gene-miRNA set analysis method was developed. Thousands of new small RNAs (miRNAs and piwi-interacting RNAs) were predicted and a 13 small RNA signature was developed to predict spread type from formalin-fixed paraffin-embedded tissues. Furthermore, integrative analyses of RNA sequencing and small RNA sequencing data revealed a global upregulation of the competing endogenous RNA network in tumor tissues of non-miliary compared to miliary spread, i.e. higher expression of circular RNAs and long non-coding RNAs compared to coding RNAs but unchanged abundance of small RNAs. This global deregulated expression pattern could be co-responsible for the spread characteristic, miliary or non-miliary, in ovarian cancer. PMID:27172797
Shah, Lopa; Tiesi, Gregory; Bamboat, Zubin; McCain, Donald; Siegel, Andrew; Mannion, Ciaran
Metastatic cancer to the pancreas accounts for less than 2% of all pancreatic malignancies. In contrast to other metastatic tumors, renal cell carcinoma (RCC) has a propensity to metastasize as a solitary pancreatic lesion. While symptomatic patients may present with obstructive jaundice, abdominal pain, or gastrointestinal bleeding, the diagnosis of metastatic pancreatic involvement is often made in asymptomatic patients, during follow-up evaluation in the aftermath of an initial diagnosis of renal cell carcinoma. Microcystic serous cystadenoma of the pancreas is an uncommon pancreatic exocrine neoplasm that morphologically resembles conventional (clear cell) RCC, in so far as both tumors are characterized by neoplastic cells with clear cytoplasm, relatively uniform nuclei and scant associated tumor stroma. Herein, we report 2 immunohistochemically confirmed cases of unsuspected metastatic RCC to the pancreas, with the metastatic tumor in each case confined to a preexisting microcystic serous cystadenoma of the pancreas.
Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard
Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651
Bartel, Frank; Balschun, Katharina; Gradhand, Elise; Strauss, Hans G; Dittmer, Jürgen; Hauptmann, Steffen
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.
Ciucci, Alessandra; Zannoni, Gian Franco; Buttarelli, Marianna; Lisi, Lucia; Travaglia, Daniele; Martinelli, Enrica; Scambia, Giovanni; Gallo, Daniela
The notion that menopausal estrogen replacement therapy increases ovarian cancer risk, but only for the two more common types (i.e. serous and endometrioid), while possibly decreasing risk for clear cell tumors, is strongly suggestive of causality. However, whether estradiol (E2) is tumorigenic or promotes development of occult preexisting disease is unknown. The present study investigated molecular and cellular mechanisms by which E2 modulates the growth of high grade serous ovarian cancer (HGSOC). Results showed that ERα expression was necessary and sufficient to induce the growth of HGSOC cells in in vitro models. Conversely, in vivo experimental studies demonstrated that increasing the levels of circulating estrogens resulted in a significant growth acceleration of ERα-negative HGSOC xenografts, as well. Tumors from E2-treated mice had significantly higher proliferation rate, angiogenesis, and density of tumor-associated macrophage (TAM) compared to ovariectomized females. Accordingly, immunohistochemical analysis of ERα-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women. This study describes novel insights into the impact of E2 on tumor microenvironment, independently of its direct effect on tumor cell growth, thus supporting the idea that multiple direct and indirect mechanisms drive estrogen-induced tumor growth in HGSOC.
Adams, Sarah F.; Levine, Douglas A.; Cadungog, Mark G.; Hammond, Rachel; Facciabene, Andrea; Olvera, Narciso; Rubin, Stephen C.; Boyd, Jeff; Gimotty, Phyllis A.; Coukos, George
Background We sought to determine whether tumor-infiltrating lymphocytes and/or tumor mitotic activity could identify subgroups of patients with advanced serous epithelial ovarian cancer who would maximally benefit from aggressive surgical cytoreduction. Methods Snap-frozen specimens from 134 consecutive patients with stage III or IV serous or poorly differentiated ovarian adenocarcinoma undergoing primary debulking surgery from a single US institution were characterized based on CD3+, CD8+, FoxP3+ tumor infiltrating lymphocytes, and Ki67 expression. Kaplan-Meier survival curves were estimated and compared using a log-rank statistic. A multivariate Cox model was used to estimate adjusted hazard ratios (HR). Interactions were modeled using recursive partitioning based on maximal prognostic differentiation. Results Brisk intraepithelial CD8+ cells (p=0.035) and low Ki67 expression (p=0.042) portended prolonged survival. T cell infiltration was more likely to occur in tumors with high proliferation index. Patients whose tumors exhibited low Ki67 expression and high intraepithelial CD8+ frequency had a 5-year survival rate of 73.3%. Patients with aggressive tumor behavior, i.e. whose tumors exhibited low frequency of intraepithelial CD8+ T cells or high Ki67 expression were more likely to draw benefit from aggressive surgical cytoreduction. Survival was similar for patients with brisk CD8+ T cells who had optimal or suboptimal debulking. Likewise, survival was similar for patients with low Ki67 expression who had optimal or suboptimal debulking. Conclusions These novel interactions of T cells, tumor proliferation index and surgical treatment reveal for the first time that biological prognosticators may be useful for surgical decision making in ovarian cancer. PMID:19472394
Vasquez, Liliana; Tello, Mariela; Maza, Ivan; Oscanoa, Monica; Dueñas, Milagros; Castro, Haydee; Latorre, Alan
Ovarian and paraovarian neoplasms are uncommon in children, mainly originating from germ cell tumors and, least frequently, epithelial tumors. There is an association between genital tract tumors and Proteus syndrome, a rare, sporadic, and progressive entity, characterized by a postnatal overgrowth in several tissues caused by a mosaic mutation in the AKT1 gene. We describe a 20-month-old asymptomatic infant with Proteus syndrome who developed an endometrioid paraovarian borderline cystic tumor. This is the youngest patient so far reported in the literature with this rare syndrome and an adnexal tumor of borderline malignancy. A total of nine patients have been described with female tract tumors and associated Proteus syndrome, which includes bilateral ovarian cystadenomas and other benign masses. A paraovarian neoplasm is extremely rare in children and could be considered a criterion for Proteus syndrome. Standardized staging and treatment of these tumors are not well established; however, most authors conclude that these neoplasms must be treated as their ovarian counterparts. PMID:26558123
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
Cömert, Duygu Kavak; Üreyen, Işın; Karalok, Alper; Taşçı, Tolga; Türkmen, Osman; Öcalan, Reyhan; Turan, Taner; Tulunay, Gökhan
Objective To analyze the clinicopathologic features, recurrence and survival rates, reproductive history, and treatment of patients with mucinous borderline ovarian tumors (mBOTs). Material and Methods Patients with a diagnosis of mBOT were evaluated retrospectively. Patients with borderline ovarian tumors other than mucinous type and concomitant invasive cancer were excluded. Results A total of 75 patients were identified. Median age was 38 years. The most common symptom was pain (42.7%). Median CA-125 level was 23.5 IU/mL (range, 1–809 IU/mL). Median tumor size was 200 mm (range, 40–400 mm), and 6.7% of mBOTs were bilateral. Thirty-six (48%) patients underwent staging surgery. Two patients (5.9%) had nodal involvement. One patient received platinum-based adjuvant chemotherapy. One (1.3%) patient had recurrence. None of the patients died because of the ovarian tumor. A total of 43 patients had conservative surgery. Conclusion Prognosis of mBOTs is excellent, and fertility-sparing surgery should be considered in the reproductive age group. Furthermore, the necessity of staging surgery is controversial. PMID:27403076
Singh, Harmeet; Li, Ying; Fuller, Peter J; Harrison, Craig; Rao, Jyothsna; Stephens, Andrew N; Nie, Guiying
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.
Labidi-Galy, S I; Clauss, A; Ng, V; Duraisamy, S; Elias, K M; Piao, H-Y; Bilal, E; Davidowitz, R A; Lu, Y; Badalian-Very, G; Györffy, B; Kang, U-B; Ficarro, S; Ganesan, S; Mills, G B; Marto, J A; Drapkin, R
High-grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirm that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients. Elafin confers a proliferative advantage to tumor cells through the activation of the MAP kinase pathway. This mitogenic effect can be neutralized by RNA interference, specific antibodies and a MEK inhibitor. Elafin expression in patient-derived samples was also associated with chemoresistance and strongly correlates with bcl-xL expression. We extended these findings into the examination of 1100 primary breast tumors and six breast cancer cell lines. We observed that Elafin is overexpressed and secreted specifically by BLBC tumors and cell lines, leading to a similar mitogenic effect through activation of the MAP kinase pathway. Here too, Elafin overexpression is associated with poor overall survival, suggesting that it may serve as a biomarker and therapeutic target in this setting.
Vang, Russell; Shih, Ie-Ming; Kurman, Robert J.
Ovarian serous carcinomas have been graded using various systems. Recently, a 2-tier system in which tumors are subdivided into low-grade and high-grade has been proposed. This approach is simplistic, reproducible, and based on biologic evidence indicating that both tumors develop via different pathways. Low-grade serous carcinomas exhibit low-grade nuclei with infrequent mitotic figures. They evolve from adenofibromas or borderline tumors, have frequent mutations of the KRAS, BRAF, or ERBB2 genes, and lack TP53 mutations (Type I pathway). The progression to invasive carcinoma is a slow step-wise process. Low-grade tumors are indolent and have better outcome than high-grade tumors. In contrast, high-grade serous carcinomas have high-grade nuclei and numerous mitotic figures. Identification of a precursor lesion in the ovary has been elusive and therefore the origin of ovarian carcinoma has been described as de novo. More recently, studies have suggested that a proportion appear to originate from intraepithelial carcinoma in the fallopian tube. The development of these tumors is rapid (Type II pathway). The vast majority are characterized by TP53 mutations and lack mutations of KRAS, BRAF, or ERBB2. Although both types of serous carcinomas evolve along different pathways, rare high-grade serous carcinomas seem to arise through the Type I pathway. Immunohistochemical stains for p53, p16, and Ki-67 for distinction of low- from high-grade tumors are of limited value but can be helpful in selected instances. This review provides an update on the pathogenesis and clinicopathologic features of these two types of serous carcinomas and addresses some of the diagnostic problems that are encountered in routine practice. PMID:19700937
Adur, Javier; Pelegati, Vitor B.; Costa, Leverson F. L.; Pietro, Luciana; de Thomaz, Andre A.; Almeida, Diogo B.; Bottcher-Luiz, Fatima; Andrade, Liliana A. L. A.; Cesar, Carlos L.
We used a multimodal nonlinear optics microscopy, specifically two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG/THG) microscopies, to observe pathological conditions of ovarian tissues obtained from human samples. We show that strong TPEF + SHG + THG signals can be obtained in fixed samples stained with hematoxylin and eosin (H&E) stored for a very long time, and that H&E staining enhanced the THG signal. We then used the multimodal TPEF-SHG-THG microscopies in a stored file of H&E stained samples of human ovarian cancer to obtain complementary information about the epithelium/stromal interface, such as the transformation of epithelium surface (THG) and the overall fibrillary tissue architecture (SHG). This multicontrast nonlinear optics microscopy is able to not only differentiate between cancerous and healthy tissue, but can also distinguish between normal, benign, borderline, and malignant specimens according to their collagen disposition and compression levels within the extracellular matrix. The dimensions of the layers of epithelia can also be measured precisely and automatically. Our data demonstrate that optical techniques can detect pathological changes associated with ovarian cancer.
Gentile, Lori F; Gaillard, William Foster; Wallace, Jodi-Ann; Spiguel, Lisa R P; Alizadeh, Layla; Lentz, Ashley; Shaw, Christiana
Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester.
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
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
Chuong, Michael D.; Frakes, Jessica M.; Figura, Nicholas; Hoffe, Sarah E.; Shridhar, Ravi; Mellon, Eric A.; Hodul, Pamela J.; Malafa, Mokenge P.; Springett, Gregory M.
Background While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. Methods This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. Results We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. Conclusions These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients. PMID:27034789
Della Pepa, Chiara; Tonini, Giuseppe; Santini, Daniele; Losito, Simona; Pisano, Carmela; Di Napoli, Marilena; Cecere, Sabrina Chiara; Gargiulo, Piera; Pignata, Sandro
Low Grade Serous Ovarian Carcinoma, LGSOC, is certainly a rare disease, accounting for only a small proportion of all ovarian carcinomas, nevertheless in the last decade we have acquired many data about its molecular and clinical features and it has been largely accepted that it has distinct pathogenesis, genetic aberrations and clinical behavior compared to High Grade Serous Ovarian Carcinoma, HGSOC, which is the most common ovarian cancer histotype. A large number of series pointed out the high rate of KRAS and BRAF mutations in LGSOCs and Serous Borderline Tumors, SBLTs, in contrast with their rarity in HGSOC. Such finding, together with the recurrent observation of focus of LGSOC associated with areas of SBLT in the same lesion, led to abandon the traditional histology classification, defining three types of serous carcinomas, in favor of a new dualistic grading system which recognizes only LG and HG carcinomas corresponding to distinct tumorigenesis pathways, the former based on KRAS/BRAF mutations and alteration of the MAP/ERK signaling, the latter characterized by early genetic instability and wild type status of KRAS and BRAF. LGSOC shows favorable overall survival, compared to general ovarian cancer population, but worrying resistance to conventional treatments. MEK inhibitors are emerging as active agents and may well represent an effective therapeutic strategy in the near future.
Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S
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.
Lockyer, Megan G; Deavers, Michael T; Zarrin-Khameh, Neda
A 64-yr-old postmenopausal woman with high-grade squamous intraepithelial lesion and atypical glandular cell of undetermined significance on her Pap test was found to have endometrial serous carcinoma (high grade) involving a polyp in a subsequent endometrial biopsy. She underwent hysterectomy and bilateral salpingo-oophorectomy with multiple biopsies of the peritoneum. Microscopic examination of the entirely submitted uterus showed no residual serous carcinoma. Multiple foci of low-grade serous tumor with extensive calcifications and psammoma bodies were identified on the surfaces of the left fallopian tube, ovaries, and biopsies of the peritoneum, consistent with peritoneal primary low-grade serous carcinoma. To our knowledge, this is the first reported case of low-grade serous carcinoma of the peritoneum with a concurrent (high-grade) serous carcinoma of the endometrium arising from an endometrial polyp.
Fadare, Oluwole; James, Samuel; Desouki, Mohamed M; Khabele, Dineo
The purpose of this study is to assess whether composite or coordinate immunoexpression patterns of estrogen receptor (ER), progesterone receptor (PR), and Wilms tumor 1 (WT1) gene can significantly distinguish between endometrial serous carcinoma (ESC) and ovarian serous carcinoma (OSC). Immunohistochemical analyses were performed on whole tissue sections from 22 uterus-confined ESCs and on a tissue microarray of 140 high-grade, pan-stage OSCs, using antibodies to ER, PR, and WT-1. Estrogen receptor, PR, and WT1 expressions were present in 37%, 49%, and 81% of OSC, respectively, but these markers were also present in 18%, 27%, and 36% of ESC. The ER+/PR+/WT1+ coordinate profile was identified in 33.6% of OSC but in none of ESC (P = .0006), resulting in a calculated sensitivity and specificity of this profile for OSC of 33.6% and 100%, respectively. By contrast, the ER-/PR-/WT1- coordinate profile was identified in 41% of ESC but in only 6.4% of OSC (P = .0001), resulting in a calculated sensitivity and specificity of this profile for ESC of 50% and 94%. In summary, in the differential diagnosis between OSC and ESC, positivity for all 3 markers favors an extrauterine origin, whereas negativity for all 3 markers is supportive of an endometrial origin. The use of single markers for this purpose is not recommended, as each lacks optimal discriminatory power. Coordinate profiles, in general, have a high specificity but low sensitivity in this differential diagnosis.
Way, Gregory P.; Rudd, James; Wang, Chen; Hamidi, Habib; Fridley, Brooke L.; Konecny, Gottfried E.; Goode, Ellen L.; Greene, Casey S.; Doherty, Jennifer A.
Four gene expression subtypes of high-grade serous ovarian cancer (HGSC) have been previously described. In these early studies, a fraction of samples that did not fit well into the four subtype classifications were excluded. Therefore, we sought to systematically determine the concordance of transcriptomic HGSC subtypes across populations without removing any samples. We created a bioinformatics pipeline to independently cluster the five largest mRNA expression datasets using k-means and nonnegative matrix factorization (NMF). We summarized differential expression patterns to compare clusters across studies. While previous studies reported four subtypes, our cross-population comparison does not support four. Because these results contrast with previous reports, we attempted to reproduce analyses performed in those studies. Our results suggest that early results favoring four subtypes may have been driven by the inclusion of serous borderline tumors. In summary, our analysis suggests that either two or three, but not four, gene expression subtypes are most consistent across datasets. PMID:27729437
Kurman, R J
A new paradigm for the pathogenesis of ovarian cancer has recently been proposed which helps to explain persistent problems in describing the development and diverse morphology of these neoplasms. The paradigm incorporates recent advances in our understanding of the molecular pathogenesis of epithelial 'ovarian' cancer with new insights into the origin of these tumors. Correlated clinicopathologic and molecular genetic studies led to the development of a dualistic model that divides all the various histologic types of epithelial ovarian carcinomas into two broad categories designated 'type I' and 'type II'. The prototypic type I tumor is low-grade serous carcinoma and the prototypic type II tumor is high-grade serous carcinomas (HGSCs). As the serous tumors comprise ∼70% of all epithelial ovarian tumors and account for the majority of deaths, the serous tumors will be the subject of this review. There are marked differences between the low-grade and high-grade serous tumors. Briefly, the former are indolent, present in stage I (tumor confined to the ovary) and develop from well-established precursors, so-called 'atypical proliferative (borderline) tumors,' which are characterized by specific mutations, including KRAS, BRAF and ERBB2; they are relatively genetically stable. In contrast, HGSCs are aggressive, present in the advanced stage, and develop from intraepithelial carcinomas in the fallopian tube. They harbor TP53 mutations in over 95% of cases, but rarely harbor the mutations detected in the low-grade serous tumors. At the time of diagnosis they demonstrate marked chromosomal aberrations but over the course of the disease these changes remain relatively stable. Along with the recent advances in understanding the molecular pathogenesis of these tumors, studies have demonstrated that the long sought for precursor of ovarian HGSC appears to develop from an occult intraepithelial carcinoma in the fimbrial region of the fallopian tube designated 'serous tubal
Güler, Sertaç Ata; Uğurlu, M. Ümit; Güllüoğlu, Bahadır M.
Phyllodes tumors are large breast tumors representing only 1% of breast neoplasms and are rarely seen in young women. Histologically, phyllodes tumors are classified as benign, borderline, or malignant based on the characteristics of the stroma. Although wide local excision is recommended for the treatment modality, the reoccurrence rate after surgical excision varies between 36% and 65%, with recurrence more likely in those with the tumor at the margins of excision. Our aim was to report -a case in a 15-year-old girl with a 115-mm borderline phyllodes tumor in her left breast mimicking a juvenile fibroadenoma. We presented a 5-year disease-free follow-up after wide local excision with negative margins.
Dikmen, Kursat; Bostanci, Hasan; Yildirim, Ali Cihat; Sakrak, Omer; Kerem, Mustafa
Serous cystadenomas are rare tumors comprising 1-2% of exocrine pancreas tumors. They are mostly known as benign conditions but malign transformation as serous cystadenocarcinoma is also reported. It is usually seen in females. Non-specific symptoms, such as abdominal pain or symptoms due to mass affect, are usually seen. A 64-year old female patient was investigated for abdominal pain. Physical and laboratory findings were normal. Abdomen ultrasonography confirmed an 11×9.5 cm solid cystic lesion and abdomen computed tomography scan confirmed a 12×11 cm lobulated cystic solid lesion which had central cystic necrotic areas extending from liver hilus inferiorly. Fine needle biopsy confirmed benign cytology and trucut biopsy of the pancreatic mass reported chronic inflamation. Nevertheless, this mass could have malignant contents and transformation potential. A laparatomy was decided due to patient's symptoms and mass effect. Due to vascular invasion of the tumor, Whipple procedure was performed. The pathology report confirmed serous microcystic adenoma. These rare tumors are usually benign but pre-operative malignity criterias are not identified. There are few differential diagnostic tools for excluding malignity. We suggest surgical resection as best treatment approach for selected cases.
Gilks, C Blake; Irving, Julie; Köbel, Martin; Lee, Chenghan; Singh, Naveena; Wilkinson, Nafisa; McCluggage, W Glenn
Most nonuterine high-grade serous carcinomas (HGSCs) in women with hereditary breast and ovarian cancer syndrome, due to germline BRCA1/2 mutation, arise in the fimbria of the fallopian tube. However, the site of origin of sporadic HGSC, which is usually widely disseminated at presentation, is not well established. We sought to characterize cases of HGSC discovered incidentally in patients not known to be at high risk, in order to determine the site distribution and possible origin of sporadic HGSC. Incidental microscopic, non-mass-forming cases of serous tubal intraepithelial carcinoma or HGSC in salpingo-oophorectomy specimens in which the tubes and ovaries had been extensively examined were identified. No patients were known or suspected BRCA1/2 mutation carriers. Twenty-one cases were identified (mean age: 57 y). Surgery was for benign disease (n=15), uterine endometrioid adenocarcinoma or atypical hyperplasia (n=3), bladder carcinoma (n=1), or ovarian serous borderline tumor (n=2). In 16 of 21 cases, the lesion was confined to the fallopian tube (unilateral in 14 cases, bilateral in 2). There was serous tubal intraepithelial carcinoma in all cases and invasive HGSC into the underlying lamina propria in 8 of these 16 cases; the invasive focus measured 1.3 cm or less in every case. In the remaining 5 cases, there was fallopian tube mucosal and ovarian involvement; in 2 of these cases, there was also microscopic peritoneal involvement. Sporadic cases of nonuterine HGSC arise in the fallopian tube fimbria in a large majority of cases, providing further evidence for the tubal origin of these neoplasms.
Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M.; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M.; Gehrig, Paola A.; Zhou, Chunxiao; Bae-Jump, Victoria L.
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
Gualtieri, C. Thomas C.; And Others
The use of the diagnosis "borderline" was evaluated with 16 children (6 to 13 years old) who were referred for comprehensive evaluation. None met DSM III criteria for borderline personality disorder. The borderline label had a negative impact on some children and was not helpful for treatment planning or disposition. (Author/SEW)
Puls, L; Heidtman, E; Hunter, J E; Crane, M; Stafford, J
This study evaluated the effect ovarian weight has on the accuracy of frozen sections in serous and mucinous ovarian tumors. The study group included 294 patients who had an initial frozen section (189 serous and 105 mucinous tumors) at surgery. The pathology reports were separated into subgroups (benign, borderline, or malignant). Tumors were broken down into three weight categories: < or = 450 g, > 450 to < or = 1360 g, and > 1360 g. In each weight category, accuracy, sensitivity, specificity, and positive and negative predicative values were calculated on frozen sections. The mean weight of the ovarian tumors was 1042 g. As the weight increased in serous tumors, the sensitivity fell from 96.2 to 93.8 to 75%, respectively, in each weight category. The same trend was noted with mucinous tumors as sensitivity fell from 91.7 to 87.5 to 66.7%, respectively. With an increase in the size of ovarian tumors, a decrease in the sensitivity of frozen section was observed. With tumors greater than 1360 g, sensitivity was only 69%. Twenty-three percent of ovarian tumors revealing borderline diagnosis at frozen section were malignant on the final pathology report, with the greatest misclassification in > 1360-g mucinous tumors (50%). For patients with large ovarian tumors, consideration should be given to performing staging at the time of the initial laparotomy.
Toyoda, Yasuhiro; Hojo, Shigeyuki; Yoshioka, Setsuko; Kojima, Fumiyoshi; Matsunaga, Hiroki; Fujie, Yujiro; Fukunaga, Hiroki; Ota, Hirofumi; Endo, Wakio; Maeura, Yoshiichi
A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.
Zheng, Wenxin; Xiang, Li; Fadare, Oluwole; Kong, Beihua
Endometrial serous carcinomas constitute no more than 10% of endometrial adenocarcinomas, but frequently present at an advanced stage and have a significantly worse prognosis than the more common low-grade and intermediate-grade endometrioid adenocarcinomas. The neoplasm's potential for rapid tumor progression and the high mortality that is associated with advanced-stage disease underscore the importance of understanding endometrial serous carcinogenesis so that its precancers can be diagnosed and an effective therapeutic intervention can be administered. In this study, the authors summarize the current state of knowledge on endometrial serous carcinogenesis and propose a model for its development based on recent work from our group and published data from other researchers. In this model, endometrial serous carcinoma arises predominantly in the resting endometrium, manifesting first as p53 immunoreactive, morphologically normal endometrial cells (p53 signatures), evolving to endometrial glandular dysplasia (which is the first morphologically identifiable precursor lesion), then to serous endometrial intraepithelial carcinoma (a carcinoma with a noninvasive growth pattern in the uterus but which is not infrequently associated with extrauterine disease), and finally into fully developed serous carcinoma. Endometrial glandular dysplasia is a lesion, which can be diagnosed by routine microscopic evaluation, whose ablation or removal may potentially offer the opportunity to prevent the development of the associated malignancy. The diagnostic criteria, practical applicability, and evidentiary basis for the delineation of this lesion are studied.
Kuhn, Elisabetta; Wang, Tian-Li; Doberstein, Kai; Bahadirli-Talbott, Asli; Ayhan, Ayse; Sehdev, Ann Smith; Drapkin, Ronny; Kurman, Robert J; Shih, Ie-Ming
Aberration in chromosomal structure characterizes almost all cancers and has profound biological significance in tumor development. It can be facilitated by various mechanisms including overexpression of cyclin E1 and centrosome amplification. As ovarian high-grade serous carcinoma has pronounced chromosomal instability, in this study we sought to determine whether increased copy number of CCNE1 which encodes cyclin E1 and centrosome amplification (>2 copies) occurs in its putative precursor, serous tubal intraepithelial carcinoma. We found CCNE1 copy number gain/amplification in 8 (22%) of 37 serous tubal intraepithelial carcinomas and 12 (28%) of 43 high-grade serous carcinomas. There was a correlation in CCNE1 copy number between serous tubal intraepithelial carcinoma and high-grade serous carcinoma in the same patients (P<0.001). There was no significant difference in the percentage of CCNE1 gain/amplification between serous tubal intraepithelial carcinoma and high-grade serous carcinoma (P=0.61). Centrosome amplification was recorded in only 5 (14%) of 37 serous tubal intraepithelial carcinomas, and in 10 (40%) of 25 high-grade serous carcinomas. The percentage of cells with centrosome amplification was higher in high-grade serous carcinoma than in serous tubal intraepithelial carcinoma (P<0.001). Induced expression of cyclin E1 increased the percentage of fallopian tube epithelial cells showing centrosome amplification. Our findings suggest that gain/amplification of CCNE1 copy number occurs early in tumor progression and precedes centrosome amplification. The more prevalent centrosome amplification in high-grade serous carcinoma than in serous tubal intraepithelial carcinoma supports the view that serous tubal intraepithelial carcinoma precedes the development of many high-grade serous carcinomas.
Saito, Yuki; Suzuki, Yasuhiro; Inomoto, Chie; Kumaki, Nobue; Yokoyama, Kozue; Ogiya, Rin; Oshitanai, Risa; Terao, Mayako; Tsuda, Banri; Morioka, Tooru; Niikura, Naoki; Okamura, Takuho; Masuda, Shinobu; Tokuda, Yutaka
We report a patient with a giant phyllodes tumor of the right breast associated with a hypoglycemic attack. A 48-year-old woman experienced a loss of consciousness and was transferred via ambulance to our hospital emergency department. Upon arrival, her blood glucose level was 26 mg/dl, and a giant tumor (>20 cm in diameter) with skin ulceration was observed on the right breast. Core needle biopsy led to a histological diagnosis of a phyllodes tumor of the breast. Ultrasonography and computed tomography detected neither distant metastasis nor a pancreatic endocrine tumor. Her preoperative serum insulin-like growth factor (IGF)-II and insulin levels were 1,330 ng/ml (normal range, 519-1067 ng/ml) and <1.0 µU/ml, respectively. Following a simple mastectomy, the 24-h postoperative serum IGF-II and insulin levels were 496 ng/ml and 10.0 µU/ml, respectively. The IGF-II levels detected in the phyllodes tumor and normal breast tissue were 10,600 ng/Wg (wet weight in grams) and 855 ng/Wg. We conclude from these findings that the hypoglycemic attack was related to the elevated IGF-II level in the giant phyllodes tumor of the breast.
Jia, Lin; Yuan, Zeng; Wang, Yiying; Cragun, Janiel M; Kong, Beihua; Zheng, Wenxin
Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is currently unclear where does the extrauterine disease come from. This study addressed this issue. A total of 135 samples from 21 serous endometrial intraepithelial carcinoma patients were studied. Cellular lineage relationships between intrauterine and extrauterine serous carcinomas were determined by TP53-mutation analysis and correlated to the clinicopathologic features. There were three conditions contributing the extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n=10) showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n=5) had discordant TP53 mutations, and the mixed cellular origin cases (n=6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (<2 cm) in extrauterine sites and without finding of serous tubal intraepithelial carcinoma, while extrauterine disease with adnexal or tubal origin commonly had larger tumor masses in extrauterine sites including ovary and omentum and serous tubal intraepithelial carcinoma. The majority of extrauterine diseases associated with serous endometrial intraepithelial carcinoma are metastasized from the endometrium. Serous endometrial intraepithelial carcinoma is frequently associated with serous cancers of adnexal or tubal origin, indicating that endometrial and adnexal or tubal serous cancers may share similar etiologies. TP53-mutation analysis provides a strong linkage for cellular lineage analysis. Tumor size in extrauterine disease and presence of serous tubal intraepithelial carcinoma or not are useful clinicopathologic features to determine primary cancer site, which helps in clinical management.
Zhang, Liping; Liu, Yuxin; Hao, Suyang; Woda, Bruce A; Lu, Di
Among various endometrial adenocarcinomas, endometrioid carcinoma can be very difficult to separate from serous carcinomas. Various biomarkers have been studied with proven value, including p53, Ki-67, and p16. In this study, we present data on another biomarker, IMP2, which we believe is sensitive and specific. Using 320 endometrial biopsy cases, we demonstrate that IMP2 is normally expressed in all proliferative and inactive endometrial glandular cells. The pattern of such expression is unchanged in serous carcinomas. IMP2 expression is, however, lost in all cases of endometrioid carcinomas by at least 25% to >95% of tumor cell populations. Therefore, loss of IMP2 expression can differentiate endometrioid from serous carcinomas. Such finding of IMP2 expression remained the same in mixed endometrioid and serous carcinomas; IMP2 expression is lost in all endometrioid components by at least 25% of tumor cell population, whereas it remained diffuse and strong in all serous components of carcinomas.
M.V, Rashmi.; P, Pavithra; G.M, Shivakumarappa
Dermatofibrosarcoma protruberans is a relatively uncommon slow growing, locally aggressive fibrous tumor of the skin. It has a prospensity of progressing to fibrosarcomatous change in 5% of the cases. We present a case of a 56 yr old male with presented to the outpatient department of surgery, Sri Siddhartha Medical College, Tumkur with a chest swelling in 2013. FNAC was inconclusive and the mass was excised. On histopathology, areas of benign fibrohistiocytic tumor, dermatofibrosarcoma protruberans and fibrosarcomatous dermatofibrosarcoma were identified in the same tumor. Immunohistochemistry confirmed the diagnosis of DFSP with fibrosarcomatous change. Although, transformed DFSP is more aggressive, the prognosis is influenced by the extent of excision and with wide excision, there may be little increased risk for recurrence and metastasis over that of conventional DFSP. PMID:27799980
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
Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination
Miyoshi, Ai; Miyatake, Takashi; Hara, Takeya; Tanaka, Asuka; Komura, Naoko; Komiya, Shinnosuke; Kanao, Serika; Takeda, Masumi; Mimura, Mayuko; Nagamatsu, Masaaki; Yokoi, Takeshi
Borderline ovarian tumors are benign but relatively large tumors that are often initially mistaken as ovarian cancers. We report three cases of stage I borderline ovarian tumors having massive ascites that we (preoperatively) suspected of being advanced ovarian cancer. The three patients (35, 47, and 73 years old) reported feeling fullness of the abdomen before consulting their gynecologist. By CT scan, they were diagnosed with a pelvic tumor accompanied by massive ascites, the diameters of which were 11, 20, and 11 cm, respectively. Postsurgical pathology showed all were stage I borderline ovarian tumors without dissemination; two were mucinous and one was serous. The amount of ascites was 6,300, 2,600, and 3,600 mL, respectively, and was serous in all. Cytodiagnosis of the ascites found that one was positive for tumor cells and two were negative. After resection of the mass, the ascites disappeared in all three cases. No pleural effusion was present at any time. The literature is reviewed concerning ascites and pleural effusions linked to ovarian tumors, and a supposition is forwarded of why pleural effusion presents sporadically in these cases. PMID:26858849
Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna
Aims Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. Results PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively). Conclusions Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity. PMID:26625204
Nakamura, Kohei; Nakayama, Kentaro; Ishibashi, Tomoka; Ishikawa, Noriyoshi; Ishikawa, Masako; Katagiri, Hiroshi; Minamoto, Toshiko; Sato, Emi; Sanuki, Kaori; Yamashita, Hitomi; Iida, Kouji; Sultana, Razia; Kyo, Satoru
Ovarian low-grade serous carcinoma is thought to begin as a serous cystadenoma or adenofibroma that progresses in a slow stepwise fashion. Among the low-grade serous carcinomas, there is a high frequency of activating mutations in the KRAS or BRAF genes; however, it remains unclear as to how these mutations contribute to tumor progression. This is the first report to track the histopathological progression of serous adenofibroma to low-grade serous carcinoma. Each stage was individually analyzed by pathological and molecular genetic methods to determine what differences occur between the distinct stages of progression.
Koncoro, Hendra; Putra, I Komang W D; Wibawa, I Dewa N
Macrocystic serous cystadenoma is an unusual and essentially benign pancreatic tumor. Herein, we report on a 40-year-old woman diagnosed with macrocystic serous cystadenoma who presented with obstructive jaundice. A cystic lesion in the head and body of the pancreas was revealed by abdominal computed tomography. Intraoperative pancreatic cyst aspiration ruled out mucinous cystic neoplasm which has a malignant potential. The pancreatic cyst fluid cytology was basophilic amorph materials concluded as benign cystic lesion. Internal drainage was performed instead of pancreatic resection which showed good outcome. Biliary obstruction is a rare complication of serous cystadenoma. This case describes an unusual clinical presentation of macrocystic serous cystadenoma.
Carlson, Joseph; Roh, Michael H.; Chang, Martin C.; Crum, Christopher P.
Summary In the past 50 years, the concept of serous ovarian cancer has been progressively refined, with the distinction of the borderline serous tumour, identification of a smaller subset of well-differentiated serous malignancies and, recently, closer attention to the pathogenesis of high-grade serous malignancies. High-grade serous carcinoma, traditionally presumed to arise within Müllerian inclusion cysts of the ovarian surface, cortex and peritoneum, has recently been linked to the distal fallopian tube. This review addresses the disparate forms of serous neoplasia, which reflect both different genetic abnormalities and stages of differentiation of Müllerian epithelium. The significance of these different origins is addressed in the context of ovarian cancer prevention. PMID:20953242
Reid, Michelle D; Choi, Hyejeong; Balci, Serdar; Akkas, Gizem; Adsay, Volkan
We herein summarize the pathology and most recent advances in the molecular genetics of serous cystic neoplasms of the pancreas. They typically present as relatively large, well-demarcated tumors (mean size, 6cm), predominantly occurring in females. Pre-operative diagnosis remains challenging; imaging findings and cyst fluid analysis often prove non-specific and fine-needle aspiration often does not yield diagnostic cells. Pathologically, they are characterized by a distinctive cytology referred to as "serous." Although they have ductal differentiation, they distinctly lack the mucin production that characterizes most other pancreatic ductal tumors, including ductal adenocarcinoma and its variants, intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). They instead produce abundant glycogen (glycogen-rich adenoma). Serous cystadenomas also lack the molecular alterations that characterize ductal neoplasms, such as mutation of KRAS (high prevalence in most mucinous ductal neoplasms), inactivation of SMAD4 (seen in ductal adenocarcinomas), and mutations in GNAS (seen in some IPMNs) and RNF43 (detected in MCNs and IPMNs). Instead, new molecular and immunohistochemical observations place serous pancreatic tumors closer to "clear cell neoplasms" seen in various other organs that are associated with the von Hippel-Lindau (VHL) pathway, such as clear cell renal cell carcinomas and capillary hemangioblastomas. Patients with VHL syndrome have an increased risk of developing serous pancreatic tumors and somatic mutations of the VHL gene are common in these tumors along with modification of its downstream effectors including hypoxia-inducible factor (HIF1), glucose uptake and transporter-1 (GLUT-1), a common factor in clear cell (glycogen-rich) tumors, as well as expression of vascular endothelial growth factor (VEGF), thought to be a factor in the striking capillarization of serous cystadenomas and other non-pancreatic clear cell tumors. VEGF may
Liang, Li; Jiang, Yi; Chen, Jun-Song; Niu, Na; Piao, Jin; Ning, Jing; Zu, Youli; Zhang, Jing; Liu, Jinsong
The B7 family of immune costimulatory ligands is a group of cell surface proteins that bind to the surface receptors of lymphocytes to fine-tune immune responses. The aberrant expression of these proteins plays a key role in tumor immune evasion. Immunotherapy targeting certain B7 family members, including programmed death ligand 1, has proven quite effective in suppressing tumor growth. However, why such therapy works in only a subgroup of tumors is unclear. We hypothesized that other B7 family members, either alone or in concert with programmed death ligand 1, play a crucial role in tumor pathogenesis and progression. We therefore examined the expression of a newly discovered B7 family member, B7-H4, in 306 cases of ovarian serous carcinoma by immunohistochemistry. We found that 91% (267/293) of the high-grade ovarian serous carcinomas and 69% (9/13) of the low-grade ovarian serous carcinomas expressed B7-H4. The difference between B7-H4 expression in high-grade and low-grade ovarian serous carcinoma was statistically significant (P=.002). Moreover, B7-H4 protein expression in high-grade serous carcinoma was associated with tumor stage (P<.01) but not overall survival or disease-free survival. In conclusion, B7-H4 is frequently expressed in ovarian serous carcinomas, especially high-grade serous carcinomas, and may represent a novel immunotherapeutic target in this cancer.
Kuhn, Elisabetta; Bahadirli-Talbott, Asli; Shih, Ie-Ming
Uterine serous carcinoma accounts for only 10% of all uterine epithelial cancers, but is the leading cause of death among them. The pathogenesis of this aggressive neoplasm has been largely elusive until recently, when comprehensive genome-wide analyses of uterine serous carcinoma have been performed. Among amplified cancer-related genes, CCNE1, encoding for cyclin E1, is frequently amplified in uterine serous carcinoma. In the current study we applied fluorescence in situ hybridization (FISH) to determine CCNE1 copy number in uterine serous carcinoma and concurrent endometrial intraepithelial carcinoma, the noninvasive component of uterine serous carcinoma, and the results were correlated with clinicopathological and molecular features. We found that 20 (45%) of 44 uterine serous carcinomas and 11 (41%) of 27 endometrial intraepithelial carcinomas showed CCNE1 amplification. Overall, we found high concordance in CCNE1 copy number in concurrent uterine serous carcinoma and endometrial intraepithelial carcinoma pairs (P-value=0.0003). No correlation was observed between CCNE1 copy number and clinicopathological features, as well as common mutations previously reported in uterine serous carcinoma. In summary, we confirm that amplification of CCNE1 is a frequent molecular genetic change in uterine serous carcinoma. Moreover, the identification of CCNE1 amplification in many endometrial intraepithelial carcinomas suggests that this genetic event occurs early during tumor progression.
AlAli, Alaa; Bushehri, Ahmad; Park, Jonathan C.; Krema, Hatem
Purpose: To report a case of multifocal serous retinal detachments associated with pimasertib. Methods: The authors report a 26-year-old patient who developed bilateral multifocal serous retinal detachments appearing 2 days after starting pimasertib (as part of a clinical trial investigating its use in low-grade metastatic ovarian cancer) and rapidly resolving 3 days after stopping it. Conclusion: The mechanism of MEK inhibitor induced visual toxicity remains unclear. The pathophysiology of multifocal serous retinal detachments as a complication of pimasertib is still poorly understood. PMID:26444523
Ren, Caixia; Du, Juan; Xi, Chenguang; Yu, Yu; Hu, Ajin; Zhan, Jun; Guo, Hongyan; Fang, Weigang; Liu, Congrong; Zhang, Hongquan
Kindlin-2 has been known to promote most cancer progression through regulation of multiple signaling pathways. However, a novel tumor suppressive role of Kindlin-2 was identified in serous epithelial ovarian cancer progression, which sharply contrasts to the tumor promoting roles for Kindlin-2 in most other cancers. While we demonstrated that Kindlin-2 was highly expressed in control tissues, a drastic low expression of Kindlin-2 was found in the tumor tissues of serous epithelial ovarian cancer, especially in the high-grade serous epithelial ovarian cancer. Importantly, Kindlin-2 inhibited serous epithelial ovarian cancer cell peritoneal dissemination in a mouse model. For clinical relevance, low Kindlin-2 expression correlated with higher tumor grade and older patients. Intriguingly, decreased Kindlin-2 expression predicts poor overall and progression-free survivals in serous epithelial ovarian cancer patients. Mechanistically, Kindlin-2 induced a mesenchymal to epithelial transition in serous epithelial ovarian cancer cells, at least in part, by up-regulation of estrogen receptor α which was recruited to the promoter of E-cadherin and thereby enhanced the transcription of E-cadherin. Collectively, we concluded that inadequate Kindlin-2 is an independent risk factor for serous epithelial ovarian cancer patients.
Ono, Kyoko; Hayashi, Hiroyuki; Tateno, Masatoshi; Tanaka, Reiko; Suzuki, Rie; Maruyama, Yasuyo; Miyagi, Yohei; Furuya, Mitsuko
Uterine superficial serous carcinoma (SSC) and serous endometrial intraepithelial carcinoma (SEIC) are unique malignancies found primarily in postmenopausal women. SSC and SEIC lesions measuring 1 cm or less are categorized as minimal uterine serous carcinoma (MUSC). Less well understood, however, the clinical behavior of SSC and SEIC lesions measuring more than 1 cm. We investigated 6 postmenopausal patients, aged 69-83 years, with SSC or SEIC and without hyperestrogenism. All but 1 patient had tumors originating from the surface of polyps, including 3 patients who each had an enormous polyp occupying the entire uterine cavity. Two patients had extensive SEICs measuring more than 1 cm; the others had SSCs, including 1 MUSC. The mesenchymal cells of the cancer-bearing polyps lacked the morphologic characteristics of endometrial stroma, and the cancer glands often immunostained negatively for estrogen receptors and progesterone receptors. Diffuse immunostaining for human epidermal growth factor receptor 2 was detected in 3 patients, and p53 was detected in all. Cyclin E, a downstream molecule of the F-box and WD repeat domain-containing 7 (FBXW7), was detected in all patients. Microdissected cancer glands showed p53 mutations in 2 patients and a FBXW7 mutation in 1 patient. These findings suggest that mutations of FBXW7 and p53 may contribute to the carcinogenesis of less invasive tumor subtypes. Pathologists and physicians should carefully evaluate SSC and SEIC lesions involving large polyps but lacking myometrial invasion.
Izadi-Mood, Narges; Samadi, Nasrin; Sarmadi, Soheila; Eftekhar, Zahra
Adenocarcinoma arising from adenomyosis uteri is rare. Herein, we reported a patient with papillary serous carcinoma arising from adenomyosis. The patient was a 61-year-old woman who received tamoxifen for treatment of her breast cancer over the past five years. In hysterectomy specimen taken for investigating her uncontrolled bleeding with suspicion of uterine myoma, multiple adenomyotic foci were found in the uterine wall. In one of these foci, papillary serous carcinoma was found. No evidence of tumor was seen in endometrial surface, peritoneum, and both adnexa.
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
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
Vang, Russell; Levine, Douglas A; Soslow, Robert A; Zaloudek, Charles; Shih, Ie-Ming; Kurman, Robert J
The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the
Kakkar, Aanchal; Sharma, Mehar C; Yadav, Rajni; Panwar, Rajesh; Mathur, Sandeep R; Iyer, Venkateswaran K; Sahni, Peush
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.
Aust, Stefanie; Felix, Sophie; Auer, Katharina; Bachmayr-Heyda, Anna; Kenner, Lukas; Dekan, Sabine; Meier, Samuel M.; Gerner, Christopher; Grimm, Christoph; Pils, Dietmar
Immune-evasion and immune checkpoints are promising new therapeutic targets for several cancer entities. In ovarian cancer, the clinical role of programmed cell death receptor ligand 1 (PD-L1) expression as mechanism to escape immune recognition has not been clarified yet. We analyzed PD-L1 expression of primary ovarian and peritoneal tumor tissues together with several other parameters (whole transcriptomes of isolated tumor cells, local and systemic immune cells, systemic cytokines and metabolites) and compared PD-L1 expression between primary tumor and tumor recurrences. All expressed major histocompatibility complex (MHC) I genes were negatively correlated to PD-L1 abundances on tumor tissues, indicating two mutually exclusive immune-evasion mechanisms in ovarian cancer: either down-regulation of T-cell mediated immunity by PD-L1 expression or silencing of self-antigen presentation by down-regulation of the MHC I complex. In our cohort and in most of published evidences in ovarian cancer, low PD-L1 expression is associated with unfavorable outcome. Differences in immune cell populations, cytokines, and metabolites strengthen this picture and suggest the existence of concurrent pathways for progression of this disease. Furthermore, recurrences showed significantly increased PD-L1 expression compared to the primary tumors, supporting trials of checkpoint inhibition in the recurrent setting. PMID:28266500
Hedley, Catherine; Sriraksa, Ruethairat; Showeil, Rania; Van Noorden, Susan; El-Bahrawy, Mona
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.
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…
Kainuma, Osamu; Yamamoto, Hiroshi; Cho, Akihiro; Arimitsu, Hidehito; Yanagibashi, Hiroo; Takiguchi, Nobuhiro; Nabeya, Yoshihiro; Kawana, Hidetada
Serous cystic neoplasms (SCN) of the pancreas are typically honeycombed microcystic masses, which are believed to be benign entity. This report describes a case of a 69-year-old man with a rare solid type of serous cystadenocarcinoma of the pancreas with liver metastases. A 6-cm well enhanced pancreatic tumor and multiple liver nodules were depicted with contrast medium on computed tomography scan. Distal pancreatectomy was performed at first operation. The cut surface of the tumor was solid and glossy appearance. Second operation of liver resection for all metastatic nodules was performed 27 months after the initial operation. The tumor cells in both the pancreas and the liver had cytoplasmic periodic acid-Schiff positive granules, which were completely digested by diastase. Eleven cases of serous cystadenocarcinoma of the pancreas have been reported in the literature. To our knowledge, this is the first case of a solid type serous cystadenocarcinoma.
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
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
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
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.
Zang, Xingxing; Sullivan, Peggy S; Soslow, Robert A; Waitz, Rebecca; Reuter, Victor E; Wilton, Andrew; Thaler, Howard T; Arul, Manonmani; Slovin, Susan F; Wei, Joyce; Spriggs, David R; Dupont, Jakob; Allison, James P
B7-H3 and B7x are members of the B7 family of immune regulatory ligands that are thought to attenuate peripheral immune responses through co-inhibition. Previous studies have correlated their overexpression with poor prognosis and decreased tumor-infiltrating lymphocytes in various carcinomas including uterine endometrioid carcinomas, and mounting evidence supports an immuno-inhibitory role in ovarian cancer prognosis. We sought to examine the expression of B7-H3 and B7x in 103 ovarian borderline tumors and carcinomas and study associations with clinical outcome. Using immunohistochemical tissue microarray analysis on tumor specimens, we found that 93 and 100% of these ovarian tumors express B7-H3 and B7x, respectively, with expression found predominantly on cell membranes and in cytoplasm. In contrast, only scattered B7-H3- and B7x-positive cells were detected in non-neoplastic ovarian tissues. B7-H3 was also expressed in the endothelium of tumor-associated vasculature in 44% of patients, including 78% of patients with high-stage tumors (FIGO stages III and IV), nearly all of which were high-grade serous carcinomas, and 26% of patients with low-stage tumors (FIGO stages I and II; P<0.001), including borderline tumors. Analysis of cumulative survival time and recurrence incidence revealed that carcinomas with B7-H3-positive tumor vasculature were associated with a significantly shorter survival time (P=0.02) and a higher incidence of recurrence (P=0.03). The association between B7-H3-positive tumor vasculature and poor clinical outcome remained significant even when the analysis was limited to the high-stage subgroup. These results show that ovarian borderline tumors and carcinomas aberrantly express B7-H3 and B7x, and that B7-H3-positive tumor vasculature is associated with high-grade serous histological subtype, increased recurrence and reduced survival. B7-H3 expression in tumor vasculature may be a reflection of tumor aggressiveness and has diagnostic and
Enomoto, T.; Weghorst, C. M.; Inoue, M.; Tanizawa, O.; Rice, J. M.
To explore the role of mutational activation of members of the ras family of cellular protooncogenes in the development of human ovarian neoplasms, a series of 37 ovarian tumors from Japanese patients was studied. These included 30 common epithelial tumors (1 mucinous tumor of borderline malignancy, 7 mucinous adenocarcinomas, and 22 nonmucinous carcinomas: 10 serous, 3 clear cell, 8 endometrioid, and 1 undifferentiated), 5 tumors of germ cell origin, and 2 sex cord/stromal cell tumors. Polymerase chain reaction was performed from selected areas of deparaffinized sections of formalin-fixed paraffin-embedded tissue, and the presence of activating point mutations in codons 12, 13, and 61 of the H-, N-, and K-ras genes was probed by dot-blot hybridization analysis with mutation specific oligonucleotides. Mutations in K-ras were also looked for by direct genomic sequencing. The overall frequency of ras gene mutations was 10/37 (27%). Mutations were detected only in K-ras, and were found in most of the mucinous tumors, including the one such tumor of borderline malignancy (6/8; 75%). In one mucinous adenocarcinoma, two mutations were detected in paraffin-embedded material that had not previously been found in high molecular weight DNA isolated from frozen tissue from the same case. K-ras mutations occurred significantly more frequently in mucinous tumors (6/8, 75%) than in serous carcinomas (2/10, 20%; P = 0.031) or in all nonmucinous types of epithelial ovarian tumors combined (3/22, 14%; P = 0.0031). Images Figure 1 Figure 2 PMID:1656759
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
American Psychiatric Association. Borderline personality disorder. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013:663-666. Blais MA, Smallwood P, Groves ...
Green, Maurice R.
Describes characteristics of borderline adolescents and reviews diagnostic issues. Uses two case studies to illustrate general treatment strategies that could be useful to clinicians in mental health programs and family courts. (JAC)
Brandone, Nicolas; Poizat, Flora; Thomassin-Piana, Jeanne; Turrini, Olivier; Popovici, Cornel; Terris, Benoît
Cystic pancreatic neoplasms concern 1 to 2% of the pancreatic tumours. The serous ones are considered benign tumours but since 1989, several pancreatic serous cystadenocarcinomas (SCAC) cases have been reported. We report the case of a SCAC with a particular pattern. An 80-year-old female patient presented a 4-cm tumour in the neck of the pancreas associated with liver lesions evoking, on imagery exams, focal nodular hyperplasia nests. A cephalic duodenopancreatectomy and a resection of the liver lesions were carried out. The gross exam showed a tumour with a pattern mostly solid and an area made of cysts. The microscopic exam displayed two patterns: the solid one, predominant, made of mild atypical clear cells, and the cystic one. The liver lesions revealed solid pattern similar to the pancreatic tumour one. The tumoral cells were cytokeratin 7, AE1/AE3 and inhibin positives. The Periodic-acid Schiff showed cytoplasmic granulations, which were digested after diasatasis. Only the presence of metastases allows distinguishing a pancreatic serous cystadenoma from a SCAC. To date, thirty cases of pancreatic SCAC have been reported. Immunohistochemistry cannot confirm the malignancy nature of the lesion but it needs to be done in order to cross out the differential diagnosis, that is pancreatic metastatic clear cell renal carcinoma. Nevertheless, it remains a pathology with good prognosis. Only two cases have been reported but ours case a predominant solid pattern.
Saglam, Ozlen; Xiong, Yin; Marchion, Douglas C; Strosberg, Carolina; Wenham, Robert M; Johnson, Joseph J; Saeed-Vafa, Daryoush; Cubitt, Christopher; Hakam, Ardeshir; Magliocco, Anthony M
Few data exist on the prognostic and predictive impact of erb-b2 receptor tyrosine kinase 4 (ERBB4) in ovarian cancer. Thus, we evaluated ERBB4 expression by immunohistochemistry in a tumor microarray consisting of 100 ovarian serous carcinoma specimens (50 complete responses [CRs] and 50 incomplete responses [IRs] to platinum-based therapy), 51 normal tissue controls, and 16 ovarian cancer cell lines. H scores were used to evaluate expression and were semiquantitatively classified into low, intermediate, and high categories. Category frequencies were compared between tumor specimens vs controls using an unpaired t test. Among tumors, category frequencies were compared between CR and IR to chemotherapy. Overall survival (OS) was stratified by category. In total, 74 ovarian serous carcinoma samples (32 CRs and 42 IRs), 28 normal controls, and 16 ovarian cancer cell lines were evaluable. High-level ERBB4 expression was observed at a significantly higher frequency in ovarian serous carcinoma compared with normal control tissue. Among tumor specimens, ERBB4 expression was significantly higher for those with an IR to chemotherapy compared with CR (P = .033). OS was inversely correlated with ERBB4 expression levels. Median rates of OS were 18, 22, and 58 months among high-, intermediate-, and low-expression tumors, respectively. Our results indicate that ERBB4 expression by immunohistochemistry may correlate with chemotherapy-resistant ovarian serous carcinoma and shortened OS.
Mingels, Marjanka J J M; van Ham, Maaike A P C; de Kievit, Ineke M; Snijders, Marc P M L; van Tilborg, Angela A G; Bulten, Johan; Massuger, Leon F A G
Serous ovarian cancer is suggested to develop from epithelium embryologically derived from the Müllerian ducts. The aim of the current study is to thoroughly, analyze the epithelium derived from the Müllerian ducts (cervix, endometrium and fallopian tubes) in serous ovarian cancer patients. Sixty women diagnosed with serous ovarian carcinoma were included in this multicentre, observational study. Tissues were embedded completely for histological assessment, in accordance with the SEE-Fim and SEE-End protocol (Sectioning and Extensively Examining of the Fimbriated end; and-Endometrium), and prevalence of cervical, as well as endometrial and tubal pathology was analyzed. In 31 (52%) cases, a pathologic lesion was identified, and in 16 (27%) of these cases coexistence of pathologic lesions. In 1 case, severe dysplasia was found in the cervix, in 9 (15%) cases endometrial intraepithelial carcinoma, in 19 (32%) cases atypical hyperplasia, and in 23 (43%) cases serous tubal intraepithelial carcinoma. Serous tubal intraepithelial carcinoma was seen significantly more often concurrent with endometrial atypical hyperplasia or endometrial intraepithelial carcinoma than with benign endometrium (64 vs 28%; P=0.01). To conclude, histological assessment of epithelium derived from Müllerian ducts of serous ovarian cancer patients resulted in the identification of endometrial intraepithelial carcinoma, serous tubal intraepithelial carcinoma and/or endometrial atypical hyperplasia in more than half of cases. Coexistence of these pathologic lesions was common, and might represent an effect of field carcinogenesis or tumor implantation of migrating cells.
Green, Ann E.; Nielsen, Julie S.; Nelson, Brad H.; Drescher, Charles W.; Brown, Patrick O.
Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5′ exons of ESRRA, encoding a ligand-independent member of the nuclear-hormone receptor superfamily, to the 3′ exons of C11orf20, a conserved but uncharacterized gene located immediately upstream of ESRRA in the reference genome. To estimate the prevalence of the fusion, we tested 67 cases of serous ovarian cancer by RT-PCR and sequencing and confirmed its presence in 10 of these. Targeted resequencing of the corresponding genomic region from two fusion-positive tumor samples identified a nearly clonal chromosomal rearrangement positioning ESRRA upstream of C11orf20 in one tumor, and evidence of local copy number variation in the ESRRA locus in the second tumor. We hypothesize that the recurrent novel fusion transcript may play a role in pathogenesis of a substantial fraction of serous ovarian cancers and could provide a molecular marker for detection of the cancer. Gene fusions involving adjacent or nearby genes can readily escape detection but may play important roles in the development and progression of cancer. PMID:21949640
Ovarian serous cystadenocarcinoma is a common malignant tumor of female genital organs. Treatment is generally less effective as patients are usually diagnosed in the late stage. Therefore, a well-designed prognostic marker provides valuable data for optimizing therapy. In this study, we analyzed 303 samples of ovarian serous cystadenocarcinoma and the corresponding RNA-seq data. We observed the correlation between gene expression and patients' survival and eventually established a risk assessment model of five factors using Cox proportional hazards regression analysis. We found that the survival time in high-risk patients was significantly shorter than in low-risk patients in both training and testing sets after Kaplan-Meier analysis. The AUROC value was 0.67 when predicting the survival time in testing set, which indicates a relatively high specificity and sensitivity. The results suggest diagnostic and therapeutic applications of our five-gene model for ovarian serous cystadenocarcinoma. PMID:27478834
Togami, Shinichi; Sasajima, Yuko; Kasamatsu, Takahiro; Oda-Otomo, Rie; Okada, Satoshi; Ishikawa, Mitsuya; Ikeda, Shun-ichi; Kato, Tomoyasu; Tsuda, Hitoshi
Serous adenocarcinoma of the cervix (SACC) is a very rare tumor. Our study aimed to characterize the immune profile and human papillomavirus (HPV) status of SACC, in comparison with other serous adenocarcinomas arising in the female genital tract. The pathological specimens obtained from 81 patients with serous carcinoma of the uterine cervix (n = 12), 29 endometrium, 20 ovary and 20 patients with mucinous carcinoma of the uterine cervix were reviewed. We assessed the expression of WT-1, p53, p16, HER2, CEA, and CA125 by immunohistochemistry and HPV DNA by PCR in 12 SACC samples. Their immune profile was compared with that of uterine papillary serous carcinoma (UPSC), ovarian serous adenocarcinoma (OSA), and mucinous endocervical adenocarcinoma (MEA). WT-1 and HER2 were expressed in very few SACC samples (0 and 0%, respectively), but p16, CA125, CEA and p53 were present in 100, 92, 58 and 50%, respectively. The difference in WT-1 expression between SACC and UPSC, MEA is not significant, but SACC differ significantly from OSA (p < 0.01). HPV DNA (type 16 or 18) was detected in 4 of the 12 SACC. The immunophenotype of SACC was similar to UPSC, whereas the frequency of expression of WT-1 was significantly lower in SACC than OSA. It appeared that p53 expression was associated with worse clinical outcome in patients with SACC, and that HPV infection was related to its occurrence.
Hunter, Sally M; Anglesio, Michael S; Ryland, Georgina L; Sharma, Raghwa; Chiew, Yoke-Eng; Rowley, Simone M; Doyle, Maria A; Li, Jason; Gilks, C Blake; Moss, Phillip; Allan, Prue E; Stephens, Andrew N; Huntsman, David G; deFazio, Anna; Bowtell, David D; Gorringe, Kylie L; Campbell, Ian G
Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial ovarian tumours, with little known of the molecular drivers and facilitators of tumorigenesis beyond classic oncogenic RAS/RAF mutations. With a move towards targeted therapies due to the chemoresistant nature of this subtype, it is pertinent to more fully characterise the genetic events driving this tumour type, some of which may influence response to therapy and/or development of drug resistance. We performed genome-wide high-resolution genomic copy number analysis (Affymetrix SNP6.0) and mutation hotspot screening (KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53) to compare a large cohort of ovarian serous borderline tumours (SBTs, n = 57) with low grade serous carcinomas (LGSCs, n = 19). Whole exome sequencing was performed for 13 SBTs, nine LGSCs and one mixed low/high grade carcinoma. Copy number aberrations were detected in 61% (35/57) of SBTs, compared to 100% (19/19) of LGSCs. Oncogenic RAS/RAF/ERBB2 mutations were detected in 82.5% (47/57) of SBTs compared to 63% (12/19) of LGSCs, with NRAS mutations detected only in LGSC. Some copy number aberrations appeared to be enriched in LGSC, most significantly loss of 9p and homozygous deletions of the CDKN2A/2B locus. Exome sequencing identified BRAF, KRAS, NRAS, USP9X and EIF1AX as the most frequently mutated genes. We have identified markers of progression from borderline to LGSC and novel drivers of LGSC. USP9X and EIF1AX have both been linked to regulation of mTOR, suggesting that mTOR inhibitors may be a key companion treatment for targeted therapy trials of MEK and RAF inhibitors.
Hunter, Sally M.; Anglesio, Michael S.; Ryland, Georgina L.; Sharma, Raghwa; Chiew, Yoke-Eng; Rowley, Simone M.; Doyle, Maria A.; Li, Jason; Gilks, C. Blake; Moss, Phillip; Allan, Prue E.; Stephens, Andrew N.; Huntsman, David G.; deFazio, Anna; Bowtell, David D.
Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial ovarian tumours, with little known of the molecular drivers and facilitators of tumorigenesis beyond classic oncogenic RAS/RAF mutations. With a move towards targeted therapies due to the chemoresistant nature of this subtype, it is pertinent to more fully characterise the genetic events driving this tumour type, some of which may influence response to therapy and/or development of drug resistance. We performed genome-wide high-resolution genomic copy number analysis (Affymetrix SNP6.0) and mutation hotspot screening (KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53) to compare a large cohort of ovarian serous borderline tumours (SBTs, n = 57) with low grade serous carcinomas (LGSCs, n = 19). Whole exome sequencing was performed for 13 SBTs, nine LGSCs and one mixed low/high grade carcinoma. Copy number aberrations were detected in 61% (35/57) of SBTs, compared to 100% (19/19) of LGSCs. Oncogenic RAS/RAF/ERBB2 mutations were detected in 82.5% (47/57) of SBTs compared to 63% (12/19) of LGSCs, with NRAS mutations detected only in LGSC. Some copy number aberrations appeared to be enriched in LGSC, most significantly loss of 9p and homozygous deletions of the CDKN2A/2B locus. Exome sequencing identified BRAF, KRAS, NRAS, USP9X and EIF1AX as the most frequently mutated genes. We have identified markers of progression from borderline to LGSC and novel drivers of LGSC. USP9X and EIF1AX have both been linked to regulation of mTOR, suggesting that mTOR inhibitors may be a key companion treatment for targeted therapy trials of MEK and RAF inhibitors. PMID:26506417
Sipos, V; Schweiger, U
Characteristics of a borderline personality disorder include emotional instability and a self-threatening lack of impulsive control. As a result, interpersonal relationships are rendered difficult. The central elements of treatment are psychoeducation, self-management, improved stress tolerance and awareness, emotion managment and training in social competence.
Hisada, H; Awaya, S
Central serous chorioretinopathy (CRS) is one of the typical diseases that accompany micropsia. However very little is known about micropsia of CRS, because of the difficulty to measure "aniseikonia" in terms of micropsia. Aniseikonia in 65 cases of CRS was measured quantitatively by Awaya's New Aniseikonia Tests (NAT). The tests were performed at two different distances of 40 cm (visual angle: 6 degrees) and 20 cm (12 degrees) and under 4 meridians of the halfmoon on NAT, horizontal, 45 degrees, vertical and 135 degrees, respectively. The mean value of aniseikonia under each testing condition was as follows: 6 degrees horizontal -3.13%, 45 degrees -2.56%, vertical -2.13%, 135 degrees -2.57%, 12 degrees; horizontal -1.38%, 45 degrees -1.69%, vertical -1.84%, 135 degrees -1.50%. At 6 degrees aniseikonia is larger in the horizontal meridian than in the vertical with statistical significance (t-test, p less than 0.05), while at 12 degrees aniseikonia is smaller than at 6 degrees and shows no particular tendency in terms of meridian. The phenomenon observed at 6 degrees may be what is called "oriented metamorphopsia".
Buza, Natalia; Hui, Pei
Significant heterogeneity of HER2 protein expression has been recently observed in HER2 positive endometrial serous carcinomas. Tumor cells with HER2 overexpression and/or gene amplification in a heterogeneous tumor may represent a biologically more aggressive subclone that is clinically relevant to prognosis and potential targeted therapy. To correlate with HER2 protein heterogeneity, we investigated the heterogeneity of HER2/NEU gene amplification in endometrial serous carcinoma. A total of 17 endometrial serous carcinomas with heterogeneous HER2 protein expression were selected for the study, including nine cases with a 3+ and eight cases with a 2+ immunohistochemical score. Initial reflex HER2 FISH was available for seven of the eight 2+ cases, five of which showed HER2/NEU gene amplification. All 17 cases underwent repeat FISH targeting larger tumor tissue areas. Ten cases (72%) displayed striking heterogeneity of HER2/NEU gene copy number in the form of cluster amplification. Diffuse HER2 amplification was observed in four cases, no amplification was seen in three tumors. In cases with cluster amplification, HER2 protein overexpression by immunohistochemistry closely correlated at the cellular level with HER2/NEU gene amplification. In conclusion, the significant percentage of cases with heterogeneous HER2/NEU gene amplification indicates that the existing HER2 testing guidelines designed for breast cancer may not be applicable to endometrial serous carcinoma. Clinical testing on multiple different tumor samples or large tumor tissue sections is recommended for both immunohistochemistry and FISH assessment of HER2 status. Direct comparison with the HER2 immunostaining pattern may be helpful in detecting HER2 amplified areas in a heterogeneous tumor.
Bousquet, Elodie; Beydoun, Talal; Rothschild, Pierre-Raphaël; Bergin, Ciara; Zhao, Min; Batista, Rui; Brandely, Marie-Laure; Couraud, Benedicte; Farman, Nicolette; Gaudric, Alain; Chast, François
Purpose: To evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, for nonresolving central serous chorioretinopathy. Methods: This is a prospective, randomized, double-blinded, placebo-controlled crossover study. Sixteen eyes of 16 patients with central serous chorioretinopathy and persistent subretinal fluid (SRF) for at least 3 months were enrolled. Patients were randomized to receive either spironolactone 50 mg or placebo once a day for 30 days, followed by a washout period of 1 week and then crossed over to either placebo or spironolactone for another 30 days. The primary outcome measure was the changes from baseline in SRF thickness at the apex of the serous retinal detachment. Secondary outcomes included subfoveal choroidal thickness and the ETDRS best-corrected visual acuity. Results: The mean duration of central serous chorioretinopathy before enrollment in study eyes was 10 ± 16.9 months. Crossover data analysis showed a statistically significant reduction in SRF in spironolactone treated eyes as compared with the same eyes under placebo (P = 0.04). Secondary analysis on the first period (Day 0–Day 30) showed a significant reduction in subfoveal choroidal thickness in treated eyes as compared with placebo (P = 0.02). No significant changes were observed in the best-corrected visual acuity. There were no complications related to treatment observed. Conclusion: In eyes with persistent SRF due to central serous chorioretinopathy, spironolactone significantly reduced both the SRF and the subfoveal choroidal thickness as compared with placebo. PMID:26017871
Yemelyanova, Anna; Ji, Hongxiu; Shih, Ie-Ming; Wang, Tian-Li; Wu, Lee-Shu-Fune; Ronnett, Brigitte M
Uterine serous carcinomas typically have a characteristic morphology (papillary architecture, high-grade nuclei) and immunoprofile (diffuse/strong p53 expression, loss of hormone receptor expression) that distinguish them from most endometrial endometrioid carcinomas. However, glandular variants of serous carcinoma can simulate Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade 2 endometrioid carcinomas, and some serous carcinomas lack p53 expression and retain hormone receptor expression, making classification difficult. P16 expression patterns distinguish endometrioid carcinomas (patchy) from human papillomavirus (HPV)-related endocervical adenocarcinomas (diffuse/strong) but utility for distinction of serous carcinomas from endometrioid carcinomas and endocervical adenocarcinomas has not been evaluated in a large series. Immunohistochemical analysis of p16 expression was performed on 201 uterine and endocervical adenocarcinomas in hysterectomy specimens, including 49 serous carcinomas, 101 endometrial endometrioid carcinomas (44 FIGO grade 1, 40 FIGO grade 2, and 17 FIGO grade 3), and 51 HPV-related endocervical adenocarcinomas. All serous carcinomas demonstrated diffuse/moderate-strong p16 expression, with percentage of positive tumor cells ranging from 90% to 100% (mean/median: 95%/100%). In contrast, endometrial endometrioid carcinomas exhibited less diffuse and less intense expression, with percent of positive tumor cells ranging from 10% to 90% (mean/median: 38%/30%; staining intensity: variable). Similar to serous carcinomas, all endocervical adenocarcinomas exhibited diffuse/moderate-strong p16 expression, with percentage of positive tumor cells ranging from 90% to 100% (mean/median: 94%/90%). P16 can serve as an additional diagnostic marker, used as part of an immunohistochemical panel, including p53 and hormone receptors, for distinction of uterine serous carcinomas from endometrioid carcinomas. Distinction of serous carcinomas
Wei, Linxuan; Liu, Xiaolin; Zhang, Wenjing; Wei, Yuyan; Li, Yingwei; Zhang, Qing; Dong, Ruifen; Kwon, Jungeun Sarah; Liu, Zhaojian; Zheng, Wenxin; Kong, Beihua
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.
Gil, Tsvi E
Borderline personality is a well known concept in psychiatric literature, however, not fully understood as to its very nature. This article presents a short review of hypothesized etiologies of the borderline personality, starting with so called traditional theories, namely, borderline personality as a consolidated personality organization, in which the patient pathologically deals with his or her inner aggression, or with an enduring developmental failure. More modern hypotheses focus on possible childhood sexual abuse as the origin of the borderline, viewing the adult personality as a chronic, unresolved, post-traumatic disorder. Additionally, a neuro-epigenetic view hypothesized that a unique congenital neurological structure interacts with consequential events in early childhood to create the borderline personality.
TAJIMA, HIDEHIRO; OHTA, TETSUO; KITAGAWA, HIROHISA; SHINBASHI, HIROYUKI; HIROSE, ATSUSHI; SAKAI, SEISHO; MAKINO, ISAMU; HAYASHI, HIRONORI; NAKAGAWARA, HISATOSHI; ONISHI, ICHIRO; TAKAMURA, HIROYUKI; NINOMIYA, ITASU; FUSHIDA, SACHIO; TANI, TAKASHI; FUJIMURA, TAKASHI; KAYAHARA, MASATO; KODA, WATARU; MATSUI, OSAMU
Serous microcystic adenomas are rare and account for 1–2% of all exocrine pancreatic tumors and 25% of all pancreatic cystic neoplasms. Recently, with advances in imaging techniques, these adenomas have been identified at an increasing frequency. A 63-year-old woman visited her doctor in 1999 due to a gastric deformity detected by upper gastrointestinal endoscopy. An abdominal computed tomography scan revealed a cystic lesion measuring 6.0 cm in diameter, resulting in a diagnosis of serous microcystic adenoma of the pancreatic head. During follow-up, the tumor increased steadily in size, measuring 6.0 cm in diameter in 1999 and 13.0 cm in 2008, while remaining asymptomatic throughout this period of time. The risk of malignant transformation appears to be low even over the long-term. However, some cases of malignant transformation to serous cystadenocarcinoma have recently been reported. In this case, assessment of the relationship between the tumor and adjacent vascular structures, such as massive drainage vein development on the surface or tumor flow into the portal and superior mesenteric veins and the celiac and superior mesenteric arteries, was critical for determining tumor resectability. The risk of massive intra-operative hemorrhage was felt to be considerable, given the extent of the veins on the surface of the tumor, as well as the size and location of the primary pancreatic mass. Therefore, preoperative embolization of the tumor-feeding arteries arising from the celiac axis (gastroduodenal, splenic and dorsal pancreatic arteries) was performed. Tumor resection with pancreaticoduodenectomy was performed without a blood transfusion, with an estimated blood loss of 570 ml. The final pathology confirmed the diagnosis of serous microcystic adenoma. The patient is currently alive and disease-free. Preoperative partial embolization of the tumor feeding arteries and intra-operative resection of the right gastric and inferior pancreatoduodenal arteries, allowed
Peng, Jin; Yoshioka, Yumiko; Mandai, Masaki; Matsumura, Noriomi; Baba, Tsukasa; Yamaguchi, Ken; Hamanishi, Junzo; Kharma, Budiman; Murakami, Ryusuke; Abiko, Kaoru; Murphy, Susan K; Konishi, Ikuo
Members of the transforming growth factor-β (TGF-β) superfamily transduce signals via SMAD proteins. SMAD2 and SMAD3 mediate TGF-β signaling, whereas SMAD1, SMAD5, and SMAD8/9 transduce bone morphogenetic protein (BMP) signals. We would like to identify the function of BMP/SMAD5 signaling in serous ovarian cancer. The protein levels of total SMAD5 and phosphorylated SMAD5 (pSMAD5) were examined by immunohistochemical analysis using clinical serous ovarian cancer samples. Following treatment with either recombinant BMP2 (rBMP2) or Dorsomorphin (DM), western blotting was performed to observe pSMAD5 protein in the cytoplasm and the nucleus, separately. Cell proliferation was detected in SMAD5 knockdown serous ovarian cancer cell lines cultured with DM or rBMP2. The impact of DM or rBMP2 on tumor growth was observed in a mouse model of serous ovarian cancer. An inverse correlation was observed between pSMAD5 levels in the nucleus and the prognosis of patients with serous ovarian cancer. The treatment of SK-OV-3 with rBMP2 stimulated pSMAD5 translocation from the cytoplasm to the nucleus, and the addition of DM inhibited this effect. The proliferation of ovarian cancer cell lines was enhanced by BMP2 and suppressed by DM via SMAD5 in vitro. In vitro and in vivo experiments clearly demonstrated BMP2-stimulated proliferation of serous ovarian cancer and inhibition of this effect by DM. Our data suggests that BMP/SMAD5 signaling plays an important role and, therefore, becomes a potential therapeutic target in serous ovarian cancer. © 2015 Wiley Periodicals, Inc.
Chanen, Andrew M; Thompson, Katherine N
Summary Accurate diagnosis is fundamental to effective management of borderline personality disorder, but many patients remain undetected. The first-line management for borderline personality disorder is psychosocial treatment, not drugs. There are major prescribing hazards including polypharmacy, overdose and misuse. Drug treatment might be warranted for patients who have a co-occurring mental disorder such as major depression. If a drug is prescribed for borderline personality disorder, it should only be as an adjunct to psychosocial treatment. There should be clear and collaborative goals that are regularly reviewed with the patient. Use single drugs prescribed in limited quantities for a limited time. Stop drugs that are ineffective. PMID:27340322
Malmberg, Karin; Klynning, Charlotta; Flöter-Rådestad, Angelique; Carlson, Joseph W
Ovarian carcinoma is the deadliest gynecological malignancy. Previous studies have suggested that the fallopian tube may be the primary site for high-grade serous carcinoma. In prophylactic salpingo-oophorectomies from women with hereditary high risk for ovarian cancer, precursors can be assessed prior to onset and studied as a model for serous cancer precursor lesions. Epidemiologic studies indicate that carcinogenesis may be a result of chronic fallopian tube injury. The aims of this study were to (1) to examine the incidence of serous tubal intraepithelial carcinoma (STIC) in relation to other clinical parameters and (2) to evaluate whether chronic fallopian tube injury was related to cancer development. This study enrolled 101 women, comprising the following three groups: hereditary (n = 60), sporadic serous cancer (n = 18; endometrial cancers were excluded), and control (n = 23). The cases were histologically examined and clinical risk factors were collected. The histological changes were compared between different patients and correlated to clinical risk factors. STICs were identified primarily on the fallopian tube fimbria. The incidence of STIC was 3 % in the hereditary patients. In sporadic serous cancer cases, 61 % were associated with STIC and tubal carcinoma (p < 0.001). No differences in tubal injury or inflammation were seen when comparing the sporadic serous cancer group and the control group or within the hereditary group. STIC and invasive cancer were seen more often in the older patients than in the younger patients (p = 0.528). This small study, no correlation with chronic tubal injury or inflammation was identified.
Hasby, Eiman Adel
This study aims to investigate the immunohistochemical expression of mammary serine protease inhibitor (maspin) and CD138 in primary ovarian high-grade serous carcinomas (HGSC) as compared to low-grade serous carcinomas (LGSC) and clear cell carcinomas and investigate if the studied markers have a correlation to International Federation of Gynaecology and Obstetrics (FIGO) stage, Ki67 proliferation index, and to each other. Maspin cellular location varied significantly between studied groups with only nuclear expression seen in 46.7 % of LGSC group, mixed nuclear and cytoplasmic in 13.3, 28.6, and 20 % of LGSC, HGSC, and clear cell carcinoma, respectively, and was only cytoplasmic in 26.7, 71.4, and 80 % of LGSC, HGSC, and clear cell carcinoma, respectively. Mean maspin and CD138 counts were significantly higher in HGSC and clear cell carcinoma compared to LGSC. Both maspin and CD138 scores varied significantly between studied groups and were positively correlated with adverse prognostic factors in studied carcinomas including FIGO stage and Ki67 proliferation index. Besides, both maspin and CD138 had significant correlation to each other. These findings suggest that epithelial cytoplasmic expression of maspin and CD138 may have a significant role in tumorigenesis in ovarian high-grade serous carcinomas and clear cell carcinomas; these markers may regulate tumor cell proliferation, and their significant correlation to each other may suggest that CD138 probably induces maspin expression to protect tumor growth factors from being lysed by proteolytic enzymes.
histological subtype of ovarian cancer and is the most lethal gynecologic malignancy. The relationship between stage at presentation and survival in serous ...among and within stages of epithelial ovarian cancer , focusing on serous , mucinous and endometrioid subtypes (1-18 Months). a. Collections and...not serous or mucinous epithelial ovarian tumors. Cancer Res 58: 2095-2097, 1998. 7. Aikhionbare FO et al:.: Is cumulative frequency of mitochondrial
El-Sahwi, Karim S; Schwartz, Peter E; Santin, Alessandro D
Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis. By contrast, type II ECs develop in older patients, are not hormone dependent and are responsible for most recurrences and deaths from EC. Uterine serous cancer constitutes up to 10% of all endometrial tumors, and represents the most biologically aggressive variant of type II EC. This article will describe the most salient molecular markers that have been identified in uterine serous cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a series of therapeutic markers for the treatment of this highly-aggressive subset of ECs.
Huntsman, David; Resau, James H.; Klineberg, Eric; Auersperg, Nelly
The transmembrane tyrosine kinase receptor c-met with its ligand, hepatocyte growth factor/scatter factor (HGF/SF), acts as a mitogen, motogen, and morphogen in many normal epithelia. HGF/SF-met signaling has also been implicated in neoplastic progression and metastasis. In this study, immunofluorescence staining and quantitative laser scanning confocal microscopy were used to measure c-met expression in ovarian surface epithelial tumors from 17 oophorectomy specimens. These specimens were from patients aged 25 to 81 (mean age, 52) and included 10 malignant tumors, 4 borderline tumors, and five benign tumors including a Brenner tumor. For comparison, c-met expression was measured in normal tissues from the same patients, including 4 ovarian surface epithelia, 4 fallopian tube epithelia, 2 endometria, and 3 endocervical epithelia, as well as 3 cases of endometriosis. Relative pixel intensity values of c-met expression ranged from 0.4 in a normal ovarian surface epithelium to 22.3 in a borderline serous tumor. Malignant tumors (mean, 9.6) and borderline tumors (mean, 12.9) had higher average c-met expression levels than normal tissues (mean, 3.6) and endometriosis (mean, 1.8). The expression levels of benign tumors were intermediate (mean, 7.9). Among the normal tissues, c-met expression in fallopian tubes (mean, 8.2; range, 3.4–12.9) was higher than that of the other normal epithelia (mean, 1.6; range, 0.4–4.3). In eight cases where both normal and malignant tissues were sampled, c-met expression was significantly greater in malignant than in normal epithelia (P = 0.01). These findings indicate that c-met plays a role in the biology of the normal tissues examined. They confirm that its expression increases in the malignant progression of ovarian surface epithelial tumors, and suggest that increases comparable to those in frankly malignant carcinomas have already been reached in borderline lesions, ie, early in the neoplastic process. PMID:10433927
Quddus, M Ruhul; Sung, C James; Zhang, Cunxian; Lawrence, W Dwayne
Most endometrial carcinomas contain only 1 Müllerian cell type although the presence of 2 or more cell types within 1 tumor, for example a predominantly low-grade endometrioid carcinoma with a minor component (arbitrarily defined as 30% or less) of high-grade serous and/or clear cell carcinoma, is not uncommon. The current study attempts to evaluate whether the presence of minor serous or clear cell components exerts an adverse effect on the prognosis in stage-I endometrial carcinomas of ''mixed-type.'' The study cases include 22 cases of stage-I endometrioid carcinoma with a minor component of serous carcinoma and 14 cases of endometrioid carcinoma with a minor component of clear cell carcinoma. Minor components were arbitrarily defined as representing anywhere between 5% and 30% of the total tumor. The study cases were compared with 56 cases of histologically pure age-matched and stage-matched endometrioid carcinomas, 6 pure serous carcinomas, and 13 pure clear cell carcinomas. All study and control cases were fully staged. Treatment history and outcome status were obtained and follow-up ranged from 56 to 140 months. Our study suggests that the presence of minor components of serous and clear cell carcinoma, defined as between 5% and 30%, within a mixed-type endometrial carcinoma appears to adversely influence the long-term survival of stage-I tumors, although a larger study is needed to corroborate our findings.
The term ‘Borderline Personality Disorder’ (BPD) refers to a psychiatric syndrome that is characterized by emotion dysregulation, impulsivity, risk-taking behavior, irritability, feelings of emptiness, self-injury and fear of abandonment, as well as unstable interpersonal relationships. BPD is not only common in psychiatric populations but also more prevalent in the general community than previously thought, and thus represents an important public health issue. In contrast to most psychiatric disorders, some symptoms associated with BPD may improve over time, even without therapy, though impaired social functioning and interpersonal disturbances in close relationships often persist. Another counterintuitive and insufficiently resolved question is why depressive symptoms and risk-taking behaviors can occur simultaneously in the same individual. Moreover, there is an ongoing debate about the nosological position of BPD, which impacts on research regarding sex differences in clinical presentation and patterns of comorbidity. In this review, it is argued that many features of BPD may be conceptualized within an evolutionary framework, namely behavioral ecology. According to Life History Theory, BPD reflects a pathological extreme or distortion of a behavioral ‘strategy’ which unconsciously aims at immediate exploitation of resources, both interpersonal and material, based on predictions shaped by early developmental experiences. Such a view is consistent with standard medical conceptualizations of BPD, but goes beyond classic ‘deficit’-oriented models, which may have profound implications for therapeutic approaches. PMID:26929090
Ricardo, Sara; Marcos-Silva, Lara; Pereira, Daniela; Pinto, Rita; Almeida, Raquel; Söderberg, Ola; Mandel, Ulla; Clausen, Henrik; Felix, Ana; Lunet, Nuno; David, Leonor
The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum assays. Our aim was to refine ovarian cancer biomarkers by detection of aberrant glycoforms (Tn, STn, and T) of MUC16 and MUC1 in ovarian cancer tissue using Proximity Ligation Assays (PLA). We studied two series of serous ovarian tumours, a pilot series of 66 ovarian tumours (27 cystadenomas, 16 borderline tumours and 23 adenocarcinomas) from Centro Hospitalar S. João, Porto and a validation series of 89 ovarian tumours (17 cystadenomas, 25 borderline tumours and 47 adenocarcinomas) from the Portuguese Institute of Oncology Francisco Gentil, Lisbon. PLA reactions for MUC16/Tn, MUC16/STn, MUC1/Tn and MUC1/STn were negative in benign lesions but often positive in borderline and malignant lesions, in both series. An even better yield was obtained based on positivity for any of the four glyco-mucin profiles, further increasing sensitivity to 72% and 83% in the two series, respectively, with 100% specificity. The strategy is designated glyco-mucin profiling and provides strong support for development of PLA-based serum assays for early diagnosis.
Chen, Wenqian; Husain, Arjumand; Nelson, Gregg S; Rambau, Peter F; Liu, Shuhong; Lee, Cheng-Han; Lee, Sandra; Duggan, Máire A; Köbel, Martin
Endometrial serous carcinoma (ESC) is an aggressive neoplasm mainly seen in older women. The objective of this study was to refine immunohistochemical (IHC) panels for the differential diagnoses against endometrial endometrioid grade 3 (EC3), endometrial clear cell, and ovarian high-grade serous carcinoma as well as exploring the prognostic role of selected IHC markers. Fifty-two ESC from a single institution were assessed for 20 IHC markers, including ARID1A, CCNE1, CDKN2A, ERBB2, ESR1, HNF1B, FBXW7, IGF2BP3, MLH1, MSH2, MSH6, NAPSA, PAX8, PGR, PMS2, PTEN, TFF3, TP53, VIM, and WT1. ERBB2 chromogenic in situ hybridization was evaluated on tissue microarrays. Statistical analysis was performed. All ESC showed aberrant TP53, normal mismatch repair protein, and retained ARID1A and PTEN expression. ESR1 expression was present in 80% of ESC. A combination of TP53, PTEN, and CDKN2A had a sensitivity of 93.6% [95% confidence interval (CI), 84%-98%] and specificity of 87.8% (95% CI, 75%-95%) for ESC versus EC3. A combination of NAPSA and ESR1 had a sensitivity of 97.9% (95% CI, 89%-99%) and specificity of 72.2% (95% CI, 46%-90%) for ESC versus clear cell carcinoma. Absence of WT1 alone had a sensitivity of 66.0% (95% CI, 51%-79%) and specificity of 98.0% (95% CI, 94%-99%) for ESC versus ovarian high-grade serous carcinoma. Among all 52 ESCs, ERBB2 amplification was present in 23%, FBXW7 expression was absent in 10%, and CCNE1 was overexpressed in 59%, however, none were associated with prognosis. Our data support the value of IHC marker panels for histotyping of high-grade endometrial carcinomas.
Malpica, Anais; Deavers, Michael T; Tornos, Carmen; Kurman, Robert J; Soslow, Robert; Seidman, Jeffrey D; Munsell, Mark F; Gaertner, Erich; Frishberg, David; Silva, Elvio G
Although grading has been demonstrated to be an important prognostic factor in ovarian serous carcinoma, there is no system universally used to perform this task. A few years ago, we proposed a two-tier system for grading ovarian serous carcinoma that is based primarily on the assessment of nuclear atypia (uniformity vs. pleomorphism) in the worst area of the tumor. Tumor grade in this two-tier system is correlated with survival. After being used by numerous pathologists and trainees at The University of Texas M.D. Anderson Cancer Center (MDACC) for 15 years, we have observed that this system is user-friendly and reproducible. We undertook this study to evaluate the interobserver and intraobserver variability among a group of 7 gynecologic pathologists and 2 general surgical pathologists using this grading system. A total of 80 cases of ovarian serous carcinoma, 40 low-grade and 40 high-grade, were circulated twice among these pathologists. Slides with examples of low-grade and high-grade serous carcinoma were sent with the unknowns. A website was used to provide diagnostic criteria, images of examples of ovarian low-grade and high-grade carcinoma, and a log form to facilitate data entry. Statistical analysis demonstrated an overall kappa statistic among the different observers of 0.909. The intergrader kappa's ranged from 0.717 to 1.000 in the first round of the review and from 0.701 to 1.000 in the second round. Eight of the participants had an intragrader kappa ranging from 0.775 to 1.000 (excellent agreement), whereas a single participant had an intragrader kappa of 0.725 (good agreement). This study demonstrates that the two-tier grading system (the MDACC grading system) for ovarian serous carcinoma on the basis of the assessment of nuclear atypia is easy to learn and is highly reproducible. These findings would support its universal use, which would be beneficial for the standardization of clinical trials and protocols, thus facilitating the understanding of
Gil, Tsvi E
The present article critically discusses diagnosing borderline personality, demonstrating ideas raised with a treated case. In contrast to routine diagnoses made by psychiatrists according to common diagnosing systems (such as the American DSM or the WHO's ICD), we wonder whether this diagnosis reflects a medico-social construct, which is associated to the female status in masculine (or even patriarch) society, and probably associated even to the context of a woman diagnosed by a psychiatric system. In the context of critically viewing aetiological hypotheses to borderline personality (presented in our former article as a personality constellated around complex and prolonged trauma) in this article we suggest viewing borderline behaviours and symptoms as manifestations of coping and survival of a woman-victim in abusing surroundings.
Faluyi, Olusola; Mackean, Melanie; Gourley, Charlie; Bryant, Andrew; Dickinson, Heather O
Background The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown. Objectives To evaluate the benefits and harm of different treatment modalities offered for borderline ovarian tumours. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and EMBASE to 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) that compared different interventions in adult women diagnosed with borderline ovarian tumours of any histological variant. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed. Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intraperitoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias. One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral
Chui, M Herman; Wang, Yihong; Wu, Ren-Chin; Seidman, Jeffrey; Kurman, Robert J; Wang, Tian-Li; Shih, Ie-Ming
Tumor-initiating cells are thought to share features with normal somatic stem cells. In mice, stem cells at the ovarian hilum have been shown to express the stem cell marker, aldehyde dehydrogenase isoform 1A1 (ALDH1A1), and are prone to malignant transformation. The potential relevance of this finding to humans has not been established. In this study, we used immunohistochemistry to assess the distribution of ALDH1A1 staining in the epithelium of human fallopian tubes, with particular reference to the transition of tubal epithelium to mesothelium (ie, tubal-mesothelial junction), ovarian surface epithelium, as well as putative precursors of ovarian high-grade serous carcinoma, namely, serous tubal intraepithelial carcinoma and 'p53 signatures,' and overt serous carcinoma. Expression of ALDH1A1 was detected in both secretory and ciliated tubal epithelial cells, tubal-mesothelial junctions and ovarian surface epithelium, but was absent in serous tubal intraepithelial carcinoma and p53 signatures. Positive staining in high-grade serous carcinoma, when present, was typically limited to rare tumor cells. In silico analyses of the mRNA expression data set from The Cancer Genome Atlas revealed downregulation of ALDH1A1 transcripts in high-grade serous carcinoma relative to normal tubal epithelium, and no association between ALDH1A1 expression levels and overall survival. Our results do not support ALDH1A1 as a specific marker of stem cells in human fallopian tube and demonstrate that its loss of expression is an early event in the development of high-grade serous carcinoma.
Kaldawy, Anis; Segev, Yakir; Lavie, Ofer; Auslender, Ron; Sopik, Victoria; Narod, Steven A
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.
Kawamura, Ryosuke; Ideta, Hidenao; Hori, Hideyuki; Yuki, Kenya; Uno, Tsuyoshi; Tanabe, Tatsurou; Tsubota, Kazuo; Kawasaki, Tsutomu
Background Central serous chorioretinopathy (CSC) has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT) utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC. Methods We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50–250 mW, spot size of 500–1200 μm, and exposure time of 13–60 seconds to minimize retinal damage. Results In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA) ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30). Final BCVA ranged from 20/200 to 20/20 (mean, 20/25; median, 20/20). BCVA improved in all cases. Only two eyes with persistent subretinal fibrin and existing retinal pigment epithelial alternations in macular area showed limited improvement of BCVA despite the absence of
Lubana, Sandeep Singh; Singh, Navdeep; Tuli, Sandeep S.; Seligman, Barbara
Patient: Female, 60 Final Diagnosis: UPSC with adrenal metastasis Symptoms: Post menopausal bleeding Medication: — Clinical Procedure: Adrenalectomy Specialty: Oncology Objective: Rare disease Background: Uterine papillary serous carcinoma (UPSC) is a highly malignant form of endometrial cancer with a high propensity for metastases and recurrences even when there is minimal or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, and peritoneum. However, adrenal metastases from UPSC is extremely rare. Here, we present a case of UPSC with adrenal metastasis that occurred 6 years after the initial diagnosis. Case Report: A 60-year-old woman previously diagnosed with uterine papillary serous carcinoma at an outside facility presented in September of 2006 with postmenopausal bleeding. She underwent comprehensive surgical staging with FIGO (International Federation of Gynecology and Obstetrics) stage 2. Post-operatively, the patient was treated with radiation and chemotherapy. The treatment was completed in April of 2007. The patient had no evidence of disease until July 2009 when she was found to have a mass highly suspicious for malignancy. Subsequently, she underwent right upper lobectomy. The morphology of the carcinoma was consistent with UPSC. She refused chemotherapy due to a previous history of chemotherapy-induced neuropathy. The patient was followed up with regular computed tomography (CT) scans. In October 2012 a new right adrenal nodule was seen on CT, which showed intense metabolic uptake on positron emission tomography (PET)/CT scan. The patient underwent right adrenalectomy. Pathology of the surgical specimen was consistent with UPSC. Conclusions: UPSC is an aggressive variant of endometrial cancer associated with high recurrence rate and poor prognoses. Long-term follow-up is needed because there is a possibility of late metastases, as in this case. PMID:27117594
Zheng, Wenxin; Yi, Xiaofang; Fadare, Oluwole; Liang, Sharon X; Martel, Maritza; Schwartz, Peter E; Jiang, Zhong
Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors but rarely found in adult benign tissues. The aim of this study is to determine the expression of IMP3 in benign endometrium, endometrial cancer, and its precursor lesions, trying to see whether IMP3 has any diagnostic usage. Two hundred ninety-eight endometrial samples were examined for IMP3 expression by immunohistochemistry. These included benign endometrium (n=68), atypical hyperplasia or endometrial intraepithelial neoplasia (n=35), endometrial glandular dysplasia (n=21), endometrial intraepithelial carcinoma (n=18), endometrioid carcinoma (n=70), mucinous carcinoma (n=8), serous carcinoma (n=51), clear cell carcinoma (n=12), and other malignancies (n=15). Maturational patterns in the 68 benign endometrial samples included atrophic (n=12), proliferative (n=18), secretory (n=14), menstrual (n=8), and gestational (n=16). Most of the carcinomas were histologically pure; where mixed, the second component constituted <10% of the total tumor volume. The extent and intensity of IMP3 expression was semiquantitatively determined and scored for all samples. A renal cell carcinoma with known IMP3 expression was used as positive control for each immunohistochemistry run. Among the malignant cases, IMP3 expression was predominantly found in endometrial serous carcinoma and its putative precursor lesions, with 3 (14%) of 21 endometrial glandular dysplasia, 16 (89%) of 18 serous endometrial intraepithelial carcinoma, and 48 (94%) of 51 serous carcinomas (P<0.001). In contrast, the frequency of IMP3 expression was significantly lesser in nonserous malignancies with 0 (0%) of 35, 5 (7%) of 70, 0 (0%) of 8, 3 (25%) of 12, and 5 (33%) of 15 positive expression rates in atypical hyperplasia or endometrial intraepithelial neoplasia, endometrioid, mucinous, clear cell carcinomas, and other malignancies, respectively. The IMP3 staining was
Kaliaperumal, Subashini; Deb, Amit Kumar; Babu, K. Ramesh; Srinivasan, Renuka
We report a case of bimatoprost induced serous macular detachment and choroidal folds following uneventful cataract surgery. A 66-year-old male using topical bimatoprost in both eyes for open angle glaucoma underwent uneventful cataract surgery in the right eye. Postoperatively, he was restarted on topical bimatoprost and antibiotic-steroids combination drops. One week after surgery, he presented with conjunctival hyperemia, serous macular detachment, and choroidal folds at the posterior pole. Fundus fluorescein angiography showed perifoveal leaks in early stage with pooling of dye in late stage. Discontinuation of bimatoprost led to resolution of serous detachment and choroidal folds within 3 weeks with significant improvement in visual acuity. Occurrence of serous macular detachment and choroidal folds in this case could be probably related to the proinflammatory property of bimatoprost. Hence, it should be used with caution in the immediate postoperative period after cataract surgery. PMID:27957367
Yang, Dong; Eliott, Dean
Central serous chorioretinopathy (CSCR) is a challenging disease characterized by subretinal serous fluid accumulation. The complex pathogenesis is still not fully understood, but is thought to be multifactorial and involves exogenous and endogenous factors affecting the choroid and retinal pigment epithelium. The involvement of corticosteroids is undisputed, while the contribution of mineralocorticoid pathways is under investigation. This review addresses the proposed pathogenesis models and the evidence for systemic treatment of CSCR with mineralocorticoid antagonists.
Zhou, Jun; Zeng, Yu-Rong; Lin, Xiao-Feng; Min, Jun
Purpose. To report the clinical features and CT manifestations of giant pancreatic serous cystadenoma (≥10 cm). Methods. We retrospectively reviewed the clinical features and CT findings of 6 cases of this entity. Results. All 6 patients were symptomatic. The tumors were 10.2 cm–16.5 cm (median value, 13.0 cm). CT imaging revealed that all 6 cases showed microcystic appearances (n = 5) or mixed microcystic and macrocystic appearances (n = 1). Five patients with tumors at the distal end of the pancreas received distal pancreatectomy. Among these 5 patients, 2 patients underwent partial transverse colon resection or omentum resection due to close adhesion. One patient whose tumor was located in the pancreatic head underwent pancreaticoduodenectomy; however, due to encasement of the portal and superior mesenteric veins, the tumor was incompletely resected. One patient had abundant draining veins on the tumor surface and suffered large blood loss (700 mL). After 6–49 months of follow-up the 6 patients showed no tumor recurrence or signs of malignant transformation. Conclusions. Giant pancreatic serous cystadenoma necessitates surgical resection due to large size, symptoms, uncertain diagnosis, and adjacent organ compression. The relationship between the tumors and the neighboring organs needs to be carefully assessed before operation on CT image. PMID:27610132
Sansone, R A; Chu, J W; Wiederman, M W; Lam, C
According to the empirical literature, there are high rates of borderline personality disorder (BPD) among individuals with formal diagnoses of eating disorders, and high rates of eating disorders among individuals with BPD. In this study, we examined relationships between three eating disorder symptoms (i.e., binge eating, starving oneself, abusing laxatives) and borderline personality symptomatology according to two self-report measures (the borderline personality scale of the Personality Diagnostic Questionnaire-4 and the Self- Harm Inventory) in a sample of psychiatric inpatients (N=126) and in a sample of internal medicine outpatients (N=419). Each individual eating disorder item, as well as a composite score of all three items, demonstrated statistically significant correlations with both measures of borderline personality symptomatology in both samples. In addition, endorsement of all three symptoms was invariably associated with borderline personality symptomatology on both measures. Specific eating disorder symptoms, alone, may predict for borderline personality symptomatology.
Frank, H; Paris, J
To test psychodynamic hypotheses about the etiology of the borderline syndrome, female borderline patients were asked whether they remembered their mothers and fathers as having responded with approval, disinterest, or criticism to dependent and independent behaviors. Comparisons were made with a group of normal controls and with a group of neurotics and patients with personality disorders. The main finding was that borderline patients remembered their fathers as neglectful. The recollections did not support an overprotection hypothesis.
Slucki, Daniel; Wikinski, Mariana
A bibliographic review of the last year's psychoanalytic literature on borderline personality is presented. We expose diagnostic considerations, with special emphasis on those which refer to the boundaries between borderline personality, neurosis and psychosis on one hand, and those which distinguish between borderline personality and narcissistic disorders on the other. Vicissitudes of these patient's object relationships, their bond with other significant persons, their main psychic mechanisms, clinical traits and technical difficulties in the treatment are also described.
Yoshimura, Mayumi; Terai, Yoshito; Konishi, Hiromi; Tanaka, Yoshimichi; Tanaka, Tomohito; Sasaki, Hiroshi; Ohmichi, Masahide
Primary carcinoma of the vermiform appendix is a rare disease with few clinical symptoms. Accordingly, preoperative diagnosis of appendiceal cancer is challenging because of the lack of specific symptoms. We herein report a case of appendicular adenocarcinoma found unexpectedly during laparoscopic surgery in a 69-year-old Japanese female patient diagnosed with serous papillary adenocarcinoma, in order to determine whether optimal cytoreduction could successfully be achieved at the time of primary surgery. We performed diagnostic laparoscopic surgery in order to make a correct diagnosis based on the histological tissue. The vermiform appendix was found to contain a tumor measuring 1.5 cm wide and 4.5 cm long. Laparoscopic appendectomy, partial omentectomy, and partial resection of the lesion in the peritoneum were performed. The histological diagnosis was mucinous adenocarcinoma of the vermiform appendix, and the stage was T4NxM1. The patient received adjuvant chemotherapy with mFOLFOX 6 (5FU, leucovorin, and oxaliplatin). She achieved stable disease and was alive with disease eleven months after surgery. We therefore recommend that gynecologists should not rule out the possibility of appendiceal cancer, even in cases with preoperative findings similar to those of serous papillary adenocarcinoma of the peritoneum with peritoneal disseminated tumors. PMID:24383020
ZANARINI, MARY C.; FRANKENBURG, FRANCES R.
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
Idrees, Romana; Din, Nasir Ud; Fatima, Saira; Kayani, Naila
Uterine serous carcinoma (USC) is a rare variant of endometrial cancer that is not related to increased estrogen level; rather, it arises in a background of atrophic endometrium. Our aim was to describe clinicopathologic features of 4 cases of USC arising in endometrial polyps (EPs). The mean age of the patients at presentation was 53 years (range, 50-61 years). All patients presented with postmenopausal bleeding. In 3 patients, endometrial curretings were done before surgery, which was reported as EP with superficial foci of USC, EP with few clusters of atypical cells, and high-grade serous carcinoma, respectively. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and omental sampling. The uterine cavity showed an EP in all cases ranging in size from 2 to 3.5 cm (mean, 3 cm). The hysterectomy specimens revealed USC in EP as well as the adjacent endometrium in 3 patients. The nonneoplastic endometrium was atrophic in all cases. Residual tumor was not found in the endometrium in 1 case. Omental metastatic deposits were found in all cases. Tumor deposits were also seen in the serosa of uterus, fallopian tubes, and parametrium in 1 case. Two patients died of disease 2 years after diagnosis. The remaining 2 patients are alive after a follow-up of 3 years, respectively. In conclusion, USC is a rare aggressive tumor, and to establish the diagnosis, it is important to look for the small foci of the tumor in the atrophic endometrium and on the surface of the polyps as these patients are likely to harbor additional disease in the uterus or extrauterine sites. The postmenopausal group is at high risk for developing these tumors; therefore, all the endometrial biopsies/curettings and the EPs in this age group should be thoroughly sampled.
Morrison, Jane C; Blanco, Luis Z; Vang, Russell; Ronnett, Brigitte M
A precursor for invasive ovarian/pelvic high-grade serous carcinoma, termed serous tubal intraepithelial carcinoma (STIC), has been identified and characterized through careful analysis of the fallopian tubes in both prophylactic salpingo-oophorectomy specimens obtained from women with either a family history of breast and/or ovarian cancer or germline mutations of BRCA1 and BRCA2 and in cases of pelvic high-grade serous carcinoma. Data on incidental STICs and clinically occult microscopic invasive high-grade serous carcinomas are limited. We analyzed the clinicopathologic features of 22 cases, including 15 pure STICs and 7 STICs associated with microscopic invasive high-grade serous carcinomas, identified incidentally in fallopian tubes removed for nonprophylactic indications. Patient age ranged from 39 to 79 years (mean: 62.7; median: 61), with only 1 patient under the age of 50. No patients were known to carry BRCA1 or BRCA2 mutations. Of the 12 pure STICs for which the location in the fallopian tube could be established, 9 were in the fimbriated portion, 1 was at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. Of the 7 STICs with associated invasive high-grade serous carcinoma, 3 were located in the fimbriated portion, 2 were at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. The invasive components were in the fallopian tube in 6 cases, 4 in subepithelial stroma of tubal mucosa, and 2 as an intramucosal (exophytic) luminal lesion without invasion of underlying subepithelial stroma (size range: 1 to 4 mm). The remaining case had a microscopic focus of high-grade serous carcinoma within the ipsilateral ovary (1.3 mm cortical focus) identified only on deeper sections, without an associated invasive component in the fallopian tube. The preferential finding of atypical epithelium with the cytologic features of high-grade serous carcinoma, namely STIC, in the fallopian tubes rather than the
Bromley, Amy B; Altman, Alon D; Chu, Pamela; Nation, Jill G; Nelson, Gregg S; Ghatage, Praful; Kalloger, Steve E; Han, Guangming; Köbel, Martin
We describe the architectural patterns of advanced ovarian/pelvic high-grade serous carcinomas that have been treated with upfront surgery, followed by adjuvant chemotherapy or neoadjuvant chemotherapy, followed by interval debulking to explore the association with the chemotherapeutic response. For 70 cases of advanced (i.e. stage III/IV) high-grade serous carcinomas (33 platinum resistant/intermediate, 37 platinum sensitive; 24 neoadjuvantly treated, 44 primary surgery), all tumor-containing histologic slides were reviewed by 1 of 3 pathologists. Histologic type was confirmed and the following features were assessed: major architectural pattern and the presence of any of 8 predefined minor architectural patterns (papillary, transitional cell carcinoma-like, micropapillary, microcystic, nested papillary, slit-like, glandular, solid). A semiquantitative assessment of psammoma bodies, histiocytic response, necrosis, nuclear atypia, and single-cell invasion was performed. Mitotic count was performed in 10 HPF and 1 HPF was counted for intraepithelial lymphocytes. The morphologic features were tested for an association with previous neoadjuvant chemotherapy and response to chemotherapy (resistant/intermediate versus chemotherapy-sensitive cases stratified by neoadjuvant chemotherapy), which was carried out using χ tests for categorical variables and analysis of variance for continuous data. Combinations of features were analyzed using unsupervised clustering (Wald). Although 8 of 18 features were significantly different when samples from neoadjuvantly treated patients were compared with those not previously treated, no individual histomorphologic feature or a combination of features was associated with response to chemotherapy. Further subtyping of high-grade serous carcinomas will likely need ancillary molecular markers that may have a greater potential to identify cases that will not respond to platinum-based chemotherapy.
Pich, Achille; Galliano, Diego
A 44-year-old man presented with painless right scrotal swelling of 2 years duration. A cystic tumor strictly attached to the head of the epididymis was surgically resected. The pathologic examination revealed a unilocular cyst with a thin fibrous capsule, lined by ciliated cubical or cylindrical columnar cells, mostly arranged in a single layer. No papillary projection could be detected. Immunohistochemical staining was positive for epithelial membrane antigen, low- and high molecular weight cytokeratins, progesterone receptor, vimentin, and S-100 protein, but was negative for carcinoembryonic antigen, CD10, p53 protein, and calretinin. Single MIB-1 positive cells were noted. Histologic and immunohistochemical features suggest a Müllerian origin or differentiation. The lesion was diagnosed as pure serous cystadenoma of the epididymis, possibly originating from vestigial remnants of the Müller duct in male. The differential diagnosis to spermatocele and adenomatoid tumor of the epididymis is discussed.
Background. Malignant neoplasms arising in Meckel's diverticulum, a vitelline duct remnant, are rare yet well-documented. Case Presentation. A 53-year-old previously healthy female presented with an enlarging midline abdominal wall mass. A computed tomography scan revealed a mass involving the linea alba, bilateral rectus abdominis, and subcutaneous fat. Extensive clinical workup failed to demonstrate other lesions, except local and paratracheal/hilar lymphadenopathy. Histopathologic examination of the resected tumor demonstrated a spectrum of serous neoplasia including serous cystadenoma, papillary serous carcinoma with numerous Psammoma bodies, and a poorly differentiated component. Immunophenotypically, the tumor cells were strongly positive for CK7, CK19, CA19.9, and MUC1 but negative for other lineage markers, findings suggestive of pancreatobiliary type differentiation. The patient died of the disease one year after the initial presentation despite chemotherapy, radiation, and surgery. Conclusion. We present a case of adenocarcinoma arising from the anterior midline abdominal wall, from presumed vitelline duct remnant, with histologic and immunophenotypic features of serous cystadenocarcinoma of pancreatobiliary origin. Though the origin from vitelline duct remnant is difficult to prove in this single case, understanding tumorigenesis of embryonic remnant origin is potentially important to improve the management of cancer of unknown primary. PMID:27999702
Johnson, Harriette C.
Reviews current research on treatment of borderline clients with medication, individual counseling, and family interventions. Notes that recent studies indicate that borderline personality is heterogeneous condition in which different underlying disorders (affective, schizotypal, and neurological) may be present. Reviews effectiveness of various…
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…
BRODIE, FRANK L.; CHARLSON, EMILY S.; ALEMAN, TOMAS S.; SALVO, REBECCA T.; GEWAILY, DINA Y.; LAU, MARISA K.; FARREN, NEIL D.; ENGELHARD, STEPHANIE B.; PISTILLI, MAXWELL; BRUCKER, ALEXANDER J.
Purpose The purpose of this study was to determine if there is an association between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSCR). Methods Patients with CSCR without a history of steroid use or secondary retinal disease were matched based on age/gender/body mass index with control patients and administered the Berlin Questionnaire to assess for OSA risk. Patients were scored “OSA+” if they were at “high risk” on the Berlin Questionnaire or reported a previous OSA diagnosis. Rates of OSA+ were compared between the 2 groups, odds ratio and its 95% confidence interval was calculated using exact conditional logistic regression. Results Forty-eight qualifying patients with CSCR were identified. There were no statistically significant differences between the CSCR and control groups by age (mean = 55 years), gender (79% male), body mass index (mean = 28.2), history of diabetes, or hypertension. Within the CSCR group, 22 patients (45.8%) were OSA+ versus 21 control patients (43.8%) (difference = 2.1%; 95% confidence interval, −18.2% to 22.2%; exact odds ratio = 1.08, 95% confidence interval, 0.47–2.49; P = 1.00). Conclusion When compared with matched controls, patients with CSCR did not have statistically significant higher rates of OSA risk or previous diagnosis. This finding contrasts with previous work showing a strong association between the diseases. The divergence is likely due to our matching controls for body mass index, a significant risk factor for OSA. PMID:25127049
Precursor Lesions of Ovarian Serous Carcinoma PRINCIPAL INVESTIGATOR: Robert Kurman, M.D...5a. CONTRACT NUMBER Elucidation of Molecular Alterations in Precursor Lesions of Ovarian Serous Carcinoma 5b. GRANT NUMBER W81XWH-09-1-0249...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT 15. SUBJECT TERMS prevention, p53 mutations, high grade serous
A) MOE cells were treated with different concentrations (0, 1, 10, 50, and 100 ng/ml) of...grade serous cancer cell lines (Figure 7). Intriguingly, the viability of the human high grade serous cancer cell lines on the 3D collagen was...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Many now believe that the fallopian tube epithelium is the progenitor cell
Eskander, Jonathan P.; Kuris, Eren O.; Younghein, Andrew J.; Landsman, Samuel; Japko, Leonard; Eskander, Mark S.
Study Design Case report. Objective This case exemplifies the importance of a high index of suspicion when dealing with intractable pain and neurologic symptoms in patients with a history of cancer. Fallopian tube cancer is relatively uncommon, accounting for less than 0.2% of all female malignancies. Because of a low index of suspicion, it is often detected at an advanced stage. From an orthopedic perspective, osseous metastasis from primary fallopian tube malignancies is rare with only a few documented cases in the medical literature. Methods This case report documents a 68-year-old woman who developed back pain and leg weakness after undergoing surgical resection with adjuvant therapy of a primary fallopian tube adenocarcinoma. Her hospital course and follow-up are documented. Results Imaging revealed a compression fracture in the L1 vertebral body that when a biopsy confirmed a soft tissue diagnosis of a high-grade serous papillary adenocarcinoma of fallopian tube origin. The patient underwent a surgical decompression, posterior stabilization, and tumor debulking with postoperative resolution of her symptoms. Conclusions This is the first reported case of a spine metastasis from a fallopian tube serous carcinoma in a living patient. This case documents the diagnosis of a pathologic vertebral fracture due to metastasis of an atypical cancer. PMID:26430604
Background Ovarian cancer is a heterogeneous disease and prognosis for apparently similar cases of ovarian cancer varies. Recurrence of the disease in early stage (FIGO-stages I-II) serous ovarian cancer results in survival that is comparable to those with recurrent advanced-stage disease. The aim of this study was to investigate if there are specific genomic aberrations that may explain recurrence and clinical outcome. Methods Fifty-one women with early stage serous ovarian cancer were included in the study. DNA was extracted from formalin fixed samples containing tumor cells from ovarian tumors. Tumor samples from thirty-seven patients were analysed for allele-specific copy numbers using OncoScan single nucleotide polymorphism arrays from Affymetrix and the bioinformatic tool Tumor Aberration Prediction Suite. Genomic gains, losses, and loss-of-heterozygosity that associated with recurrent disease were identified. Results The most significant differences (p < 0.01) in Loss-of-heterozygosity (LOH) were identified in two relatively small regions of chromosome 19; 8.0-8,8 Mbp (19 genes) and 51.5-53.0 Mbp (37 genes). Thus, 56 genes on chromosome 19 were potential candidate genes associated with clinical outcome. LOH at 19q (51-56 Mbp) was associated with shorter disease-free survival and was an independent prognostic factor for survival in a multivariate Cox regression analysis. In particular LOH on chromosome 19q (51-56 Mbp) was significantly (p < 0.01) associated with loss of TP53 function. Conclusions The results of our study indicate that presence of two aberrations in TP53 on 17p and LOH on 19q in early stage serous ovarian cancer is associated with recurrent disease. Further studies related to the findings of chromosomes 17 and 19 are needed to elucidate the molecular mechanism behind the recurring genomic aberrations and the poor clinical outcome. PMID:22967087
Coenegrachts, L; Garcia-Dios, D A; Depreeuw, J; Santacana, M; Gatius, S; Zikan, M; Moerman, P; Verbist, L; Lambrechts, D; Matias-Guiu, Xavier; Amant, Frédéric
Clinical outcome of 23 patients with mixed endometrioid and serous endometrial carcinomas (mixed EEC-SC) was compared to that of pure endometrioid (EEC) and pure serous (SC) carcinomas. Hotspot mutation frequencies in KRAS, PIK3CA, PTEN, and TP53 and microsatellite instability (MSI) status were determined in mixed EEC-SC, as well as in their EEC and SC microdissected components separately, and alterations were compared to frequencies in pure EEC and SC. Relapse-free (RFS) and overall survival (OS) differed significantly between mixed EEC-SC and pure EEC and SC, revealing that outcome of mixed EEC-SCs was intermediate to that of pure EEC and pure SC. PTEN mutations were absent in pure SC, but occurred in 20 % of pure EEC, and 13 % of mixed EEC-SC. In contrast, TP53 mutations were more frequent in pure SC (17 %) and mixed EEC-SC (22 %) than in pure EEC (2 %). Mutations in mixed EEC-SC were shared by the two microdissected components in 30 %, whereas in 35 %, some mutations were component-specific. Mutation analysis confirms similarities between the EEC and SC components of mixed EEC-SC with pure EEC and pure SC, respectively. However, PTEN and KRAS mutations were more frequent in the SC component of mixed EEC-SC than in pure SC, while TP53 mutations were more frequent in the EEC component of mixed EEC-SC than in pure EEC. Presence of different clonal mutation pattern between EEC and SC components of mixed EEC-SC raises the possibility of divergent tumor heterogeneity or biclonal origin in some cases.
Stein, Dan J
Several psychiatric disorders, including borderline personality disorder (BPD), are characterized by emotional dysregulation and impulse dyscontrol. More specifically, symptoms in patients with BPD often occur within the context of disruptions in attachment and related distortions in cognitive-affective processing of the self and others. From a neurocircuitry perspective, findings include prefrontal hypoactivity, amygdala hyperreactivity, and alterations in prefrontal-limbic interaction. Molecular pathways relevant to these circuits include the serotonergic, noradrenergic, and dopaminergic systems, and there is some evidence that pharmacotherapy with agents that act on these systems may be useful. Given the disruptions in attachment and schemas of the self and others in BPD, establishing a therapeutic alliance is crucial while psychotherapy remains the cornerstone of an integrated approach to management.
Griffiths, Dorothy E.
Every family practice includes people who are difficult to manage. Persons with a borderline personality disorder can be the most difficult of all. They will trust no one, and consequently few, if any, others will be able to tolerate their profoundly difficult interpersonal communication style. These patients will present to their family physician more and more often with a variety of somatic and emotional symptoms. They will demand, either verbally or silently, that these symptoms be relieved immediately. This increasing demand for immediate response may eventually cause the physician to reject the patient. An understanding of this condition and how it develops in infancy may enable the physician to help the patient. A family physician who can set appropriate limits to the patient's demands may slowly convince the patient that he can trust and not be hurt. PMID:21248944
... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by or linked with viruses are: Cervical cancer (human papillomavirus) Most anal cancers (human papillomavirus) Some throat ...
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
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.
Zanarini, Mary C.; Weingeroff, Jolie L.; Frankenburg, Frances R.
This study assessed the defensive functioning of 290 criteria-defined borderline patients and compared it to that of 72 patients with other forms of axis II psychopathology. The Defense Style Questionnaire, a self-report measure with demonstrated criterion validity and internal consistency, was administered to 362 axis II inpatients diagnosed using semistructured interviews of proven reliability. Borderline patients had significantly higher scores than axis II comparison subjects on three of the four defense styles assessed by the DSQ: self-sacrificing, maladaptive action, and image-distorting defenses. They also had significantly higher scores than axis II comparison subjects on eight of the 19 defense mechanisms studied. More specifically, borderline patients had significantly higher scores on one neurotic-level defense (undoing), four immature defenses (acting out, emotional hypochondriasis, passive aggression, and projection), and two image- distorting/borderline defenses (projective identification and splitting). In contrast, axis II comparison subjects had a significantly higher score than borderline patients on one mature defense (suppression). When all significant defenses were considered together, three were found to be significant predictors of a borderline diagnosis: acting out, emotional hypochondriasis, and undoing. This model has both good sensitivity (.95) and positive predictive power (.86). Taken together, the results of this study suggest that the defensive profile of borderline patients is distinct from that of patients with other forms of axis II pathology. They also suggest that the defensive triad of acting out, emotional hypochondriasis, and undoing may serve as a useful clinical marker for the borderline diagnosis, particularly in settings where the base rate of the disorder is high. PMID:19379090
Ogłodek, Ewa; Araszkiewicz, Aleksander
For many years, the borderline personality disorders have mainly been researched in terms of psychoanalytical theories, such as theories on relations with the object. Nowadays, there are three kinds of concepts that are distinguishable. The first ones are those which are group models, serving attempts to made characteristic sets of qualities, represented by individuals suffering from the borderline personality disorders, more precise. The remaining concepts are models of conflict and deficit, which explain complicated mechanisms of interactions of social, psychological and biological factors, and therefore, contribute to better understanding of the genesis of the symptoms of this disorder. Upon the basis of the attempts made so far in the field of describing the borderline personality disorders, one may indicate certain criteria, representative for the entire group of individuals with this diagnosis, regardless of the assumptions applicable to the genesis of the disorder and its symptoms, even though the population of the infirm suffering from the borderline personality disorders is not internally homogenous. The interest of psychologists, attempting to describe the borderline personality disorders, is focused upon certain sets of qualities, presented as the examples of descriptive models. Among the researchers, working on the issues of the borderline personality disorders in this manner, there are: Gunderson, Kernberg, Kohut, Winnicot, Guntrip, Fairbaim, Adler and Buie.
Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi
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.
Expression of PH Domain Leucine-rich Repeat Protein Phosphatase, Forkhead Homeobox Type O 3a and RAD51, and their Relationships with Clinicopathologic Features and Prognosis in Ovarian Serous Adenocarcinoma
Zhang, Jun; Wang, Jun-Chao; Li, Yue-Hong; Wang, Rui-Xue; Fan, Xiao-Mei
Background: Ovarian serous adenocarcinoma can be divided into low- and high-grade tumors, which exhibit substantial differences in pathogenesis, clinicopathology, and prognosis. This study aimed to investigate the differences in the PH domain leucine-rich repeat protein phosphatase (PHLPP), forkhead homeobox type O 3a (FoxO3a), and RAD51 protein expressions, and their associations with prognosis in patients with low- and high-grade ovarian serous adenocarcinomas. Methods: The PHLPP, FoxO3a, and RAD51 protein expressions were examined in 94 high- and 26 low-grade ovarian serous adenocarcinomas by immunohistochemistry. The differences in expression and their relationships with pathological features and prognosis were analyzed. Results: In high-grade serous adenocarcinomas, the positive rates of PHLPP and FoxO3a were 24.5% and 26.6%, while in low-grade tumors, they were 23.1% and 26.9%, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). The positive rates of RAD51 were 70.2% and 65.4% in high- and low-grade serous adenocarcinomas, respectively (P < 0.05 vs. the control specimens; low- vs. high-grade: P > 0.05). Meanwhile, in high-grade tumors, Stage III/IV tumors and lymph node and omental metastases were significantly associated with lower PHLPP and FoxO3a and higher RAD51 expression. The 5-year survival rates of patients with PHLPP- and FoxO3a-positive high-grade tumors (43.5% and 36.0%) were significantly higher than in patients with PHLPP-negative tumors (5.6% and 7.2%, respectively; P < 0.05). Similarly, the 5-year survival rate of RAD51-positive patients (3.0%) was significantly lower than in negative patients (42.9%; P < 0.05). In low-grade tumors, the PHLPP, FoxO3a, and RAD51 expressions were not significantly correlated with lymph node metastasis, omental metastasis, Federation of Gynecology and Obstetrics stage, or prognosis. Conclusions: Abnormal PHLPP, FoxO3a, and RAD51 protein expressions may be involved in the development
Szabova, Ludmila; Bupp, Sujata; Kamal, Muhaymin; Householder, Deborah B.; Hernandez, Lidia; Schlomer, Jerome J.; Baran, Maureen L.; Yi, Ming; Stephens, Robert M.; Annunziata, Christina M.; Martin, Philip L.; Van Dyke, Terry A.
The high mortality rate from ovarian cancers can be attributed to late-stage diagnosis and lack of effective treatment. Despite enormous effort to develop better targeted therapies, platinum-based chemotherapy still remains the standard of care for ovarian cancer patients, and resistance occurs at a high rate. One of the rate limiting factors for translation of new drug discoveries into clinical treatments has been the lack of suitable preclinical cancer models with high predictive value. We previously generated genetically engineered mouse (GEM) models based on perturbation of Tp53 and Rb with or without Brca1 or Brca2 that develop serous epithelial ovarian cancer (SEOC) closely resembling the human disease on histologic and molecular levels. Here, we describe an adaptation of these GEM models to orthotopic allografts that uniformly develop tumors with short latency and are ideally suited for routine preclinical studies. Ovarian tumors deficient in Brca1 respond to treatment with cisplatin and olaparib, a PARP inhibitor, whereas Brca1-wild type tumors are non-responsive to treatment, recapitulating the relative sensitivities observed in patients. These mouse models provide the opportunity for evaluation of effective therapeutics, including prediction of differential responses in Brca1-wild type and Brca1–deficient tumors and development of relevant biomarkers. PMID:24748377
Katabathina, Venkata S; Amanullah, Farhan S; Menias, Christine O; Chen, Melissa M; Valente, Philip T; Chintapalli, Kedar N; Prasad, Srinivasa R
The spectrum of extrauterine pelvic serous carcinomas includes ovarian serous carcinoma, primary peritoneal serous carcinoma, and primary fallopian tube carcinoma. Ovarian serous carcinoma, the most common ovarian malignant epithelial neoplasm, consists of two distinct entities: high-grade and low-grade serous carcinomas. Primary peritoneal serous carcinoma and primary fallopian tube carcinoma are rare malignancies that share many characteristics of high-grade serous carcinomas. Recent advances in the genetics and molecular biology of gynecologic cancers have suggested a common origin of many extrauterine pelvic serous carcinomas from fallopian tube epithelium. With the exception of low-grade serous carcinomas, which arise from cortical inclusion cysts lined by tubal epithelium, most extrauterine pelvic serous carcinomas are believed to originate from serous tubal intraepithelial carcinomas and show similar clinical-biologic behaviors and natural histories. Indeed, the International Federation of Gynecology and Obstetrics Committee on Gynecologic Oncology recently recognized that these cancers should be considered collectively, with a common system of staging and management strategies for ovarian, primary peritoneal, and fallopian tube cancers. A paradigm shift has occurred in our understanding of the pathogenesis of extrauterine pelvic serous carcinomas that has the potential to change current strategies for screening, prevention, diagnosis, and management. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging, and combined positron emission tomography and CT are pivotal in screening, initial diagnosis, and treatment follow-up; however, because of this paradigm shift, new radiologic techniques, such as contrast material-enhanced US and molecular US imaging, and various optical imaging techniques are being investigated as important screening and diagnostic tools. Because of evolving knowledge of genetic and molecular changes underlying the
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.
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
Chen, Yu-Li; Chang, Ming-Cheng; Huang, Chia-Yen; Chiang, Ying-Cheng; Lin, Han-Wei; Chen, Chi-An; Hsieh, Chang-Yao; Cheng, Wen-Fang
The alpha-folate receptor (α-FR) is highly-expressed in various non-mucinous tumors of epithelial origin, including ovarian carcinoma. The aim of this study was to investigate the relationship between alpha-folate receptor (α-FR) and the clinico-pathologic features and outcomes of serous ovarian carcinoma patients and the possible mechanism of α-FR to chemo-resistance. Therefore, semi-quantitative reverse-transcription polymerase chain reactions for α-FR expression were performed in the 91 specimens of serous ovarian carcinomas. The expression of α-FR in each ovarian cancer tissue specimen was defined as the ratio of density of α-FR to density of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In vitro apoptotic experiments were tested in the original OVCAR-3 tumor cells and various OVCAR-3 α-FR-transfectants. Patients with an increased α-FR expression level had poorer responses to chemotherapy (per α-FR expression level increase: odds ratio (OR): 8.97 (95% confidence interval (CI): 1.40-57.36), p = 0.021). An increased α-FR expression level was an independently poor prognostic factor for disease free interval (DFI) (per α-FR expression level increase: hazard ratio (HR): 2.45 (95% CI: 1.16-5.18), p = 0.02) and had a negative impact on overall survival (OS) of these serous ovarian cancer patients (per α-FR expression level increase: HR: 3.6 (95% CI: 0.93-13.29), p = 0.03) by multivariate analyses. α-FR inhibited cytotoxic drug-induced apoptosis in our in vitro apoptotic assays. α-FR could induce chemo-resistance via regulating the expression of apoptosis-related molecules, Bcl-2 and Bax. Therefore, α-FR can be a potential biomarker for the prediction of chemotherapeutic responses and clinical prognosis. It also could be the target of ovarian cancer treatment.
The author outlines his concept of reflective function or mentalization, which is defined as the capacity to think about mental states in oneself and in others. He presents evidence to suggest that the capacity for reflective awareness in a child's caregiver increases the likelihood of the child's secure attachment, which in turn facilitates the development of mentalization in the child. He proposes that a secure attachment relationship offers the child a chance to explore the mind of the caregiver, and in this way to learn about minds; he formulates this model of the birth of the psychological self as a variation on the Cartesian cogito: "My caregiver thinks of me as thinking and therefore I exist as a thinker." This model is then applied to provide insight into some personality-disordered individuals who were victims of childhood abuse. The author proposes (1) that individuals who experience early trauma may defensively inhibit their capacity to mentalize to avoid having to think about their caregiver's wish to harm them; and (2) that some characteristics of severe borderline personality disorder may be rooted in developmental pathology associated with this inhibition. He offers evidence for and some qualifications of this model, and argues that the therapeutic effect of psychoanalysis depends on its capacity to activate patients' ability to evolve an awareness of mental states and thus find meaning in their own and other people's behavior.
Baker, L; Silk, K R; Westen, D; Nigg, J T; Lohr, N E
Malevolent object relations as well as splitting have long been considered by psychodynamic theorists as central features of borderline personality disorder. We tested the hypotheses that borderlines would a) perceive their parents more negatively than both nonborderline major depressive patients and nonpatient normal controls, and b) split their representations of their parents into opposites more than the comparison subjects. Borderlines (N = 31), who were identified by the Diagnostic Interview for Borderlines, Research Diagnostic Criteria major depressives (N = 15), and nonpatient controls (N = 14) were asked to rate each parent on the Adjective Check List (ACL; Gough and Heilbrun, 1983). Seven ACL scales were studied: Favorable, Unfavorable, Critical Parent, Nurturing Parent, Nurturance, Aggression, and Dominance. Correlations were performed between scores for mother and father on the various scales for each of the three cohorts. Analysis of variance and one-way t-tests with Bonferroni correction were used to test group differences. Borderlines rated their parents, especially their fathers, not only as more unfavorable on negative scales than depressives or normals, but as less favorable on positive scales than the comparison groups. Analysis of covariance revealed that a significant portion of the variance in father scores, but not in mother scores, was related to age of respondent and history of sexual abuse. While borderlines did not appear to split their parents into one good and one bad parent, they did show significantly less correlation between parents on the Favorable scale when compared with either depressives or normal subjects. The results imply that borderlines have a greater tendency to view the world in negative, malevolent ways than to split their object representations.
Devor, Eric J; Hovey, Adriann M; Goodheart, Michael J; Ramachandran, Shyam; Leslie, Kimberly K
microRNAs (miRNAs) control a multitude of pathways in human cancers. Differential expression of miRNAs among different histological types of tumors within the same type of tissue offers insight into the mechanism of pathogenesis and may help to direct treatment to improve prognosis. We assessed expression of 667 miRNAs in endometrial endometrioid and serous adenocarcinomas using RNA extracted from benign endometrium as well as from primary endometrial tumors. Quantitative miRNA profiling of endometrial adenocarcinomas revealed four overlapping groups of significantly overexpressed and underexpressed miRNAs. The first group was composed of 20 miRNAs significantly dysregulated in both adenocarcinoma types compared with benign endometrium, two groups were composed of miRNAs significantly dysregulated in either endometrioid adenocarcinomas or in serous adenocarcinomas compared with benign endometrium, and the fourth group was composed of 17 miRNAs that significantly distinguished between endometrioid adenocarcinomas and serous adenocarcinomas themselves. Validation of the expression levels of the selected miRNAs was carried out in a second panel composed of ten endometrioid and five serous tumors. Experimentally validated mRNA targets of these dysregulated miRNAs were identified using published sources, whereas TargetScan was used to predict targets of miRNAs in the first and fourth profile groups. These validated and potential miRNA target lists were filtered using published lists of genes displaying significant overexpression or underexpression in endometrial cancers compared to benign endometrium. Our results revealed a number of dysregulated miRNAs that are commonly found in endometrial (and other) cancers as well as several dysregulated miRNAs not previously identified in endometrial cancers. Understanding these differences may permit the development of both prognostic and diagnostic biomarkers.
Miše, Branka Petrić; Telesmanić, Vesna Dobrić; Tomić, Snježana; Šundov, Dinka; Čapkun, Vesna; Vrdoljak, Eduard
To analyze correlation between immunoexpression of E-cadherin and efficacy of first line platinum-based chemotherapy in patients with advanced-stage high-grade serous ovarian carcinoma. The expression of E-cadherin was analyzed immunohistochemically in formalin-fixed, paraffin-embedded samples from 98 patients with advanced-stage high-grade serous ovarian cancer and related to clinical features (stage according to the International Federation of Gynecology and Obstetrics (FIGO) and residual tumors after initial cytoreductive surgery), response to platinum-based chemotherapy (according to Response Evaluation Criteria in Solid tumors (RECIST 1.1 criteria)), platinum sensitivity (according to platinum free interval (PFI) as platinum-refractory, platinum-resistant and platinum-sensitive) and patients progression free survival (PFS) and overall survival (OS). E-cadherin immunostaining was positive in 74 and negative in 24 serous ovarian carcinomas. E-cadherin immunoreactivity was not associated with FIGO stage, residual tumor after initial cytoreductive surgery and number of chemotherapy cycles. Positive E-cadherin expression predict significantly better response to first line platinum-based chemotherapy (p < 0.001) and platinum sensitivity (p < 0.001). Moreover, positive E-cadherin expression predict significantly longer PFS (p < 0.001) and OS (p < 0.001). The multivariate analysis for OS showed that positive E-cadherin expression is predictor to platinum sensitivity (p < 0.001) and longer OS (p = 0.01). Positive E-cadherin expression seems to be a predictor of better response to first line platinum-based chemotherapy, platinum sensitivity and favorable clinical outcome in patients with advanced-stage serous ovarian cancer. Negative E-cadherin expression was shown to be significant, independent predictor of poorer PFS and OS. E-cadherin as a marker has predictive and prognostic value.
Kocyigit, Murat; Ortekin, Safiye Giran; Cakabay, Taliye; Ozkaya, Guven; Bezgin, Selin Ustun; Adali, Mustafa Kemal
Introduction Otitis media with effusion is the fluid in the middle ear with no signs or symptoms of acute ear infection. Objective This study aims to research the frequency of serous otitis media in patients referred to the pediatric clinic between 3–16 years of age without any active ear, nose, and throat complaints. Methods This study included 589 children patients (280 boys, 309 girls; mean age: 9.42; range 3–16) who were administered to the pediatric clinic without otolaryngologic complaints. Patients underwent examination with flexible nasopharyngoscopy for adenoid hypertrophy. An otorhinolaryngologist examined all children on both ears using an otoscope and tested with tympanometry. We used tympanometry results to diagnose SOM. Results The study included 589 patients that underwent fiber optic examination of the nasopharynx with an endoscope. Adenoid vegetation was present in 58 patients (9.8%) and was not detected in 531 patients (90.2%). We found serous otitis media in 94 (15.9%) patients. We obtained Type A tympanogram in 47 (81%) of 58 patients with adenoid vegetation, 6 (10.3%) Type B, and 5 (8.6%) Type C. When comparing 58 patients with adenoid vegetation with 538 patients without adenoid vegetation for serous otitis media, the frequency was not statistically significant (p > 0.05). Conclusion We believe that in children without any ear, nose, and throat complaints, it is possible to detect serous otitis media with adenoid vegetation. Thus, pediatric patients should undergo screening at regular intervals. PMID:28382124
Chen, Ning; Yi, Xiaofang; Abushahin, Nisreen; Pang, Shujie; Zhang, Donna; Kong, Beihua; Zheng, Wenxin
Endometrial serous carcinoma (ESC) is the most aggressive subtype of endometrial cancer. Its aggressive behavior and poor clinical outcome may be partially attributed to lack of early diagnostic markers and unclear patho-genesis. The transcription factor Erythroid-E2-related factor 2 (Nrf2) is a recently identified protein marker, which plays a role in carcinogenesis as well as responsible for poor prognosis of many human cancers. The aim of this study is to determine the Nrf2 expression in benign endometrium (n=28), endometrial cancers (n=122) as well as their precursor lesions (n=81) trying to see whether Nrf2 has any diagnostic usage and is potentially involved in endometrial carcinogenesis. The level of Nrf2 was evaluated by immunohistochemical (IHC) and verified by using Western blots. Among the malignant cases, Nrf2 was positive in 28 (68%) of 50 ESCs, which was significantly more than in 3 (6%) of 50 endometrioid carcinomas (p < 0.001) and 2 (13%) of 15 clear cell carcinomas (p = 0.001) and other histologic types of endometrial cancers. Among endometrial precursor lesions, both serous endometrial glandular dysplasia (EmGD, 40%) and serous endometrial intraepithelial carcinoma (EIC, 44%) showed a significantly higher Nrf2 expression than that in atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (0%), clear cell EmGD (10%), and clear cell EIC (25%), respectively. We conclude that Nrf2 overexpression is closely associated with endometrial neoplasms with serous differentiation. Alteration of Nrf2 expression may represent one of the early molecular events in ESC carcinogenesis and overexpression of Nrf2 may used as a diagnostic marker in surgical pathology.
Gashi, A.A.; Borson, D.B.; Finkbeiner, W.E.; Nadel, J.A.; Basbaum, C.B.
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 P 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.
was discussed. Dr. Soslow asked how to evaluate endometrial serous cancers if there is a lesion in the tubes and if peritoneal carcinoma was...received by all participants as well as from DoD OCRP staff. 15. SUBJECT TERMS prevention, p53 mutations, high grade serous ovarian cancer and STIC...ovarian cancer by characterizing the early lesions involved in the development of high-grade ovarian serous carcinoma, and 2) to provide biomarkers
Cevher, Selim; Sahinoglu-Keskek, Nedime; Unal, Fikret; Demirduzen, Selahaddin; Oksuz, Huseyin
32-year-old Turkish male patient presented with an optic disk pit and serous macular detachment in the left eye. Spectral domain optical coherence tomography revealed serous macular detachment and retinoschisis. After vitrectomy the retina gradually flattened and vision was gradually improved. We aimed to report a case of serous macula detachment secondary to optic pit and long term result of surgical treatment. PMID:26881159
Song, Jae-Won; Lee, Ju-Hong; Choi, Joon-Hyuk; Chun, Seok-Ju
Generally, pathological diagnosis using an electron microscope is time-consuming and likely to result in a subjective judgment, because pathologists perform manual screening of tissue slides at high magnifications. Recently, the advent of digital pathology technology has provided the basis for convenient screening and quantitative analysis by digitizing tissue slides through a computer system. However, a screening process with high magnification still takes quite a long time. To solve these problems, recently the use of computer-aided design techniques for performing pathologic diagnosis has been increasing in digital pathology. For pathological diagnosis, we need different diagnostic methods for different regions with different characteristics. Therefore, in order to effectively diagnose different lesions and types of diseases, a quantitative method for extracting specific features is required in computerized pathologic diagnosis. This study is about an automated differential diagnosis system to differentiate between benign serous cystadenoma and possibly-malignant mucinous cystadenoma. In order to diagnose cystic tumors, the first step is identifying a cystic region and inspecting its epithelial cells. First, we identify the lumen boundary of a cyst using the Direction Cumulative Map considering 8-ways. Then, the Epithelial Nuclei Identification algorithm is used to discern epithelial nuclei. After that, three morphological features for the differential diagnosis of mucinous and serous cystadenomas are extracted. To demonstrate the superiority of the proposed features, the experiments compared performance of the classifiers learned by using the proposed morphological features and the classical morphological features based on nuclei. The classifiers in the simulations are as follows; Bayesian Classifier, k-Nearest Neighbors, Support Vector Machine, and Artificial Neural Network. The results show that all classifiers using the proposed features have the best
Blutner, Reinhard; Pothos, Emmanuel M; Bruza, Peter
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.
Gentile, Julie P.; Correll, Terry L.
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
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
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.
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
GABBARD, GLEN O.
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
Cheon, Dong-Joo; Tong, Yunguang; Sim, Myung-Shin; Dering, Judy; Berel, Dror; Cui, Xiaojiang; Lester, Jenny; Beach, Jessica A.; Tighiouart, Mourad; Walts, Ann E.; Karlan, Beth Y.; Orsulic, Sandra
Purpose To elucidate molecular pathways contributing to metastatic cancer progression and poor clinical outcome in serous ovarian cancer. Experimental Design Poor survival signatures from three different serous ovarian cancer datasets were compared and a common set of genes was identified. The predictive value of this gene signature was validated in independent datasets. The expression of the signature genes was evaluated in primary, metastatic, and/or recurrent cancers using qPCR and in situ hybridization. Alterations in gene expression by TGFβ1 and functional consequences of loss of COL11A1 were evaluated using pharmacologic and knockdown approaches, respectively. Results We identified and validated a 10-gene signature (AEBP1, COL11A1, COL5A1, COL6A2, LOX, POSTN, SNAI2, THBS2, TIMP3, VCAN) that is associated with poor overall survival in patients with high-grade serous ovarian cancer. The signature genes encode extracellular matrix proteins involved in collagen remodeling. Expression of the signature genes is regulated by TGFβ1 signaling and is enriched in metastases in comparison to primary ovarian tumors. We demonstrate that levels of COL11A1, one of the signature genes, continuously increase during ovarian cancer disease progression, with the highest expression in recurrent metastases. Knockdown of COL11A1 decreases in vitro cell migration and invasion and tumor progression in mice. Conclusion Our findings suggest that collagen-remodeling genes regulated by TGFβ1 signaling promote metastasis and contribute to poor overall survival in patients with serous ovarian cancer. Our 10-gene signature has both predictive value and biological relevance and thus may be useful as a therapeutic target. PMID:24218511
Unger, Ulrike; Denkert, Carsten; Braicu, Ioana; Sehouli, Jalid; Dietel, Manfred; Loibl, Sibylle; Darb-Esfahani, Silvia
HER3 is a member of the epidermal growth factor family and was predominantly described as a negative prognostic factor in various solid tumors as well as in ovarian cancer. In this study, we investigated HER3 on protein and mRNA expression in histologically defined subtypes of ovarian cancer looking for an influence on patient's survival. Altogether, we examined HER3 in ovarian high-grade serous (HGSC, n = 320), low-grade serous (LGSC, n = 55), endometrioid (EC, n = 33), and clear cell (CCC, n = 48) carcinomas using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR (qRT-PCR). Univariate and multivariate analyses were performed to explore the association between HER3 and overall survival (OS) as well as progression-free survival (PFS). In HGSC, high HER3 mRNA expression was a favorable prognostic factor for PFS (P = 0.008) and OS (P = 0.052), while for high HER3 protein expression, a trend towards better survival was seen (OS P = 0.064; PFS P = 0.099). A subgroup of HGSC with negative HER3 staining and negative HER3 mRNA levels showed most unfavorable OS and PFS (P = 0.002 and P = 0.004, respectively). Using the multivariate Cox regression model, HER3 was predictive for prolonged PFS (HR, 0.48; 95% CI, 0.26-0.88; P = 0.018). All in all, we cannot confirm the reported negative prognostic impact of HER3 expression in high-grade serous ovarian carcinoma and moreover find a rather positive prognostic implication of HER3 in this major ovarian cancer histological subtype.
Ludolph, P S; Westen, D; Misle, B; Jackson, A; Wixom, J; Wiss, F C
Adult criteria for borderline personality disorder distinguished a group of 27 inpatient adolescent girls from 23 nonborderline inpatient female comparison subjects. The two groups were compared on retrospectively assessed variables measuring psychological, familial, and constitutional factors. Variables most likely to predict borderline personality disorder included history of disrupted attachments, maternal neglect, maternal rejection, grossly inappropriate parental behavior, number of mother and father surrogates, physical abuse, and sexual abuse. Families of borderline adolescents were chronically disrupted, particularly during the patients' early childhoods. The traumatic childhood experiences of the borderline adolescents were similar to those of adults with borderline personality disorder in recent studies.
Howitt, Brooke E; Hanamornroongruang, Suchanan; Lin, Douglas I; Conner, James E; Schulte, Stephanie; Horowitz, Neil; Crum, Christopher P; Meserve, Emily E
Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only ∼40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET", >50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%, P=0.11), had a significantly younger mean age than those with classic HGSC in BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical outcome in both groups combined (P=0.024). STIC was significantly more frequent in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA tumors with classic morphology (83%) versus those with SET morphology (22%, P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy.
Peltopuro, Minna; Ahonen, Timo; Kaartinen, Jukka; Seppälä, Heikki; Närhi, Vesa
The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health…
Sansone, Lori A.
Obesity is a significant health problem in the United States. Therefore, it is extremely important to understand potential clinical associations with obesity, including personality pathology. From studies of personality disorders in other types of eating pathology, it appears that restrictive personality disorders (e.g., obsessive-compulsive disorder) are associated with restrictive eating pathology (e.g., anorexia nervosa, restricting type) whereas impulsive personality disorders (e.g., borderline personality disorder) are associated with impulsive eating pathology (e.g., anorexia nervosa, binge-eating/purging type; bulimia nervosa, binge eating disorder). Because binge eating disorder is oftentimes associated with an obese status, it seems likely that borderline personality disorder may also be associated with obesity. At the present time, there appear to be nine accessible studies in this area, comprising 639 obese individuals. While rates of borderline personality disorder in these studies vary from 2.2 to 94.1 percent, 10 of 19 measures detected this disorder at rates of 25 percent or higher, and the average of all percentages is 26.9 percent. Findings appear to support the association between impulsive personality pathology and impulsive eating pathology, and underscore that a significant minority of obese individuals may suffer from borderline personality disorder. PMID:23696958
Norouzpour, Amir; Abrishami, Majid
Central serous chorioretinopathy (CSC) is characterized by a localized accumulation of subretinal fluid and an idiopathic focal leakage from choroidal vessels. The exact pathogenesis of CSC, however, still remains obscure. In this paper, we hypothesized that CSC may result from a response of choroidal vessels to an acute increase in the environmental light intensity leading to a focal leakage from the choroidal vessels. High levels of glucocorticoids, in our proposed model, may cause persistence rather than initiation of the focal leakage, probably by suppressing the synthesis of collagen and extracellular matrix components and inhibiting fibroblastic activity. PMID:26949657
Conrad, Rupert; Weber, Nina Friederike; Lehnert, Matthias; Holz, Frank Gerhard; Liedtke, Reinhard; Eter, Nicole
The authors studied 31 consecutive patients newly diagnosed with central serous chorioretinopathy (CSC) as compared with 31 age- and gender-matched control subjects, assessing emotional distress (ED), nine psychopathological symptoms, critical life events, and alexithymia. Results showed no difference in the number of critical life events; however CSC patients showed elevated ED and elevated scores on seven psychopathological symptoms, including hostility. Controlling for ED, CSC patients showed elevated alexithymia sum scores. Alexithymia was correlated with hostility. Our findings point to personality-based difficulties in emotional regulation associated with hostility in CSC.
Wilson, Andrew J; Fadare, Oluwole; Beeghly-Fadiel, Alicia; Son, Deok-Soo; Liu, Qi; Zhao, Shilin; Saskowski, Jeanette; Uddin, Md Jashim; Daniel, Cristina; Crews, Brenda; Lehmann, Brian D; Pietenpol, Jennifer A; Crispens, Marta A; Marnett, Lawrence J; Khabele, Dineo
Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors.
Wilson, Andrew J.; Fadare, Oluwole; Beeghly-Fadiel, Alicia; Son, Deok-Soo; Liu, Qi; Zhao, Shilin; Saskowski, Jeanette; Uddin, Md. Jashim; Daniel, Cristina; Crews, Brenda; Lehmann, Brian D.; Pietenpol, Jennifer A.; Crispens, Marta A.; Marnett, Lawrence J.; Khabele, Dineo
Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors. PMID:25972361
Abushahin, Nisreen; Zhang, Tingguo; Chiang, Sarah; Zhang, Xiangsheng; Hatch, Kenneth; Zheng, Wenxin
Serous endometrial intraepithelial carcinoma (serous EIC) arising in adenomyosis is rare. It may be underrecognized because of its deceiving morphology when embedded in the foci of adenomyosis. Although there is no connection to peritoneal cavity, some cases may be associated with extrauterine disease. It is currently unknown what the etiology for such a disease is. More studies are in need to elucidate the pathogenesis of such a grave malady. We report a series of 5 cases of serous EIC, which may arise in adenomyosis. The 5 cases are in 5 different patients or whom on histopathological examination of their hysterectomy specimens, the finding of adenomyosis involved with serous intraepithelial neoplasia was identified. The finding of interest was the presence of multifoci of adenomyosis; some of those foci were involved in serous EIC. In addition to EIC, lesions of endometrial glandular dysplasia were present in the foci of adenomyosis. To rule out the possibility of endometrial serous carcinoma (ESC) invading into the areas of the adenomyosis, all of the 5 uteri were extensively examined. Among the 5 uteri, the eutopic endometirum showed 1 invasive ESC, 2 serous EIC, and 2 benign resting endometrium without any cancer or precancerous lesions. In 1 uterus with ESC, we did not see any direct spatial connection between the invasive component of ESC and the areas of EIC in the foci of adenomyosis. In 2 uteri with serous EIC within the endometrial cavity, there was a distance of at least 0.5 cm between the lesions within the endometrial cavity and the serous EIC in adenomyosis. The remaining 2 uteri showed no evidence of endometrial malignancy in the endometrial cavity, whereas serous EIC was present only in areas of adenomyosis. Clinicopathologic data including characterized immunohistochemical stainings and p53 gene sequence analysis are presented and clinical significance is discussed.
Sun, Yan; Guo, Fei; Bagnoli, Marina; Xue, Feng-Xia; Sun, Bao-Cun; Shmulevich, Ilya; Mezzanzanica, Delia; Chen, Ke-Xin; Sood, Anil K.; Yang, Da; Zhang, Wei
Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This “paradox” can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer. PMID:25556616
Rahman, W; Horgan, N; Hungerford, J
We describe a rare case of bilateral circumscribed choroidal haemangioma in an otherwise healthy male, which mimicked chronic central serous chorioretinopathy (CSCR). A 52-year-old Asian man presented with a one-year history of visual decline in his left eye. The vision in the right eye had been reduced for 15 years. Visual acuity was 6/60 in the right eye and 6/18 in the left eye. Fundus examination of the right eye revealed an area of discoloration with overlying retinal pigment epithelial changes in the macula and evidence of prior surrounding argon laser photocoagulation. The left macula showed a raised choroidal lesion with overlying retinal pigment epithelial changes and associated subretinal fluid. This appearance illustrates how chronic retinal pigment epithelial alterations associated with longstanding subretinal fluid exudation from circumscribed choroidal haemangiomas may mimick the appearance of chronic central serous chorioretinopathy. B-scan ultrasonography, fluorescein angiography, indocyanine green angiography and optical coherence tomography helped to establish the diagnosis. The active lesion in the left eye was treated with verteporfin photodynamic therapy with improvement in vision.
Zhou, Jun; Gong, Guanghui; Tan, Hong; Dai, Furong; Zhu, Xin; Chen, Yile; Wang, Junpu; Liu, Ying; Chen, Puxiang; Wu, Xiaoying; Wen, Jifang
MicroRNAs (miRNAs) can serve as biomarkers in human cancer. To determine the clinical value of urinary miRNAs for ovarian serous adenocarcinoma, we collected urine samples from 39 ovarian serous adenocarcinoma patients, 26 patients with benign gynecological disease and 30 healthy controls. The miRNA microarray data showed that only miR-30a-5p was upregulated and 37 miRNAs were downregulated in the urine samples of ovarian serous adenocarcinoma patients, when compared to healthy controls, which was confirmed after conducting quantitative PCR. The upregulation of urinary miR-30a-5p was closely associated with early stage of ovarian serous adenocarcinoma as well as lymphatic metastasis. Receiver operator characteristic (ROC) analysis demonstrated the potential use of urinary miR-30a-5p as a diagnostic marker for ovarian serous adenocarcinoma. Furthermore, a lower urine level of miR-30a-5p was found in 20 gastric cancer and 20 colon carcinoma patients when compared to ovarian serous adenocarcinoma, suggesting that the upregulation of urinary miR-30a-5p may be specific for ovarian serous adenocarcinoma. miR-30a-5p was also upregulated in ovarian serous adenocarcinoma tissues and cell lines, while urinary miR-30a-5p from ovarian cancer patients was notably reduced following the surgical removal of ovarian serous adenocarcinoma, suggesting that urinary miR-30a-5p was derived from the ovarian serous adenocarcinoma tissue. Notably, miR-30a-5p was concentrated with exosomes from the ovarian cancer cell supernatant or urine from ovarian serous adenocarcinoma patients, supporting a pathway for excretion into the urine. The results also showed that the knockdown of miR-30a-5p significantly inhibited the proliferation and migration of ovarian cancer cells. In summary, to the best of our knowledge, the present study provided the first evidence of increased miR-30a-5p in the urine of ovarian serous adeno-carcinoma patients, while the inhibition of miR-30a-5p suppressed the
Khaki, Fariba; Javanbakht, Javad; Sharifzad, Samieh; Gharagozlou, Mohammad Javad; Khadivar, Farshid; Manesh, Javad Yaghoobi Yeganeh; Hosseini, Seyed Hojjat; Anissian, Ali; Touni, Seyed Rashid; Gilvari, Alireza; Abdi, Fatemeh Soghra
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.
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
Crum, Christopher P; McKeon, Frank D; Xian, Wa
In recent years, the distal oviduct has emerged as a critical organ in the pathogenesis of pelvic ("ovarian") serous cancer. Studies have uncovered early serous tubal intraepithelial carcinomas in approximately 8% of asymptomatic women with germline BRCA1 or BRCA2 mutations, linked serous tubal intraepithelial carcinomas to one half of serous cancers irrespective of genetic risk, and described a precursor lesion in the distal tube with early alterations in p53 function (the p53 signature). This work has established a linear serous carcinogenic sequence in a single focus within the fimbria. In addition, a more broadly distributed array of gene alterations has been discovered in the oviduct, manifested as secretory (or stem) cell outgrowths that are increased in frequency as a function of older age and serous cancer status. These "surrogate precursors" expand the existing model beyond the fimbria, implying that the molecular events leading to serous cancer are distributed over space and time. The potential promise of these discoveries is "targeted prevention" by discovering of multiple pathways integral to carcinogenesis and successfully preventing malignancy by interrupting one or a few of these pathways.
Ussakli, Cigdem; Usubutun, Alp; Dincer, Nazmiye; Dolgun, Anil; Bülbül, Diilek; Isikdogan, Zuhal; Haberal, Nihan; Ozen, Ozlem; Tezel, Gaye Guler
We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER, PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.
Biskin, Robert S.
Objectives: Borderline personality disorder (BPD) is frequently encountered in both adult and youth populations. There is a robust literature supporting psychotherapy for adults with BPD, but the literature supporting its use for BPD in youth is more limited. Methods: A literature review was conducted using the keywords “borderline personality disorders” and “adolescence.” Relevant articles were reviewed for inclusion. Results: Several specialized treatments have been studied with mixed results. Dialectical behaviour therapy has no randomized controlled trials in adolescents, emotion regulation training has not demonstrated superiority of treatment as usual, and cognitive analytic therapy has demonstrated more rapid recovery but little difference at follow-up. Mentalization-based treatment has one study supporting its use in self-harming adolescents. Pharmacotherapy has no evidence supporting its use in this population. Conclusions: Structured therapy may be the most important therapeutic component in this population. PMID:23970912
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.
Ovarian cancer remains the most lethal gynecological malignancy in the developed world, despite recent advances in genomic information and treatment. To better understand this disease, define an integrated proteogenomic landscape, and identify factors associated with homologous repair deficiency (HRD) and overall survival, we performed a comprehensive proteomic characterization of ovarian high-grade serous carcinomas (HGSC) previously characterized by The Cancer Genome Atlas (TCGA). We observed that messenger RNA transcript abundance did not reliably predict abundance for 10,030 proteins across 174 tumors. Clustering of tumors based on protein abundance identified five subtypes, two of which correlated robustly with mesenchymal and proliferative subtypes, while tumors characterized as immunoreactive or differentiated at the transcript level were intermixed at the protein level. At the genome level, HGSC is characterized by a complex landscape of somatic copy number alterations (CNA), which individually do not correlate significantly with survival. Correlation of CNAs with protein abundances identified loci with significant trans regulatory effects mapping to pathways associated with proliferation, cell motility/invasion, and immune regulation, three known hallmarks of cancer. Using the trans regulated proteins we also created models significantly correlated with patient survival by multivariate analysis. Integrating protein abundance with specific post-translational modification data identified subnetworks correlated with HRD status; specifically, acetylation of Lys12 and Lys16 on histone H4 was associated with HRD status. Using quantitative phosphoproteomics data covering 4,420 proteins as reflective of pathway activity, we identified the PDGFR and VEGFR signaling pathways as significantly up-regulated in patients with short overall survival, independent of PDGFR and VEGFR protein levels, potentially informing the use of anti-angiogenic therapies. Components of
Levallius, Johanna; Rydén, Göran; Norring, Claes
Patients with borderline personality disorder have a characteristic and extreme personality associated with psychopathology. The aim was to investigate personality change in relation to suicidality following treatment. 21 patients were assessed before and after psychotherapy on personality (NEO PI-R) and suicidality (SUAS). At follow-up, Neuroticism and Conscientiousness normalized along with six lower-order facets; Depression, Impulsiveness, Competence, Achievement Striving, Self-Discipline and Deliberation. Thirteen patients showed a positive personality development paralleled by a lesser degree of suicidality.
Vender, Simone; Callegari, Camilla; Poloni, Nicola
The borderline personality disorders are very frequent in modern society because of cultural and social reasons. The authors analyze the disturbed mental processes (impulsiveness and memory) because they represent risk factors for the treatment of diseases. On the base of experience of consultation-liaison psychiatry, the authors show some guidelines in the medical practice (primary care and general hospital) in order to overcome the troubles of the treatment.
Wang, Yiying; Li, Li; Wang, Yue; Tang, Sarah Ngocvi; Zheng, Wenxin
Recent advances suggest that precancerous lesions of pelvic serous carcinoma originate from tubal secretory cells. The purpose of our study was to determine if an increased number of secretory cells varies with age or location in the fallopian tube and to examine its association with serous neoplasia. Three groups (benign control, high-risk, and pelvic serous carcinoma) of age-matched patients were studied. The age data were stratified into 10-year intervals ranging from 20-29 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data were analyzed by standard contingency table and Poisson distribution methods after age justification. We found that the absolute number of tubal secretory cells increased significantly with age in all three groups. But a more dramatic increase of secretory cells was observed in high-risk and pelvic serous carcinoma patients. Secretory cell expansion is more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and is significantly associated with serous neoplasia (P < 0.001). Furthermore, age remained a significant risk factor for serous neoplasia after age adjustment. These findings suggest that secretory cell expansion could serve as a potential sensitive biomarker for early serous carcinogenesis within the fallopian tube. The study also supports a relationship between serous neoplasia and increased secretory to ciliated cell ratios, and the relationship between frequency of secretory cell expansion within the fallopian tube and increasing age and-more significantly-presence of high-risk factors or co-existing serous cancers.
Ricciardelli, Carmela; Lokman, Noor A; Pyragius, Carmen E; Ween, Miranda P; Macpherson, Anne M; Ruszkiewicz, Andrew; Hoffmann, Peter; Oehler, Martin K
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.
Wang, Yiying; Li, Li; Wang, Yue; Tang, Sarah Ngocvi; Zheng, Wenxin
Recent advances suggest that precancerous lesions of pelvic serous carcinoma originate from tubal secretory cells. The purpose of our study was to determine if an increased number of secretory cells vary with age or location in the fallopian tube and to examine its association with serous neoplasia. Three groups (benign control, high-risk, and pelvic serous carcinoma) of age-matched patients were studied. The age data were stratified into 10-year intervals ranging from 20-29 to older than 80. The number of secretory and ciliated cells from both tubal fimbria and ampulla segments was counted by microscopy and immunohistochemical staining methods. The data were analyzed by standard contingency table and Poisson distribution methods after age justification. We found that the absolute number of tubal secretory cells increased significantly with age in all three groups. But a more dramatic increase of secretory cells was observed in high-risk and pelvic serous carcinoma patients. Secretory cell expansion is more prevalent than secretory cell outgrowth in both fimbria and ampulla tubal segments and is significantly associated with serous neoplasia (p < 0.001). Furthermore, age remained a significant risk factor for serous neoplasia after age adjustment. These findings suggest that secretory cell expansion could serve as a potential sensitive biomarker for early serous carcinogenesis within the fallopian tube. The study also supports a relationship between serous neoplasia and increased secretory to ciliated cell ratios, and the relationship between frequency of secretory cell expansion within the fallopian tube and increasing age and-more significantly-presence of high-risk factors or co-existing serous cancers.
Carey, Mark S.; Agarwal, Roshan; Gilks, Blake; Swenerton, Kenneth; Kalloger, Steve; Santos, Jennifer; Ju, Zhenlin; Lu, Yiling; Zhang, Fan; Coombes, Kevin; Miller, Dianne; Huntsman, David; Mills, Gordon B.; Hennessy, Bryan T
Purpose: Using Reverse Phase Protein Array (RPPA) we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage high-grade serous ovarian cancer. Experimental Design: Tumor samples were obtained from forty-five patients with advanced high-grade serous cancers from the Gynecology Tumor Bank at the British Columbia Cancer Agency. Treatment consisted of platinum-based chemotherapy following debulking surgery. Protein lysates were prepared from fresh frozen tumor samples and 80 validated proteins from signaling pathways implicated in ovarian carcinogenesis were measured by RPPA. Normalization of Ca-125 by the 3rd cycle of chemotherapy was chosen as the primary outcome measure of chemotherapy response. Logistic regression was used for multivariate analysis to identify protein predictors of Ca-125 normalization, and Cox regression to test for the association between protein expression and PFS. A significance level of p ≤ 0.05 was used. Results: The mean age at diagnosis was 56.8 years. EGFR, YKL-40 and several TGFβ pathway proteins (c-Jun N-terminal kinase JNK, JNK phosphorylated at residues 183 and 185, PAI-1, Smad3, TAZ) showed significant associations with Ca-125 normalization on univariate testing. On multivariate analysis, EGFR (p < 0.02), JNK (p < 0.01), and Smad3 (p < 0.04) were significantly associated with normalization of Ca-125. Contingency table analysis of pathway-classified proteins revealed that the selection of TGFβ pathway proteins was unlikely due to false discovery (p < 0.007, Bonferroni-adjusted). Conclusion: TGFβ pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted. PMID:20460476
SANTISTEBAN, DANIEL A.; MUIR, JOAN A.; MENA, MAITE P.; MITRANI, VICTORIA B.
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
Cheng, Zhongping; Yang, Weihong; Guo, Jing; Luo, Ning; Chen, Li; Xie, Yan; Qu, Xiaoyan; Hu, Liping; Dai, Hong; Zuo, Xiaoming
The present report aimed to study genetic alterations underlying extraovarian peritoneal serous papillary carcinoma (EPSPC), which have not previously been systematically investigated. A case of EPSPC was identified, and its genetic alterations were assessed by combining comparative genomic hybridization and whole-exome sequencing technologies to investigate the genomic landscape, including copy number variations and mutations in EPSPC. It was found that a large number of germline mutations were present, which may have predisposed the patient to the occurrence of this disease. Copy number gains were found in a range of chromosomes, including 4q, 5q, 8q, 10q, 15q, 16p, 18q, 20p, 20q and Xq. Large-scale copy number loss occurred in chromosomes 2p, 13q, 16q, 17p and 17q. Through use of whole-exome sequencing, germline mutations were widely found that were associated with cancer development, including mutations in the BRCA1, DNA repair associated (BRCA1), BRCA2, tumor protein 53, erb-b2 receptor tyrosine kinase 2, matrix metalloproteinases and ADAM metallopeptidase domain-containing genes. In addition, 165 somatic mutations, including 52 missense mutations and 7 short insertions or deletions, were also identified. In summary, the EPSPC was undergoing profound genomic rearrangement and somatic mutation, which may have led to its initiation and development, and the present study discussed the genetic basis of this highly malignant cancer. PMID:27698805
Chen, Xiaoxiang; Zhang, Jing; Zhang, Zhihong; Li, Hongxia; Cheng, Wenjun; Liu, Jinsong
Although epithelial ovarian cancer cells are eliminated by debulking surgery and chemotherapy during initial treatment, it is believed that only a subset of cancer cells, that is, cancer stem cells, may be an important source of tumor recurrence and drug resistance. This review highlights our current understanding of high-grade serous carcinoma, ovarian cancer stem cells, common methods for enrichment of ovarian cancer stem cells, mechanisms involved in drug resistance, and potential strategies for overcoming drug resistance, with associated potential controversies and pitfalls. We also review the potential relationship between epithelial-to-mesenchymal transition and cancer stem cells and how we can induce cancer cells to differentiate into benign stromal fibroblasts in response to certain chemotherapy drugs.
Zhang, Lihua; Coletti, Caroline; Vathipadiekal, Vinod; Castro, Cesar M.; Birrer, Michael J.; Nagano, Osamu; Saya, Hideyuki; Lage, Kasper; Donahoe, Patricia K.; Pépin, David
CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8-10 in patient ascites samples was correlated with significantly worse prognosis (p<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be
Vieira, Luisa; Silva, Nuno Aguiar; Medeiros, Marco Dutra; Flores, Rita; Maduro, Vitor
Acute lymphoblastic leukemia is a malignant hematopoietic neoplasia, which is rare in adults. Although ocular fundus alterations may be commonly observed in the course of the disease, such alterations are rarely the presenting signs of the disease. Here we describe the case of a patient with painless and progressive loss of visual acuity (right eye, 2/10; left eye, 3/10) developing over two weeks, accompanied by fever and cervical lymphadenopathy. Fundus examination showed bilateral macular serous detachment, which was confirmed by optical coherence tomography. Fluorescein angiography revealed hyperfluorescent pinpoints in the posterior poles. The limits of the macular detachment were revealed in the late phase of the angiogram. The results of blood count analysis triggered a thorough, systematic patient examination. The diagnosis of acute lymphoblastic leukemia B (CD10+) was established, and intensive systemic chemotherapy was immediately initiated. One year after the diagnosis, the patient remains in complete remission without any ophthalmologic alterations.
Seeber, Laura M S; Zweemer, Ronald P; Marchionni, Luigi; Massuger, Leon F A G; Smit, Vincent T H B M; van Baal, W Marchien; Verheijen, René H M; van Diest, Paul J
Promoter methylation is a gene- and cancer type-specific epigenetic event that plays an important role in tumour development. As endometrioid (endometrioid endometrial carcinoma, EEC) and serous endometrial cancers (uterine papillary serous carcinoma, UPSC) exhibit different clinical, histological and molecular genetic characteristics, we hypothesized that these differences may be reflected in epigenetic phenomena as well. Identification of a panel of methylation biomarkers could be helpful in a correct histological classification of these two subtypes, which solely on the basis of morphology is not always easy. Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of different tumour suppressor genes in EEC and UPSC. Methylation results were correlated with histology and survival. The median cumulative methylation index of all genes was significantly higher in EEC (124) than in UPSC (93) (P<0.001). Promoter methylation of CDH13 and MLH1 was more frequently present in EEC, while CDKN2B and TP73 were more frequently methylated in UPSC. Almost 90% of EEC and 70% of UPSC could be predicted by CDH13 and TP73. In EEC, methylation of MLH1 was associated with a shorter disease-free survival (DFS; P<0.0001) and overall survival (OS; P=0.005). In a multivariate model, MLH1 methylation emerged as an additional prognostic factor to stage for DFS (P=0.002). In conclusion, promoter methylation is more common in EEC than UPSC. A panel of methylation biomarkers could be useful to distinguish between the two histological subtypes of endometrial cancer. Furthermore, methylation of MLH1 may have prognostic value in EEC.
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
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
women who were BRCA heterozygotes, overexpression natural killer cells. 42 of p53 and mutation of p53 were found in all early invasive Recently, apoE...Frequent PTEN/MMAC mutations in endo- 42 Urosovic M. Willers J Mueller B. Kempf W, Burg G, Dummer R: motrboid but not serous or mucinous epithelial...absence of BRAF assessment of clonality. 42 It is possible that clonal and KRAS mutations in all of the serous cystadeno- proliferation occurs only focally
van den Doel, E M
The diagnosis of a "serous apoplexy," customary in the first half of the 19th century, was based on the lack of knowledge regarding the normal presence of the cerebrospinal fluid. Balzac's descriptions of three cases of serous apoplexy draw our attention to the fact that the discovery of the cerebrospinal fluid by François Magendie was not assimilated into clinical medicine until the second half of the 19th century.
Stringer-Reasor, Erica M.; Baker, Gabrielle M.; Skor, Maxwell N.; Kocherginsky, Masha; Lengyel, Ernst; Fleming, Gini F.; Conzen, Suzanne D.
Objectives To test the hypothesis that glucocorticoid receptor (GR) activation increases resistance to chemotherapy in high-grade serous ovarian cancer (HGS-OvCa) and that treatment with a GR antagonist will improve sensitivity to chemotherapy. Methods GR expression was assessed in OvCa cell lines by qRT-PCR and Western blot analysis and in xenografts and primary human tumors using immunohistochemistry (IHC). We also examined the effect of GR activation versus inhibition on chemotherapy-induced cytotoxicity in OvCa cell lines and in a xenograft model. Results With the exception of IGROV-1 cells, all OvCa cell lines tested had detectable GR expression by Western blot and qRT-PCR analysis. Twenty-five out of the 27 human primary HGS-OvCas examined expressed GR by IHC. No cell line expressed detectable progesterone receptor (PR) or androgen receptor (AR) by Western blot analysis. In vitro assays showed that in GR-positive HeyA8 and SKOV3 cells, dexamethasone (100 nM) treatment upregulated the pro-survival genes SGK1 and MKP1/DUSP1 and inhibited carboplatin/gemcitabine-induced cell death. Concurrent treatment with two GR antagonists, either mifepristone (100 nM) or CORT125134 (100 nM), partially reversed these effects. There was no anti-apoptotic effect of dexamethasone on chemotherapy-induced cell death in IGROV-1 cells, which did not have detectable GR protein. Mifepristone treatment alone was not cytotoxic in any cell line. HeyA8 OvCa xenograft studies demonstrated that adding mifepristone to carboplatin/gemcitabine increased tumor shrinkage by 48% compared to carboplatin/gemcitabine treatment alone (P=0.0004). Conclusions These results suggest that GR antagonism sensitizes GR+ OvCa to chemotherapy-induced cell death through inhibition of GR-mediated cell survival pathways. PMID:26115975
Villella, J A; Cohen, S; Smith, D H; Hibshoosh, H; Hershman, D
Uterine papillary serous carcinoma (UPSC) is a highly aggressive variant of endometrial cancer with features similar to high-grade ovarian cancer. Patients tend to be elderly, thin, have a high grade tumor with extensive extrauterine disease at the time of diagnosis. The transmembrane receptor encoded by the HER-2 cellular oncogene is amplified in several types of human carcinomas and provides an attractive therapeutic target. HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is overexpressed by immunohistochemistry in <25% of ovarian cancers and 20-30% of breast cancers, and <10% of endometrial cancer. There are prognostic and therapeutic implications associated with the overexpression of this transmembrane protein. Herceptin, a humanized murine monoclonal antibody directed against the extracellular domain of the HER-2/neu protein, is being used to treat breast cancer that overexpresses HER-2/neu. We reviewed all patients diagnosed with UPSC between 1999-2001. Twenty-six patients were identified, and 19 patients had specimens available for evaluation. We performed immunohistochemical analysis (Herceptest, Dako, Carpinteria, CA) on 19 paraffin embedded blocks of UPSC tumors looking for HER-2/neu over expression. Five out of 19 (26%) stained heavily (3+) for HER-2/neu receptor protein. Four of these five patients had advanced disease at diagnosis. Two of these patients were subsequently treated with Herceptin; one with complete response and one with stable disease based on CT scan and CA-125 findings. Targeting HER-2/neu may be beneficial for a select group of patients with UPSC. We are continuing to evaluate samples for HER-2/neu over expression by fluorescence in situ hybridization (FISH).
Buza, Natalia; English, Diana P; Santin, Alessandro D; Hui, Pei
HER2 overexpression and/or amplification have been reported in endometrial serous carcinoma, suggesting that HER2 may be a promising therapeutic target. However, there is considerable variation in the reported rates of HER2 overexpression and amplification, likely--at least in part--resulting from variability in the testing methods, interpretation, and scoring criteria used. Unlike in breast and gastric cancer, currently there are no established guidelines for HER2 testing in endometrial carcinoma. A total of 108 endometrial carcinoma cases--85 pure serous carcinomas and 23 mixed endometrial carcinomas with serous component--were identified over a 4-year period. All H&E and HER2 immunohistochemical slides were reviewed and HER2 FISH results (available on 52 cases) were retrieved from pathology reports. HER2 immunohistochemical scores were assigned according to the FDA criteria and the current breast ASCO/CAP scoring criteria. Clinical information was retrieved from the patients' medical records. Thirty-eight cases (35%) showed HER2 overexpression and/or gene amplification, 20 of which (53%) had significant heterogeneity of protein expression by immunohistochemistry. Lack of apical membrane staining resulting in a lateral/basolateral staining pattern was observed in the majority of HER2-positive tumors. Five of the HER2-positive cases (13%) demonstrated discrepant immunohistochemical scores when using the FDA versus ASCO/CAP scoring system. The overall concordance rate between HER2 immunohistochemistry and FISH was 75% (39/52) when using the FDA criteria, compared with 81% (42/52) by the ASCO/CAP scoring system. In conclusion, in this largest comprehensive study, 35% of endometrial serous carcinoma harbors HER2 protein overexpression and/or gene amplification, over half of which demonstrate significant heterogeneity of protein expression. The current breast ASCO/CAP scoring criteria provide the highest concordance between immunohistochemistry and FISH. Assessment of
Ayre, Karyn; Owen, Gareth S.; Moran, Paul
The use of the Mental Capacity Act 2005 in assessing decision-making capacity in patients with borderline personality disorder (BPD) is inconsistent. We believe this may stem from persisting confusion regarding the nosological status of personality disorder and also a failure to recognise the fact that emotional dysregulation and characteristic psychodynamic abnormalities may cause substantial difficulties in using and weighing information. Clearer consensus on these issues is required in order to provide consistent patient care and reduce uncertainty for clinicians in what are often emergency and high-stakes clinical scenarios. PMID:28184315
Biskin, Robert S
Borderline personality disorder (BPD) has historically been seen as a lifelong, highly disabling disorder. Research during the past 2 decades has challenged this assumption. This paper reviews the course of BPD throughout life, including childhood, adolescence, and adulthood. BPD can be accurately identified in adolescence, and the course of the disorder, in adolescence and adulthood, is generally similar, with reductions in symptoms over time. Functional recovery is less consistent, and further research on factors or treatments that may improve the long-term functional outcome of patients with BPD is warranted. PMID:26175388
WILKINSON, SALLYE M.; GABBARD, GLEN O.
The therapeutic use of countertransference disclosure as a means of highlighting the borderline patient’s intrapsychic and interpersonal use of the therapist is discussed. Countertransference disclosure is narrowly defined as a form of clinical honesty that focuses on the therapist’s experience of the patient in the here-and-now moment of the session. The effects of disclosure on transference exploration, neutrality, and patient revelations are explored through examination of detailed process notes of therapy sessions. Technical issues such as indirect versus direct disclosure and responses to direct questions are also addressed. PMID:22700154
Sansone, Randy A.; Wiederman, Michael W.; Sansone, Lori A.
Reviews possible links between obesity and borderline-personality disorder and discusses treatment approaches for those individuals demonstrating such comorbidity. Approaches include modification of current techniques for obesity treatment and incorporation of psychodynamic counseling specific to borderline-personality disorder. (Author/GCP)
PLAKUN, ERIC M.
Patients with borderline personality disorder often exhibit lethal or nonlethal self-destructive behavior. The author offers seven principles for establishing and maintaining a therapeutic alliance in the insight-oriented psychodynamic psychotherapy of borderline personality disorder patients with self-destructive behavior serious enough to threaten the continuity of the therapy. PMID:22700187
Showeil, Rania; Romano, Claudia; Valganon, Mikel; Lambros, Maryou; Trivedi, Pritesh; Van Noorden, Susan; Sriraksa, Ruethairat; El-Kaffash, Dalal; El-Etreby, Nour; Natrajan, Rachael; Foroni, Letizia; Osborne, Richard; El-Bahrawy, Mona
The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear
Fonseca-Pedrero, Eduardo; Lemos-Giráldez, Serafín; Paino, Mercedes; Sierra-Baigrie, Susana; Muñiz, José
The main objective of the present investigation was to analyze the relationship between self-reported schizotypal and borderline personality traits in a sample of 759 college students (M = 19.63 years; SD = 2.03). For this purpose, the Schizotypal Personality Questionnaire-Brief (SPQ-B; Raine and Benishay, 1995) and Borderline Personality Questionnaire (BPQ; Poreh et al., 2006) were administered. The results showed that schizotypal and borderline features are partially related at subclinical level. The exploratory factor analysis conducted on the subscales revealed a three-factor solution comprised of the following factors: Identity/Interpersonal, Lack of Control and Schizotypal. The canonical correlation analysis showed that schizotypal features and borderline personality traits shared 34.8% of the variance. The data highlight the overlap between schizotypal and borderline personality traits in nonclinical young adults. Future studies should continue to examine the relationship and the degree of overlap between these traits in community samples.
Hilvo, Mika; de Santiago, Ines; Gopalacharyulu, Peddinti; Schmitt, Wolfgang D.; Budczies, Jan; Kuhberg, Marc; Dietel, Manfred; Aittokallio, Tero; Markowetz, Florian; Denkert, Carsten; Sehouli, Jalid; Frezza, Christian
Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but is often challenging because the symptoms of ovarian cancer are subtle and become apparent only during advanced stages of the disease. Therefore, the identification of robust biomarkers of early disease is a clinical priority. Metabolomic profiling is an emerging diagnostic tool enabling the detection of biomarkers reflecting alterations in tumor metabolism, a hallmark of cancer. In this study, we performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ovarian cancer (HGSOC) and 100 control patients with benign or non-neoplastic lesions. We report metabolites of hydroxybutyric acid (HBA) as novel diagnostic and prognostic biomarkers associated with tumor burden and patient survival. The accumulation of HBA metabolites caused by HGSOC was also associated with reduced expression of succinic semialdehyde dehydrogenase (encoded by ALDH5A1), and with the presence of an epithelial-to-mesenchymal transition (EMT) gene signature, implying a role for these metabolic alterations in cancer cell migration and invasion. In conclusion, our findings represent the first comprehensive metabolomics analysis in HGSOC and propose a new set of metabolites as biomarkers of disease with diagnostic and prognostic capabilities. PMID:26685161
Roelofsen, Thijs; Geels, Yvette P; Pijnenborg, Johanna M A; van Ham, Maaike A P C; Zomer, Saskia F; van Tilburg, Johanna M Wiersma; Snijders, Marc P M L; Siebers, Albert G; Bulten, Johan; Massuger, Leon F A G
The aim of this study was to determine the frequency of abnormal cervical cytology in preoperative cervical cytology of patients diagnosed with uterine papillary serous carcinoma (UPSC) and endometrioid endometrial carcinoma (EEC). In addition, associations between abnormal cervical cytology and clinicopathologic factors were evaluated. In this multicentre study, EEC patients diagnosed at two hospitals from 1999 to 2009 and UPSC patients diagnosed at five hospitals from 1992 to 2009, were included. Revision of the histologic slides was performed systematically and independently by 3 gynecopathologists. Cervical cytology within six months before histopathologic diagnosis of endometrial carcinoma was available for 267 EEC and 80 UPSC patients. Cervical cytology with atypical, malignant, or normal endometrial cells in postmenopausal women was considered as abnormal cytology, specific for endometrial pathology. Abnormal cervical cytology was found in 87.5% of UPSC patients, compared with 37.8% in EEC patients. In UPSC, abnormal cytology was associated with extrauterine spread of disease (P=0.043). In EEC, abnormal cytology was associated with cervical involvement (P=0.034). In both EEC and UPSC patients, abnormal cervical cytology was not associated with survival. In conclusion, abnormal cervical cytology was more frequently found in UPSC patients. It was associated with extrauterine disease in UPSC patients, and with cervical involvement in EEC patients. More prospective research should be performed to assess the true clinical value of preoperative cervical cytology in endometrial cancer patients.
Singh, Rishi P; Sears, Jonathan E; Bedi, Rumneek; Schachat, Andrew P; Ehlers, Justis P; Kaiser, Peter K
AIM To examine eplerenone (Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy (CSCR). METHODS A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit, spectral domain optical coherence tomography (SD-OCT) imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy. RESULTS A total of 17 eyes of 13 patients treated with 25 and 50 mg of oral eplerenone per day were identified. Subretinal fluid (SRF) decreased over time following eplerenone therapy (P= 0.007 and P = 0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 µm at baseline to 15.3 µm at day 181+. SRF diameter decreased from an average of 2174.4 µm at baseline to 46.9 µm at day 181+. LogMAR visual acuity improved from 0.42 (Snellen equivalent: 20/53) at baseline to 0.29 (Snellen equivalent: 20/39) at day 181+ (P = 0.024). Central subfield thickness (CST) decreased from 339.5 µm at baseline to 270.3 µm at day 181+ (P = 0.029). CONCLUSION Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR. PMID:25938046
Moon, Hoseok; Lee, Dae Yeong; Nam, Dong Heun
AIM To evaluate the axial length (AXL) in unilateral idiopathic central serous chorioretinopathy (CSC). METHODS This retrospective case-control study was comprised of a consecutive case series of 35 patients with acute unilateral idiopathic CSC, and age- and sex-matched 50 control eyes. AXL of both eyes of unilateral CSC patients and the control eyes were investigated. AXL was measured by ultrasonic biometry, and the adjusted AXL was calculated for CSC eyes as measured AXL plus differences of foveal thickness between CSC and normal fellow eyes in millimeters. The main outcome measures were comparison of AXL between CSC, fellow and control eyes. RESULTS The mean age of 35 CSC patients was 45.5y, and 31 males were included. The adjusted AXL of CSC eyes was 23.52 mm, and the AXL of fellow eyes was 23.46 mm, and of control eyes 23.94 mm. The AXL of both CSC and fellow eyes were significantly shorter than control eyes (CSC vs control, P=0.044; fellow vs control, P=0.026). There was no statistically significant difference in AXL between CSC and fellow eyes. CONCLUSION In unilateral idiopathic CSC, the AXL of CSC and fellow eyes are shorter than that of control eyes. Short AXL may be related with choroidal circulation abnormality in CSC. PMID:27275428
Distel, Marijn A; Smit, Johannes H; Spinhoven, Philip; Penninx, Brenda W J H
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.
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.
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.
Raines, J M; Raines, L C; Singer, M
It has been proposed that Bram Stoker's novel Dracula can best be understood as a dramatic, hyperbolic, and fantastic expression of themes consistent with contemporary psychoanalytic conceptions of borderline personality disorder organization. Such an understanding may, in turn, shed further light on the nature of the intrapsychic world and experiences of borderline patients. Excerpts from the novel can be used to support the conceptualization of recent contributions to object relations theory and the understanding of borderline personality organization. It is uncanny how consistent Dracula's characteristics are to the generally seen complaints of patients suffering from this disorder.
Kazuko, Tamura; Inoue, Kako
This study investigated some discriminative features of Borderline Personality Disorder (BPD) with both clinical and normal samples using a self-report questionnaire. This questionnaire was administered to 116 clinical outpatients (diagnoses: thirty two BPD; twenty four schizophrenia; twenty six depression; twenty nine neurosis; and five other mental disorders) and to 216 college students as a normal sample. Factor analysis produced six factors: emptiness; hallucination and egorrhea; distortional body image and acts of self-inflicted injury; impulsive acting-out; loss of emotional control; and grandiose omnipotence. Distortional body image and acts of self-inflicted injury discriminated BPD the most from the other samples. No significant differences were seen between the BPD and Schizophrenia samples in terms of the hallucination or egorrhea subscales. An intense loss of emotional control, particularly control of negative emotions such as rage, was apparent in the clinical samples, which was not evident in the normal sample.
Peter, Mathell; Schuurmans, Hanneke; Vingerhoets, Ad J J M; Smeets, Guus; Verkoeijen, Peter; Arntz, Arnoud
The present study investigated emotional intelligence (EI) in borderline personality disorder (BPD). It was hypothesized that patients with BPD (n = 61) compared with patients with other personality disorders (PDs; n = 69) and nonpatients (n = 248) would show higher scores on the ability to perceive emotions and impairments in the ability to regulate emotions. EI was assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test (Mayer, Salovey, and Caruso [New York: MHS, 2002]). As compared with the PD group and the nonpatient group, the patients with BPD displayed the anticipated deficits in their ability to understand, whereas no differences emerged with respect to their ability to perceive, use, and regulate emotions. In addition, a negative relationship was found between the severity of BPD and total EI score. However, this relationship disappeared when intelligence quotient was partialled out. These results suggest that BPD is associated with emotion understanding deficits, whereas temporary severity of BPD is associated with emotion regulation deficits.
Hill, Jonathan; Stepp, Stephanie D; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q; Steele, Miriam; Steele, Howard; Pilkonis, Paul A
Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25-36. Study 2 consisted of a psychiatric sample (N = 138) aged 21-60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction.
Feske, Ulrike; Tarter, Ralph E; Kirisci, Levent; Pilkonis, Paul A
The association between borderline personality disorder (BPD) and substance use disorder (SUD) was examined in a predominantly psychiatric (77.6%) sample of 232 women. BPD proved to be a significant predictor of a lifetime diagnosis of SUD across four different categories: any SUD (including alcohol); alcohol use; drug use; and heroin, cocaine, or poly-substance use. BPD continued to be a predictor of SUD even when the effects of other cluster B and all cluster C PDs were controlled statistically. Antisocial personality disorder generally yielded larger odds ratios than BPD and emerged as a partial mediator of the relation between BPD and SUD. Histrionic PD was the only other PD that showed meaningful relations with SUD.
Suvak, Michael K.; Litz, Brett T.; Sloan, Denise M.; Zanarini, Mary C.; Barrett, Lisa Feldman; Hofmann, Stefan G.
This study examined the affective dysregulation component of borderline personality disorder (BPD) from an emotional granularity perspective, which refers to the specificity in which one represents emotions. Forty-six female participants meeting criteria for BPD and 51 female control participants without BPD and Axis I pathology completed tasks that assessed the degree to which participants incorporated information about valence (pleasant–unpleasant) and arousal (calm–activated) in their semantic/conceptual representations of emotions and in using labels to represent emotional reactions. As hypothesized, participants with BPD emphasized valence more and arousal less than control participants did when using emotion terms to label their emotional reactions. Implications and future research directions are discussed. PMID:21171723
Ripoll, Luis H
The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning.
Huang, Lu-Qi; Yuan, Yuan; Cui, Guang-Hong; Dai, Zhu-Bo; Xiao, Pei-Gen
Pharmacognosy has developed rapidly in recent years and now represents a highly interdisciplinary science. At the boundary between pharmacognosy and molecular biology, molecular pharmacognosy has developed as a new borderline discipline. Using the method and technology of molecular biology, molecular pharmacognosy focuses on resolving a wide range of challenging problems, such as distinguishing herbal and animal drug populations by molecular marker assay, conserving and utilizing wild resources on the basis of knowledge of genetic diversity, investigating the mechanism of active compound accumulation and obtaining new resources with higher quality through genetic engineering. Recent research results show that molecular pharmacognosy has extended the scope of pharmacognostical science and plays an important role in the safe and efficient usage of crude drugs.
Goodman, Marianne; Patel, Uday; Oakes, Allison; Matho, Andrea; Triebwasser, Joseph
Due to the higher diagnostic prevalence of borderline personality disorder (BPD) in females, there exists a dearth of literature on the manifestations of BPD in men and minimal information on male developmental trajectories to the disorder. To identify precursors of BPD in males, surveys were administered to parents about their BPD male offspring and non-BPD male siblings. Questions covered aspects of probands' lives from infancy to late adolescence. BPD offspring were identified through self-reported clinical diagnoses and standardized diagnostic criteria embedded within the survey. A total of 263 male offspring (97 meeting strict criteria for BPD and 166 non-BPD siblings) were studied. The authors found that parents describe the early emergence of a constellation of symptoms in their BPD sons that include separation anxiety starting in infancy, body image concerns in childhood, and impulsivity, emptiness, and odd thinking in adolescence. This trajectory differs from the developmental course found in females diagnosed with BPD.
Flynn, Ciaran; Oxley, Jon; McCullagh, Paul; McCluggage, W Glenn
Serous carcinomas most commonly arise within the uterine corpus or ovary/fallopian tube, but there are 2 prior case reports of primary vaginal serous carcinoma. We report 2 examples of high-grade serous carcinoma arising within the urethra or a urethral diverticulum (1 case each). Both neoplasms exhibited the classic morphologic features of high-grade serous carcinoma, and a combination of clinical, radiologic, and pathologic examination excluded other possible sites of primary neoplasm.
Dagli, Necati; Turgut, Burak; Tanyildizi, Rumeysa; Kobat, Sabiha; Kobat, Mehmet Ali; Dogdu, Orhan
AIM To evaluate QT dispersion (QTD) in patients with central serous chorioretinopathy (CSC). METHODS This clinical, comperative, case-control study included 30 patients with CSC at acute phase (Group 1) and 30 age- and sex-matched healthy subjects (Group 2, the control group). From all subjects, a 12-lead surface electrocardiography was obtained. The heart rate (HR), QT maximum (QTmax), QT minimum (QTmin), QT corrected (QTc), QTD and Tmean were manually measured and analyzed. Student's t-test and Pearson's method of correlation were used for statistical analysis. RESULTS The patient and control groups were matched for age, smoking status (rate and duration) and gender. There were no significant differences with regard to these among the groups (P>0.05). The participants included 19 men (63.3%) and 11 women (36.7%) in Group 1, 20 men (66.7%) and 10 women (33.3%) in Group 2. QTmax, QTD and QTc were significantly higher than those of healthy controls (P<0.001 for QTmax, P=0.01 for QTD and P=0.001 for QTc). QTmin, Tmean and HR did not differ significantly between the study groups (P=0.28 for QTmin, P=0.56 for Tmean and P>0.05 for HR). No significant correlation was found between duration of the disorder and QTD values (r=0.13, P>0.05). CONCLUSION These findings suggest that CSC may be associated with an increase in QTD and that the patients might be at risk for ventricular arrhythmia. PMID:25709909
Schultheis, Anne M; Martelotto, Luciano G; De Filippo, Maria R; Piscuglio, Salvatore; Ng, Charlotte K Y; Hussein, Yaser R; Reis-Filho, Jorge S; Soslow, Robert A; Weigelt, Britta
Endometrial carcinomas (ECs) are heterogeneous at the genetic level. Although TP53 mutations are highly recurrent in serous endometrial carcinomas (SECs), these are also present in a subset of endometrioid endometrial carcinomas (EECs). Here, we sought to define the frequency, pattern, distribution, and type of TP53 somatic mutations in ECs by performing a reanalysis of the publicly available data from The Cancer Genome Atlas (TCGA). A total of 228 EECs (n=186) and SECs (n=42) from the TCGA data set, for which an integrated genomic characterization was performed, were interrogated for the presence and type of TP53 mutations, and for mutations in genes frequently mutated in ECs. TP53 mutations were found in 15% of EECs and 88% of SECs, and in 91% of copy-number-high and 35% of polymerase (DNA directed), epsilon, catalytic subunit (POLE) integrative genomic subtypes. In addition to differences in prevalence, variations in the type and pattern of TP53 mutations were observed between histologic types and between integrative genomic subtypes. TP53 hotspot mutations were significantly more frequently found in SECs (46%) than in EECs (15%). TP53-mutant EECs significantly more frequently harbored a co-occurring PTEN mutation than TP53-mutant SECs. Finally, a subset of TP53-mutant ECs (22%) was found to harbor frameshift or nonsense mutations. Given that nonsense and frameshift TP53 mutations result in distinct p53 immunohistochemical results that require careful interpretation, and that EECs and SECs display different patterns, types, and distributions of TP53 mutations, the use of the TP53/p53 status alone for the differential diagnosis of EECs and SECs may not be sufficient.
Gramajo, A L; Marquez, G E; Torres, V E; Juárez, C P; Rosenstein, R E; Luna, J D
Purpose To evaluate the efficacy and safety of melatonin for the treatment of chronic central serous chorioretinopathy (CSCR). Methods Prospective comparative case series. A total of 13 patients with chronic CSCR were treated for 1 month: 8 patients were treated orally with 3 mg melatonin t.i.d., and 5 with placebo. All patients had 20/40 or worse Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) in the affected eye or presented an incapacitating scotoma. Most of the patients had previous failed treatments for their condition. Observational procedures included ETDRS BCVA, and complete ophthalmic examination. Optical coherence tomography (OCT) was performed at day 1 and week 4. Fluorescein angiography was performed at baseline only for diagnostic purposes. Data were subjected to two-sample t-test statistical analysis. P-values of <0.05 were considered statistically significant. Results At 1-month follow-up, BCVA significantly improved in 87.5% of patients treated with melatonin (7 of 8 patients, P<0.05). All patients showed a mean significant reduction (P<0.01) of central macular thickness (CMT) when compared with the baseline, with 3 patients (37.5%) exhibiting complete resolution of subretinal fluid at 1-month follow-up. No significant side effects were observed. No changes in BCVA or CMT were noted in the control group. Conclusions These results suggest that melatonin is safe, well tolerated, and effective in the treatment of chronic CSCR, as it significantly improved BCVA and CMT in patients with this pathology. Further evaluations with longer follow-up and a larger patient population are desirable. PMID:26160525
Chien, Jeremy; Sicotte, Hugues; Fan, Jian-Bing; Humphray, Sean; Cunningham, Julie M; Kalli, Kimberly R; Oberg, Ann L; Hart, Steven N; Li, Ying; Davila, Jaime I; Baheti, Saurabh; Wang, Chen; Dietmann, Sabine; Atkinson, Elizabeth J; Asmann, Yan W; Bell, Debra A; Ota, Takayo; Tarabishy, Yaman; Kuang, Rui; Bibikova, Marina; Cheetham, R Keira; Grocock, Russell J; Swisher, Elizabeth M; Peden, John; Bentley, David; Kocher, Jean-Pierre A; Kaufmann, Scott H; Hartmann, Lynn C; Shridhar, Viji; Goode, Ellen L
To determine early somatic changes in high-grade serous ovarian cancer (HGSOC), we performed whole genome sequencing on a rare collection of 16 low stage HGSOCs. The majority showed extensive structural alterations (one had an ultramutated profile), exhibited high levels of p53 immunoreactivity, and harboured a TP53 mutation, deletion or inactivation. BRCA1 and BRCA2 mutations were observed in two tumors, with nine showing evidence of a homologous recombination (HR) defect. Combined Analysis with The Cancer Genome Atlas (TCGA) indicated that low and late stage HGSOCs have similar mutation and copy number profiles. We also found evidence that deleterious TP53 mutations are the earliest events, followed by deletions or loss of heterozygosity (LOH) of chromosomes carrying TP53, BRCA1 or BRCA2. Inactivation of HR appears to be an early event, as 62.5% of tumours showed a LOH pattern suggestive of HR defects. Three tumours with the highest ploidy had little genome-wide LOH, yet one of these had a homozygous somatic frame-shift BRCA2 mutation, suggesting that some carcinomas begin as tetraploid then descend into diploidy accompanied by genome-wide LOH. Lastly, we found evidence that structural variants (SV) cluster in HGSOC, but are absent in one ultramutated tumor, providing insights into the pathogenesis of low stage HGSOC.
Braamhorst, Wouter; Lobbestael, Jill; Emons, Wilco H M; Arntz, Arnoud; Witteman, Cilia L M; Bekker, Marrie H J
This study investigated sex bias in the classification of borderline and narcissistic personality disorders. A sample of psychologists in training for a post-master degree (N = 180) read brief case histories (male or female version) and made DSM classification. To differentiate sex bias due to sex stereotyping or to base rate variation, we used different case histories, respectively: (1) non-ambiguous case histories with enough criteria of either borderline or narcissistic personality disorder to meet the threshold for classification, and (2) an ambiguous case with subthreshold features of both borderline and narcissistic personality disorder. Results showed significant differences due to sex of the patient in the ambiguous condition. Thus, when the diagnosis is not straightforward, as in the case of mixed subthreshold features, sex bias is present and is influenced by base-rate variation. These findings emphasize the need for caution in classifying personality disorders, especially borderline or narcissistic traits.
Ambwani, Suman; Morey, Leslie C
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.
Goldberg, R L; Mann, L S; Wise, T N; Segall, E A
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.
DeShong, Hilary L; Kurtz, John E
Impulsivity is a shared criterion for the diagnosis of antisocial and borderline personality disorders, and this link may account for the high comorbidity rates between the two disorders. The current study aimed to differentiate between borderline and antisocial personality disorders using the four factors of impulsivity identified by Whiteside and Lynam (2001). Five hundred thirty-six undergraduate participants completed the personality assessment inventory (PAI; Morey, 1991) to assess borderline and antisocial personality features and the NEO personality inventory, third edition (NEO-PI-3; McCrae & Costa, 2010) to assess the four factors of impulsivity. Results indicate that negative urgency and lack of perseverance were significantly and uniquely related to borderline features, while sensation seeking and lack of premeditation were significantly and uniquely related to antisocial features. The implications of these results for improved differential diagnosis are discussed.
Jazaeri, Amir A; Bryant, Jennifer L; Park, Hong; Li, Hui; Dahiya, Neetu; Stoler, Mark H; Ferriss, James Stuart; Dutta, Anindya
Although controversial, recent studies suggest that serous ovarian carcinomas may arise from fallopian tube fimbria rather than ovarian surface epithelium. We developed an in vitro model for serous carcinogenesis in which primary human fallopian tube epithelial cells (FTECs) were exposed to potentially oncogenic molecular alterations delivered by retroviral vectors. To more closely mirror in vivo conditions, transformation of FTECs was driven by the positive selection of growth-promoting alterations rather antibiotic selection. Injection of the transformed FTEC lines in SCID mice resulted in xenografts with histologic and immunohistochemical features indistinguishable from poorly differentiated serous carcinomas. Transcriptional profiling revealed high similarity among the transformed and control FTEC lines and patient-derived serous ovarian carcinoma cells and was used to define a malignancy-related transcriptional signature. Oncogene-treated FTEC lines were serially analyzed using quantitative reverse transcription-polymerase chain reaction and immunoblot analysis to identify oncogenes whose expression was subject to positive selection. The combination of p53 and Rb inactivation (mediated by SV40 T antigen), hTERT expression, and oncogenic C-MYC and HRAS accumulation showed positive selection during transformation. Knockdown of each of these selected components resulted in significant growth inhibition of the transformed cell lines that correlated with p27 accumulation. The combination of SV40 T antigen and hTERT expression resulted in immortalized cells that were nontumorigenic in mice, whereas forced expression of a dominant-negative p53 isoform (p53DD) and hTERT resulted in senescence. Thus, our investigation supports the tubal origin of serous carcinoma and provides a dynamic model for studying early molecular alterations in serous carcinogenesis. PMID:22028616
Jarboe, Elke A; Pizer, Ellen S; Miron, Alexander; Monte, Nick; Mutter, George L; Crum, Christopher P
Both serous intraepithelial carcinoma and endometrial glandular dysplasia are associated with uterine serous carcinoma. Recently a candidate serous cancer precursor containing p53 mutations (p53 signature) was described in the fallopian tube. We analyzed normal and neoplastic endometrium for a similar entity. In total 10 endometrial polyps involved by intraepithelial and/or invasive carcinoma and 137 benign polyps were studied. All were stained for p53 and MIB-1. A subset of p53 signatures and carcinomas were analyzed for gamma-H2AX and p53 mutations. p53 signatures were identified in 7 of 10 cases intraepithelial carcinoma and were multicentric in 2. In one case, the signature was in continuity with intraepithelial carcinoma. Of 137 benign polyps (4%), 6 contained p53 signatures. The MIB-1 fraction in most signatures was less than 5%, and ranged from 50 to 90% in carcinomas. DNA damage (gamma-H2AX) was demonstrated in both p53 signatures and adjacent carcinomas but not in benign polyps. Shared identical p53 mutations were found in paired signatures and carcinomas in two of three cases analyzed, including one case with multiple signatures. In one, a coexistent invasive serous cancer was not found to contain a p53 mutation. In a third, a p53 signature and an invasive cancer harbored two different p53 mutations. This is the first description of p53 signatures adjacent to carcinoma, suggesting a role for this entity in the genesis of serous malignancy. The significance of p53 signatures in benign conditions (polyps) remains to be determined. The role of the p53 signature in early serous neoplasia is discussed.
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.
Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh
Background: Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. Objective: To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Materials and Methods: 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. Results: 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 10th 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. Conclusion: There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10th percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI. PMID:27981256
Zhang, Xiao-Peng; Yu, Zhong-Xun; Zhao, Yu-Pei; Dai, Meng-Hua
Pancreatic cystic neoplasms have been increasingly recognized recently. Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic neoplasms are uncommon benign lesions that are usually asymptomatic and found incidentally. Despite overall low risk of malignancy, these pancreatic cysts still generate anxiety, leading to intensive medical investigations with considerable financial cost to health care systems. This review discusses the general background of serous cystic neoplasms, including epidemiology and clinical characteristics, and provides an updated overview of diagnostic approaches based on clinical features, relevant imaging studies and new findings that are being discovered pertaining to diagnostic evaluation. We also concisely discuss and propose management strategies for better quality of life. PMID:27022447
Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J
Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls (t=-3.536, P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group (r=0.494, P<0.01), and the same correlation as CEA and CA(199) group (r=0.897, P<0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group (P>0
Vathipadiekal, Vinod; Saxena, Deepa; Mok, Samuel C; Hauschka, Peter V; Ozbun, Laurent; Birrer, Michael J
Identification of gene expression profiles of cancer stem cells may have significant implications in the understanding of tumor biology and for the design of novel treatments targeted toward these cells. Here we report a potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma. Affymetrix U133 Plus 2.0 microarrays were used to interrogate the differentially expressed genes between side population (SP) and main population (MP), and the results were analyzed by paired T-test using BRB-ArrayTools. We identified 138 up-regulated and 302 down-regulated genes that were differentially expressed between all 10 SP/MP pairs. Microarray data was validated using qRT-PCR and17/19 (89.5%) genes showed robust correlations between microarray and qRT-PCR expression data. The Pathway Studio analysis identified several genes involved in cell survival, differentiation, proliferation, and apoptosis which are unique to SP cells and a mechanism for the activation of Notch signaling is identified. To validate these findings, we have identified and isolated SP cells enriched for cancer stem cells from human ovarian cancer cell lines. The SP populations were having a higher colony forming efficiency in comparison to its MP counterpart and also capable of sustained expansion and differentiation in to SP and MP phenotypes. 50,000 SP cells produced tumor in nude mice whereas the same number of MP cells failed to give any tumor at 8 weeks after injection. The SP cells demonstrated a dose dependent sensitivity to specific γ-secretase inhibitors implicating the role of Notch signaling pathway in SP cell survival. Further the generated SP gene list was found to be enriched in recurrent ovarian cancer tumors.
Cheon, Dong-Joo; Li, Andrew J; Beach, Jessica A; Walts, Ann E; Tran, Hang; Lester, Jenny; Karlan, Beth Y; Orsulic, Sandra
ADAM metallopeptidase domain 12 (ADAM12) is a promising biomarker because of its low expression in normal tissues and high expression in a variety of human cancers. However, ADAM12 levels in ovarian cancer have not been well characterized. We previously identified ADAM12 as one of the signature genes associated with poor survival in high-grade serous ovarian carcinoma (HGSOC). Here, we sought to determine if high levels of the ADAM12 protein and/or messenger RNA (mRNA) are associated with clinical variables in HGSOC. We show that high protein levels of ADAM12 in banked preoperative sera are associated with shorter progression-free and overall survival. Tumor levels of ADAM12 mRNA were also associated with shorter progression-free and overall survival as well as with lymphatic and vascular invasion, and residual tumor volume following cytoreductive surgery. The majority of genes co-expressed with ADAM12 in HGSOC were transforming growth factor (TGF)β signaling targets that function in collagen remodeling and cell-matrix adhesion. In tumor sections, the ADAM12 protein and mRNA were expressed in epithelial cancer cells and surrounding stromal cells. In vitro data showed that ADAM12 mRNA levels can be increased by TGFβ signaling and direct contact between epithelial and stromal cells. High tumor levels of ADAM12 mRNA were characteristic of the mesenchymal/desmoplastic molecular subtype of HGSOC, which is known to have the poorest prognosis. Thus, ADAM12 may be a useful biomarker of aggressive ovarian cancer for which standard treatment is not effective.
UCAR, DUYGU; LIN, DOUGLAS I.
High-grade serous carcinoma (HGSC) of the ovary is an aggressive and devastating neoplasm and the identification of novel therapeutic targets may result in a significant decrease in patient morbidity and mortality. Over the last few years, chromatin regulators have become attractive targets for cancer therapy. More specifically, bromodomain-containing protein 4 (BRD4), a protein that is associated with acetylated chromatin and transcriptional activation, has been shown to selectively regulate the transcription of key oncogenic drivers, such as CMYC, in several tumor types. The Cancer Genome Atlas (TCGA) Project has molecularly characterized the genome of ovarian serous carcinomas, which enabled us to study the association of genomic alterations of BRD4 with patient survival and clinicopathological characteristics. Our analysis using clinical and genomic data from the TCGA ovarian carcinoma samples revealed that somatic amplification of BRD4 (observed in 12% of the cases) was correlated with increased BRD4 mRNA levels and is significantly associated with worse overall and progression-free survival compared to wild-type cases. These findings support the hypothesis that future studies and trials investigating newly developed BRD4 inhibitors are required in a subset of patients with ovarian HGSC. PMID:26807235
Salehi, Mahsa; Wenick, Adam S; Law, Hua Andrew; Evans, Jennifer R; Gehlbach, Peter
Background Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy. Objectives To compare the relative effectiveness of interventions for central serous chorioretinopathy. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015. Selection criteria Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control. Data collection and analysis Two
Yen, Shirley; Gagnon, Kerry; Spirito, Anthony
The diagnosis of borderline personality disorder (BPD) in adolescents has been controversial. Thus, few studies have examined BPD in suicidal adolescents, even though it is strongly associated with suicidal behaviours in adults. This study examines differences between suicidal adolescents with (n = 47) and without (n = 72) BPD on history and characteristics of suicidal behaviour, Axis I co-morbidity, affect regulation and aggression. Assessments were completed with both adolescents and parents, and consensus ratings based on best available data were analysed. BPD participants were more likely to have a history of suicide attempts and to have been admitted because of a suicide attempt (vs. suicidal ideation). There were no significant differences in self-injurious behaviours or degree of suicidal ideation. BPD participants also had more psychiatric co-morbidity and higher aggression scores but no significant differences in affective dysregulation compared with suicidal adolescents without BPD. Diagnostic stability over 6 months was modest. Our results demonstrate that, compared with other acutely suicidal adolescents, the clinical profile of BPD participants is unique and suggests an increased risk for suicidal behaviours. This extends upon other studies that support the construct validity of BPD during adolescence and suggests that BPD should be considered in suicide risk assessment for adolescents.
Pec, Ondrej; Bob, Petr; Raboch, Jiri
Background Dissociation likely plays a key role in schizophrenia and borderline personality disorder (BPD), although empirical studies that compare specific manifestations of these symptoms in schizophrenia and BPD are rare. In this context, the purpose of this study was to compare the occurrence of dissociative and other psychopathological symptoms in these disorders, and to assess the possible influence of antipsychotic medication on the dissociative symptoms. Methods We assessed 31 patients with schizophrenia and 36 patients with BPD. Dissociative symptoms were measured by the Dissociative Experiences Scale (DES), symptoms related to stress and traumatic experiences were assessed using the Trauma Symptom Checklist-40 (TSC-40), and other psychopathological symptoms were measured with the Health of the Nation Outcome Scales (HoNOS). We also assessed actual daily doses of antipsychotic medication in chlorpromazine equivalents in all participants. Results The results show that symptoms of traumatic stress measured by the TSC-40 had significantly higher scores in the BPD group. The data also show that dissociative symptoms (DES) were significantly correlated with symptoms of traumatic stress (TSC-40) and with symptoms assessed by the HoNOS. Remarkably significant correlations were found between levels of antipsychotic medication and the DES and between antipsychotic medication and the depersonalization/derealization component of the DES in BPD patients. Conclusion The results support an important role of dissociative processes in schizophrenia and BPD and suggest a significant relationship between manifestations of dissociative symptoms in BPD and antipsychotic medication. PMID:24672239
Pec, Ondrej; Bob, Petr; Raboch, Jiri
Background Splitting describes fragmentation of conscious experience that may occur in various psychiatric disorders. A purpose of this study is to examine relationships between psychological process of splitting and disturbed cognitive and affective functions in schizophrenia and borderline personality disorder (BPD). Methods In the clinical study, we have assessed 30 patients with schizophrenia and 35 patients with BPD. The symptoms of splitting were measured using self-reported Splitting Index (SI). As a measure of semantic memory disorganization we have used verbal fluency test. Other psychopathological symptoms were assessed using Health of the Nation Outcome Scale (HoNOS). Results Main results show that SI is significantly higher in BPD group than in schizophrenia, and on the other hand, verbal fluency is significantly lower in schizophrenia group. Psychopathological symptoms measured by HoNOS are significantly higher in the BPD group than in schizophrenia. Significant relationship was found between verbal fluency and the SI “factor of others” (Spearman r = −0.52, p<0.01) in schizophrenia patients. Conclusions Processes of splitting are different in schizophrenia and BPD. In BPD patients splitting results to mental instability, whereas in schizophrenia the mental fragmentation leads to splitting of associations observed as lower scores of verbal fluency, which in principle is in agreement with Bleuler’s historical concept of splitting in schizophrenia. PMID:24603990
Sansone, Randy A; Chang, Joy; Jewell, Bryan; Sellbom, Martin; Bidwell, Mark
In this study, the authors investigated the relationship between compulsive buying and borderline personality disorder (BPD) symptomatology--two disorders possibly linked through impulsivity. Using a survey methodology in a cross-sectional consecutive sample of nonemergent female outpatients from an obstetrics/gynecology clinic, the authors assessed compulsive buying with the compulsive buying scale (CBS) and BPD symptomatology through the BPD scale of the personality diagnostic questionnaire-4 (PDQ-4) and the self-harm Inventory (SHI). In this sample, 8% of Caucasian women and 9% of African-American women scored positively for compulsive buying. The correlations between scores on the CBS and the PDQ-4 and SHI were 0.43 and 0.41, respectively-both statistically significant at the p < .001 level. Compared to Caucasian women, African-American women demonstrated statistical associations between the BPD measures and the CBS scale scores that were significantly larger. Findings suggest relationships between compulsive buying and BPD, particularly among African-American women.
Semerari, Antonio; Carcione, Antonino; Dimaggio, Giancarlo; Nicoló, Giuseppe; Pedone, Roberto; Procacci, Michele
Many authors consider that patients suffering from Borderline Personality Disorder (BPD) are hampered in their ability to metarepresent, which is the correct ascribing of states of mind to oneself and to others and the reflecting thereon. Although the ability to mentalize is generally described as being uniform, various authors pinpoint problems which appear to be of a diverse psychological nature. Some describe difficulties in identifying emotions or a shortfall in their regulation, others identify a lack of integration between representations of self and those of others, and yet others focus on the failure to distinguish between fantasy and reality. In the present research all sessions during the first year of therapy of four patients suffering from BPD were tape-recorded and transcribed, and then analyzed using the Metacognition Assessment Scale (MAS), which is designed for the evaluation of the ability to metarepresent in clinical reports. The results support the hypothesis that there is a metarepresentation impairment in BPD but that it is more selective than was thought until now. In particular, such patients maintain their ability to identify internal states, whereas they are impaired in the integration of representations of self and others and in the differentiation between fantasy and reality.
Alakeely, Adel G.; Alrashaed, Saba
Dome-shaped macula (DSM) was first described by Gaucher et al. as a convex protrusion of macula within a staphyloma in highly myopic eyes that cause visual impairment associated with serous foveal detachment (SFD). We describe a patient with persistent SFD in DSM documented by serial spectral domain optical coherence tomography for 7 years with stable vision. PMID:27994399
that i) reproductive hormone signaling is altered in HGSC, that ii) reproductive hormone receptor status (ERα/PR) may be an important indicator of...microenvironment ovulatory stresses, which may include altered reproductive hormone levels and the ovulatory inflammatory response. The...inflammatory response and altered reproductive hormone physiology. Keywords: BRCA, fallopian tube epithelium, high-grade serous carcinoma INTRODUCTION In 2013
Seidman, Jeffrey D
Recent data suggest that intraepithelial carcinoma of the fallopian tube [serous tubal intraepithelial carcinoma (STIC)] is the precursor of high-grade extrauterine serous carcinoma. A more specific location for the origin of this lesion is suggested by the recently described junction between the fallopian tubal epithelium and the peritoneum [tubal-peritoneal junction (TPJ)]. Fallopian tubes from 202 patients with advanced-stage high-grade extrauterine serous carcinoma or carcinosarcoma were evaluated histologically as were 124 prophylactic salpingo-oophorectomy specimens. These included 54 patients with BRCA or other high-risk mutation or a family history of BRCA mutation and 70 with a personal or family history of breast carcinoma. STIC was found in 81 of 202 patients with serous carcinoma (40.1%). STIC was present in 73 of 141 (52%) cases in which the fimbriae were present and in 62 of 100 (62%) cases in which the TPJ was present (P not significant). In comparison with these groups, when fimbriae and TPJ were absent, STIC was found in 8 of 61 (13%) cases (P<0.0001). None of the prophylactic specimens contained STIC. The mean size of STIC was 1.7 mm. In 32 cases (39.5%), the lesion was flat and in 49 (60.5%), papillary. The mean size of flat STICs was 0.8 mm as compared with 2.3 mm for papillary STICs (P=0.00005). STIC was identified in the same tissue fragment as the junction in 48 cases. The mean distance of STIC to the junction was 1.8 mm. In 11 cases, STIC was flanked by peritoneal mesothelium on one side and tubal epithelium on the opposite side. In 51 patients, the mean distance of invasive carcinoma from the TPJ was 1.8 mm. This distance was 1.9 mm when STIC was present (37 cases) in comparison with 1.5 mm when STIC was absent (14 cases) (P not significant). In 27 of 42 cases (64%), STIC was contiguous with invasive carcinoma. Lamina propria invasion was present in 71% of cases in which STIC was present as compared with 26% of cases in which STIC was
Nagendra, Deepak C; Burke, James; Maxwell, G Larry; Risinger, John I
Recently unbiased sequencing efforts identified PPP2R1A mutations in clear cell ovarian cancers (OCC). Similar mutations were also noted with high frequency in uterine serous carcinoma. Because the endometrium develops from the same developmental precursors we further examined the hypothesis that PPP2R1A mutations might also occur in diverse histologic subtypes of uterine cancer. We sequenced the PPP2R1A in 22 cell line models of uterine cancer and 10 primary cancers. We found no mutations in the cell lines originally derived from endometrioid (n = 13), undifferentiated (n = 3), clear cell (n = 1), and carcinosarcoma (n = 3) cancers. However, we found a CCC (Pro) to CGC (Arg) codon 179 mutation in the ACI-158 serous carcinoma cell line, a CCC (Pro) to CTC (Leu) in a primary serous carcinoma as well as a CGC (Arg) to CAC (His) codon 258 mutation in a poorly differentiated endometrioid cancer. We sequenced a large panel of endometrial malignancies (n = 181) and found 12 mutants. Importantly, we confirmed a high frequency of mutation in 8 of 25 (32%) serous carcinomas a subtype with well-recognized poor prognosis. Mutations were infrequent in endometrioid cancer and absent in clear cell and carcinosarcoma subtypes. The PPP2R1A mutation regions are conserved among species and known to interact with the regulatory subunits of the PP2A enzyme. PPP2R1A mutant endometrial cancers may represent good candidates for personalized drug therapies particularly for women with the lethal serous histologic variant of uterine cancer.
Seijo Ríos, Susana; Lariño Noia, José; Iglesias García, Julio; Lozano León, Antonio; Domínguez Muñoz, Juan Enrique
Primary cystic pancreatic neoplasms are rare tumors, with an approximate prevalence of 10% of cystic pancreatic lesions. Most of these lesions correspond to mucinous cystic neoplasm, serous cystoadenoma and intraductal papillary mucinous tumor (IPMT). IPMT is characterized by diffuse dilatation of the main pancreatic duct and/or side branches with inner defects related to mucin or tumor, or mucin extrusion from a patent ampulla. IPMT has a low potential for malignancy, with a low growth rate, a low rate of metastatic spread and postsurgical recurrence. Over the last few years, major advances have been made in the diagnostic and therapeutic management of this tumor.
Yalch, Matthew M; Levendosky, Alytia A
Borderline personality pathology can be conceptualized as one of many conditions within a broader spectrum of borderline personality organization (BPO). This spectrum is composed of several specific dimensions of psychological functioning (primitive psychological defenses, identity diffusion, and reality testing). Although several theories associate trauma with borderline pathology, betrayal trauma theory specifies that trauma with a high degree of betrayal has an especially pernicious influence on borderline pathology. In addition, betrayal trauma theorists propose that constructs related to each BPO dimension are influenced by traumatic betrayal, but this has not yet been tested within the context of borderline pathology specifically. In this article, we examine the relation between trauma with varying levels of betrayal and the specific dimensions of BPO using a Bayesian approach to multiple regression. Results indicated that trauma with a high degree of betrayal was associated with each dimension of BPO, that medium betrayal trauma was associated with problems in reality testing, and that low betrayal trauma was associated with primitive psychological defenses. These effects differed by gender. Limitations of the study and directions for future research are also discussed.
Sansone, Randy A; Farukhi, Shahzad; Wiederman, Michael W
Previous studies indicate that individuals with borderline personality disorder come from families marked by high levels of psychopathology as well as dysfunctional parenting styles-themes that tend to engender negative attitudes toward parents. However, we are not aware of any studies that have examined perceptions of parenting quality and borderline personality symptoms in a clinical but non-psychiatric population-the purpose of the present study. Using a cross-sectional self-report survey methodology in a sample of internal medicine outpatients, we examined participants' perceptions of the quality of parental caretaking using a one-item assessment, and examined borderline personality symptomatology using two measures. Ratings of the quality of parental care were statistically significantly inversely correlated with scores on both measures of borderline personality symptomatology. After controlling for the number of caretakers during childhood, the observed statistical relationships remained statistically significant. In this primary care sample, participants with borderline personality symptomatology perceived parents more negatively than those without such symptomatology.
Perry, J Christopher; Presniak, Michelle D; Olson, Trevor R
Numerous authors have theorized that defense mechanisms play a role in personality disorders. We reviewed theoretical writings and empirical studies about defenses in schizotypal, borderline, antisocial, and narcissistic personality disorders, developing hypotheses about these differential relationships. We then examined these hypotheses using dynamic interview data rated for defenses in a study of participants (n = 107) diagnosed with these four personality disorder types. Overall, the prevalence of immature defenses was substantial, and all four disorders fit within the broad borderline personality organization construct. Defenses predicted the most variance in borderline and the least variance in schizotypal personality disorder, suggesting that dynamic factors played the largest role in borderline and the least in schizotypal personality. Central to borderline personality were strong associations with major image-distorting defenses, primarily splitting of self and other's images, and the hysterical level defenses, dissociation and repression. Narcissistic and antisocial personality disorders shared minor image-distorting defenses, such as omnipotence or devaluation, while narcissistic also used splitting of self-images and antisocial used disavowal defenses like denial. Overall, differential relationships between specific defenses and personality disorder types were largely consistent with the literature, and consistent with the importance that the treatment literature ascribes to working with defenses.
So, Wai-Kin; Cheng, Jung-Chien; Fan, Qianlan; Wong, Alice S T; Huntsman, David G; Gilks, C Blake; Leung, Peter C K
Sprouty (SPRY) proteins are well-characterized factors that inhibit receptor tyrosine kinase signaling. Our Human Exonic Evidence-Based Oligonucleotide (HEEBO) microarray results showed that the mRNA levels of SPRY2, but not of SPRY1 or SPRY4, are down-regulated in high-grade serous ovarian carcinoma (HGSC) tissues and epithelial ovarian cancer (EOC) cell lines. Molecular inversion probe (MIP) copy number analysis showed the deletion of the SPRY2 locus in HGSC. Overexpression of SPRY2 reduced EGF-induced cell invasion by attenuating EGF-induced E-cadherin down-regulation. Moreover, a positive correlation between SPRY2 and E-cadherin protein levels was observed in HGSC tissues. This study reveals the loss of SPRY2 in HGSC and indicates an important tumor-suppressive role for SPRY2 in mediating the stimulatory effect of EGF on human EOC progression.
Background The aims of this study were to assess the prevalence of a comorbid Attention Deficit Hyperactivity Disorder (ADHD) diagnosis in Borderline Personality Disorder (BPD), and its impact on the clinical presentation of BPD in adolescents, and to determine which type of impulsivity specifically characterizes adolescents with BPD-ADHD. Methods ADHD diagnoses were sought in a sample of 85 DSM-IV BPD adolescents drawn from the EURNET BPD. Axis-I and -II disorders were determined with the K-SADS-PL and the SIDP-IV, respectively. Impulsivity was assessed with the BIS-11. Results 11% (N = 9) of BPD participants had a current ADHD diagnosis. BPD-ADHD adolescents showed higher prevalence of Disruptive disorders (Chi2 = 9.09, p = 0.01) and a non-significant trend for a higher prevalence of other cluster B personality disorders (Chi2 = 2.70, p = 0.08). Regression analyses revealed a significant association between Attentional/Cognitive impulsivity scores and ADHD (Wald Z = 6.69; p = 0.01; Exp(B) = 2.02, CI 95% 1.19-3.45). Conclusions Comorbid ADHD influences the clinical presentation of adolescents with BPD and is associated with higher rates of disruptive disorders, with a trend towards a greater likelihood of cluster B personality disorders and with higher levels of impulsivity, especially of the attentional/cognitive type. A subgroup of BPD patients may exhibit developmentally driven impairments of the inhibitory system persisting since childhood. Specific interventions should be recommended for this subsample of BPD adolescents. PMID:21961882
Alkema, Nicolette G; Wisman, G Bea A; van der Zee, Ate G J; van Vugt, Marcel A T M; de Jong, Steven
High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among all gynecological cancers. Patients are generally diagnosed in an advanced stage with the majority of cases displaying platinum resistant relapses. Recent genomic interrogation of large numbers of HGSOC patient samples 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
Endris, Volker; Stenzinger, Albrecht; Pfarr, Nicole; Penzel, Roland; Möbs, Markus; Lenze, Dido; Darb-Esfahani, Silvia; Hummel, Michael; Sabine-Merkelbach-Bruse; Jung, Andreas; Lehmann, Ulrich; Kreipe, Hans; Kirchner, Thomas; Büttner, Reinhard; Jochum, Wolfram; Höfler, Gerald; Dietel, Manfred; Weichert, Wilko; Schirmacher, Peter
With the approval of olaparib as monotherapy treatment in platinum-sensitive, relapsed high-grade serous ovarian cancer by the European Medical Agency (EMA), comprehensive genotyping of BRCA1 and BRCA2 in tumor tissue has become a mandatory pre-therapeutic test. This requires significant advances in routine tumor test methodologies due to the large size of both genes and the lack of mutational hot spots. Classical focused screening approaches, like Sanger sequencing, do not allow for a sensitive, rapid, and economic analysis of tumor tissue. Next-generation sequencing (NGS) approaches employing targeted panels for BRCA1/2 to interrogate formalin-fixed and paraffin-embedded tumor samples from either surgical resection or biopsy specimens can overcome these limitations. Although focused NGS methods have been implemented by few centers in routine molecular diagnostics for the analysis of some druggable oncogenic mutations, the reliable diagnostic testing of the entire coding regions of BRCA1 and BRCA2 was a new challenge requiring extensive technological improvement and quality management. Here, we describe the implementation and results of the first round robin trial for BRCA1/2 mutation testing in tumor tissue that was conducted in central Europe on May 2015, shortly after the approval and prior to the official release of olaparib. The high success rate of 81 % (21/26 test centers) demonstrates that BRCA1/2 multicenter mutation testing is well feasible in FFPE tumor tissue, extending to other tumor entities beyond ovarian cancer. The high number of test centers passing the trial demonstrates the success of the concerted efforts by German, Swiss, and Austrian pathology centers to ensure quality-controlled NGS-based testing and proves the potential of this technology in routine molecular pathology. On the basis of our results, we provide recommendations for predictive testing of tumor tissue for BRCA1/2 to clinical decision making in ovarian cancer patients.
Ruiz, Martín; Vairo, María Carolina
In the last decade, literature concerning gender and borderline personality disorder has aroused much controversy and little lightness. Recently, borderline personality disorder has been characterized as the "bad girl" of the psychiatric terms; this implies a bigger use of this diagnose in women and a biased gender in the identification of this disorder. The Diagnostic and Statistical Manual of Mental Disorders states that borderline personality disorder is mostly diagnosed in women (75%). The essential question to discuss is whether the larger prevalence in women is due to a biased sample or a biased diagnoses or it reflects a sociocultural and biological difference between men and women. The aim of this paper is to analyze some issues about the difference 3:1 women and men in this disorder.
Loranger, A W; Tulis, E H
The lifetime expectancy (morbid risk) of alcoholism was determined in the parents and siblings of 83 women with DSM-III borderline personality disorder and compared with that in the parents and siblings of 100 women with DSM-III schizophrenia and 100 women with DSM-III bipolar disorder. The relatives of the borderline probands had two to three times more alcoholism than the relatives of the bipolar and schizophrenic probands. The condition was most common in the fathers of the borderline probands, almost one third of whom were either alcoholics or heavy drinkers. When the three groups of probands were subdivided according to whether they, themselves, had occasionally abused alcohol, there were no longer any significant differences in alcoholism among their relatives.
Sansone, Lori A.
According to clinical experience, the Diagnostic and Statistical Manual of Mental Disorders, and authorities in the field, patients with borderline personality disorder tend to be hyper-reactive to environmental stimuli. In addition to the preceding clinical impressions and experiences, the majority of empirical studies in this area have concluded that patients with borderline personality disorder are indeed hyper-responsive to experimental environmental stimuli, whether the stimuli are negative, positive, or even neutral or ambiguous. While two empirical studies did not find hyper-responsiveness, both were undertaken in inpatients with borderline personality disorder, and the potential for emotional blunting from psychotropic medications may have been a potential confound. These findings have several clinical implications in both mental health and primary care settings. PMID:20941347
Šarenac, Olivera; Lozić, Maja; Drakulić, Srdja; Bajić, Dragana; Paton, Julian F; Murphy, David; Japundžić-Žigon, Nina
This study investigates blood pressure (BP) and heart rate (HR) short-term variability and spontaneous baroreflex functioning in adult borderline hypertensive rats and normotensive control animals kept on normal-salt diet. Arterial pulse pressure was recorded by radio telemetry. Systolic BP, diastolic BP and HR variabilities and baroreflex were assessed by spectral analysis and the sequence method, respectively. In all experimental conditions (baseline and stress), borderline hypertensive rats exhibited higher BP, increased baroreflex sensitivity and resetting, relative to control animals. Acute shaker stress (single exposure to 200 cycles min-1 shaking platform) increased BP in both strains, while chronic shaker stress (3-day exposure to shaking platform) increased systolic BP in borderline hypertensive rats alone. Low- and high-frequency HR variability increased only in control animals in response to acute and chronic shaker (single exposure to restrainer) stress. Acute restraint stress increased BP, HR, low- and high-frequency variability of BP and HR in both strains to a greater extent than acute shaker stress. Only normotensive rats exhibited a reduced ratio of low- to high-frequency HR variability, pointing to domination of vagal cardiac control. In borderline hypertensive rats, but not in control animals, chronic restraint stress (9-day exposure to restrainer) increased low- and high-frequency BP and HR variability and their ratio, indicating a shift towards sympathetic cardiovascular control. It is concluded that maintenance of BP in borderline hypertensive rats in basal conditions and during stress is associated with enhanced baroreflex sensitivity and resetting. Imbalance in sympathovagal control was evident only during exposure of borderline hypertensive rats to stressors. PMID:21421701
Šarenac, Olivera; Lozić, Maja; Drakulić, Srdja; Bajić, Dragana; Paton, Julian F; Murphy, David; Japundžić-Žigon, Nina
This study investigates blood pressure (BP) and heart rate (HR) short-term variability and spontaneous baroreflex functioning in adult borderline hypertensive rats and normotensive control animals kept on normal-salt diet. Arterial pulse pressure was recorded by radio telemetry. Systolic BP, diastolic BP and HR variabilities and baroreflex were assessed by spectral analysis and the sequence method, respectively. In all experimental conditions (baseline and stress), borderline hypertensive rats exhibited higher BP, increased baroreflex sensitivity and resetting, relative to control animals. Acute shaker stress (single exposure to 200 cycles min-1 shaking platform) increased BP in both strains, while chronic shaker stress (3-day exposure to shaking platform) increased systolic BP in borderline hypertensive rats alone. Low- and high-frequency HR variability increased only in control animals in response to acute and chronic shaker (single exposure to restrainer) stress. Acute restraint stress increased BP, HR, low- and high-frequency variability of BP and HR in both strains to a greater extent than acute shaker stress. Only normotensive rats exhibited a reduced ratio of low- to high-frequency HR variability, pointing to domination of vagal cardiac control. In borderline hypertensive rats, but not in control animals, chronic restraint stress (9-day exposure to restrainer) increased low- and high-frequency BP and HR variability and their ratio, indicating a shift towards sympathetic cardiovascular control. It is concluded that maintenance of BP in borderline hypertensive rats in basal conditions and during stress is associated with enhanced baroreflex sensitivity and resetting. Imbalance in sympathovagal control was evident only during exposure of borderline hypertensive rats to stressors.
Elzy, Meredith B.
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…
Drass, Jessica Masino
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…
Dubovsky, Amelia N; Kiefer, Meghan M
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.
the molecular circuits that control cell fate during develop - ment. Aberrant activation of this pathway contributes to tumorigenesis . The role of Notch...acute lymphoblastic leukemia (T-ALL). While Notch1 signaling is essential for normal development of T-cell progenitors (4), constitutive activation...expression causes mammary tumors in mice (10) and Notch1 -activating mutations contribute to the development of T-ALL. A recent study further shows that
of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res 60, 6281-6287. Wang, T.L., Maierhofer, C ., Speicher, M.R...tumor demonstrates an intense Rsf-1 immunoreactivity (4) and displays Rsf-1 gene amplification. ( c ) Rsf-1 protein expression correlates with the Rsf-1...Garnis C , Coe BP, Zhang L, et al.: Overexpression of LRP12, a gene con- tained within an 8q22 amplicon identified by high-resolution array CGH analy- sis
Moschos, Marilita M; Gouliopoulos, Nikolaos Stefanos
A 35-year-old water polo player was struck in his right eye during a water polo game. At presentation to our hospital, his visual acuity, intraocular pressure, fundus examination and neurological examination were normal. He received the appropriate treatment (no corticosteroids were applied), but 1 week later he reported blurred vision in his left eye. Visual acuity in the left eye was 6/10 Snellen chart, fluorescein angiography showed a focal retinal pigment epithelium leakage, while optical coherence tomography through the macula revealed mild neurosensory retinal detachment with an increase in retinal thickness. Two weeks later, the situation improved, and 1 month later no signs or symptoms of central serous chorioretinopathy were present. Currently, 9 months later, the situation remains unchanged. Post-traumatic stress was recognised as the key factor for development of central serous chorioretinopathy in our patient, since it was followed by excessive release of catecholamines and increased endogenous cortisol levels.
Wasel, Bassam Abu; Keough, Valerie; Huang, Weei-Yuan; Molinari, Michele
Malignant serous cystic neoplasms (SCN) of the pancreas are exceptionally rare, and only a few cases have been reported. As a result, SCN have been unanimously classified as benign tumours. Contrary to this conviction, in 1989, George et al published the very first case of a patient found to have a malignant pancreatic SCN. Up to the time of the submission of this paper, 27 cases of serous cystoadenocarcinomas have been published. In all the previously published cases of malignant SCN, the correct diagnosis was made postoperatively or at the time of autopsy. The authors present a case of a 68-year-old patient who was incidentally found to have a large liver mass on transthoracic echocardiogram ordered for suspected coronary artery insufficiency. Subsequent investigations revealed an additional large mass in the pancreas and percutaneous biopsies of both lesions revealed histological features consistent with malignant SCN metastasised to the left hepatic lobe.
Sato, Emi; Nakayama, Kentaro; Ishikawa, Masako; Nakamura, Kohei; Ishibashi, Tomoka; Kyo, Satoru
Although epithelial ovarian cancer commonly originates from the ovarian surface epithelium and/or ovarian inclusion cysts, it was recently proposed that high-grade serous ovarian cancer (HGSC) develops from the Fallopian tubes. In our department, we encountered a case of HGSC that contradicts the hypothesis of a tubal origin for HGSC. A 51-year-old postmenopausal woman had undergone hysterectomy, left oophorectomy and bilateral salpingectomy for uterine myoma. Three years later, the patient was diagnosed with stage IV ovarian cancer and underwent primary debulking surgery. The pathological examination revealed HGSC, although there was no evidence of serous tubal intraepithelial carcinoma or any other type of cancer in the previously resected left ovary and bilateral Fallopian tubes. Moreover, p53 overexpression was not detected in the right ovarian cancer specimen, while paired box gene 8, a marker of Fallopian tube epithelium, was highly expressed. Therefore, HGSC may develop from an inclusion cyst with metaplasia of from the ovarian surface epithelium.
Bassam, Abu-Wasel; Keough, Valerie; Huang, Weei-Yuan; Molinari, Michele
Malignant serous cystic neoplasms (SCN) of the pancreas are exceptionally rare, and only a few cases have been reported. As a result, SCN have been unanimously classified as benign tumours. Contrary to this conviction, in 1989, George et al published the very first case of a patient found to have a malignant pancreatic SCN. Up to the time of the submission of this paper, 27 cases of serous cystoadenocarcinomas have been published. In all the previously published cases of malignant SCN, the correct diagnosis was made postoperatively or at the time of autopsy. The authors present a case of a 68-year-old patient who was incidentally found to have a large liver mass on transthoracic echocardiogram ordered for suspected coronary artery insufficiency. Subsequent investigations revealed an additional large mass in the pancreas and percutaneous biopsies of both lesions revealed histological features consistent with malignant SCN metastasised to the left hepatic lobe. PMID:23370947
Guerrero-Martínez, Elly; Mateos-Vizcayno, Julio; Huerta-Hentschel, José Manuel
Brenner tumor is a rare tumor that represents approximately 1.5% of the tumors of ovary. It is defined as a tumor of transitional cells composed by urothelial cells arranged in solid or cystic groups absorbed in a fibrous stroma. It classifies in benign Brenner tumor (95%), borderline (3-4%) and malignant (1%). Let's sense beforehand the clinical case of a 46-year-old patient who underwent surgery having an adnexal mass of which the pathological intraoperative report brought a benign Brenner tumor.
This study investigated the cognitive strategies that underpin assessors' holistic judgments of a school-based vocationally-related portfolio performance. Using a portfolio already identified as containing borderline qualities, quantitative data were gathered about features that six assessors attended to as they holistically evaluated the…
Sansone, Randy A.; Gage, Mark D.; Wiederman, Michael W.
Clients (N=32) who were involuntarily hospitalized in a psychiatric facility were assessed for borderline personality disorder (BPD) using an interview and two self-report questionnaires. The majority (53.1%) met criteria for BPD on all three measures, 18.8% on two measures, and 18.8% on only one measure. Implications of these findings are…
Craig, Stephen E.; Fall, Kevin A.
Borderline-personality disorder in adolescence is thought to develop through environmental sources, and object-relations theory posits a developmental arrest in the separation-individuation phase of development. This article discusses gender and race considerations, issues related to counseling, general treatment strategies such as coping-skills…
Ruggero, Camilo J.; Zimmerman, Mark; Chelminski, Iwona; Young, Diane
Recent reports suggest bipolar disorder is not only under-diagnosed but may at times be over-diagnosed. Little is known about factors that increase the odds of such mistakes. The present work explores whether symptoms of borderline personality disorder increase the odds of a bipolar misdiagnosis. Psychiatric outpatients (N = 610) presenting for treatment were administered the Structured Clinical Interview for DSM-IV (SCID) and the Structured Interview for DSM-IV Personality for DSM-IV axis II disorders (SIDP-IV), as well as a questionnaire asking if they had ever been diagnosed with bipolar disorder by a mental health care professional. Eighty-two patients who reported having been previously diagnosed with bipolar disorder but who did not have it according to the SCID were compared to 528 patients who had never been diagnosed with bipolar disorder. Patients with borderline personality disorder had significantly greater odds of a previous bipolar misdiagnosis, but no specific borderline criteria was unique in predicting this outcome. Patients with borderline personality disorder, regardless of how they meet criteria, may be at increased risk of being misdiagnosed with bipolar disorder. PMID:19889426
Bradley, Rebekah; Zittel Conklin, Carolyn; Westen, Drew
Background: This study aimed to identify personality features characterizing adolescent girls and boys with borderline personality disorder (BPD) and to see whether meaningful patterns of heterogeneity exist among adolescents diagnosed with the disorder. Methods: Two hundred and ninety-four randomly selected doctoral-level clinicians described…
Bandelow, Borwin; Schmahl, Christian; Falkai, Peter; Wedekind, Dirk
The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids…
Brodsky, Beth S.; Groves, Shelly A.; Oquendo, Maria A.; Mann, J. John; Stanley, Barbara
Borderline personality disorder (BPD) is often characterized by multiple low lethality suicide attempts triggered by seemingly minor incidents, and less commonly by high lethality attempts that are attributed to impulsiveness or comorbid major depression. The relationships among life events, impulsiveness, and type of suicidal behavior has hardly…
An increasing prevalence of borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) diagnoses among women illustrates problems and limitations of the medical model system. Article explores overlapping relationship between BPD and PTSD and critiques how both are viewed within the mental health community. Previous research is…
Bornovalova, Marina A.; Hicks, Brian M.; Patrick, Christopher J.; Iacono, William G.; McGue, Matt
Although large epidemiological data sets can inform research on the etiology and development of borderline personality disorder (BPD), they rarely include BPD measures. In some cases, however, proxy measures can be constructed using instruments already in these data sets. In this study, the authors developed and validated a self-report measure of…
Weinberg, Anna; Klonsky, E. David; Hajcak, Greg
Recent research suggests that emotional dysfunction in psychiatric disorders can be reflected in autonomic abnormalities. The present study examines sympathetic and parasympathetic autonomic nervous system activity in individuals with Borderline Personality Disorder (BPD) before, during, and following a social stressor task. Data were obtained…
Green, Maurice R.
A recent revision of the proposed DSM III description of the borderline category is presented with reference to the work of Masterson and Grinker. The contributions of Roger Shapiro and his group to a psychoanalytic formulation of the developmental and familial dynamics are summarized with reference to genetic factors and the lack of validation,…
Bhebhe, Siziwe; Fuller, Mark
An inpatient service for women with borderline personality disorder adapted a therapeutic approach developed for use with outpatients. Mentalisation-based therapy helps clients to understand the meaning of their own behaviour and that of others, and allows positive risk-taking. It has led to real improvements in clients' progress towards more independent life.
Shulruf, Boaz; Poole, Phillippa; Jones, Philip; Wilkinson, Tim
A new probability-based standard setting technique, the Objective Borderline Method (OBM), was introduced recently. This was based on a mathematical model of how test scores relate to student ability. The present study refined the model and tested it using 2500 simulated data-sets. The OBM was feasible to use. On average, the OBM performed well…
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.
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
Rajkumar, Anirudh; Rajkumar, J. S.; Guru, Venkatesan
Adnexal torsion is responsible for 2.7% of all gynecological emergencies. Ectopic pregnancy is relatively common, occurring in 2% of all pregnancies. We report the second case of ruptured right tubal ectopic gestation with torsion of serous cystadenoma of left ovary. This was diagnosed after emergency laparoscopy done for acute abdomen. Right salpingectomy and left ovarian detorsion followed by cystectomy were done laparoscopically. PMID:27840755
membralin molecules were confined to high-grade serous carcinomas. This project, designed to test our proposed model of diverse pathways in the pathogenesis...carcinoma are characterized by distinctive molecular genetic alterations and specific gene expression. This project, designed to test our proposed...Z, Chan DW, Kurman RJ, Shih IM. Assessment of plasma DNA levels, allelic imbalance and CA 125 as diagnostic tests for cancer. J Natl Can Inst, 94
Longobardi, Giuseppe; Ciamberlini, Claudio; Guarnieri, Vittorio; Panzardi, G.; Donati, M. C.
ICG videoangiography has widely demonstrated its importance as an investigation method in several ocular pathologies. By means of an optoelectronic system developed by the authors, many cases of age related macular degeneration and central serous coroidopathy affecting patients of different ages have been investigated. The analysis of the eye fundus infrared-light images obtained allows the clinician to draw medical conclusions otherwise not obtainable with traditional visible-light techniques. A comprehensive survey and discussion of the most significant cases are presented.
69:4036- 42 Amplification of a chromatin remodeling gene , Rsf-1HBXAP, in ovarian carcinoma Ie-Ming Shih*†, Jim Jinn-Chyuan Sheu*, Antonio Santillan...displays Rsf-1 gene amplification. ( c ) Rsf-1 protein expression correlates with the Rsf-1 gene copy number in high-grade ovarian carcinomas. Tumors...et al.: Serial analysis of gene expres- sion. Science 1995, 270:484–487. 9 Wang TL, Maierhofer C , Speicher MR, et al.: Digital karyotyping. Proc Natl
Zimmerman, Mark; Martinez, Jennifer; Young, Diane; Chelminski, Iwona; Morgan, Theresa A; Dalrymple, Kristy
Both bipolar disorder and borderline personality disorder are associated with elevated rates of attempted suicide; however, no studies have examined whether there is an independent, additive risk for suicide attempts in patients diagnosed with both disorders. In the present study from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, 3,465 psychiatric outpatients were interviewed with semistructured interviews. Compared to the bipolar patients without borderline personality disorder, the patients diagnosed with both bipolar and borderline personality disorder were significantly more likely to have made a prior suicide attempt. The patients with borderline personality disorder and bipolar disorder were nonsignificantly more likely than the borderline patients without bipolar disorder to have made a prior suicide attempt. Bipolar disorder and borderline personality disorder were each associated with an increased rate of suicide attempts. The co-occurrence of these disorders conferred an additive risk, although the influence of borderline personality disorder was greater than that of bipolar disorder.
Sun, Zhuli; Shi, Fei; Xiang, Dehui; Chen, Haoyu; Chen, Xinjian
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.
Oliver Perez, M Reyes; Magriñá, Javier; García, Alvaro Tejerizo; Jiménez Lopez, Jesus Salvador
At present, there is no effective screening of ovarian cancer. Primary prevention may be the only strategy to decrease the mortality from ovarian cancer, not only in women at high risk but also at low risk. Several recent studies have identified the distal fimbriae end of the fallopian tubes as primary precursor of High-grade serous carcinoma. Serous tubal intraepithelial carcinomas and occult invasive serous carcinomas have been identified in 2-17% of the fallopian tubes of BRCA1/2 positive women undergoing risk-reducing salpingo-oophorectomy. Removal of the fallopian tubes with ovarian preservation has been suggested as a reasonable strategy that could reduce the risk of developing ovarian carcinoma in both low and high-risk women. It has been proposed after childbearing in women at high risk to be followed by bilateral oophorectomy at a later date. Bilateral salpingectomy is also suggested for low risk women, at the time of other benign gynaecologic surgery as a primary preventive strategy. Some studies have shown a risk reduction of ovarian cancer in women with bilateral prophylactic salpingectomy. Current research regarding bilateral salpingoophorectomy as primary prevention approach of ovarian cancer is reviewed here. In addition, the potential use of bilateral salpingectomy as prevention approach of ovarian cancer is discussed.
Leffers, N; Fehrmann, R S N; Gooden, M J M; Schulze, U R J; ten Hoor, K A; Hollema, H; Boezen, H M; Daemen, T; de Jong, S; Nijman, H W; van der Zee, A G J
Background: Tumour-infiltrating lymphocytes (TILs) are predictors of disease-specific survival (DSS) in ovarian cancer. It is largely unknown what factors contribute to lymphocyte recruitment. Our aim was to evaluate genes and pathways contributing to infiltration of cytotoxic T lymphocytes (CTLs) in advanced-stage serous ovarian cancer. Methods: For this study global gene expression was compared between low TIL (n=25) and high TIL tumours (n=24). The differences in gene expression were evaluated using parametric T-testing. Selectively enriched biological pathways were identified with gene set enrichment analysis. Prognostic influence was validated in 157 late-stage serous ovarian cancer patients. Using immunohistochemistry, association of selected genes from identified pathways with CTL was validated. Results: The presence of CTL was associated with 320 genes and 23 pathways (P<0.05). In addition, 54 genes and 8 pathways were also associated with DSS in our validation cohort. Immunohistochemical evaluation showed strong correlations between MHC class I and II membrane expression, parts of the antigen processing and presentation pathway, and CTL recruitment. Conclusion: Gene expression profiling and pathway analyses are valuable tools to obtain more understanding of tumour characteristics influencing lymphocyte recruitment in advanced-stage serous ovarian cancer. Identified genes and pathways need to be further investigated for suitability as therapeutic targets. PMID:20664601
Stoffers, Jutta; Völlm, Birgit A; Rücker, Gerta; Timmer, Antje; Huband, Nick; Lieb, Klaus
Background Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders (“off-label use”), mostly targeting affective or impulsive symptom clusters. Objectives To assess the effects of drug treatment in BPD patients. Search methods We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field. Selection criteria Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects. Data collection and analysis Two authors selected trials, assessed quality and extracted data, independently. Main results Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants. The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed. Adverse event data were scarce
Lecointe, P; Bernoussi, A; Masson, J; Schauder, S
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.
Albu, Dinu Florin; Albu, Cristina CrenguŢa; Văduva, Constantin Cristian; Niculescu, Mihaela; Edu, Antoine
Ovarian epithelial tumors are the most common ovarian neoplasms, standing for more than half of all ovarian tumors. Borderline ovarian tumors represent a distinct group recognized by the World Health Organization (WHO), histologically distinct low ovarian carcinomas. They are tumors with low grade of malignancy with good progress and prognosis. The authors present a case of an ovarian tumor with diagnosis problems. It was the case of a 38-year-old patient with no genital pathological history, presenting hypogastric pain, dysmenorrhea, abdominal distension. The imaging performed examinations suggested an ovarian tumor with potential malignancy. The symptoms were nonspecific and the treatment was surgical. The piece was processed by paraffin inclusion and microscopically examined. Although the imaging examinations may be suggestive for potentially malignant lesions, the histopathological relation with the immunohistochemical one is the one that establishes the diagnosis. Following these examinations, there was established an ovarian borderline tumor. This is included in the lesions with low malignancy, the further evolution of the patient being a good one. The purpose of this presentation was the warning of the importance of histopathological examination linked with the immunohistochemical one, although the imaging may present lesions with malignancy criteria. Also, it was performed a literature review of borderline tumors in young women in terms of diagnosis and therapeutic conduct.
De Moor, Marleen H. M.; Distel, Marijn A.; Trull, Timothy J.; Boomsma, Dorret I.
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,…
Ip, Andrew; Cardona, Kenneth; Alese, Olatunji B.; Maithel, Shishir K.; Kooby, David; Landry, Jerome; El-Rayes, Bassel F.
Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) account for approximately 30% of newly diagnosed cases of PC. The objective of BRPC therapy is to downstage the tumor to allow resection; the objective of LAPC therapy is to control disease and improve survival. There is no consensus on the definitions of BRPC and LAPC, which leads to major limitations in designing clinical trials and evaluating their results. A multimodality approach is always needed to ensure proper utilization and timing of chemotherapy, radiation, and surgery in the management of this disease. Combination chemotherapy regimens (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, and gemcitabine [FOLFIRINOX] and gemcitabine/nab-paclitaxel) have improved overall survival in metastatic disease. The role of combination chemotherapy regimens in BRPC and LAPC is an area of active investigation. There is no consensus on the dose, modality, and role of radiation therapy in the treatment of BRPC and LAPC. This article reviews the literature and highlights the areas of controversy regarding management of BRPC and LAPC. Implications for Practice: Pancreatic cancer is one of the worst cancers with regard to survival, even at early stages of the disease. This review evaluates all the evidence for the stages in which the cancer is not primarily resectable with surgery, known as borderline resectable or locally advanced unresectable. Recently, advancements in radiation techniques and use of better combination chemotherapies have improved survival and tolerance. There is no consensus on description of stages or treatment sequences (chemotherapy, chemoradiation, radiation), nor on the best chemotherapy regimen. The evidence behind the treatment paradigm for these stages of pancreatic cancer is summarized. PMID:26834159
Gerull, Friederike; Meares, Russell; Stevenson, Janine; Korner, Anthony; Newman, Louise
The harmful effect of borderline patients on their families is an important but relatively neglected aspect of outcome studies. This study concerns changes in perceived quality of relationships with partners and children of 24 patients suffering Borderline Personality Disorder (BPD) after 12 months of treatment with the Conversational Model (CM). They were compared to 21 parents with BPD receiving "Treatment as Usual" (TAU) from their referring clinicians for the same period. Both groups developed naturalistically giving the study a quasi-experimental design. The Social Adjustment Scale (SAS-SR) was administered on intake and again after 12 months. The subscales dealing with relationships with children, with partners and with the family unit were scored and compared between groups. It was found that the perceived relationships with children and partners improved significantly for the CM group but not for the TAU group.
Pesic, Danilo; Peljto, Amir; Lukic, Biljana; Milovanovic, Maja; Svetozarevic, Snezana; Lecic Tosevski, Dusica
An increasing number of findings confirm the significance of cerebellum in affecting regulation and early learning. Most consistent findings refer to association of congenital vermis anomalies with deficits in nonmotor functions of cerebellum. In this paper we presented a young woman who was treated since sixteen years of age for polysubstance abuse, affective instability, and self-harming who was later diagnosed with borderline personality disorder. Since the neurological and neuropsychological reports pointed to signs of cerebellar dysfunction and dysexecutive syndrome, we performed magnetic resonance imaging of brain which demonstrated partially developed vermis and rhombencephalosynapsis. These findings match the description of cerebellar cognitive affective syndrome and show an overlap with clinical manifestations of borderline personality disorder.
Levy, Kenneth N; Beeney, Joseph E; Temes, Christina M
This article reviews the recent literature on attachment and attachment-related constructs in borderline personality disorder, with attention given to how recent findings in this area may inform understanding of the mechanisms underlying the etiology, maintenance, and treatment of the disorder. Most findings on this topic have stemmed from three major areas of research, each of which is reviewed in this article: 1) developmental psychopathology studies; 2) experimental psychopathology studies, particularly those using a neuroscience approach; and 3) treatment studies that have examined variables relevant to attachment. Overall, these findings suggest that attachment and related constructs may factor greatly into the underlying psychopathology of borderline personality disorder and may significantly impact the process and outcome of psychotherapy for the disorder. These findings are discussed as they relate to existing theories and ongoing debates in the field, and the implications for future research and clinical practice are highlighted.
Bhar, Sunil S; Brown, Gregory K; Beck, Aaron T
This study examined the factor structure of the Borderline Personality Disorder subscale of the Personality Beliefs Questionnaire (PBQ-BPD; Butler, Brown, Beck, & Grisham, 2002), and the relationships between the emergent factors and psychopathology. The sample comprised 184 patients diagnosed with borderline personality disorder (BPD). Exploratory factor analysis yielded three factors relating respectively to dependency, distrust, and the belief that one should act preemptively to avoid threat. Although the three factors were significantly associated with depression, only dependency and distrust significantly correlated with hopelessness. Distrust was the sole factor that correlated significantly with suicide ideation. These findings support the dimensional structure of the PBQ-BPD. Given its multidimensional structure, the scale can be used as a measure of belief profiles associated with BPD and as an aid to conceptualizing beliefs underlying a range of psychopathology associated with patients with BPD.
Jopling, Ellen N; Khalid-Khan, Sarosh; Chandrakumar, Shivani F; Segal, Shira C
With an estimated lifetime prevalence as high as 5.9% in the general population, borderline personality disorder (BPD) is a psychiatric disorder characterized by marked impulsivity as well as difficulties in interpersonal relationships, self-image, and affects. The burden on the health care system is immense with BPD patients accounting for 10%-20% of the patients in mental health outpatient facilities and 15%-40% in mental health inpatient facilities. Further, while 75%-80% of BPD patients attempt to commit suicide, 10% succeed; this mortality rate exceeds even that of anorexia nervosa which, with a weighted mortality rate of 5.1%, has often been considered to have the highest mortality rate of any mental disorder. In order to provide treatment and to implement preventative measures, a risk profile as well as clinical features must be identified within the adolescent population. This is presently crucial, as the current criteria for BPD are not developmentally focused, and as a result, criteria initially developed for the adult population are being applied in diagnoses of adolescents. A population of adolescents (n=80) between 16 and 19 years of age meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria either for BPD traits (n=46) or for BPD (n=36) were included in a retrospective chart review; a control group consisting of n=30 mood and anxiety control subjects were included to allow for further comparisons. Complex significant differences were discovered between the three groups in the following areas: history of sexual abuse, suicidal ideation, internalizing/externalizing symptoms, interpersonal difficulties, impulsivity, pre-perinatal stress, bullying, substance abuse, anxiety disorders, disruptive disorders, and finally, learning disorders.
Kyratsous, Michalis; Sanati, Abdi
Miranda Fricker's concept of epistemic injustice has been quite a novel idea in epistemology. It brings something new to the fields of epistemology and ethics. Fricker draws our attention to a distinctive species of injustice, the epistemic injustice, in which someone is specifically wronged in his capacity as a knower. There has been a significant amount of work done in epistemic injustice, both in race and gender studies. The application of the concept in the context of mental health is less explored. Here, we aim to apply the concept of epistemic injustice in attributing responsibility to patients with borderline personality disorder. Attributing responsibility involves holding someone accountable for his presumed wrongdoings, making judgments on whether the agent has control on his action, on whether is aware of its consequences. It is generally agreed that in order to be morally responsible for an action the person should be worthy of praise or blame for it. Following Aristotle, we focus on epistemic condition in attribution of responsibility. We will discuss the role of epistemic injustice in assessment of epistemic condition of responsibility. We will show that we can misinterpret the agent's intentions because of the presence of systematic prejudices. We will focus on patients suffering from borderline personality disorder. We provide a case vignette to show a tendency in the professionals in holding these patients responsible for their action when it can be argued otherwise. We argue that prejudice against the patient with borderline personality disorder where the person is seen as manipulative plays a significant role in the process of epistemic injustice. The suggested manipulative nature of patients with borderline personality disorder leads to professionals to ascribe agency and knowledge where it is not due.
Ross, Colin A; Ferrell, Lynn; Schroeder, Elizabeth
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.
Carmona, Euridice; Portelance, Lise; Arcand, Suzanna L.; Rahimi, Kurosh; Tonin, Patricia N.; Provencher, Diane; Mes-Masson, Anne-Marie
Few cell line models of epithelial ovarian cancer (EOC) have been developed for the high-grade serous (HGS) subtype, which is the most common and lethal form of gynaecological cancer. Here we describe the establishment of six new EOC cell lines spontaneously derived from HGS tumors (TOV2978G, TOV3041G and TOV3291G) or ascites (OV866(2), OV4453 and OV4485). Exome sequencing revealed somatic TP53 mutations in five of the cell lines. One cell line has a novel BRCA1 splice-site mutation, and another, a recurrent BRCA2 nonsense mutation, both of germline origin. The novel BRCA1 mutation induced abnormal splicing, mRNA instability, resulting in the absence of BRCA1 protein. None of the cell lines harbor mutations in KRAS or BRAF, which are characteristic of other EOC subtypes. SNP arrays showed that all of the cell lines exhibited structural chromosomal abnormalities, copy number alterations and regions of loss of heterozygosity, consistent with those described for HGS. Four cell lines were able to produce 3D-spheroids, two exhibited anchorage-independent growth, and three (including the BRCA1 and BRCA2 mutated cell lines) formed tumors in SCID mice. These novel HGS EOC cell lines and their detailed characterization provide new research tools for investigating the most common and lethal form of EOC. PMID:26622941
Davis, Sally J; Sheppard, Karen E; Anglesio, Michael S; George, Joshy; Traficante, Nadia; Fereday, Sian; Intermaggio, Maria P; Menon, Usha; Gentry-Maharaj, Aleksandra; Lubinski, Jan; Gronwald, Jacek; Pearce, Celeste Leigh; Pike, Malcolm C; Wu, Anna; Kommoss, Stefan; Pfisterer, Jacobus; du Bois, Andreas; Hilpert, Felix; Ramus, Susan J; Bowtell, David D L; Huntsman, David G; Pearson, Richard B; Simpson, Kaylene J; Campbell, Ian G; Gorringe, Kylie L
Identification of genomic alterations defining ovarian carcinoma subtypes may aid the stratification of patients to receive targeted therapies. We characterized high-grade serous ovarian carcinoma (HGSC) for the association of amplified and overexpressed genes with clinical outcome using gene expression data from 499 HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2, ZFP36, and URI. The Australian Ovarian Cancer Study and The Cancer Genome Atlas datasets were also used to assess the correlation between gene expression, patient survival, and tumor classification. In a multivariate analysis, high GAB2 expression was associated with improved overall and progression-free survival (P = 0.03 and 0.02), whereas high BMP8B and ATP13A4 were associated with improved progression-free survival (P = 0.004 and P = 0.02). GAB2 overexpression and copy number gain were enriched in the AOCS C4 subgroup. High GAB2 expression correlated with enhanced sensitivity in vitro to the dual PI3K/mTOR inhibitor PF-04691502 and could be used as a genomic marker for identifying patients who will respond to treatments inhibiting PI3K signaling.
Ghamande, Sharad A.; Bush, Stephen; Ferris, Daron; Zhi, Wenbo; He, Mingfang; Wang, Meiyao; Wang, Xiaoxiao; Miller, Eric; Hopkins, Diane; Macfee, Michael; Guan, Ruili; Tang, Jinhai; She, Jin-Xiong
Background Biomarkers play critical roles in early detection, diagnosis and monitoring of therapeutic outcome and recurrence of cancer. Previous biomarker research on ovarian cancer (OC) has mostly focused on the discovery and validation of diagnostic biomarkers. The primary purpose of this study is to identify serum biomarkers for prognosis and therapeutic outcomes of ovarian cancer. Experimental Design Forty serum proteins were analyzed in 70 serum samples from healthy controls (HC) and 101 serum samples from serous OC patients at three different disease phases: post diagnosis (PD), remission (RM) and recurrence (RC). The utility of serum proteins as OC biomarkers was evaluated using a variety of statistical methods including survival analysis. Results Ten serum proteins (PDGF-AB/BB, PDGF-AA, CRP, sFas, CA125, SAA, sTNFRII, sIL-6R, IGFBP6 and MDC) have individually good area-under-the-curve (AUC) values (AUC = 0.69–0.86) and more than 10 three-marker combinations have excellent AUC values (0.91–0.93) in distinguishing active cancer samples (PD & RC) from HC. The mean serum protein levels for RM samples are usually intermediate between HC and OC patients with active cancer (PD & RC). Most importantly, five proteins (sICAM1, RANTES, sgp130, sTNFR-II and sVCAM1) measured at remission can classify, individually and in combination, serous OC patients into two subsets with significantly different overall survival (best HR = 17, p<10−3). Conclusion We identified five serum proteins which, when measured at remission, can accurately predict the overall survival of serous OC patients, suggesting that they may be useful for monitoring the therapeutic outcomes for ovarian cancer. PMID:24244307
McCluggage, W Glenn; McBride, Hilary A
Uterine serous carcinoma (USC) is an aggressive variant of Type 2 endometrial carcinoma, which in most cases exhibits, at least focally, a papillary architecture. Occasionally, especially in small biopsy specimens, it may be difficult to distinguish between USC and a variety of metaplastic or reactive processes. In particular, papillary syncytial metaplasia (PSM), as a result of endometrial breakdown, may be confused with USC or its precursor serous endometrial intraepithelial carcinoma. In such cases, immunohistochemistry is often undertaken, the panel of markers usually including estrogen receptor (ER), p53, p16, and MIB1. The expected immunoprofile of USC is ER negative, p53 and p16 positive, and a high MIB1 proliferation index, although studies have shown that significant numbers of cases deviate from this immunophenotype. With regard to the aforementioned markers, PSM has not been studied extensively, but intuitively, the expected immunophenotype would be ER positive, p53 and p16 negative, and a low MIB1 proliferation index. After 2 index cases in which breaking down menstrual endometrium with florid PSM was misdiagnosed on an endometrial biopsy as USC or suspected USC, in part due to the observed immunophenotype, we studied the expression of ER, p53, p16, MIB1, and HMGA2 (a recently described useful marker of USC) in 10 further cases of PSM associated with endometrial breakdown. We illustrate that compared with a nonbreaking down endometrium, PSM is characterized by a decreased expression of ER and an increased expression of p53 (although still wild-type staining) and p16, the latter marker typically being diffusely positive. HMGA2 is negative, and there is a low MIB1 proliferation index. In cases of PSM, which are morphologically problematic, the immunophenotype may further heighten the suspicion of serous malignancy and potentially result in a misdiagnosis.
Delfino, Giovanni; Giachi, Filippo; Malentacchi, Cecilia; Nosi, Daniele
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.
Goleva, O V; Kharit, S M; Cherniaeva, T V; Aksenov, O A; Davidkin, I; Kolyshkin, V M
The morbidity structure was analyzed in children vaccinated against epidemic parotitis in 1993-2002. Eight children (4 with serous meningitis and 4 with lesions of the salivary glands) underwent virologic and immunologic examinations. The molecular typing of the SH-gene fragment of the parotitis virus showed the process in 7 cases to be provoked by the vaccination strain. Presumedly, progressing vaccine-associated meningitis inhibits antibody formation. The total incidence of vaccine-associated meningitis was shown, according to Saint Petersburg data, to be not high, which testifies to a low reactogenicity of the Russian vaccine strain.
He, Hong-Lin; Lee, Ying-En; Chang, Chi-Chang
Hilus cell heterotopia is the presence of normal hilus cells in an abnormal site. It is rare and there are only a few case reports or case series. It has been reported in the fimbrial stroma of the fallopian tube, paratubal cyst wall and beneath ovarian capsule. Most cases are more than 40 years of age, and some of them are associated with other underlying pelvic pathology. Hilus cells are ovarian counterpart of testicular Leydig cells, carrying similar morphological and immunohistochemical findings. In this report, we described a patient having bilateral serous cystadenomas with an incidental finding of hilus cells in the fallopian tube. PMID:24696744
Purpose To report the anatomic and functional outcome of intravitreal dobesilate to treat recurrent central serous chorioretinopathy (CSC). Methods This is an interventional case report in which dobesilate was intravitreally injected in a case of recurrent CSC. Main measures included fundoscopy, Snellen visual acuity (VA) testing, fluorescein angiography and optical coherence tomography (OCT). Results We present anatomical and functional evidences, obtained as early as eleven days after the treatment, of the efficacy of intravitreal dobesilate, in the treatment of chronic CSC condition. The effect after intravitreal dobesilate injection for CSC might be related to the normalization of retinal architecture. Conclusions Intravitreal dobesilate may be an effective treatment option for recurrent CSC. PMID:22788836
Chen, Ming; Jin, Ying; Bi, Yalan; Yin, Jie; Wang, Yongxue; Pan, Lingya
Ovarian low-grade serous carcinoma (LGSC) and high-grade serous carcinoma have distinct molecular profiles, clinical behaviors, and treatment responses. The survival advantage for patients with low-grade carcinoma compared with patients with high-grade histology remains controversial. We retrospectively reviewed the medical charts of 381 patients with ovarian serous carcinoma at Peking Union Medical College Hospital from 2007 to 2010. Patients were classified into two groups according to MD Anderson two-tier system: 35 (9.2%) cases with LGSC and 346 with high-grade serous carcinoma. Patients with low-grade serous ovarian cancer had a significantly younger age at diagnosis (46 versus 56 years, P=0.046), and their median progression-free survival (PFS) and overall survival values were 35.0 and 54.0 months, respectively. A multivariate analysis showed that, for serous ovarian cancer, the histological grade was a significant prognostic factor for PFS but not for overall survival (P=0.022 and P=0.0566, respectively). When stratified by the existence of a residual disease, patients with low-grade disease who underwent cytoreductive surgery without macroscopic residual disease (>1 cm) had a significantly improved median PFS time (36.0 months) compared with that of patients with high-grade carcinoma who received optimal cytoreductive surgery (16.0 months, P=0.017). Conversely, patients with low-grade and high-grade carcinoma who were left with macroscopic residue (>1 cm) experienced a similarly shorter median PFS (10.0 and 13.0 months, respectively, P=0.871). The International Federation of Gynecology and Obstetrics stage and residual disease were significant prognostic factors of low-grade carcinoma, while positive ascites was associated with a worse PFS value. Our data showed that LGSC is a different entity from high-grade carcinoma and that LGSC was associated with improved PFS after optimal cytoreductive surgery but not suboptimal operation.
Zimmerman, Mark; Gazarian, Doug
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.
Lheureux, Stéphanie; N'Diaye, Monique; Blanc-Fournier, Cécile; Dugué, Audrey Emmanuelle; Clarisse, Bénédicte; Dutoit, Soizic; Giffard, Florence; Abeilard, Edwige; Briand, Mélanie; Labiche, Alexandre; Grellard, Jean-Michel; Crouet, Hubert; Martin, Sandrine; Joly, Florence; Poulain, Laurent
Ovarian cancers are addicted to Bcl-xL and Mcl-1, antiapoptotic members of the Bcl-2 family. Bcl-xL can be inhibited by the BH3-mimetic ABT-737. In vitro, ABT-737 can induce apoptosis of cancer cells, and its activity is potentiated by Mcl-1 inactivation. Herein, we assessed the sensitivity of human ovarian tumor nodes to ABT-737 when combined with carboplatin, which can indirectly inhibit Mcl-1. Fresh samples from 25 patients with high-grade serous ovarian cancer (HGSOC) who were chemo-naïve and had undergone surgery were prospectively exposed ex vivo to ABT-737 ± carboplatin. The treatment effect was studied on sliced tumor nodes by assessment of cleaved-caspase 3 immunostaining. We also studied the association between baseline Bcl-2 family protein expression (via immunohistochemistry) and the response of nodes to treatment. ABT-737 induced apoptosis as a single agent but its efficacy was not improved by the addition of carboplatin. Bim was frequently expressed (20/25) and its absence or low expression was associated with the absence of response to ABT-737, p value = 0.019 by Fisher's test and sensitivity = 93%, (95% confidence interval, 66-100). Moreover, we observed that in tumors in which Bim was expressed, a low expression of phospho-Erk1/2 or Mcl-1 improved the proportion of responses. This pilot study showed that ABT-737 has promise as monotherapy for HGSOC in a specific subgroup of tumors. Bim, Mcl-1, and phospho-Erk1/2 appeared to be relevant biomarkers that could be used for the selection of patients in the design of clinical trials using Navitoclax (an orally available compound related to ABT-737).
Scoazec, J Y; Vullierme, M P; Barthet, M; Gonzalez, J M; Sauvanet, A
Incidentally discovered cystic tumors of the pancreas (CTP) are an increasingly frequent entity. It is essential to differentiate lesions whose malignant potential is either nil or negligible (pseudocyst, serous cystadenoma, simple cysts) from lesions with intermediate malignant potential (intraductal papillary mucinous tumor of the pancreas [IPMN] involving the secondary ducts, cystic endocrine tumor) or those with high malignant potential (mucinous cystadenoma, solid pseudopapillary tumors and IPMN involving the main pancreatic duct). The approach to defining malignant potential is based on diagnostic CT scan, magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS), often complemented by EUS-guided cyst puncture for biochemical and cytological analysis of cyst fluid. Surgery for diagnostic purposes should be avoided because of its significant morbidity. For pseudocysts, simple cysts and serous cystadenomas, abstention is the general rule. Resection, preserving as much pancreatic parenchyma as possible, is the rule for IPMN involving the main pancreatic duct, mucinous cystadenomas, solid and pseudopapillary tumors, and cystic endocrine tumors. Resection is rarely indicated at the outset for IPMN involving secondary pancreatic ducts; morphologic observation is the general rule and preventive excision may be indicated secondarily. Good collaboration between surgeons, radiologists and endosonographists is necessary for optimal management of CTP.
Zhang, Zhe; Huang, Ke; Gu, Chenglei; Zhao, Luyang; Wang, Nan; Wang, Xiaolei; Zhao, Dongsheng; Zhang, Chenggang; Lu, Yiming; Meng, Yuanguang
Classification of ovarian cancer by morphologic features has a limited effect on serous ovarian cancer (SOC) treatment and prognosis. Here, we proposed a new system for SOC subtyping based on the molecular categories from the Cancer Genome Atlas project. We analyzed the DNA methylation, protein, microRNA, and gene expression of 1203 samples from 599 serous ovarian cancer patients. These samples were divided into nine subtypes based on RNA-seq data, and each subtype was found to be associated with the activation and/or suppression of the following four biological processes: immunoactivity, hormone metabolic, mesenchymal development and the MAPK signaling pathway. We also identified four DNA methylation, two protein expression, six microRNA sequencing and four pathway subtypes. By integrating the subtyping results across different omics platforms, we found that most RNA-seq subtypes overlapped with one or two subtypes from other omics data. Our study sheds light on the molecular mechanisms of SOC and provides a new perspective for the more accurate stratification of its subtypes. PMID:27184229
Hurvitz, Andrew P; Hodapp, Kristin L; Jadgchew, Jason; Solomon, Daniel J; Stolldorf, Hunter S; Provencher, Matthew T
Complications from shoulder corticosteroid injections are uncommon. This article presents a case of altered color perception and visual disturbances in a 29-year-old male active duty Navy SEAL following an intra-articular glenohumeral corticosteroid injection, previously unreported in the orthopedic literature. The corticosteroid injection was administered for the treatment of right-shoulder stiffness occurring approximately 3 months following an arthroscopic superior labrum anterior-posterior (SLAP) repair and subacromial decompression of the ipsilateral shoulder. The patient experienced immediate relief after the injection. Seven days later, however, he began to notice visual disturbances with color and image distortion of his right eye. He also developed a papular, nonpruritic rash on his upper trunk that eventually extended down his legs. He was diagnosed by an ophthalmologist as having central serous chorioretinopathy, a condition in which serous fluid accumulates in the subretinal space of the eye, causing detachment of the retina from the underlying retinal pigment epithelium. The reaction spontaneously resolved within approximately 10 to 12 weeks without treatment. Although intra-articular corticosteroid injections are frequently performed with a low rate of complication, clinicians should be familiar with this rare yet distressing condition. Furthermore, patients with increased production of endogenous corticosteroids (eg, those with Cushing's syndrome, type A personality, hypertension, or obstructive sleep apnea) should be warned of the potential of chorioretinopathy after an intra-articular corticosteroid injection.
Venter, Alina Cristiana; Roşca, Elena; Daina, Lucia Georgeta; Muţiu, Gabriela; Pirte, Adriana Nicoleta; Rahotă, Daniela
Phyllodes tumors are rare breast tumors, accounting for less than 1% of all primary tumors of the breast. Histologically, phyllodes tumors can be divided into benign (60%), borderline (20%) and malignant (20%). The mammography examination was performed by means of a digital mammography system Giotto 3D Images; the ultrasound examination was performed through a GE Logiq P6 device and histological confirmation was possible after surgery or following the histological biopsy. We grouped the nine patients who presented clinically palpable nodules into two groups, namely: the six patients presenting histological benign results into Group I, and Group II where we included those with borderline and malignant histological results. Mammography performed in 77.7% revealed a well-circumscribed round or oval opacity or with contour lobules. Ultrasound examination was performed in all patients. Mammography and ultrasound have limitation in differentiating between benign lesion and phyllodes tumor. In the nine analyzed cases, mammographic and ultrasound examinations did not allow the differentiation into the three groups of phyllodes tumor. Histopathological examination is considered the golden standard for their diagnosis. Correlations between mammographic and microscopic aspects were inconclusive for determining the degree of differentiation, ultrasound changes could be correlated with the histopathological aspects.
Korzekwa, Marilyn I; Dell, Paul F; Pain, Clare
Dissociation occurs in about two thirds of people with borderline personality disorder (BPD) but is still not well understood by clinicians. In the past decade, however, research has used new measures of dissociation that provide some of the detail that clinicians need to understand and treat the dissociative symptoms of patients with BPD. In particular, this review examines BPD's comorbidity with the dissociative disorders, the neurobiology of dissociation in BPD, the role of trauma and disorganized attachment in the etiology of dissociation in BPD, and the clinical assessment and treatment of dissociation in BPD.
Whitmont, E C
Homeopathy is presented as a modality of potential usefulness in the treatment of borderline patients refractory to psychoanalytic work. In these instances a minimally adequate centre of consciousness did not solidify from the identity with the psychoid stratum. In the view of Alchemy, this failure of the mind to separate from the unio naturalis or massa confusa could be remedied by a medicamentum spagyricum, an archtypal essence acting according to the simile principle, which was to be extracted from various substances. Homeopathy is described as a modern, clinically effective modification of the alchemistic method. Two cases example are given for illustration.
A borderline personality disorder is associated with highly impulsive acts that cannot be controlled by cognitive inhibition. In a psychopathic/antisocial personality disorder emotional inhibition of hostile acts is lacking. The patient has a high proclivity for risk-seeking, and is incapable of responding appropriately to punishment. In both disorders, the result is (auto)aggressive behavior. The family doctor must refer such patients to a specialist, when there is an acute danger of self-harm or when a grave functional limitation in the areas of work or interpersonal relationship has persisted over a long period of time.
Allen, D M; Farmer, R G
Current, ongoing interactions between adults exhibiting borderline personality disorder (BPD) traits and their families of origin may influence and maintain self-destructive behavior. Family interactions in such patients are often characterized by coexisting extremes of overinvolvement and underinvolvement by parental figures. Such parental behavior may trigger preexisting role relationship schemata in vulnerable individuals. Negative family reactions to new behavior patterns may make change difficult. A model for how present-day interpersonal patterns lead to self-destructive behavior, based on clinical observations, is proposed and case examples are presented.
Brown, Linda G; Denning, Krista L; Pacioles, Toni
Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified
Shenouda, Mina; Brown, Linda G; Denning, Krista L; Pacioles, Toni
Oncocytic neoplasms are tumors composed predominantly or exclusively of oncocytes (large polygonal cells with granular eosinophilic cytoplasm due to abnormal mitochondrial accumulation). These tumors are frequently reported in the thyroid, kidneys, and salivary glands. However, they are distinctly rare in the adrenal cortex. Oncocytic adrenocortical neoplasms (OAN) are classified regarding their biological behavior by their histological features according to the Lin-Weiss-Bisceglia system (LWB). Here, we report a case of OAN of borderline or uncertain malignant potential (BMP) with subsequently identified papillary thyroid carcinoma (PTC). A 34-year-old female with a nine-month history of fatigue presented with chest pain. A right adrenal mass was incidentally found while ruling out pulmonary embolism. A CT-guided adrenal biopsy, although not routinely indicated, was performed and interpreted as malignant with no definitive origin. Hormonal workup was unremarkable. PET-scan showed hypermetabolic adrenal mass with peak standardized uptake value of 15, suspicious of malignancy. A hypermetabolic thyroid nodule was also identified, but there was no evidence of metastatic disease. The patient underwent adrenalectomy, and the initial pathology report was interpreted as atypical pink cell tumor. A second pathology report from another laboratory favored OAN based on the morphology and immunohistochemical staining. While the histologic criteria of malignancy were not met, the large tumor size makes it compatible with BMP according to LWB criteria. A follow-up thyroid ultrasound revealed a complex thyroid nodule. A total thyroidectomy was performed, and pathology was consistent with PTC. Of interest, PTC frequently shows an increase in mitochondrial content, which is characteristic of oncocytic tumors. This case illustrates that OAN, although rare, should be considered in the differential diagnosis of adrenal masses. When OAN is identified, it should be classified
Sharma, Binali; Dunlop, Boadie W.; Ninan, Philip T.; Bradley, Rebekah
Objective: The authors describe the use of dialectical behavior therapy (DBT) in treating borderline personality disorder during psychiatry residency, and assess the status of DBT education within psychiatry residencies in the United States. Method: The authors present a patient with borderline personality disorder treated by a resident using DBT,…
Winograd, Greta; Cohen, Patricia; Chen, Henian
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.…
Schuppert, H. Marieke; Timmerman, Marieke E.; Bloo, Josephine; van Gemert, Tonny G.; Wiersema, Herman M.; Minderaa, Ruud B.; Emmelkamp, Paul M. G.; Nauta, Maaike H.
Objective: To evaluate the effectiveness of Emotion Regulation Training (ERT), a 17-session weekly group training for adolescents with borderline personality disorder (BPD) symptoms. Method: One hundred nine adolescents with borderline traits (73% meeting the full criteria for BPD) were randomized to treatment as usual only (TAU) or ERT + TAU.…
Shulruf, Boaz; Jones, Phil; Turner, Rolf
The determination of Pass/Fail decisions over Borderline grades, (i.e., grades which do not clearly distinguish between the competent and incompetent examinees) has been an ongoing challenge for academic institutions. This study utilises the Objective Borderline Method (OBM) to determine examinee ability and item difficulty, and from that…
Petricevic, Josko; Punda, Hrvoje; Brakus, Snjezana Mardesic; Vukojevic, Katarina; Govorko, Danijela Kalibovic; Alfirevic, Darko; Kvesic, Ante; Saraga-Babic, Mirna
The spatial and temporal distribution of epithelial membrane antigen (EMA), mesothelin and nestin was immunohistochemically analyzed in developing and adult human serous membranes and mesotheliomas in order to detect possible differences in the course of mesenchymal to epithelial transformation, which is associated with differentiation of mesothelial cells during normal development and tumorigenesis. Pleura and pericardium developing from the visceral mesoderm gradually transform into mesothelial cells and connective tissue. EMA appeared in mesothelium of both serous membranes during the early fetal period, whereas during further development, EMA expression was retained only in the pericardial mesothelium. It increased in both pleural mesothelium and connective tissue. Mesothelin appeared first in pericardial submesothelial cells and later in surface mesothelium, while in pleura it was immediately localized in mesothelium. In adult serous membranes, EMA and mesothelin were predominantly expressed in mesothelium. Nestin never appeared in mesothelium, but in connective tissues and myocardial cells and subsequently decreased during development, apart from in the walls of blood vessels. Mesothelial cells in the two serous membranes developed in two separate developmental pathways. We speculate that submesothelial pericardial and mesothelial pleural cells might belong to a population of stem cells. In epithelioid mesotheliomas, 13% of cells expressed nestin, 39% EMA and 7% mesothelin.
Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L; English, Diana P; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D
HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu-amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0-G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy.
Zimmermann, Anne-Katrin; Imig, Jochen; Klar, Agnes; Renner, Christoph; Korol, Dimitri; Fink, Daniel; Stadlmann, Sylvia; Singer, Gad; Knuth, Alexander; Moch, Holger; Caduff, Rosmarie
MAGE-C1/CT7, NY-ESO-1, GAGE and MAGE-A4 are members of the cancer/testis (CT) antigen family, which have been proposed as potential targets for cancer immunotherapy. To determine the prevalence and biologic relevance of the novel CT antigen MAGE-C1/CT7 and other antigens, 36 ovarian borderline tumours (BTs), 230 primary ovarian carcinomas (OCs) and 80 recurrent OCs were immunohistochemically analysed using the monoclonal antibodies CT7-33 (MAGE-C1/CT7), E978 (NY-ESO-1), clone 26 (GAGE) and 57B (MAGE-A4). Positivity of at least one CT antigen was present in 39.5 % (81/205) of primary OC and in 50 % (26/52) of all recurrences. Expression of the novel CT antigen MAGE-C1/CT7 was most commonly seen with positivity in 24.5 % of primary and 35.1 % of recurrent OC. MAGE-A4, GAGE and NY-ESO-1 expressions were seen in 22.7, 13.9 and 7.1 % of primary and 22.6, 17.5 and 8.9 % of recurrent OC, respectively. Analysis of histological subtypes (serous, endometrioid, clear cell, mucinous and transitional) exhibited variable expression with negativity in all mucinous OC. High-grade serous OC revealed CT antigen expression in 5.6 to 28 % with MAGE-C1/CT7 being the most frequent, but without correlation with stage or overall survival. MAGE-C1/CT7 expression and coexpression of CT antigens were significantly correlated with grade of endometrioid OC. None of the BT showed CT antigen expression. No significant correlation was seen with stage, overall survival or response to chemotherapy. In summary, CT antigens are expressed in a certain subset of OC with no expression in BT or OC of mucinous histology. These findings may have implications for the design of polyvalent vaccination strategies for ovarian carcinomas.
Clarke, Stephanie B.; Rizvi, Shireen L.; Resick, Patricia A.
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…
Raynal, Patrick; Chabrol, Henri
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.
Yalch, Matthew M; Hopwood, Christopher J; Fehon, Dwain C; Grilo, Carlos M
Suicide is a leading cause of death among adolescents and suicidal behavior is one of the primary risk factors for youth psychiatric hospitalizations. A number of studies indicate that depression and substance abuse are associated with suicide risk in this population, but less is known about the role of borderline personality features or their incremental influence over other known risk factors in indicating suicidal behavior among adolescents. This study examined whether borderline features were associated with suicide risk when controlling for symptoms of depression and substance abuse in a sample of adolescents hospitalized in an inpatient psychiatric facility. Self-report data from 477 adolescent psychiatric inpatients were used to test hypotheses about the association of borderline features with suicide risk after controlling for other common risk factors. Borderline features were significantly related to suicide risk even after accounting for symptoms of depression and substance abuse. These findings underscore the clinical value of routinely assessing borderline features among adolescents.
Hecht, Kathryn F; Cicchetti, Dante; Rogosch, Fred A; Crick, Nicki R
Child maltreatment has been established as a risk factor for borderline personality disorder (BPD), yet few studies consider how maltreatment influences the development of BPD features through childhood and adolescence. Subtype, developmental timing, and chronicity of child maltreatment were examined as factors in the development of borderline personality features in childhood. Children (M age = 11.30, SD = 0.94), including 314 maltreated and 285 nonmaltreated children from comparable low socioeconomic backgrounds, provided self-reports of developmentally salient borderline personality traits. Maltreated children had higher overall borderline feature scores, had higher scores on each individual subscale, and were more likely to be identified as at high risk for development of BPD through raised scores on all four subscales. Chronicity of maltreatment predicted higher overall borderline feature scores, and patterns of onset and recency of maltreatment significantly predicted whether a participant would meet criteria for the high-risk group. Implications of findings and recommendations for intervention are discussed.
Reuter, Tyson R; Sharp, Carla; Kalpakci, Allison H; Choi, Hye J; Temple, Jeff R
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.
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
Aliagas, Elisabet; Vidal, August; Texidó, Laura; Ponce, Jordi; Condom, Enric; Martín-Satué, Mireia
One of the strategies used by tumors to evade immunosurveillance is the accumulation of extracellular adenosine, which has immunosupressive and tumor promoting effects. The study of the mechanisms leading to adenosine formation at the tumor interstitium are therefore of great interest in oncology. The dominant pathway generating extracellular adenosine in tumors is the dephosphorylation of ATP by ecto-nucleotidases. Two of these enzymes acting sequentially, CD39 and CD73, efficiently hydrolyze extracellular ATP to adenosine. They have been found to play a crucial role in a variety of tumors, but there were no data concerning endometrial cancer, the most frequent of the invasive tumors of the female genital tract. The aim of the present work is to study the expression of CD39 and CD73 in human endometrial cancer. We have analyzed protein and gene expression, as well as enzyme activity, in type I endometrioid adenocarcinomas and type II serous adenocarcinomas and their nonpathological endometrial counterparts. High levels of both enzymes were found in tumor samples, with significantly increased expression of CD39 in type II serous tumors, which also coincided with the higher tumor grade. Our results reinforce the involvement of the adenosinergic system in cancer, emphasizing the relevance of ecto-nucleotidases as emerging therapeutic targets in oncology. PMID:24707115
Siamakpour-Reihani, Sharareh; Owzar, Kouros; Jiang, Chen; Turner, Taylor; Deng, Yiwen; Bean, Sarah M.; Horton, Janet K.; Berchuck, Andrew; Marks, Jeffrey R.; Dewhirst, Mark W.; Secord, Angeles Alvarez
Objectives To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC). Methods 51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts were determined using CD31and CD105. Association between mRNA expression levels and overall survival were assessed using rank score statistic. Effect size was estimated as a hazard ratio (HR) under a proportional hazards model. The Storey q-value method was used to account for multiple testing within the false-discovery rate (FDR) framework. Publicly available databases including TCGA and GSE were used for external confirmation. Results Thirty-one angiogenic-related genes were significantly associated with survival (q ≤ 0.05). Of these 31 genes, 4 were also associated with outcome in the TCGA data: AKT1 (q=0.02; TCGA p= 0.01, HR=0.8), CD44 (q= 0.003; TCGA p=0.05, HR=0.9), EPHB2 (q= 0.01; TCGA p=0.05, HR=1.2), and ERBB2 (q= 0.02; TCGA p= 0.05, HR=1.2). While 5 were associated with outcome in the GSE database: FLT1 (q= 0.03; GSE26712 p=0.01, HR=3.1); PF4 (q= 0.02; GSE26712 p=0.01, HR=3.0), NRP1 (q= 0.02; GSE26712 p < 0.04, HR>1.4), COL4A3 (q= 0.04; GSE26712 p= 0.03, HR=1.3), ANGPTL3 (q= 0.02; GSE14764 p=0.02, HR=1.5). High AKT1 and CD44 were associated with longer survival. In contrast, high expression of EPHB2, ERBB2, FLT1; PF4, NRP1, COL4A3, and ANGPTL3 were associated with shorter survival. CD105-MVD and CD31-MVD were not significantly associated with angiogenic gene expression. Conclusions Thirty-one angiogenic-related genes were associated with survival in advanced HGSC and nine of these genes were confirmed in independent publicly available databases. PMID:26260910
Korzekwa, Marilyn I; Dell, Paul F; Links, Paul S; Thabane, Lehana; Fougere, Philip
The objective of the present study was to assess in detail the whole spectrum of normal and pathological dissociative experiences and dissociative disorder (DD) diagnoses in borderline personality disorder (BPD) as diagnosed with the Revised Diagnostic Interview for Borderlines. Dissociation was measured comprehensively in 21 BPD outpatients using the Structured Clinical Interview for DSM-IV Dissociative Disorders-Revised, the Multidimensional Inventory of Dissociation (MID), the Dissociative Experiences Scale pathological taxon analysis, and the Somatoform Dissociation Questionnaire. The frequencies of DDs in this BPD sample were as follows: 24% no DD, 29% mild DD (dissociative amnesia and depersonalization disorder), 24% DD Not Otherwise Specified (DDNOS), and 24% dissociative identity disorder. With regard to the dissociative experiences endorsed, almost all patients reported identity confusion, unexplained mood changes, and depersonalization. Even those BPD patients with mild DD reported derealization, depersonalization, and dissociative amnesia. BPD patients with DDNOS reported frequent depersonalization, frequent amnesia, and notable experiences of identity alteration. BPD patients with dissociative identity disorder endorsed severe dissociative symptoms in all categories. Analysis of the MID pathological dissociation items revealed that 32% of the items were endorsed at a clinically significant level of frequency by more than 50% of our BPD patients. In conclusion, the frequencies of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) DDs in these patients with BPD were surprisingly high. Likewise, the "average" BPD patient endorsed a wide variety of recurrent pathological dissociative symptoms.
Ivanova, Anna; Loo, Anneli; Tworoger, Shelley; Crum, Christopher P.; Fan, Isabel; McLaughlin, John R.; Rosen, Barry; Risch, Harvey; Narod, Steven A.; Kotsopoulos, Joanne
Objectives Recent studies suggest that a proportion of ovarian tumors may actually originate in the distal fallopian tube. The objective of this study was to examine the relationship between dominance (a surrogate for site of origin) and survival following a diagnosis of epithelial ovarian cancer. Methods We classified 1,386 tumors as dominant (putatively originating in the ovary and non-dominant (putatively originating in the fallopian tube), using parameters obtained from pathology reports. Dominant tumors were restricted to one ovary or one involved ovary that exceeded the other in dimension by at least two-fold, while non-dominant tumors were identified as having a greater likelihood of a tubal origin if the disease was equally distributed across the ovaries. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with dominance. Results Non-dominant tumors were more likely to be serous, stage III/IV, and be associated with a BRCA1/2 mutation, increasing parity and use of estrogen hormone replacement therapy (P ≤ 0.01). In contrast, 46% and 26% of the dominant tumors were serous and endometrioid, respectively, with a more even distribution of stage (P < 0.0001). Women with a non-dominant tumor had an increased risk of death compared to women with a dominant tumor (multivariate HR = 1.28; 95%CI 1.02–1.60). Findings were similar in our analysis restricted to serous only subtypes (HR = 1.28; 95%CI 1.01–1.63). Conclusion These preliminary findings suggest significantly worse survival among women diagnosed with a tumor putatively arising from fallopian tube. PMID:25771796
Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...
Developments in immunohistochemistry, which are closely linked with the advances in the analyses of genetic abnormalities and their associated molecular disorders as early and late histogenetic events, have contributed greatly to the improvement of pathological diagnostic confirmation and validation. Immunohistochemistry has also generated great benefit to the innovation of therapeutic strategies for various kinds of cancers. In this article, the three representative histological types of corpus cancer, namely, endometrioid adenocarcinoma, serous adenocarcinoma and clear cell adenocarcinoma, will be histologically approached in association with their immunohistochemical profiles as well as genetic disorders. First, the focus will be on 'Conventional/prototypic features,' followed by 'Controversy over conventional histological subclassification,' and subsequently 'Tumorigenesis and re-subclassification'.
Black, Jonathan D; English, Diana P; Roque, Dana M; Santin, Alessandro D
Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer. Although it only represents less than 10% of all cases, it accounts for a disproportionate number of deaths from endometrial cancer. Comprehensive surgical staging followed by carboplatin and paclitaxel chemotherapy represents the mainstay of USC therapy. Vaginal cuff brachytherapy is also of potential benefit in USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. These results emphasize the relevance of these novel therapeutic targets for biologic therapy of chemotherapy-resistant recurrent USC.
Menderes, Gulden; Clark, Mitchell; Santin, Alessandro D
Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial cancer. Although it represents only 10% of all endometrial cancer cases, USC accounts for up to 40% of all endometrial cancer-related recurrences and subsequent deaths. With such a dismal prognosis, there is an expanding role for novel targeted approaches in the treatment of USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. The results emphasize the relevance of these novel therapeutic targets for biologic therapy of USC, which will be reviewed in this article.
Nosi, D.; Delfino, G.; Quercioli, F.
A combined transmission electron microscopy (TEM) and Fourier transform analysis has been performed on the secretory granules storing active peptides/proteins in serous cutaneous glands of n = 12 anuran species. Previous TEM investigation showed that the granules are provided with remarkable repeating substructures based on discrete subunits, arranged into a consistent framework. Furthermore, TEM findings revealed that this recurrent arrangement is acquired during a prolonged post-Golgian (or maturational) processing that affects the secretory product. Maturation leads to a variety of patterns depending on the degree of subunit clustering. This variety of recurrent patterns has been plotted into a range of frequency spectra. Through this quantitative approach, we found that the varying granule substructure can be reduced to a single mechanism of peptide/protein aggregation.
Vogel, Ryan N.; Langlo, Christopher S.; Scoles, Drew; Carroll, Joseph; Weinberg, David V.; Kim, Judy E.
Purpose We improved our understanding of central serous chorioretinopathy (CSC), we performed an analysis of noninvasive, high-resolution retinal imaging in patients with active and resolved CSC. Methods Adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography (SD-OCT) were performed on five subjects with CSC. A custom AOSLO system was used to simultaneously collect confocal and split-detector images. Spectral domain–OCT volume scans were used to create en face views of various retinal layers, which then were compared to montaged AOSLO images after coregistration. Results Three distinct types of intraretinal hyperreflective clusters were seen with AOSLO. These clusters had a well-demarcated, round, and granular appearance. Clusters in active CSC over areas of serous retinal detachment were termed type-1. They were found primarily in the outer nuclear layer (ONL) and were associated with large defects in the photoreceptor mosaic and ellipsoid zone. Clusters in areas where the retina had reattached were termed type-2. They also were located primarily in the ONL but showed stability in location over a period of at least 8 months. Smaller clusters in the inner retina along retinal capillaries were termed type-3. Conclusions Retinal imaging in CSC using en face OCT and AOSLO allows precise localization of intraretinal structures and detection of features that cannot be seen with SD-OCT alone. These findings may provide greater insight into the pathophysiology of the active and resolved phases of the disease, and support the hypothesis that intraretinal hyperreflective foci on OCT in CSC are cellular in nature. PMID:28055101
gene knockout developed ovarian/ tubal tumors morphologically very similar to human ovarian serous cystadenomas in strong support of our hypothesis. We...proliferation activity in the uterus of 5 wild type and 5 mutant mice at the diestrus ad estrus phases of the estrus cycle. Histological cross- sections were...zygous knockout restricted to granulosa cells. One ovary was removed from each of 30 Brca1 flox/flox; Fshr-Cre mice at 2 months of age. Histological
Tan, Jing; Ong, Choon Kiat; Lim, Weng Khong; Ng, Cedric Chuan Young; Thike, Aye Aye; Ng, Ley Moy; Rajasegaran, Vikneswari; Myint, Swe Swe; Nagarajan, Sanjanaa; Thangaraju, Saranya; Dey, Sucharita; Nasir, Nur Diyana Md; Wijaya, Giovani Claresta; Lim, Jing Quan; Huang, Dachuan; Li, Zhimei; Wong, Bernice Huimin; Chan, Jason Yong Sheng; McPherson, John R; Cutcutache, Ioana; Poore, Gregory; Tay, Su Ting; Tan, Wai Jin; Putti, Thomas Choudary; Ahmad, Buhari Shaik; Iau, Philip; Chan, Ching Wan; Tang, Anthony P H; Yong, Wei Sean; Madhukumar, Preetha; Ho, Gay Hui; Tan, Veronique Kiak Mien; Wong, Chow Yin; Hartman, Mikael; Ong, Kong Wee; Tan, Benita K T; Rozen, Steven G; Tan, Patrick; Tan, Puay Hoon; Teh, Bin Tean
Breast fibroepithelial tumors comprise a heterogeneous spectrum of pathological entities, from benign fibroadenomas to malignant phyllodes tumors. Although MED12 mutations have been frequently found in fibroadenomas and phyllodes tumors, the landscapes of genetic alterations across the fibroepithelial tumor spectrum remain unclear. Here, by performing exome sequencing of 22 phyllodes tumors followed by targeted sequencing of 100 breast fibroepithelial tumors, we observed three distinct somatic mutation patterns. First, we frequently observed MED12 and RARA mutations in both fibroadenomas and phyllodes tumors, emphasizing the importance of these mutations in fibroepithelial tumorigenesis. Second, phyllodes tumors exhibited mutations in FLNA, SETD2 and KMT2D, suggesting a role in driving phyllodes tumor development. Third, borderline and malignant phyllodes tumors harbored additional mutations in cancer-associated genes. RARA mutations exhibited clustering in the portion of the gene encoding the ligand-binding domain, functionally suppressed RARA-mediated transcriptional activation and enhanced RARA interactions with transcriptional co-repressors. This study provides insights into the molecular pathogenesis of breast fibroepithelial tumors, with potential clinical implications.
Katz, Matthew H. G.; Shi, Qian; Ahmad, Syed A.; Herman, Joseph M.; Marsh, Robert de W.; Collisson, Eric; Schwartz, Lawrence; Frankel, Wendy; Martin, Robert; Conway, William; Truty, Mark; Kindler, Hedy; Lowy, Andrew M.; Bekaii-Saab, Tanios; Philip, Philip; Talamonti, Mark; Cardin, Dana; LoConte, Noelle; Shen, Perry; Hoffman, John P.; Venook, Alan P.
IMPORTANCE Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50–76 years]; 55% female). Patients registered between May 29, 2013, and February 7,2014. INTERVENTIONS Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy. MAIN OUTCOMES AND MEASURES Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. RESULTS The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%–83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%–88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins
Belsky, Daniel W; Caspi, Avshalom; Arseneault, Louise; Bleidorn, Wiebke; Fonagy, Peter; Goodman, Marianne; Houts, Renate; Moffitt, Terrie E
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.
BELSKY, DANIEL W.; CASPI, AVSHALOM; ARSENEAULT, LOUISE; BLEIDORN, WIEBKE; FONAGY, PETER; GOODMAN, MARIANNE; HOUTS, RENATE; MOFFITT, TERRIE E.
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
Belli, Hasan; Ural, Cenk; Akbudak, Mahir
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.
Cohn, David E; Backes, Floor J; Wallbillich, John J; Bixel, Kristin; Crafton, Sarah M; Neff, Robert; ElNaggar, Adam C; Smith, Blair; Suarez, Adrian A
A 20 year old with recurrent low-grade serous carcinoma (LGSC) is discussed. The differential diagnosis, pathology, epidemiology, treatment options are discussed. Focus on the molecular pathways of LGSC and the implications of the diagnosis on fertility are highlighted.
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.
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
Kamieniak, Marta M.; Muñoz-Repeto, Ivan; Borrego, Salud; Hernando, Susana; Hernández-Agudo, Elena; Heredia Soto, Victoria; Márquez-Rodas, Ivan; Echarri, María José; Lacambra-Calvet, Carmen; Sáez, Raquel; Redondo, Andrés; Benítez, Javier
Objective We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. Methods In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients’ survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Results Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5-silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells. Conclusion Low
Fischer, Horst; Illek, Beate; Sachs, Lorne; Finkbeiner, Walter E; Widdicombe, Jonathan H
Using cell culture models, we have investigated the relative importance of cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCC) in Cl secretion by mucous and serous cells of human airway glands. In transepithelial recordings in Ussing chambers, the CFTR inhibitor CFTR(inh)-172 abolished 60% of baseline Cl secretion in serous cells and 70% in mucous. Flufenamic acid (FFA), an inhibitor of CaCC, reduced baseline Cl secretion by ∼20% in both cell types. Methacholine and ATP stimulated Cl secretion in both cell types, which was largely blocked by treatment with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and partially by mucosal FFA or CFTR(inh)-172 with the exception of methacholine responses in mucous cells, which were not blocked by FFA and partially (∼60%) by CFTR(inh)-172. The effects of ionomycin on short-circuit current (I(sc)) were less than those of ATP or methacholine. Forskolin stimulated Cl secretion only if Cl in the mucosal medium was replaced by gluconate. In whole cell patch-clamp studies of single isolated cells, cAMP-induced Cl currents were ∼3-fold greater in serous than mucous cells. Ionomycin-induced Cl currents were 13 times (serous) or 26 times (mucous) greater than those generated by cAMP and were blocked by FFA. In serous cells, mRNA for transmembrane protein 16A (TMEM16A) was ∼10 times more abundant than mRNA for CFTR. In mucous cells it was ∼100 times more abundant. We conclude: 1) serous and mucous cells both make significant contributions to gland fluid secretion; 2) baseline Cl secretion in both cell types is mediated predominantly by CFTR, but CaCC becomes increasingly important after mediator-induced elevations of intracellular Ca; and 3) the high CaCC currents seen in patch-clamp studies and the high TMEM16A expression in intact polarized cells sheets are not reflected in transepithelial current recordings.
Marco, José H; Guillén, Veronica; Botella, Cristina
Meaning in life has been found to be a protective factor against suicidal ideation. The aim of this study was to investigate whether meaning in life can moderate and buffer the association between suicide risk factors and hopelessness in women with borderline personality disorders. One hundred twenty-four women diagnosed with borderline personality disorder completed self-report measures of suicide risk factors, hopelessness, and meaning in life. The main result from this study was that meaning in life moderated the association between suicide risk factors and hopelessness. Meaning in life is an important variable in the prevention and treatment of risk of suicide in women with borderline personality disorder.
Ross, Donald R; Favero, Marcus
The experience of many patients with borderline personality is intense and kaleidoscopic. These qualities may be represented in film in ways that reflect and convey their essential features that are less readily captured in words. Quentin Tarantino has produced a trilogy of films that bring to light and to life the borderline experience. We use these movies to illustrate and discuss five key borderline themes: the fluid nature of drive derivatives, the discontinuous experience of time and space, the coniflicted search for an idealized parent, antisocial distortions of the superego, and the organizing and stabilizing function of a central romantic fantasy.
Grosjean, Bernadette; Tsai, Guochuan E.
Studies of the neurobehavioural components of borderline personality disorder (BPD) have shown that symptoms and behaviours of BPD are partly associated with disruptions in basic neurocognitive processes, in particular, in the executive neurocognition and memory systems. A growing body of data indicates that the glutamatergic system, in particular, the N-methyl-D-aspartate (NMDA) subtype receptor, plays a major role in neuronal plasticity, cognition and memory and may underlie the pathophysiology of multiple psychiatric disorders. In this paper, we review the literature regarding BPD and its cognitive deficits and the current data on glutamatergic and NMDA neurotransmission. We propose that multiple cognitive dysfunctions and symptoms presented by BPD patients, like dissociation, psychosis and impaired nociception, may result from the dysregulation of the NMDA neurotransmission. This impairment may be the result of a combination of biological vulnerability and environmental influences mediated by the NMDA neurotransmission. PMID:17353939
Herr, Nathaniel R; Hammen, Constance; Brennan, Patricia A
Borderline personality disorder (BPD) is characterized by severe disruption of interpersonal relationships, yet very little research has examined the relationship between maternal BPD and offspring psychosocial functioning. The present study examined 815 mothers and their 15-year-old children from a community-based sample to determine (1) if there is an association between mothers' BPD symptoms and the interpersonal functioning, attachment cognitions, and depressive symptoms of their offspring, and (2) if the association of maternal BPD and youth outcomes is independent of maternal and youth depression. Measures of youth psychosocial functioning included self, mother, interviewer rated, and teacher reports. Results indicated that there was a significant association between maternal BPD symptoms and youth outcomes, and that this association remained even after controlling for maternal lifetime history of major depression, maternal history of dysthymic disorder, and youth depressive symptoms. This study provides some of the first empirical evidence for a link between mother's BPD symptoms and youth psychosocial outcomes.
Paris, J; Zweig-Frank, H; Guzder, J
The purpose of the study was to examine the role of several psychological risk factors--childhood sexual abuse (CSA) and its parameters, childhood physical abuse and its parameters, early separation or loss, and abnormal parental bonding--in male patients with borderline personality disorder (BPD). Subjects with personality disorders were divided into BPD (N = 61) and non-BPD (N = 60) groups. The risk factors were measured by a developmental interview and the Parental Bonding Index. The BPD group had a higher frequency of CSA, more severe CSA, a longer duration of physical abuse, increased rates of early separation or loss, and a higher paternal control score on the Parental Bonding Index. CSA and separation or loss were significant in the multivariate analysis. The risk factors suggest that trauma and loss, as well as problems with fathers, are important for the development of BPD in males.
Ripoll, Luis H; Snyder, Rebekah; Steele, Howard; Siever, Larry J
We present a neurobiological model of empathic dysfunction in borderline personality disorder (BPD) to guide future empirical research. Empathy is a necessary component of interpersonal functioning, involving two distinct, parallel neural networks. One form of empathic processing relies on shared representations (SR) of others' mental states, while the other is associated with explicit mental state attribution (MSA). SR processing is visceral and automatic, contributing to attunement, but also emotional contagion. MSA processing contributes to deliberate, perspectival forms of empathic understanding. Empathic dysfunction in BPD may involve hyper-reactivity of SR networks and impairment of MSA networks. Nevertheless, this empathic dysfunction is subtle, but contributes to interpersonal difficulties. Interaction between genetic factors and traumatic attachment stressors may contribute to development of BPD, with painful attachment insecurity and disorganization affecting SR and MSA network functioning. Future avenues for BPD research will include developmental assessment of attachment and neurobiological functioning under varying conditions.
Higa, Justin K; Gedo, Paul M
Transference is seen as an important change mechanism in psychotherapeutic technique, although questions remain about its therapeutic use, especially with borderline personality disorder (BPD) patients. This article illustrates the lively debate about transference interpretation through the perspective of two psychotherapeutic techniques under empirical scrutiny--transference-focused psychotherapy (TFP) and mentalization-based treatment (MBT). Each technique offers a similar understanding and appreciation of transference, but they differ in their technical use of this change mechanism. The article presents a brief case study of a BPD patient. The treatment highlights the utility of each psychotherapeutic technique in understanding the developmental progress made by the patient in therapy. The authors argue that each technique may be useful in a long-term dynamic therapy, and that one can use an epigenetic framework to understand this observation.
Badoud, Deborah; Prada, Paco; Nicastro, Rosetta; Germond, Charlotte; Luyten, Patrick; Perroud, Nader; Debbané, Martin
Insecure attachment and impairments in reflective functioning (RF) are thought to play a critical role in borderline personality disorder (BPD). In particular, the mentalization-based model argues that insecure attachment indirectly accounts for increased BPD features, notably via disruption of RF capacities. Although the mediation relationship between attachment, RF, and BPD is supported by previous evidence, it remains to be directly tested in adults with BPD. In the current study, a sample of 55 female adult BPD patients and 105 female healthy controls completed a battery of self-report measures to investigate the interplay between attachment, RF capacities, and BPD clinical status. Overall, the results showed that BPD patients predominantly reported insecure attachment, characterized by negative internal working models of the self as unlovable and unimportant to others, and decreased RF abilities. Our findings further indicated that actual RF capacities mediated the relationships between adult insecure attachment and BPD clinical status.
The aim of this paper is to explore the links between the attachment-theory derived concept of disorganized attachment, and the psychiatric diagnosis of Borderline Personality Disorder (BPD). Disorganized attachment can be understood in terms of an approach-avoidance dilemma for infants for whom stressed or traumatized/traumatizing caregivers are simultaneously a source of threat and a secure base. Interpersonal relationships in BPD including those with care givers is similarly seen in terms of approach-avoidance dilemmas, which manifests themselves in disturbed transference/countertransference interactions between therapists and BPD sufferers. Possible ways of handling these phenomena are suggested, based on notion of 'meta-cognitive monitoring', in the hope of re-instating meaning and more stable self-structures, in these patients' lives.
Hooley, Jill M; Wilson-Murphy, Molly
Borderline personality disorder (BPD) is characterized by tumultuous, unstable personal relationships, difficulty being alone, and an inability to self-soothe. This may explain why patients with BPD tend to develop strong attachments to transitional objects such as stuffed animals. Research in hospital settings has linked the use of transitional objects to the presence of BPD. Using a nonclinical community sample (N = 80) we explored the link between attachments to transitional objects and various aspects of personality pathology, as well as to childhood trauma, and parental rearing styles. People who reported intense current attachments to transitional objects were significantly more likely to meet criteria for a BPD diagnosis than those who did not; they also reported more childhood trauma, rated their early caregivers as less supportive, and had more attachment problems as adults. Heavy emotional reliance on transitional objects in adulthood may be an indicator of underlying pathology, particularly BPD.
Borderline personality disorder (BPD) is a common psychiatric disorder associated with severe functional impairment, high rates of suicide and comorbid psychiatric illness, intensive use of treatment, and high costs to society. The etiology and pathogenesis of BPD are still uncertain, although an interaction between biological and psychosocial factors has been proposed to explain how the condition develops. Attachment disturbances represent one of the developmental risk factors that have been most consistently found to be associated with BPD, with a number of studies reporting a significant strong association between insecure attachment and BPD, notwithstanding the variety of measures and attachment types employed in these studies. In this article, the author first reviews clinical descriptions and research findings concerning the association between attachment disturbances and BPD and then discusses how attachment theory may help clinicians who work with patients with BPD better understand the psychopathology of the illness and plan treatment.
The development of cognitive models and treatments for borderline personality disorder over the last two decades has been remarkable. This article presents the main ideas of the models developed by Aaron T. Beck and Arthur Freeman, Jeffrey Young and Marsha Linehan. These theories have generated psychotherapies that have proven their efficacy in controlled empirical studies in a difficult to treat population. The models of Beck Freeman and Young are based on the concept of schema. Linehan's dialectical behavior therapy is based on a biosocial transactional conception of the disorder. All these models emphasize the importance of negative experiences in early development. The article presents the structure of these treatments and describes their specific interventions.
Courtney, Darren B.; Makinen, Judy
Objective Establishing a diagnosis of Borderline Personality Disorder (BPD) in adolescents is often met with controversy, in part, due to potential stigmatizing effects. We wished to explore the adolescent patient experience of being diagnosed with BPD. Method The Impact of Diagnosis Scale (IODS) is a self-report measure we developed with questions targeting patients’ subjective experience of receiving a diagnosis of BPD. The IODS was administered to 23 adolescents approximately one month after a diagnosis of BPD had been disclosed to them. Results Twenty-one participants had analyzable data. The internal consistency of the measure demonstrated Cronbach’s alpha of 0.66. We found wide variability in responses. Patients tended to view the diagnosis as an accurate representation of their symptoms. Conclusion The IODS represents a novel means by which clinicians might better appreciate how disclosing the diagnosis of BPD may impact a patient’s understanding of one’s difficulties. PMID:27924148
Amamou, Badii; Salah, Walid Bel Hadj; Mhalla, Ahmed; Benzarti, Nejla; Elloumi, Hend; Zaafrane, Ferid; Gaha, Lotfi
Patients with borderline personality disorder (BPD) show significant impairment in functioning, particularly in the interpersonal and social domains. Prior reports suggest that clozapine may be effective in the management of BPD. We present the case of a patient with BPD who experienced persistent suicidal ideation and was treated with clozapine at a state psychiatric hospital. After treatment failure with other psychotropic medications, clozapine medication was initiated; not only did suicidal ideation cease, but social and professional functioning also greatly improved to the point of no longer requiring intensive levels of observation or restrictive procedures. Clozapine appears to be efficacious in the management of suicide attempts and self-injurious behavior. Moreover, it appears to be promising as a therapeutic measure for ameliorating the global functioning of patients with severe BPD. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings and to determine optimal dosage. PMID:27121437
Hasler, Gregor; Hopwood, Christopher J; Jacob, Gitta A; Brändle, Laura S; Schulte-Vels, Thomas
Patient-reported outcome (PRO) refers to measures that emphasize the subjective view of patients about their health-related conditions and behaviors. Typically, PROs include self-report questionnaires and clinical interviews. Defining PROs for borderline personality disorder (BPD) is particularly challenging given the disorder's high symptomatic heterogeneity, high comorbidity with other psychiatric conditions, highly fluctuating symptoms, weak correlations between symptoms and functional outcomes, and lack of valid and reliable experimental measures to complement self-report data. Here, we provide an overview of currently used BPD outcome measures and discuss them from clinical, psychometric, experimental, and patient perspectives. In addition, we review the most promising leads to improve BPD PROs, including the DSM-5 Section III, the Recovery Approach, Ecological Momentary Assessments, and novel experimental measures of social functioning that are associated with functional and social outcomes.
Davids, Eugen; Gastpar, Markus
To evaluate the association between attention deficit hyperactivity disorder (ADHD) and the diagnosis of borderline personality disorder (BPD) in adulthood, a systematic review of published follow-up data, mainly from observational studies was done. Electronic databases Medline, PsychInfo and PSYNDEXplus were searched from their earliest entries. All studies suggested significant relationships between ADHD and BPD. From a phenomenological point of view there seem to exist some similarities between these two disorders: deficits in affect regulation and impulse control, substance abuse, low self esteem and disturbed interpersonal relationship are common in both conditions. From a neuropsychological point of view dissociation in BPD might be regarded as a special form of behavioral inhibition and sustained attention comparable to ADHD. Possible therapeutic strategies of comorbid ADHD and BPD are discussed.
Patients with borderline personality disorder are frequent users of inpatient mental health units, with inpatient crisis intervention often used based on the risk of suicide. However, this can present an ethical dilemma for nursing and medical staff, with these clinician responses shifting between the moral principles of beneficence and non-maleficence, dependent on the outcomes of the actions of containing or tolerating risk. This article examines the use of crisis intervention through moral duties, intentions and consequences, culminating in an action/consequence model of risk management, used to explore potential outcomes. This model may be useful in measuring adherence and violation of the principles of beneficence and non-maleficence and therefore an aid to clinical decision making.
Warwar, Serine H; Links, Paul S; Greenberg, Leslie; Bergmans, Yvonne
This paper discusses the function of emotion, its importance in the treatment of individuals with borderline personality disorder (BPD), and the integration of emotion-focused therapy (EFT) principles in the psychotherapeutic management of patients with BPD. EFT principles involve emotional assessment; a strong therapeutic alliance as a necessary context for treatment; the therapeutic relationship as a bond that regulates affect through empathy, emotional validation, and interpersonal soothing; emotion-regulation; psychoeducation about emotional processes; the therapist as an emotional coach; and transforming emotion schemes as primary mechanisms of change. The authors discuss how EFT principles can be viewed as primary intervention strategies in the treatment of patients with BPD and how they can be incorporated into various psychotherapy approaches. Based on our experience, the integration of EFT principles into the therapy of patients with BPD shows promise as it has been helpful in targeting BPD symptoms, and is feasible and acceptable to patients.
Andrici, Juliana; Jung, Jason; Sheen, Amy; D'Urso, Lisa; Sioson, Loretta; Pickett, Justine; Parkhill, Thomas R; Verdonk, Brandon; Wardell, Kathryn L; Singh, Arjun; Clarkson, Adele; Watson, Nicole; Toon, Christopher W; Gill, Anthony J
Gynecologic and primary peritoneal serous carcinoma may be difficult to distinguish from abdominal mesotheliomas clinically, morphologically, and immunohistochemically. BAP1 double-hit inactivation and subsequent loss of protein expression have been reported in more than half of all abdominal mesotheliomas. We therefore sought to investigate the expression of BAP1 in serous carcinoma and explore its potential utility as a marker in the differential diagnosis with mesothelioma. We searched the computerized database of the Department of Anatomical Pathology, Royal North Shore Hospital, Australia, for all cases of gynecologic and peritoneal serous carcinomas and mesotheliomas diagnosed between 1998 and 2014. Immunohistochemistry for BAP1 was then performed on tissue microarray sections. Cases with completely absent nuclear staining in the presence of a positive internal control in nonneoplastic cells were considered negative. If staining was equivocal (eg, absent nuclear staining but no internal control), staining was repeated on whole sections. Loss of BAP1 expression was found in only 1 of 395 (0.3%) serous carcinomas but in 6 of 9 (67%) abdominal mesotheliomas (P < .001) and 131 of 277 (47%) thoracic mesotheliomas (P < .001). We conclude that BAP1 loss occurs extremely infrequently in gynecologic and peritoneal serous adenocarcinomas, whereas it is very common in mesotheliomas including abdominal mesothelioma. Therefore, although positive staining for BAP1 cannot be used to exclude a diagnosis of mesothelioma, loss of BAP1 expression can be used to very strongly support a pathological diagnosis of abdominal mesothelioma over serous carcinoma.
Haltigan, John D.
Objective: To examine trajectories of adolescent borderline personality (BP) features in a normative-risk cohort (n = 566) of Canadian children assessed at ages 13, 14, 15, and 16 and childhood predictors of trajectory group membership assessed at ages 8, 10, 11, and 12. Method: Data were drawn from the McMaster Teen Study, an on-going study examining relations among bullying, mental health, and academic achievement. Participants and their parents completed a battery of mental health and peer relations questionnaires at each wave of the study. Academic competence was assessed at age 8 (Grade 3). Latent class growth analysis, analysis of variance, and logistic regression were used to analyze the data. Results: Three distinct BP features trajectory groups were identified: elevated or rising, intermediate or stable, and low or stable. Parent- and child-reported mental health symptoms, peer relations risk factors, and intra-individual risk factors were significant predictors of elevated or rising and intermediate or stable trajectory groups. Child-reported attention-deficit hyperactivity disorder (ADHD) and somatization symptoms uniquely predicted elevated or rising trajectory group membership, whereas parent-reported anxiety and child-reported ADHD symptoms uniquely predicted intermediate or stable trajectory group membership. Child-reported somatization symptoms was the only predictor to differentiate the intermediate or stable and elevated or rising trajectory groups (OR 1.15, 95% CI 1.04 to 1.28). Associations between child-reported reactive temperament and elevated BP features trajectory group membership were 10.23 times higher among children who were bullied, supporting a diathesis–stress pathway in the development of BP features for these youth. Conclusions: Findings demonstrate the heterogeneous course of BP features in early adolescence and shed light on the potential prodromal course of later borderline personality disorder. PMID:27254092
This article describes a conceptual framework for describing borderline personality disorder (BPD) based on empirical studies of the phenotypic structure and genetic architecture of personality. The proposed phenotype has 2 components: (1) a description of core self and interpersonal pathology-the defining features of personality disorder-as these features are expressed in the disorder; and (2) a set of traits based on the anxious-dependent or emotional dysregulation factor of the four-factor model of PD. Four kinds of traits are described: emotional (anxiousness, emotional reactivity, emotional intensity, and pessimistic-anhedonia), interpersonal (submissiveness, insecure attachment, social apprehensiveness, and need for approval), cognitive (cognitive dysregulation), and self-harm (behaviors and ideas). Formulation of the phenotype was guided by the conceptualization of personality as a system of interrelated sub-systems. The psychopathology associated with BPD involves most components of the system. The trait structure of the disorder is assumed to reflect the genetic architecture of personality and individual traits are assumed to be based on adaptive mechanisms. It is suggested that borderline traits are organized around the trait of anxiousness and that an important feature of BPD is dysregulation of the threat management system leading to pervasive fearfulness and unstable emotions. The interpersonal traits are assumed to be heritable characteristics that evolved to deal with interpersonal threats that arose as a result of social living. The potential for unstable and conflicted interpersonal relationships that is inherent to the disorder is assumed to result from the interplay between the adaptive structure of personality and psychosocial adversity. The etiology of the disorder is discussed in terms of biological and environmental factors associated with each component of the phenotype.
Acinar Cell Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bladder Adenocarcinoma; Bronchioloalveolar Carcinoma; Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Dermoid Cyst; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metastatic Malignant Neoplasm of Unknown Primary Origin; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous Cell Carcinoma; Spindle Cell Neoplasm
Damar, Elif; Toklu, Yasin; Tuncel, Altug; Balci, Melih; Aslan, Yilmaz; Simsek, Saban; Atan, Ali
The possible effects of sildenafil citrate administration at therapeutic dosage on visual acuity, color vision, intraocular pressure, macular thickness, macular volume, and central serous chorioretinopathy in patients with erectile dysfunction were evaluated. The study consisted of 43 male patients diagnosed as having erectile dysfunction according to the first five question version of International Index of Erectile Function (IIEF-5). All patients were given sildenafil citrate 50 mg po 2 to 3 times/week for a month. The patients were evaluated at the first week and at the end of the treatment. The macular thickness and volume assessments with optic coherence tomography did not differ significantly in foveal, parafoveal areas, parafoveal superior hemisphere, parafoveal inferior hemisphere, parafoveal temporal, superior, nasal, and inferior quadrants. Central serous chorioretinopathy was not found in any of the patients.
Herazo, Fernando; Gil, Monica; Echeverri, Carolina; Ángel, Gonzalo; Borrero, Mauricio; Madrid, Jorge; Jaramillo, Ricardo
Introduction: Breast Phyllodes tumors are rare breast tumors present in less than 1% of new cases of breast cancer, usually occurring among middle-aged women (40-50 yrs). Objective: This study shows diagnostic experience, surgical management and follows up of patients with this disease during a period of ten years in a oncology referral center. Methods: Retrospectively, breast cancer registries at the institution were reviewed, identifying 77 patients with Phyllodes tumors between 2002 and 2012, who had been operated on at the Instituto de Cancerología - Clínica Las Américas, in Medellín (Colombia). Clinical and histopathological data belonging to these cases was captured and analyzed and descriptive statistics were used. Results: The follow up median was 22.5 months (IQR: 10.5-60.0), average age was 47.2 yrs (SD: 12.4), mean tumor size was 3.6 cm (SD: 4.6), 88.3% of the patients (68 cases) presented negative margins and none of them received adjuvant chemotherapy. Of the patients with Phyllodes tumors; 33.8% had benign, 31.2% had borderline and 35.0% had malignant tumor. Disease-free survival was 85.8% and overall survival was 94.5%. Discussion: Reported data in this article is in accordance with what has been reported in worldwide literature. In our cohort even the high mean size of the tumors, the risk of local relapse and metastatic disease is low than previously reported in literature. Trials with longer follow up and molecular trials in Phyllodes tumors are necessary to understand the behavior of these tumors in Hispanics population. PMID:26600624
Sansone, Randy A; Sansone, Lori A
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.
Fulford, Daniel; Eisner, Lori R; Johnson, Sheri L
Researchers and clinicians have long noted the overlap among features and high comorbidity of bipolar disorder and borderline personality disorder. The shared features of impulsivity and labile mood in both disorders make them challenging to distinguish. We tested the hypothesis that variables related to goal dysregulation would be uniquely related to risk for mania, while emotion-relevant impulsivity would be related to risk for both disorders. We administered a broad range of measures related to goal regulation traits and impulsivity to 214 undergraduates. Findings confirmed that risk for mania, but not for borderline personality disorder, was related to higher sensitivity to reward and intense pursuit of goals. In contrast, borderline personality disorder symptoms related more strongly than did mania risk with threat sensitivity and with impulsivity in the context of negative affect. Results highlight potential differences and commonalities in mania risk versus borderline personality disorder risk.
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.
Sansone, Lori A.
Borderline personality disorder is a personality dysfunction that is characterized by disinhibition and impulsivity, which oftentimes manifest as self-regulation difficulties. Patients with this disorder have always been present in medical settings, but have been described as “difficult patients” rather than patients with borderline personality disorder. According to empirical findings, a number of behaviors and medical syndromes/diagnoses are suggestive of borderline personality disorder. Suggestive behaviors in the medical setting may include aggressive or disruptive behaviors, the intentional sabotage of medical care, and excessive healthcare utilization. Suggestive medical syndromes and diagnoses in the medical setting may include alcohol and substance misuse (including the abuse of prescription medications), multiple somatic complaints, chronic pain, obesity, sexual impulsivity, and hair pulling. While not all-inclusive or diagnostic, these behaviors and syndromes/diagnoses may invite further clinical evaluation of the patient for borderline personality disorder. PMID:26351624
Sharp, Carla; Kalpakci, Allison; Mellick, William; Venta, Amanda; Temple, Jeff R
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.
Carrai, Paola; Pichi, Francesco; Bonsignore, Francesco; Ciardella, Antonio P; Nucci, Paolo
The aim the study was to describe wide-field spectral-domain optical coherence tomography morphologic relationships of the vitreous, retina, and choroid in central serous chorioretinopathy (CSCR) eyes. Standardized horizontal, vertical, and two oblique (supertemporal to inferonasal and supranasal to inferotemporal) SD-OCT sections were collected for 40 patient with CSCR. For extramacular imaging, images were obtained from eight locations: (1) nasal to the optic disk, (2) extreme nasal periphery, (3) superior to the superotemporal vascular arcade, (4) extreme superior periphery, (5) inferior to the inferotemporal vascular arcade, (6) extreme inferior periphery, (7) temporal to the macula, and (8) extreme temporal periphery. Wide-angle montage images of OCT from equator to equator were composed with a montaging software. Average subfoveal choroidal thickness was 478 ± 114 µm (range 232-695 µm) at the macular level, 367 ± 94 µm in the superior periphery, 257 ± 103 µm in the inferior periphery, 431 ± 121 and 280 ± 88 µm in the nasal and in the temporal periphery, respectively. Wide-field EDI-OCT revealed a relative thinning of the inner choroidal layer in the periphery, including the small and medium large vessels, which ranged from 86 µm nasally to 120.1 µm superiorly, with a mean of 98.8 ± 13.6 µm. Beneath the thinned inner choroidal layer, hyporeflective lumina, corresponding to the outer choroidal layer, were identified in the periphery of all eyes. The outer choroidal layer thickness ranged from 175.5 µm temporally to 235.5 µm superiorly, with a mean of 217.8 ± 41.4 µm. The novel approach of montaging SD-OCT images to examine relationships between the choroid, retina, and associated structures adjacent to and outside of the macula may have a number of relevant applications in the study of pathologic features of central serous chorioretinopathy.
Johnson, Eric D.; Gulbahce, Evin; McNally, Joseph; Buys, Saundra S.
Introduction Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported. PMID:28203179
Sansone, Randy A; Sansone, Lori A
Borderline personality disorder is a complex psychiatric syndrome that is characterized by a number of pathological interpersonal and behavioral symptoms. Because of these symptoms, individuals with borderline personality disorder tend to have difficulties in their relationships with others, including mental health clinicians. Through a literature review, we examined the perceptions and reactions of mental health clinicians toward patients with borderline personality disorder. Our findings indicate that psychiatric nurses are the most studied group of mental health clinicians in this regard, followed by samples of mixed mental health clinicians, and then psychologists. Interestingly, there is no study of psychiatrists only. While sample sizes have been generally small and methodologies have varied, the overwhelming majority of these studies indicate negative perceptions of and emotional responses toward patients with borderline personality disorder. Some researchers have interpreted such findings to suggest that mental health clinicians are more judgmental or prejudicial toward patients with borderline personality disorder, in contrast to other types of mental health patients. However, patients with borderline personality disorder have very complex interpersonal behaviors that tend to illicit negative responses from those around them. Perhaps these data simply reflect a very human reaction to the complex and pathological behaviors of these patients-a conclusion that is relevant to clinicians practicing in either mental health or primary care settings.
Nelson, David A; Coyne, Sarah M; Swanson, Savannah M; Hart, Craig H; Olsen, Joseph A
Crick, Murray-Close, and Woods (2005) encouraged the study of relational aggression as a developmental precursor to borderline personality features in children and adolescents. A longitudinal study is needed to more fully explore this association, to contrast potential associations with physical aggression, and to assess generalizability across various cultural contexts. In addition, parenting is of particular interest in the prediction of aggression or borderline personality disorder. Early aggression and parenting experiences may differ in their long-term prediction of aggression or borderline features, which may have important implications for early intervention. The currrent study incorporated a longitudinal sample of preschool children (84 boys, 84 girls) living in intact, two-parent biological households in Voronezh, Russia. Teachers provided ratings of children's relational and physical aggression in preschool. Mothers and fathers also self-reported their engagement in authoritative, authoritarian, permissive, and psychological controlling forms of parenting with their preschooler. A decade later, 70.8% of the original child participants consented to a follow-up study in which they completed self-reports of relational and physical aggression and borderline personality features. The multivariate results of this study showed that preschool relational aggression in girls predicted adolescent relational aggression. Preschool aversive parenting (i.e., authoritarian, permissive, and psychologically controlling forms) significantly predicted aggression and borderline features in adolescent females. For adolescent males, preschool authoritative parenting served as a protective factor against aggression and borderline features, whereas authoritarian parenting was a risk factor for later aggression.
Leontaridou, Maria; Urbisch, Daniel; Kolle, Susanne N; Ott, Katharina; Mulliner, Denis S; Gabbert, Silke; Landsiedel, Robert
Testing methods to assess the skin sensitisation potential of a substance usually use threshold criteria to dichotomise 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 non-conclusive due to a testing method's biological and technical variability. We quantify BRs in the prediction models of the non-animal testing methods DPRA, LuSens and h-CLAT, and of the animal test LLNA, respectively. Depending on the size of the BR we find that between 6% and 28% of the substances in the sets tested with these methods were considered borderline. If the results of individual non-animal test methods are combined into integrated testing strategies (ITS), borderline test results of individual tests can also affect the overall assessment of the skin sensitisation potential of the testing strategy. This was analysed 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 'non-conclusive' alert for cases where test results fall within the borderline range.
Following a critical discussion on the term Borderline Personality Disorder during adolescence, assessment criteria are compiled that illustrate this disorder. In an overview of the psychodynamic literature it is clearly stated that already in the 1960s Borderline Disorders were described in childhood and adolescence without any development of valid criteria for these since then. Except for numerous case studies of these Borderline Disorders, there has been no research undertaken within psychodynamic psychotherapy on this disorder during childhood and adolescence to date. Specific disorder-related therapy approaches, whose effectiveness have been confirmed in therapy studies on Borderline Disorders in adults, have so far not been adapted to treating children and adolescents that have Borderline Disorders. These are portrayed as well as the treatment prerequisites and framework conditions that allow for a disorder-specific development oriented interactional psychotherapy of adolescents with Borderline Disorders. The interactional psychotherapy in its adolescence-adapted form is only gone into on the side. In conclusion there is an overview given of the various phases of the treatment.
Hiroki, Eri; Akahira, Jun-Ichi; Suzuki, Fumihiko; Nagase, Satoru; Ito, Kiyoshi; Suzuki, Takashi; Sasano, Hironobu; Yaegashi, Nobuo
This study aimed to determine the expression profiles of microRNAs (miRNAs) in endometrial serous adenocarcinoma and to examine the association between miRNA expression and clinical outcomes. Twenty-one patients diagnosed with endometrial serous adenocarcinoma between January 2001 and December 2006 were enrolled. miRNA expression profiles were examined using miRNA microarray and qRT-PCR. miRNA expression levels were correlated with clinicopathological variables and survival rates. A total of 120 miRNAs were differentially expressed in endometrial serous adenocarcinoma compared to normal endometria. Of these, 54 miRNAs were down-regulated (>2-fold), including miR-101, miR-10b*, miR-152, and miR-29b, and the remainder were up-regulated (>2-fold), including miR-200a, miR-200b, and miR-205. Decreased expression of miR-10b*, miR-29b, and miR-455-5p was correlated with vascular invasion (P = 0.048, P = 0.013, and P = 0.032, respectively). Univariate analysis revealed that lower expression of miR-101, miR-10b*, miR-139-5p, miR-152, miR-29b, and miR-455-5p was significantly correlated with poor overall survival (P < 0.05), and reduced expression of miR-152, miR-29b, and miR-455-5p was significantly correlated with poor disease-free survival (P < 0.05). Multivariate analysis demonstrated that decreased expression of miR-152 (P = 0.021) was a statistically independent risk factor for overall survival, and decreased expression levels of miR-101 (P = 0.016) and miR-152 (P = 0.010) were statistically independent risk factors for disease-free survival. In addition, transfection of miR-101 or miR-152 precursors into an endometrial serous carcinoma cell line inhibited cell growth (P < 0.0001 and P = 0.01, respectively). Moreover, strong positive immunoreactivity of cyclooxygenase-2 (COX-2) was significantly correlated with down-regulation of miR-101 (P = 0.035). These findings suggest that the dysregulation of miRNAs is associated with the poor prognosis in endometrial serous
Park, Hyun-Kyu; Jo, Woori; Choi, Hyun-Ji; Kim, Bongcheol; Lee, Gilnam; Seo, Jeongbeob; Cho, Suk Young; Kim, Choung-Soo; Choi, Eun Kyung; Hwang, Jung Jin; Lee, Joo Yong; Yoon, Young Hee; Son, Woo-Chan
Many systemic drugs can induce ocular toxicity and several ocular side-effects have been identified in clinical studies. However, it is difficult to detect ocular toxicity in preclinical studies because of the lack of appropriate evaluation methods. Optical coherence tomography (OCT) is useful because it can provide real-time images throughout a study period, whereas histopathology only provides images of sacrificed animals. Using OCT alongside histopathology, attempts were made to find effective approaches for screening of drug-induced ocular toxicity in monkeys. Such approaches could be used in preclinical studies prior to human trials. Six male cynomolgus monkeys (Macaca fascicularis Raffles) were orally administered one of six candidate MAPK/ERK kinase (MEK) inhibitors. Central serous chorioretinopathy, a known side-effect of such inhibitors, was identified in four monkeys by OCT. Artifacts generated during tissue processing meant that histopathology could not detect edematous changes. Thus, OCT is a useful tool to detect ocular toxicity which cannot be detected by histopathology in preclinical studies.
Soriano, Amata Amy; Monticelli, Antonella; Affinito, Ornella; Cocozza, Sergio; Zannini, Mariastella
Understanding the biology and molecular pathogenesis of ovarian epithelial cancer (EOC) is key to developing improved diagnostic and prognostic indicators and effective therapies. Although research has traditionally focused on the hypothesis that high-grade serous carcinoma (HGSC) arises from the ovarian surface epithelium (OSE), recent studies suggest that additional sites of origin exist and a substantial proportion of cases may arise from precursor lesions located in the Fallopian tubal epithelium (FTE). In FTE cells, the transcription factor PAX8 is a marker of the secretory cell lineage and its expression is retained in 96% of EOC. We have recently reported that PAX8 is involved in the tumorigenic phenotype of ovarian cancer cells. In this study, to uncover genes and pathways downstream of PAX8 involved in ovarian carcinoma we have determined the molecular profiles of ovarian cancer cells and in parallel of Fallopian tube epithelial cells by means of a silencing approach followed by an RNA-seq analysis. Interestingly, we highlighted the involvement of pathways like WNT signaling, epithelial-mesenchymal transition, p53 and apoptosis. We believe that our analysis has led to the identification of candidate genes and pathways regulated by PAX8 that could be additional targets for the therapy of ovarian carcinoma. PMID:27259239
Jackson‐Jones, Lucy H.; Rückerl, Dominik; Svedberg, Freya; Duncan, Sheelagh; Maizels, Rick M.; Sutherland, Tara E.; Jenkins, Stephen J.; McSorley, Henry J.; Bénézech, Cécile; MacDonald, Andrew S.
IL‐33 plays an important role in the initiation of type‐2 immune responses, as well as the enhancement of type 2 effector functions. Engagement of the IL‐33 receptor on macrophages facilitates polarization to an alternative activation state by amplifying IL‐4 and IL‐13 signaling to IL‐4Rα. IL‐4 and IL‐13 also induce macrophage proliferation but IL‐33 involvement in this process has not been rigorously evaluated. As expected, in vivo delivery of IL‐33 induced IL‐4Rα‐dependent alternative macrophage activation in the serous cavities. IL‐33 delivery also induced macrophages to proliferate but, unexpectedly, this was independent of IL‐4Rα signaling. In a filarial nematode infection model in which IL‐4Rα‐dependent alternative activation and proliferation in the pleural cavity is well described, IL‐33R was essential for alternative activation but not macrophage proliferation. Similarly, during Alternaria alternata induced airway inflammation, which provokes strong IL‐33 responses, we observed that both IL‐4Rα and IL‐33R were required for alternative activation, while macrophage proliferation in the pleural cavity was still evident in the absence of either receptor alone. Our data show that IL‐33R and IL‐4Rα promote macrophage proliferation independently of each other, but both are essential for induction of alternative activation. PMID:27592711
Chen, Zhi-Qing; Wang, Wei
Purpose. To investigate the prevalence and characteristics of focal choroidal excavation (FCE) concurrent with central serous chorioretinopathy (CSC) using multimodal imaging. Methods. This was a retrospective single-institution study. Clinical features and multimodal imaging findings were analyzed in eyes with CSC and FCEs, using imaging methods including optical coherence tomography (OCT), OCT angiography (OCTA), fluorescein angiography (FA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), and multispectral imaging. Results. Seventeen patients (4.8%) with 21 FCEs (19 eyes) were found among 351 consecutive Chinese patients with CSC. Chronic CSC represented 47.1% of those cases. Window defects in 12 lesions identified through FA and hypoautofluorescence in 13 lesions identified through FAF revealed retinal pigment epithelial attenuation. Choroidal hemodynamic disturbances characterized by localized filling defects at the excavation and circumferential hyperperfusion were validated by both ICGA and OCTA, which were similar to the angiographic features of normal chronic CSC. The hyperreflective tissue beneath FCE, observed on B-scan OCT, presented as intensive choroidal flow signals on OCTA. Conclusions. FCE is not uncommon in patients with CSC. Multimodal imaging suggested that the aberrant choroidal circulation might be a contribution factor for leakage from the dysfunctional retinal pigment epithelium at the area of excavation. PMID:27437148
Li, Wensheng; Jiang, Fangzheng; Mao, Sihong; Tong, Yuhua
Purpose To evaluate the relationship between subfoveal choroidal thickness (SFCT) and eyes with central serous chorioretinopathy (CSC) versus fellow or control eyes. Methods We performed a meta-analysis using databases including PubMed, Embase and ISI Web of Science to find relevant studies. Weighted mean difference (WMD) was calculated for the SFCT in CSC eyes, the unaffected fellow eyes and normal controls. Results Twelve studies were selected for this meta-analysis, including 1108 eyes (397 CSC eyes, 228 unaffected fellow eyes and 483 eyes of normal controls). The meta-analysis clearly demonstrated that the subfoveal choiroid of eyes with a clinical presentation of CSC was thickened compared to unaffected fellow eyes (WMD = 52.81, 95% confidence interval (CI), 39.13–66.49, P<0.00001) and was thickened compared to control eyes (WMD = 145.03, 95%CI, 121.33–168.73, P<0.00001). The mean SFCT measurement of the unaffected fellow eyes showed also significantly increased choroidal thickness compared to that of normal control eyes (WMD = 77.20, 95% CI, 44.98–109.42, P<0.00001). Similar results were obtained in a sub-analysis based on the same instrument. Conclusion It is demonstrated that SFCT is significantly increased in eyes with clinical manifestation of CSC, and in the clinically non-manifested fellow eyes. These results support the hypothesis that CSC is a bilateral disorder with an initial unilateral clinical presentation. PMID:28076442
Chai, Yong; Liu, Rong-Qiang; Yi, Jing-Lin; Ye, Ling-Hong; Zou, Jing; Jiang, Nan; Shao, Yi
AIM To compare the effectiveness of combined fenofibrate and spironolactone with fenofibrate alone for treatment of central serous chorioretinopathy (CSCR). METHODS Totally 60 patients (60 eyes) with a history of acute CSCR were randomed into two groups: group A with combination of fenofibrate (200 mg) and spironolactone (100 mg), and group B with only fenofibrate (200 mg). They were taken half an hour before meals and once per day for 8wk. The changes of the visual acuity, subjective symptom, ocular surface disease index (OSDI), the tear film and optical coherence tomography were observed at 2, 4, 6, and 8wk before and after treatment. RESULTS The best corrected visual acuity (BCVA, logMAR) was improved to 0.22 and 0.27 after treatment from baseline of 0.35 and 0.36 in groups A and B (P<0.05), respectively. After 8wk treatment, the central subfield thickness (CST), and subretinal fluid volumn (SFV) decreased significantly to 49.5% and 78.8% in group A and 37.0% and 57.2% in group B. There were significant differences of CST and SFV in both groups (all P<0.05). CONCLUSION Fenofibrate combined with spironolactone may have more clinical efficacy in the treatment of CSCR than fenofibrate only. PMID:27803862
Hua, Guohua; Lv, Xiangmin; He, Chunbo; Remmenga, Steven W.; Rodabough, Kerry J.; Dong, Jixin; Yang, Liguo; Lele, Subodh M.; Yang, Peixin; Zhou, Jin; Karst, Alison; Drapkin, Ronny I.; Davis, John S.; Wang, Cheng
Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from Fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In the present study, we found that the Hippo/YAP signaling pathway plays a critical role in the initiation and progression of Fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous Fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation, and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine positive feedback loop to drive the progression of the FTSECs-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGFRs (such as BGJ398) can provide a novel therapeutic strategy to treat Fallopian tube and ovarian HGSC. PMID:26364602
Ciamberlini, C.; Guarnieri, V.; Longobardi, Giuseppe; Poggi, Pasquale; Donati, M. C.; Panzardi, G.; Panzardi, G.
In order to evaluate the use of low level light (LLL) indocyanine green angiography in the diagnosis and treatment of central serous choroidopathy (CSC), a new system for LLL infrared videoangiography is described. The system was coupled with a standard fundus camera employing a low-power continuous light source. The system consists of a cooled charge-coupled device (CCD) camera and a third-generation image intensifier. The CCD camera investigates the pathologies of choroidal images with very good performance in terms of spatial resolution, dynamic range, and signal- to-noise ratio. The image intensifier carries out the choroidal angiography in real time. The results of 48 cases of CSC demonstrated the following ICGV features: focal RPE leakage; hyperfluorescent areas appearing in late phases and underlying the focal leakage or pigment epithelium detachment (PED); PED in the guise of early hyperfluorescence areas; delays in choroidal filling. The findings support the hypothesis that CSC originates in the choroid with localized hyperpermeability. The system described minimized retinal illumination and demonstrated increased angiographic resolution and contrast compared with conventional ICG angiographic systems.
Leong, Huei San; Galletta, Laura; Etemadmoghadam, Dariush; George, Joshy; Köbel, Martin; Ramus, Susan J; Bowtell, David
High-grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost-effective and high-throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman-based (low-density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin-fixed, paraffin-embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo-naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials.
Yan, Shunfei; Frank, Daniel; Son, Jinbae; Hannan, Katherine M.; Hannan, Ross D.; Chan, Keefe T.; Pearson, Richard B.; Sanij, Elaine
Overall survival for patients with ovarian cancer (OC) has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC). HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR) and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC)-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting ribosome biogenesis as a novel therapeutic approach against HGSOC. PMID:28117679
Castellarin, Mauro; Milne, Katy; Zeng, Thomas; Tse, Kane; Mayo, Michael; Zhao, Yongjun; Webb, John R; Watson, Peter H; Nelson, Brad H; Holt, Robert A
High-grade serous carcinoma (HGSC) is the most common and fatal form of ovarian cancer. While most tumours are highly sensitive to cytoreductive surgery and platinum- and taxane-based chemotherapy, the majority of patients experience recurrence of treatment-resistant tumours. The clonal origin and mutational adaptations associated with recurrent disease are poorly understood. We performed whole exome sequencing on tumour cells harvested from ascites at three time points (primary, first recurrence, and second recurrence) for three HGSC patients receiving standard treatment. Somatic point mutations and small insertions and deletions were identified by comparison to constitutional DNA. The clonal structure and evolution of tumours were inferred from patterns of mutant allele frequencies. TP53 mutations were predominant in all patients at all time points, consistent with the known founder role of this gene. Tumours from all three patients also harboured mutations associated with cell cycle checkpoint function and Golgi vesicle trafficking. There was convergence of germline and somatic variants within the DNA repair, ECM, cell cycle control, and Golgi vesicle pathways. The vast majority of somatic variants found in recurrent tumours were present in primary tumours. Our findings highlight both known and novel pathways that are commonly mutated in HGSC. Moreover, they provide the first evidence at single nucleotide resolution that recurrent HGSC arises from multiple clones present in the primary tumour with negligible accumulation of new mutations during standard treatment.
Geiser, Franziska; Zur, Berndt
Psychological stress is a risk factor as well as a consequence of central serous chorioretinopathy (CSC). Impulsiveness, overachievement, emotional instability, and hard-driving competitiveness have been discussed as personality features in CSC patients. We investigated 57 consecutive CSC patients and 57 age- and gender-matched controls by means of the Symptom Checklist 90-R and the Temperament and Character Inventory. Somatic risk factors, illness characteristics, subjective assessment of severity of illness, and illness-related stress in different areas of life (work, private life) were evaluated. CSC patients showed significantly higher emotional distress as measured by the Global Severity Index. The CSC personality was characterized by lower scoring on the character dimension cooperativeness and the temperament dimension reward dependence. Cooperativeness as well as subjective assessment of severity of CSC has been recognized as significant predictors of illness-related work stress accounting for 30% of variance. Implicating competitiveness, hostility and emotional detachment, lower level of cooperativeness, and reward dependence support the existence of specific aspects of type A behaviour in CSC patients. Low perceived social support and loss of control may explain the significant contribution of this personality dimension to illness-related work stress. Treatment of CSC should thus incorporate psychoeducation about factors contributing to illness-related stress. PMID:24696654
Genovese, A M; Barbera, A; Fedele, F; Broccio, M; Lepore, V; Ciccolo, A
The case of a patient affected by an epithelial hemangioendothelioma of the arm is described. A definitive diagnosis was possible only by histologic examination. The difficulty to reliably predict the biological behaviour of these tumors is emphasized and therefore the necessity of a follow-up of the patient for many years is stressed, even in the case of a histologically benign tumor.
Fadare, Oluwole; Parkash, Vinita; Gwin, Katja; Hanley, Krisztina Z; Jarboe, Elke A; Liang, Sharon X; Quick, Charles M; Zheng, Wenxin; Rawish, Kojo R; Hecht, Jonathan L; Desouki, Mohamed M
The expression of α-methylacyl-coenzyme-A racemase (AMACR) has previously been reported in 75% to 100% of urethral/bladder clear cell carcinomas, tumors that are known to display broad phenotypic overlap with their identically named müllerian counterparts. Herein, we assess the utility of AMACR in distinguishing endometrial clear cell carcinomas (CCCs) from endometrial serous carcinomas (ESCs) and endometrial endometrioid carcinomas (EECs). A total of 111 endometrial carcinomas in a tissue microarray, including 49 CCCs, 13 ESCs, and 49 EECs, were assessed for AMACR immunoreactivity, with results scored semiquantitatively (scores 0, 1+, 2+, 3+ for 0%, 1%-5%, 6%-50%, >50% immunoreactive cells, respectively). Fifty (45%) of the 111 carcinomas were AMACR positive, with the following score distribution: CCC: 0 (n = 12), 1+ (n = 12), 2+ (n = 3), 3+ (n = 22); EEC: 0 (n = 38), 1+ (n = 4), 2+ (n = 4), 3+ (n = 3); ESC: 0 (n = 11), 1+ (n = 1), 2+ (n = 0), 3+ (n = 1). AMACR expression was significantly more frequent in CCC (75%) than in ESC (15%) or EEC (22%); P < .0001. The sensitivity and specificity of AMACR expression in classifying a carcinoma as CCC were 0.75 (95% confidence interval [CI], 0.61-0.86) and 0.79 (95% CI, 0.66-0.88), respectively, with an odds ratio of 11.62 (95% CI, 5-28; P < .001) and an area under the curve of 0.79 (95% CI, 0.68-0.88). These findings indicate that AMACR expression is strongly associated with CCC and displays a relatively robust diagnostic test performance. However, its practical utility may be limited by the focal nature of its expression in 32% of the AMACR-positive CCC cases as well as its expression in 15% to 22% of the non-CCC histotypes.
Kummar, Shivaani; Oza, Amit M.; Fleming, Gini F.; Sullivan, Daniel M.; Gandara, David R.; Naughton, Michael J.; Villalona-Calero, Miguel A.; Morgan, Robert J.; Szabo, Peter M.; Youn, Ahrim; Chen, Alice P.; Ji, Jiuping; Allen, Deborah E.; Lih, Chih-Jian; Mehaffey, Michele G.; Walsh, William D.; McGregor, Paul M.; Steinberg, Seth M.; Williams, Paul M.; Kinders, Robert J.; Conley, Barbara A.; Simon, Richard M.; Doroshow, James H.
Purpose Veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase 1 trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase 2 trial to determine the response rate of veliparib in combination with cyclophosphamide compared to cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC). Methods Adult patients were randomized to receive cyclophosphamide alone (50 mg orally once daily) or with veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the combination was allowed at disease progression. Results Seventy-five patients were enrolled and 72 were evaluable for response; 38 received cyclophosphamide alone and 37 the combination as their initial treatment regimen. Treatment was well tolerated. One complete response was observed in each arm, with three partial responses (PR) in the combination arm and six PRs in the cyclophosphamide alone arm. Genetic sequence and expression analyses were performed for 211 genes involved in DNA repair; none of the detected genetic alterations were significantly associated with treatment benefit. Conclusion This is the first trial that evaluated single agent, low dose cyclophosphamide in HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well tolerated and clinical activity was observed; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression free survival. PMID:25589624
Glenn, Catherine R.; Klonsky, E. David
Objective: Although the DSM-IV suggests that dysfunctional personality patterns can be traced back to adolescence, there is continued debate about whether borderline personality disorder (BPD) can be reliably and validly diagnosed before age 18. The current study examined the reliability and validity of BPD in a large sample of adolescent psychiatric patients. Method: BPD and Axis I disorders were assessed with validated structured interviews and a series of clinical, emotion, and personality correlates were assessed with validated self-report questionnaires. Results: Consistent with previous studies in adolescent clinical samples, approximately 30% of patients in the current sample met criteria for BPD. The nine BPD criteria demonstrated good internal consistency, equivalent to rates reported in adult samples. In addition, BPD was related to greater clinical severity and impairment as indexed by strong associations with all major Axis I disorders, as well as with dimensional measures of depression, anxiety, difficulties with emotion regulation, and impulsiveness. Notably, reliability and validity remained satisfactory even when analyses were limited to younger adolescents between the ages of 12 and 14. Conclusions: Overall, findings suggest that BPD can be reliably and validly diagnosed in adolescents as young as 12–14 years old. PMID:23970909
Fritzsche, Klaus H.; Brunner, Romuald; Henze, Romy; Meinzer, Hans-Peter; Stieltjes, Bram
As with other mental disorders, the causes of borderline personality disorder (BPD) are complex and not fully understood. In this study we aimed to determine whether adults with BPD exhibit microstructural abnormalities using diffusion tensor imaging (DTI). 56 female right-handed individuals (age range, 14-18 years), 19 with a DSM-IV diagnosis of BPD, 18 patients with a DSM-IV defined current psychiatric disorder and 19 healthy control subjects were included. Groups were matched for age and IQ. DTI Images were analyzed using Tract-Based Spatial Statistics (TBSS). The analysis revealed significanty reduced fractional anisotropy (FA) values in the group of BPD patients compared to the normal controls. Similar FA reductions could not be found comparing BPD patients to clinical controls. Several clusters of increased radial (DR), axial (DA), and mean (MD) diffusivity were consistently identified when comparing the BPD patients to clinical as well as to healthy controls. None of the measures showed significant differences between the clinical and healthy controls. Diverse possible factors have been suggested to play a role in the disease, including environmental factors, neurobiological factors, or brain abnormalities. The presented results may play an important role in this ongoing debate.
Goodman, Marianne; Patil, Uday; Steffel, Lauren; Avedon, Jennifer; Sasso, Scott; Triebwasser, Joseph; Stanley, Barbara
Minimal data exist on treatment utilization by gender in borderline personality disorder (BPD). This study used an online questionnaire to investigate initial and lifetime patterns of utilization of multiple treatment modalities by patients with BPD, and parental satisfaction with treatment. Respondents were parents of probands diagnosed with BPD who completed a 100-question anonymous Internet survey. Of the 495 surveys that were analyzed, 409 pertained to female subjects with BPD and 86 to male subjects with BPD. Results for probands with BPD across gender were notable for similar high lifetime levels of use of care, including hospitalization, day programs, and halfway houses, but not similar levels of use of drug/alcohol rehabilitation services, which was greater among the male subjects with BPD. The male subjects with BPD received significantly less lifetime psychotherapy and pharmacotherapy than the female subjects with BPD, although the duration of medication and psychotherapy treatment did not differ by gender. These results highlight the need for more research to better understand what might account for these gender differences in treatment and improve strategies to provide appropriate care for male patients with BPD.
Stepp, Stephanie D; Pilkonis, Paul A; Hipwell, Alison E; Loeber, Rolf; Stouthamer-Loeber, Magda
Little empirical evidence exists regarding developmental antecedents of borderline personality disorder (BPD) features in children and adolescents. As a first step in addressing this gap in our knowledge, this study examined the factor structure and stability of putative underlying BPD features, specifically impulsivity, negative affectivity, and interpersonal aggression, in 6-12-year-old girls. We report on results from exploratory and confirmatory factor analyses of underlying BPD dimensions as rated by parents and teachers over six successive data waves in a large, community sample of girls (N = 2,451). Six factors were derived from parent ratings (i.e., Cognitive Dyscontrol, (Lack of) Self-Control, Hostility, Depression/Anxiety, Hyperactivity, and Relational Aggression) and five factors were derived from teacher reports (i.e., Cognitive Dyscontrol, Hyperactivity, (Lack of) Self-Control, Relational Aggression, and Depression). The item composition of similar parent and teacher factors was highly consistent. The year-to-year stability from ages 6 to 12 was high for parent factor scores (r ranging from .71-.85) and moderately high for teacher factor scores (r ranging from .49-.77). These findings suggest that underlying dimensions of BPD features can be reliably measured and are stable in 6-12-year-old girls.
Zalewski, Maureen; Stepp, Stephanie D; Scott, Lori N; Whalen, Diana J; Beeney, Joseph F; Hipwell, Alison E
Maternal borderline personality disorder (BPD) symptoms are associated with poorer parenting. However, most studies conducted are with young children. In the current study, the authors examined associations between maternal BPD symptoms and parenting in an urban community sample of 15-to 17-year-old girls (n = 1,598) and their biological mothers. Additionally, the authors tested the impact of adolescent temperament on these associations. Mothers reported on their own psychopathology and their daughters' temperament. Adolescent girls reported on mothers' parenting methods in terms of psychological and behavioral control. Results demonstrated that maternal BPD symptoms were associated with aspects of psychological and behavioral control, even after controlling for maternal depression and alcohol use severity. After examining specific BPD components that may account for these associations, the authors found that affective/behavioral dysregulation, but not interpersonal dysregulation or identity disturbance, uniquely accounted for parenting. Adolescent temperament did not moderate these associations. BPD symptoms, particularly affective/behavioral dysregulation, are important targets when conducting parenting interventions.
Chlebowski, Susan M
The child whose mother is diagnosed with borderline personality disorder (BPD) is at risk for developing this disorder. The mother with BPD may be limited in her ability to negotiate a secure attachment with her baby. Mothers with BPD may have difficulties with bonding, internalization, affect attunement, and attachment. Because it is through mirroring and mentalization that a child can learn emotional regulation and master the early stages of development, the child may fail to develop object constancy and master the tasks of separation and individuation. The authors present two cases of patients with BPD. The first case is of a patient with BPD who, after surrendering custody of her two children to their father, participated in weekly Dynamic Deconstructive Psychotherapy sessions for two years. The second case is a mother with BPD who presents for dyadic therapy with her three-month-old daughter. In each case the mother developed insight regarding her relationship with her mother and how that relationship affected the relationship with her own child. The author concludes that psychiatry should consider prepartum screening for BPD and if necessary, early dyadic intervention.
Bandelow, Borwin; Schmahl, Christian; Falkai, Peter; Wedekind, Dirk
The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems, including serotoninergic, dopaminergic, and other neurotransmitter systems, have been discussed. Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids constitute part of the underlying pathophysiology of BPD. The alarming symptoms and self-destructive behaviors of the affected patients may be explained by uncontrollable and unconscious attempts to stimulate their endogenous opioid system (EOS) and the dopaminergic reward system, regardless of the possible harmful consequences. Neurobiological findings that support this hypothesis are reviewed: Frantic efforts to avoid abandonment, frequent and risky sexual contacts, and attention-seeking behavior may be explained by attempts to make use of the rewarding effects of human attachment mediated by the EOS. Anhedonia and feelings of emptiness may be an expression of reduced activity of the EOS. Patients with BPD tend to abuse substances that target mu-opioid receptors. Self-injury, food restriction, aggressive behavior, and sensation seeking may be interpreted as desperate attempts to artificially set the body to survival mode in order to mobilize the last reserves of the EOS. BPD-associated symptoms, such as substance abuse, anorexia, self-injury, depersonalization, and sexual overstimulation, can be treated successfully with opioid receptor antagonists. An understanding of the neurobiology of BPD may help in developing new treatments for patients with this severe disorder.
Morse, Jennifer Q; Hill, Jonathan; Pilkonis, Paul A; Yaggi, Kirsten; Broyden, Nichaela; Stepp, Stephanie; Reed, Lawrence Ian; Feske, Ulrike
Emotional dysregulation and attachment insecurity have been reported in borderline personality disorder (BPD). Domain disorganization, evidenced in poor regulation of emotions and behaviors in relation to the demands of different social domains, may be a distinguishing feature of BPD. Understanding the interplay between these factors may be critical for identifying interacting processes in BPD and potential subtypes of BPD. Therefore, we examined the joint and interactive effects of anger, preoccupied attachment, and domain disorganization on BPD traits in a clinical sample of 128 psychiatric patients. The results suggest that these factors contribute to BPD both independently and in interaction, even when controlling for other personality disorder traits and Axis I symptoms. In regression analyses, the interaction between anger and domain disorganization predicted BPD traits. In recursive partitioning analyses, two possible paths to BPD were identified: high anger combined with high domain disorganization and low anger combined with preoccupied attachment. These results may suggest possible subtypes of BPD or possible mechanisms by which BPD traits are established and maintained.
LeGris, Jeannette; Toplak, Maggie; Links, Paul S
The affective decision making of 41 recently treated outpatient women with borderline personality disorder (BPD) was compared to 41 healthy controls using the Iowa Gambling Task (IGT). Non-affective executive functions (EF) of working memory, interference control, and motor inhibition were also compared. Associations among affective and non-affective EF were examined. Despite normal range intelligence, Stroop interference, motor inhibition, and working memory, women with BPD made significantly more disadvantageous IGT decisions than controls (Cohen's d = .72) that were unrelated to substance abuse history, education, psychotropic use, or attentional deficits. Correlates of EF and IGT performance varied by group. Intellect, BPD, and intact behavioral control explained 35% of the adjusted variance in net IGT performance. Disadvantageous IGT decision making was the only EF to predict BPD. IGT deficits in BPD may be separable from IQ and other EF as supported by the somatic marker hypothesis and suggest a stable, trait-like vulnerability favoring immediate reward over long-term gain in women with the disorder.
Chalker, Samantha A.; Carmel, Adam; Atkins, David C.; Landes, Sara J.; Kerbrat, Amanda H.; Comtois, Katherine Anne
Few studies have examined effects of challenging behaviors of clients with borderline personality disorder (BPD) on psychotherapy outcomes. Dialectical behavior therapy (DBT) is an evidence-based treatment designed to treat chronic suicidality, self-directed violence (SDV), and emotion dysregulation, while targeting challenging behaviors. DBT has been shown to be effective with clients with BPD. We evaluated whether therapist reported challenging behaviors, such as high volume phone contacts or violating the therapist’s limits, during DBT would be associated with dropping out of DBT, severity and frequency of SDV, emotion regulation deficits, and client’s and therapist’s satisfaction of treatment. The current study examined challenging behaviors reported by therapists in a sample of 63 psychiatrically disabled outpatient DBT clients diagnosed with BPD (73% women, average age 37 years). More frequent phone contacts were associated with a decrease in dropout and psychological symptoms, and an increase in client and therapist satisfaction. More avoidance/disengagement behavior was associated with more than twice the risk of SDV and a decrease in therapist satisfaction. Findings suggest that the phone coaching might serve to maximize client satisfaction and reduce the likelihood of dropout. PMID:26496225
Menon, Preethi; Chaudhari, Bhushan; Saldanha, Daniel; Devabhaktuni, Spandana; Bhattacharya, Labanya
Background: Researchers have found elevated rates of childhood sexual abuse (CSA) in borderline personality disorder (BPD) patients. They have also implicated the role of CSA later in BPD. However, there has been a scarcity of studies regarding this in Indian population. Objectives: To profile the occurrence of CSA and its parameters in BPD patients and to document symptomatology of BPD associated with CSA. Materials and Methods: Thirty-six consecutive patients with BPD were administered with a two-staged semi-structured interview by different interviewers with the first stage for collecting sociodemographic details and confirming BPD diagnosis and the second stage for collecting information about CSA. Results: Of 36 BPD patients, 16 (44.44%) reported a history of definite CSA. The majority of CSA associated with BPD were having characteristics of onset at 7–12 years, <10 occasions of abuse, perpetrator being a close relative or a close acquaintance and genital type of CSA. Identity disturbances (P = 0.0354), recurrent suicidal/self-harm behavior (P = 0.0177), and stress-related paranoid/dissociative symptoms (P = 0.0177) were significantly associated with the presence of CSA while unstable interpersonal relationships (P = 0.001) were significantly associated with the absence of CSA. Conclusion: Significant proportion of BPD patients reported CSA. The specific symptom profile of BPD patients can be used to predict the presence of CSA in these patients, which has a direct implication in the treatment of these patients. PMID:28163415
Turhan, Sibel; Taylor, Mark
Aims and method There is currently no trial or other scientific evidence informing the efficacy of any crisis intervention for people with borderline personality disorder (BPD). We aimed to assess the patterns of service use by patients with BPD taken on for crisis resolution and home treatment between 2010 and 2013. Patients with a diagnosis of BPD were identified and demographic and clinical data were collected. Results All patients were female, and a high proportion had recurrent presentations to crisis and home treatment services in Edinburgh. Many appeared to benefit from intensive home treatment, as measured by the Clinical Global Impression scale. A small number of patients (n = 5) were responsible for more than half of all referrals. Polypharmacy, or regular use of multiple medications, was common, with 62% of all patients receiving three or more regular medications. Clinical implications Crisis and home treatment services can be beneficial to most people with BPD in crisis. The high rate of polypharmacy seen in this study is of concern. PMID:28377808
Zalewski, Maureen; Stepp, Stephanie D.; Scott, Lori N.; Whalen, Diana J.; Beeney, Joseph F.; Hipwell, Alison E.
Maternal borderline personality disorder (BPD) symptoms are associated with poorer parenting. However, most studies conducted are with young children. In the current study, the authors examined associations between maternal BPD symptoms and parenting in an urban community sample of 15- to 17-year-old girls (n = 1,598) and their biological mothers. Additionally, the authors tested the impact of adolescent temperament on these associations. Mothers reported on their own psychopathology and their daughters' temperament. Adolescent girls reported on mothers' parenting methods in terms of psychological and behavioral control. Results demonstrated that maternal BPD symptoms were associated with aspects of psychological and behavioral control, even after controlling for maternal depression and alcohol use severity. After examining specific BPD components that may account for these associations, the authors found that affective/behavioral dysregulation, but not interpersonal dysregulation or identity disturbance, uniquely accounted for parenting. Adolescent temperament did not moderate these associations. BPD symptoms, particularly affective/behavioral dysregulation, are important targets when conducting parenting interventions. PMID:24689767
Bateman, Anthony; Fonagy, Peter
Mentalization is the process by which we implicitly and explicitly interpret the actions of ourselves and others as meaningful based on intentional mental states (e.g., desires, needs, feelings, beliefs, and reasons). This process is disrupted in individuals with comorbid antisocial (ASPD) and borderline personality disorder (BPD), who tend to misinterpret others' motives. Antisocial characteristics stabilize mentalizing by rigidifying relationships within prementalistic ways of functioning. However, loss of flexibility makes the person vulnerable to sudden collapse when the schematic representation is challenged. This exposes feelings of humiliation, which can only be avoided by violence and control of the other person. The common path to violence is via a momentary inhibition of the capacity for mentalization. In this article, the authors outline their current understanding of mentalizing and its relation to antisocial characteristics and violence. This is illustrated by a clinical account of mentalization-based treatment adapted for antisocial personality disorder. Treatment combines group and individual therapy. The focus is on helping patients maintain mentalizing about their own mental states when their personal integrity is challenged. A patient with ASPD does not have mental pain associated with another's state of mind; thus, to generate conflict in ASPD by thinking about the victim will typically be ineffective in inducing behavior change.
Martin, Franziska; Flasbeck, Vera; Brown, Elliot C; Brüne, Martin
Borderline Personality Disorder (BPD) is characterized, among other symptoms, by interpersonal dysfunction and difficulties in empathizing. According to Simulation Theory empathy is linked to the activity of the mirror neuron system (MNS). Mu-rhythm desynchronization, as reflected in a suppression of electroencephalographic alpha-frequency bands (8-13Hz) provides a non-invasive electrophysiological window into MNS function. Here, we analyzed mu-desynchronization in twenty-two patients with BPD and twenty-three matched healthy controls in a reward and punishment-sensitive action observation task. In addition, we examined empathy using the Interpersonal Reactivity Index. BPD patients and controls did not differ with regard to mu-desynchronization when the entire time course was compared. However, differences in mu-suppression between groups occurred after the goal of the action became discernible. Correlations between mu-suppression and empathy ratings emerged only in controls, but not in the patient group. These findings suggest that BPD patients do not have a generalized impairment in MNS activity, though associations with contextual factors seem plausible.
HURLEMANN, RENÉ; HAWELLEK, BARBARA; MAIER, WOLFGANG; DOLAN, RAYMOND J.
Background Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion–episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence. Method To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls. Results BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects. Conclusion These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD. PMID:17224096
Liebke, Lisa; Bungert, Melanie; Thome, Janine; Hauschild, Sophie; Gescher, Dorothee Maria; Schmahl, Christian; Bohus, Martin; Lis, Stefanie
Persistent loneliness is often reported by patients with borderline personality disorder (BPD). However, empirical studies investigating this aspect of BPD psychopathology are sparse. Studies from social psychology revealed that social isolation and low social functioning contribute to loneliness, that is, the subjective feeling of being alone. The aim of the present study was to contribute to the understanding of loneliness in BPD by investigating its relation to social isolation and functioning in different domains of life. Subjective experience of loneliness was measured in 80 women (40 BPD patients, 40 healthy controls) with the UCLA Loneliness Scale. Social isolation and social functioning were assessed with the Social Network Inventory and the Social Functioning Scale. In addition, we assessed global functioning with the Global Assessment of Functioning. BPD patients reported stronger feelings of loneliness compared to healthy participants. In general, the level of loneliness was linked to network size, social engagement, and prosocial behavior. Diversity of social networks and functioning in the domain of interpersonal communication were associated with the level of loneliness only in BPD. A reduced variety of roles in social life together with impairments in interpersonal communication were particularly relevant for the experience of loneliness in BPD, suggesting an indirect path to target this psychopathological feature in therapeutic interventions. However, both social isolation and social functioning were not sufficient to explain the severely increased loneliness experienced by these patients, stressing the need for further investigation of determinants of loneliness in this clinical population. (PsycINFO Database Record
Zimmerman, Mark; Morgan, Theresa A
It is clinically important to recognize both bipolar disorder and borderline personality disorder (BPD) in patients seeking treatment for depression, and it is important to distinguish between the two. Research considering whether BPD should be considered part of a bipolar spectrum reaches differing conclusions. We reviewed the most studied question on the relationship between BPD and bipolar disorder: their diagnostic concordance. Across studies, approximately 10% of patients with BPD had bipolar I disorder and another 10% had bipolar II disorder. Likewise, approximately 20% of bipolar II patients were diagnosed with BPD, though only 10% of bipolar I patients were diagnosed with BPD. While the comorbidity rates are substantial, each disorder is nontheless diagnosed in the absence of the other in the vast majority of cases (80% to 90%). In studies examining personality disorders broadly, other personality disorders were more commonly diagnosed in bipolar patients than was BPD. Likewise, the converse is also true: other axis I disorders such as major depression, substance abuse, and post-traumatic stress disorder are also more commonly diagnosed in patients with BPD than is bipolar disorder. These findings challenge the notion that BPD is part of the bipolar spectrum.
Palmio, Johanna; Udd, Bjarne
Numerous natural or disease-related alterations occur in different tissues of the body with advancing age. Sarcopenia is defined as age-related decrease of muscle mass and strength beginning in mid-adulthood and accelerating in people older than 60 years. Pathophysiology of sarcopenia involves both neural and muscle dependent mechanisms and is enhanced by multiple factors. Aged muscles show loss in fiber number, fiber atrophy, and gradual increase in the number of ragged red fibers and cytochrome c oxidase-negative fibers. Generalized loss of muscle tissue and increased amount of intramuscular fat are seen on muscle imaging. However, the degree of these changes varies greatly between individuals, and the distinction between normal age-related weakening of muscle strength and clinically significant muscle disease is not always obvious. Because some of the genetic myopathies can present at a very old age and be mild in severity, the correct diagnosis is easily missed. We highlight this difficult borderline zone between sarcopenia and muscle disease by two examples: LGMD1D and myotonic dystrophy type 2. Muscle magnetic resonance imaging (MRI) is a useful tool to help differentiate myopathies from sarcopenia and to reach the correct diagnosis also in the elderly. PMID:25324776
Pearse, Laura J; Dibben, Claire; Ziauddeen, Hisham; Denman, Chess; McKenna, Peter J
Patients with borderline personality disorder (BPD) report psychotic symptoms, but it has been questioned whether they are intrinsic to BPD. Thirty patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for BPD were drawn from a specialist personality disorder service. Exclusion criteria included a preexisting clinical diagnosis of nonaffective psychotic disorder. Participants underwent structured psychiatric interview using the Present State Examination (PSE), lifetime version. Approximately 60% of the patients reported psychotic symptoms unrelated to drugs or affective disorder. Auditory hallucinations were the most common symptom (50%), which were persistent in the majority of cases. A fifth of the patients reported delusions, half of whom (three patients) also met DSM-IV criteria for schizophrenia, who were previously undiagnosed. The form of auditory hallucinations was similar to that in schizophrenia; the content was predominantly negative and critical. Persistent auditory hallucinations are intrinsic symptoms of BPD. This may inform current diagnostic criteria and have implications for approaches to treatment, both pharmacological and psychological. The presence of delusions may indicate a comorbid axis I disorder.
Food supplements are classified as foods. They are concentrated sources of vitamins and minerals or other substances with a nutritional or physiological effect. Their purpose is to supplement the normal diet. Food supplements have to comply with the applicable legal provisions of the food law. In order to ensure the health protection of consumers, food supplements that will be put on the market must be safe. For food supplements, regulations exist at the EU level as well as at the national level. Specific requirements are regulated in the Ordinance on Food Supplements, with which the European Directive on Food Supplements was transposed into German law. The European and German legal provisions applicable to food supplements are outlined. Important aspects regarding the delimitation between food supplements and medicinal products are addressed. These borderline issues are of special importance to food supplements which are marketed in dose forms such as capsules, tablets etc., the typical forms of medicinal products. Problems resulting from the lack of harmonized rules are described. The European harmonization of the rules is still incomplete for substances with a nutritional or physiological effect other than vitamins and minerals for use in food supplements. The setting of maximum amounts of vitamins and minerals present in food supplements as envisaged in the Directive on Food Supplements has not yet been implemented.
Reitsma, Welmoed; Mourits, Marian J E; de Bock, Geertruida H; Hollema, Harry
Serous endometrial intraepithelial carcinoma has been proposed to be a potential precursor lesion of pelvic high-grade serous carcinoma. If true, an increased incidence of uterine papillary serous carcinomas would be expected in BRCA1 and BRCA2 mutation carriers, who are at high-risk of developing pelvic high-grade serous carcinoma. This study explored particularly the occurrence of uterine papillary serous carcinoma, as well as other endometrial cancers, following risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 germline mutation attending a tertiary multidisciplinary clinic. A consecutive series of women with a BRCA1 or BRCA2 mutation who had undergone risk-reducing salpingo-oophorectomy without hysterectomy at the University Medical Center Groningen from January 1996 until March 2012 were followed prospectively. They were crossed with the histopathology list of endometrial cancer diagnoses reported by the Dutch nationwide pathology database PALGA. To assess the risk of endometrial cancer, a standardized incidence ratio was calculated comparing the observed with the expected number of endometrial cancer cases. Overall, 201 BRCA1 and 144 BRCA2 mutation carriers at a median age of 50 years (range, 32-78) were analyzed. After a median follow-up period of 6 years, after risk-reducing salpingo-oophorectomy, two cases of endometrial cancer were diagnosed, whereas the expected number was 0.94 cases (standardized incidence ratio 2.13; 95% confidence interval 0.24-7.69; P=0.27). Both endometrial cancer cases were of the endometrioid histological subtype. We showed that the incidence of endometrial cancer following risk-reducing salpingo-oophorectomy, especially uterine papillary serous carcinoma, in women at high-risk of developing pelvic high-grade serous carcinoma is not increased. On the basis of our data, the hypothesis of serous endometrial intraepithelial carcinoma being an important precursor lesion of pelvic high-grade serous carcinoma seems
Chenevix-Trench, G.; Kerr, J.; Hurst, T.
The genetic events that give rise to ovarian adenocarcinoma are poorly understood, nor is it known whether the benign, low malignant potential (LMP) and malignant tumors represent a continuum. This study reports K-ras mutation and loss of heterozygosity (LOH) analysis in 116 tumors, including benign and LMP tumors, on twelve chromosomes chosen mainly because they contain candidate suppressor genes. The data were analyzed with respect to clinicopathological information. The highest rates of LOH were on chromosomes 17 and 18. With the exception of chromosomes 2 and X, all the others were deleted in 25-50% of tumors. Significant associations were found between LOH on chromosomes 7 and 9p, and between chromosomes 5, 17 and 18. LOH was observed in benign and LMP tumors on chromosomes 7 and 9, and homozygous deletions of markers at 9p21 were detected in 2/10 ovarian tumor cell lines. The target of the 9p deletions is likely to be the MTS1/p16 cdk4 inhibitor gene and mutation analysis is under way. A single tumor had a rearrangement of the plasminogen activator inhibitor type 1 locus on chromosome 7 but deletion mapping indicates that this may not be the target of chromosome 7 LOH. K-ras mutations were detected in nine tumors, and were significantly more common in LMP than in malignant tumors. A preliminary genetic model for ovarian tumorigenesis in presented based on these and published data. This model proposes that LMP and malignant tumors arise independently in benign neoplasms in which LOH of chromosomes 7 and 9 has occurred. LMP tumors then develop following activation of the K-ras oncogene, while malignant tumors arise from inactivation of p53 and many other tumor suppressor genes.
Pătraşcu, Anca; Popescu, Carmen Florina; Pleşea, I E; Bădulescu, Adriana; Tănase, Florentina; Mateescu, Garofiţa
The frequency of mesenchymal breast tumors is very low, being represented mostly by tumors with biphasic proliferation (phyllodes tumors) and less by other types of non-epithelial tumors. From clinical point of view, phyllodes tumors (PT) can mimic a breast carcinoma. Therefore, the preoperative diagnosis by cytological examination on material obtained by fine needle aspiration (FNA) is very important for adequate treatment of these tumors. In current study, we assessed clinical aspects of 79 phyllodes tumors regarding patient's age and localization of the tumors. In 17 out of 79 cases, it has been performed FNA within the tumors with further cytological examination on the smears obtained. The median age of the patients was 46.07-year-old, being progressively higher with grade of the tumors with significant values between benign and borderline tumors (p=0.04954) and between benign and malignant ones (p=0.02890). The distinguish on the smears of stromal fragments and naked stromal nuclei with variable grade of atypia regarding the tumoral type, in detriment of epithelial elements have been conclusive for fibroepithelial lesion as cytopathological diagnosis. The preoperative differentiation between a breast phyllodes tumor and a breast carcinoma is extremely important for avoiding of a useless radical surgery for the patient. If the fine needle aspiration was correctly performed, the accuracy of the cytodiagnosis has been 82% in current study.
... Outer Ear Ear Blockages Ear Tumors External Otitis (Swimmer's Ear) Malignant External Otitis Perichondritis Tumors of the ... Outer Ear Ear Blockages Ear Tumors External Otitis (Swimmer's Ear) Malignant External Otitis Perichondritis NOTE: This is ...
It is shown that when a mammalian serous membrane bathed in dilute buffer is traversed by an electric current, liquid is caused to stream through the membrane toward the cathode when the pH value of the buffer is on the alkaline side of a certain critical hydrogen ion concentration. Streaming is toward the anode on the acid side of the reversal point. Simple means for studying this electroendosmosis quantitatively are described. The mean values of the reversal points in all cases studied with the present buffers lie between pH = 4.3 and 5.3. The membranes studied have been the mesentery of the living and dead animal, and the parietal pericardium and pleura, post mortem. The membranes of dogs, cats, rabbits, and two human pericardia have been studied. All these membranes are essentially sheets of connective tissue, bearing blood vessels, lymphatics, and nerves, and in some instances fat cells, and lined on each surface by a single layer of pavement mesothelial cells. Intercellular fibers form the major bulk of the lean membranes. These are predominantly collagenous except in the pleural region used, in which elastin fibers are present in large proportion. By using buffers alternately more acid or more alkaline than the reversal point, the direction of liquid flow across any given membrane site could be reversed an indefinite number of times. The time interval required is only that taken by the requisite manipulation in changing buffers and making the runs. The mean values of the reversal points for the several membranes when bathed in hypotonic, unbalanced buffer and in isotonic, physiologically balanced buffers showed only small and inconstant differences. The fat and lean pericardia similarly showed small difference in the positions of the mean reversal points. The apparent reversal points for the mesenteries of living animals proved to be lower than those for the mesenteries post mortem. This low value in the animals with functioning circulation is interpreted as
Zhang, Yong-Li; Chen, Jin-Hong; Lu, Wen; Li, Bi-Lan; Zhu, Qin-Yi; Wan, Xiao-Ping
Background: Ovarian cancer is the most common cause of gynecological cancer-associated death. Iatrogenic menopause might adversely affect the quality of life and health outcomes in young female cancer survivors. We evaluated whether postoperative hormone replacement therapy (HRT) had a negative influence on the progression-free survival (PFS) of patients with papillary serous ovarian cancer (SOC). Methods: We retrospectively reviewed the medical records of patients with papillary SOC, treated from January 1980 to December 2009, who suffered from menopause with or without HRT. Clinical characteristics of patients were compared between the two groups (HRT and non-HRT). Blood samples were collected from all the participants to detect serum cancer antigen (CA) 125. Hazard ratios with 95% confidential intervals for each variable were calculated by univariable and multivariable conditional Logistic regression analyses. Results: Among 112 identified patients, 31 were HRT users and 81 were not. The two groups did not significantly differ in median age at diagnosis (t = 0.652, P = 0.513), International Federation of Gynecology and Obstetrics (FIGO) stage (χ2 = 0.565, P = 0.754), differentiation (χ2 = 1.728, P = 0.422), resection status (χ2 = 0.070, P = 0.791), relapse (χ2 = 0.109, P = 0.741), chemotherapy course (t = −1.079, P = 0.282), follow-up interval (t = 0.878, P = 0.382), or PFS (t = 0.580, P = 0.562). Median Kupperman score at the onset of HRT was 30.81 and 12.19 after the therapy (t = 3.302, P = 0.001). According to the analysis, the strongest independent variables in predicting PFS were FIGO stage and disease that was not optimally debulked. Conclusions: Postoperative HRT is not a prognostic factor for PFS of patients with papillary SOC. However, multicenter studies are needed to verify and extend our findings. PMID:27231169
Purpose To compare the levels of serum cortisol and testosterone in acute and chronic central serous chorio-retinopathy (CSC). Methods Serum cortisol and testosterone levels in 30 patients with either acute or chronic CSC were evaluated using chemiluminescent immunoassay. Results The mean age was 42.43 ± 6.37 years (range, 32 to 56 years). The mean 8:00 to 9.00 a.m. serum cortisol level was 12.61 ± 4.74 µg/dL (range, 6.58 to 27.42 µg/dL). The mean serum testosterone level was 5.88 ± 1.57 ng/dL (range, 2.81 to 9.94 ng/dL). The mean visual acuity was 20 / 65.07 ± 40.56 (range, 20 / 25 to 20 / 200). There was no statistically significant difference in the mean levels of serum cortisol and testosterone between the acute and chronic cases (p > 0.05), but there was a statistically significant difference in the mean presenting visual acuity in the two groups (p < 0.05). Conclusions All except one patient in the acute group had normal levels of serum cortisol. Testosterone levels were within the normal range in both the acute and chronic cases of CSC. There is unlikely to be any statistically significant difference in the mean levels of serum cortisol and testosterone between the acute and chronic cases, but there may be a statistically significant difference in the mean presenting visual acuity in these groups. PMID:26635454
Debate about suitability or clinicians' low expectations has led to patients with personality disorders being labeled as difficult and being socially excluded from pathways of care. Traditional psychotherapeutic treatments in borderline personality disorder demand too much of these patients' fractured ego structures for meaningful (long-term) therapeutic engagement. However, these patients cause clinicians anxiety and are a burden in health care systems. This article describes the challenge for clinical care teams working in partnership arrangements-psychotherapy and psychiatry services-to provide a containing framework of care. Early access to a pragmatic psychoanalytically oriented group treatment in borderline personality disorder is aimed at offering these patients an opportunity to make transitions in borderline treatment and thus alter the trajectory of their (self-) destructive pathway. A clinical and theoretical case is made for clinicians and health strategists to re-engage in the process of making meaningful early contact with borderline vulnerability. The group-based treatment model in borderline disturbance described in this article has helped forge partnerships between psychotherapy and psychiatric teams in providing in-depth diagnostic and prognostic information early in the patients' journey.
Distel, Marijn A; Rebollo-Mesa, Irene; Willemsen, Gonneke; Derom, Catherine A; Trull, Timothy J; Martin, Nicholas G; Boomsma, Dorret I
Borderline personality disorder is a severe personality disorder for which genetic research has been limited to family studies and classical twin studies. These studies indicate that genetic effects explain 35 to 45% of the variance in borderline personality disorder and borderline personality features. However, effects of non-additive (dominance) genetic factors, non-random mating and cultural transmission have generally not been explored. In the present study an extended twin-family design was applied to self-report data of twins (N = 5,017) and their siblings (N = 1,266), parents (N = 3,064) and spouses (N = 939) from 4,015 families, to estimate the effects of additive and non-additive genetic and environmental factors, cultural transmission and non-random mating on individual differences in borderline personality features. Results showed that resemblance among biological relatives could completely be attributed to genetic effects. Variation in borderline personality features was explained by additive genetic (21%; 95% CI 17-26%) and dominant genetic (24%; 95% CI 17-31%) factors. Environmental influences (55%; 95% CI 51-60%) explained the remaining variance. Significant resemblance between spouses was observed, which was best explained by phenotypic assortative mating, but it had only a small effect on the genetic variance (1% of the total variance). There was no effect of cultural transmission from parents to offspring.
Saito, I; Takeshita, E; Saruta, T; Nagano, S; Sekihara, T
It has been reported that patients with essential hypertension have high plasma prolactin levels and suggested that reduced central dopaminergic activity may be a factor in the pathogenesis of essential hypertension. This study examines the influence of posture on plasma prolactin, plasma catecholamines, plasma renin activity, blood pressure and heart rate in 24 patients with borderline hypertension (age 19 +/- 1 years) and 20 normotensive subjects matched for age and body mass index. Supine plasma prolactin levels were similar in both groups [borderline hypertension, 11.3 +/- 0.7 ng/ml; normotensive, 10.7 +/- 0.8 ng/ml (mean +/- s.e.m.)] and no increase in plasma prolactin was observed after 10 min standing in both groups. Normotensive and borderline hypertensive subjects had similar values for supine and upright plasma renin activity and plasma norepinephrine. There were no significant correlations between supine plasma prolactin and supine blood pressure, supine plasma renin activity or plasma norepinephrine when data from both normotensive and borderline hypertensive subjects were combined. These results may provide indirect evidence against the occurrence of reduced central dopaminergic activity in borderline hypertension.
Workel, Hagma H.; Tijans, Aline M.; Terwindt, Anouk L.J.; Brunekreeft, Kim L.; Plat, Annechien; Klip, Harry G.; Eggink, Florine A.; Leffers, Ninke; Helfrich, Wijnand; Samplonius, Douwe F.; Bremer, Edwin; Wisman, G. Bea A.; Daemen, Toos; Duiker, Evelien W.; Hollema, Harry; Nijman, Hans W.; de Bruyn, Marco
CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous epithelial ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident or mucosal lymphocytes remains largely unknown. In this study, we first confirmed that CD103+ TIL from HGSC were predominantly localized in the cancer epithelium and were strongly correlated with an improved prognosis. We further demonstrate that CD103+ TIL were almost exclusively CD3+ TCRαβ+ CD8αβ+ CD4- T cells, but heterogeneously expressed T cell memory and differentiation markers. Activation of peripheral T cells in the presence of HGSC was sufficient to trigger induction of CD103 in over 90% of all CD8+ cells in a T cell receptor (TCR)- and TGFβR1-dependent manner. Finally, CD103+ TIL isolated from primary HGSC showed signs of recent activation and dominantly co-expressed key immunotherapeutic targets PD-1 and CD27. Taken together, our data indicate CD103+ TIL in HGSC are formed as the result of an adaptive anti-tumor immune response that might be reactivated by (dual) checkpoint inhibition. PMID:27650547
Khan, Muhammad Saim; Sameen, Murtaza; Lodhi, Arshad Ali; Ahmed, Munawar; Ahmed, Noman; Kamal, Mustafa; Junejo, Sameen Afzal
Objectives: To evaluate the effect of half adult dose of oral Rifampicin on mean change in best corrected visual acuity and central macular thickness in patients with central serous chorioretinopathy. Methods: Thirty-eight eyes of 31 patients with idiopathic central serous chorioretinopathy (CSCR) were registered. Unaided Visual acuity, best corrected visual acuity was documented and detailed slit lamp examination along with dilated ophthalmoscopy was performed. All subjects were treated with oral Rifampicin 300 mg (half adult dose) daily for 03 months. Patients underwent a complete ocular and systemic examination as well as central macular thickness (CMT) measurement by optical coherence tomography (OCT) every month after starting treatment until four months. Fundus fluorescein angiography (FFA) was performed in recurrent cases. Liver function tests were carried out prior to the treatment and during follow up period. Results: A total of 38 eyes of 31 patients (24 males, 07 females) were included in the study. Mean age of patients was 36.16±3.19 years (range 30-44). Mean best corrected visual acuity (BCVA) before treatment was 0.56±0.11 and improved to 0.47±0.14 at 04 weeks (P<0.001) of treatment. The mean CMT at the time of presentation was 494.39±96.29 um and was decreased to 306.90±50.71 um after 04 weeks of treatment (P<0.001). The mean induced reduction in CMT was 187.48±122 um (P<0.001) while that in BCVA 0.41±0.16 at 04 weeks of treatment (P<0.001). Liver function tests were within normal range before and after the treatment. Conclusion: Half adult dose rifampicin (300mg) is effective and safe in treatment of central serous chorioretinopathy without causing any systemic imbalance. PMID:27882013
Wang, Bo; Li, Diandian; Ou, Xuemei; Yi, Qun; Feng, Yulin
Numerous studies have investigated the utility of Ber-EP4 in differentiating metastatic adenocarcinoma (MAC) from malignant epithelial mesothelioma (MM) and/or reactive mesothelial cells (RM) in serous effusions. However, the results remain controversial. The aim of this study is to determine the overall accuracy of Ber-EP4 in serous effusions for MAC through a meta-analysis of published studies. Publications addressing the accuracy of Ber-EP4 in the diagnosis of MAC were selected from the Pubmed, Embase and Cochrane Library. Data from selected studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), and receiver operating characteristic (SROC) curve. Statistical analysis was performed by Meta-Disc 1.4 and STATA 12.0 softwares. 29 studies, based on 2646 patients, met the inclusion criteria and the summary estimating for Ber-EP4 in the diagnosis of MAC were: sensitivity 0.8 (95% CI: 0.78-0.82), specificity 0.94 (95% CI: 0.93-0.96), positive likelihood ratio (PLR) 12.72 (95% CI: 8.66-18.7), negative likelihood ratio (NLR) 0.18 (95% CI: 0.12-0.26) and diagnostic odds ratio 95.05 (95% CI: 57.26-157.77). The SROC curve indicated that the maximum joint sensitivity and specificity (Q-value) was 0.91; the area under the curve was 0.96. Our findings suggest that BER-EP4 may be a useful diagnostic adjunctive tool for confirming MAC in serous effusions.
Tylus, Magdalena; Święch-Zubilewicz, Anna; Dolar-Szczasny, Joanna; Mackiewicz, Jerzy
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.
Ruocco, Anthony C; Hudson, James I; Zanarini, Mary C; Gunderson, John G
Borderline personality disorder (BPD) and its core Diagnostic and Statistical Manual of Mental Disorders (DSM) factor-analytically derived phenotypes aggregate in families. To potentially inform future conceptualizations of BPD, this study examined the familial aggregation and co-aggregation with BPD of 3 additional candidate phenotypes for BPD psychopathology: anxiousness, aggressiveness, and cognitive dysregulation. Participants included 347 probands (126 with BPD, 128 without BPD, and 93 with major depressive disorder) and 814 parents and siblings of probands. All participants completed diagnostic assessments and scales assessing the candidate phenotypes. The familial aggregation of phenotypes (correlation of level of phenotype between family members), the familial co-aggregation of phenotypes with BPD (correlation of phenotype with BPD between family members), and the within-individual correlation of phenotypes with BPD were assessed. All 3 candidate phenotypes showed high levels of familial aggregation (rs = .14 - .53, ps < .001), the magnitudes of which were comparable with DSM-based core sectors of psychopathology. Anxiousness and cognitive dysregulation showed strong within-individual associations with BPD (rs = .55 and .46, respectively; ps < .001) and substantial familial co-aggregation with BPD (rs = .12 and .13, respectively; ps ≤ .002). In contrast, aggressiveness showed a weak within-individual association with BPD (r = .11, p = .12) and little familial co-aggregation with BPD (r = .05, p = .21). These findings suggest that anxiousness and cognitive dysregulation are promising phenotypes for BPD psychopathology that move beyond factor-analytically based conceptualizations. In contrast, aggressiveness was only weakly related to BPD, suggesting that this phenotype may not represent an essential feature of this disorder.
Kerr, Ian B; Finlayson-Short, Laura; McCutcheon, Louise K; Beard, Hilary; Chanen, Andrew M
Some concept of self has been used by many, although not all, researchers and clinicians as an 'organising construct' for borderline personality disorder (BPD). There is considerable variation in this usage and how clearly researchers have defined the self. Given this diversity, and that 'self' is often used interchangeably with parallel concepts (e.g., psyche, brain-mind, 'person') or with features of self (e.g., self-awareness, identity), unqualified use of the term is problematic. This is further complicated by the heterogeneity and 'comorbidity' of BPD and the limitations of syndromally based psychiatric nosology. Still, BPD remains in current classification systems and can be reliably diagnosed. A considerable body of research on self and BPD has accrued, including a recent profusion and confluence of neuroscientific and sociopsychological findings. These have generated supporting evidence for a supra-ordinate, functionally constituted entity of the self ranging over multiple, interacting levels from an unconscious, 'core' self, through to a reflective, phenotypic, 'idiographic' and relational self constituted by interpersonal and sociocultural experience. Important insights have been generated regarding emotional and social-cognitive dysregulation, disorder of self-awareness, relationality, identity, and coherence and continuity of the self. Many of these are shared by various trauma-related, dissociative disorders. A construct of the self could be useful as an explanatory principle in BPD, which could be construed as a 'self-state' (and relational) disorder, as opposed to a less severe disorder of aspects of the self (e.g., mood or memory). We offer a tentative description of 'Self' in this context, noting that any such construct will require a clear definition and to be evaluable.
Kogan-Goloborodko, Olga; Brügmann, Elisabeth; Repple, Jonathan; Habel, Ute; Clemens, Benjamin
Approximately 73% of patients suffering from Borderline personality disorder (BPD) exhibit aggressive behaviour, which severely hinders therapeutic work and clinical improvement. Because the underlying mechanisms of aggression in BPD are not yet completely understood, additional research in this domain has a high clinical and scientific relevance. We employed a modified version of the Taylor Aggression Paradigm (mTAP), in order to examine for the first time whether this task can be used to differentiate between BPD patients and healthy controls with regard to reactive aggression. In the mTAP, the amount of money subtracted by a virtual opponent was categorized into ‘low’ (10–20 cents) and ‘high’ (80–100 cents) provocations, enabling us to compare how much money BPD patients and healthy controls subtracted (i.e., how aggressively participants responded) following high and low provocation trials. Our results showed that, compared to healthy controls, BPD patients showed higher overall aggression, higher aggression after high provocation trials, as well as a larger difference between high and low provocation trials. This finding was corroborated by a neuropsychological assessment, demonstrating higher levels of aggression and impulsivity in BPD patients. Interestingly, reactive aggression in the mTAP was positively correlated with symptom severity and impulsivity in BPD patients. We suggest that the mTAP provides a valuable tool allowing psychiatrists to quantify reactive aggression in BPD. Therefore, clinicians and researchers might consider this task, as a short experimental measure of reactive aggression, either in future studies or to aid diagnostic assessment during clinical practice. PMID:27851804
Lenzenweger, Mark F; Clarkin, John F; Levy, Kenneth N; Yeomans, Frank E; Kernberg, Otto F
What changes and how quickly these changes occur as a result of therapy in borderline personality disorder (BPD) is an important ongoing question. The features of BPD patients that are most predictive of rates of change in such patients remain largely unknown. Using the Cornell Personality Disorders Institute (CPDI) randomized controlled trial data, we sought to determine (a) the number and nature of broad domains underlying a large number of rate of change (slope) measures across many psychological, psychiatric, and psychosocial indexes, and (b) which baseline individual difference psychological features of the BPD patients correlated with these rate of change domains. We examined the latent structure of slope (rate of change) measures gleaned from individual growth curves for each subject, studied in multiwave perspective, on separate measures of anger, aggression, impulsivity, depression, global functioning, and social adjustment. Three broad domains of change rate could be discerned. These domains were reflected in factors that are described as (a) anger/aggression change ("aggressive dyscontrol"), (b) global functioning/social adjustment change ("social adjustment/self-acceptance"), and (c) anxiety/depression/impulsivity change ("conflict tolerance/behavioral control"). Factor scores were computed for each change domain and baseline measures of personality and psychodynamic features, selected a priori, were correlated with these factor scores. Multiple regression analyses revealed (a) baseline negative affectivity and aggression predicted the aggressive dyscontrol change domain, (b) baseline identity diffusion predicted the social adjustment/self-acceptance change domain, and (c) baseline social potency predicted the conflict tolerance/behavioral control change domain. These baseline predictors suggest potential research foci for understanding those aspects of BPD that change at comparable rates over time.
... Resources Tools & Publications Tumor Types: Understanding Brain Tumors World Health Organization (WHO) Updates Official Classification of Tumors ... Central Nervous System On May 9, 2016, the World Health Organization (WHO) published an official reclassification of ...
Yabe, Rie; Higo, Ryuzaburo; Sugita, Koichi; Iwamori, Masao
Otitis media with effusion (OME) is an inflammatory disease of the middle ear cavity that is associated with middle ear effusions (MEEs), which are frequently mucous and serous for pediatric and adult patients exhibiting low and high responsiveness to medical treatment, respectively. To assess the pathological outcomes in mucous and serous MEEs, their protein compositions were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting in comparison with those in the same patients' sera. A mucin, which is immunochemically identical with nasal mucin, was a characteristic consituent of mucous MEEs (n = 25), being present at the concentration of 59.4 mg/ml and comprising about 60% of the total proteins, but it was not detected in serous MEEs (n = 30) or sera. Serum proteins with molecular weights of less than 260 kDa were detected in serous and mucous MEEs, in which albumin was the major protein. Albumin, IgM and alpha1-acid glycoprotein, and lysozyme, IgA and IgG in MEEs were present at lower and higher concentrations than in sera, respectively. The ratios of IgA, IgG, IgM and alpha1-acid glycoprotein to albumin in mucous MEEs were 4-, 3-, 1.4- and 1.0-times higher than those in the respective pediatric sera, and those in serous MEEs were 1.7-, 1.7-, 0.6- and 0.3-times higher than those in adult sera. Also, the concentrations of lysozyme in mucous and serous MEEs were 19 and 3 microg/ml, but those in pediatric and adult sera were negligible. These results indicate that the contents of these proteins, in comparison to albumin, might be useful criteria for assessing the inflammation level in MEEs.
Conway, Christopher C; Hammen, Constance; Brennan, Patricia A
Longitudinal studies of the exact environmental conditions and personal attributes contributing to the development of borderline personality disorder (BPD) are rare. Furthermore, existing research typically examines risk factors in isolation, limiting our knowledge of the relative effect sizes of different risk factors and how they act in concert to bring about borderline personality pathology. The present study investigated the prospective effects of diverse acute and chronic stressors, proband psychopathology, and maternal psychopathology on BPD features in a high-risk community sample (N = 700) of youth followed from mid-adolescence to young adulthood. Multivariate analyses revealed significant effects of maternal externalizing disorder history, offspring internalizing disorder history, family stressors, and school-related stressors on BPD risk. Contrary to expectations, no interactions between chronically stressful environmental conditions and personal characteristics in predicting borderline personality features were detected. Implications of these findings for etiological theories of BPD and early screening efforts are discussed.
Stanley, Barbara; Siever, Larry J
Borderline personality disorder is characterized by affective instability, impulsivity, identity diffusion, and interpersonal dysfunction. Perceived rejection and loss often serve as triggers to impulsive, suicidal, and self-injurious behavior, affective reactivity, and angry outbursts, suggesting that the attachment and affiliative system may be implicated in the disorder. Neuropeptides, including the opioids, oxytocin, and vasopressin, serve a crucial role in the regulation of affiliative behaviors and thus may be altered in borderline personality disorder. While clinical data are limited, the authors propose alternative neuropeptide models of borderline personality disorder and review relevant preclinical research supporting the role of altered neuropeptide function in this disorder in the hope of stimulating more basic research and the development of new treatment approaches.
Muller, R J
It is shown here that what Karen Horney called the resignation solution to the problem of basic anxiety leads to psychopathology very similar to DSM-III-R's borderline personality disorder (BPD). Both the "resigned person" and the borderline personality show instability of self-image, social relationships, and mood, and live out the associated deficits with similar styles. While not specifically using the term "splitting", Horney showed how alternating expansive and self-effacing trends can coexist in the resigned person, and how these oscillations in self-other-world constitution influence the resigned person's behavior in a way similar to borderline splitting. Horney's descriptive and psychodynamic analysis of the resignation phenomenon elaborates and gives additional credibility to DSM-III-R's BPD as a diagnostic category.
Arbabi, Mohammad; Paast, Negin; Karim, Hamid Reza; Faghfori, Sara; Memari, Amir Hossein
The aim of the present study was to determine whether patients with borderline personality disorder (BPD) show any neurological soft signs compared to healthy controls. Furthermore we sought to examine the role of common symptoms related to BPD, such as depression, anxiety or impulsivity, in association with neurological soft signs. Thirty patients with borderline personality disorder and thirty hospital-based controls were examined for neurological soft signs. The total score of neurological soft signs in BPD was significantly higher than controls. In terms of subscales, patients had higher scores in Sensory Integration and Motor Coordination and other neurological soft signs compared to control group. Multiple regression analysis showed that the impulsivity score was the best significant predictor of neurological soft signs in BPD. The increase of neurological soft signs in patients with BPD may address a non-focal neurological dysfunction in borderline personality disorder.
Stanley, Barbara; Siever, Larry J.
Borderline personality disorder is characterized by affective instability, impulsivity, identity diffusion, and interpersonal dysfunction. Perceived rejection and loss often serve as triggers to impulsive, suicidal, and self-injurious behavior, affective reactivity, and angry outbursts, suggesting that the attachment and affiliative system may be implicated in the disorder. Neuropeptides, including the opioids, oxytocin, and vasopressin, serve a crucial role in the regulation of affiliative behaviors and thus may be altered in borderline personality disorder. While clinical data are limited, the authors propose alternative neuropeptide models of borderline personality disorder and review relevant preclinical research supporting the role of altered neuropeptide function in this disorder in the hope of stimulating more basic research and the development of new treatment approaches. PMID:19952075
Treloar, Amanda Jane Commons; Lewis, Andrew J.
This paper reviews the history of the recognition of borderline personality disorder as a clinical disorder, followed by a review of the contemporary practice of diagnosing borderline personality disorder in psychiatric settings. Many researchers have cautioned against the conflation of difficult patients with the diagnostic category of borderline…
Hawes, David J.; Helyer, Rebekah; Herlianto, Eugene C.; Willing, Jonah
This study tested if children and adolescents with high levels of borderline personality features (BPF) exhibit the same shame-prone self-concept previously found to characterize adults with borderline personality disorder (Rusch et al., 2007). Self-concept was indexed using the Implicit Association Test, in a community sample of…
Gratz, Kim L.; Latzman, Robert D.; Tull, Matthew T.; Reynolds, Elizabeth K.; Lejuez, C. W.
Most of the extant literature on borderline personality disorder has focused on the course, consequences, and correlates of this disorder among adults. However, little is known about childhood borderline personality (BP) features, or the factors associated with the emergence of BP pathology in childhood. A greater understanding of childhood BP…
Wolke, Dieter; Schreier, Andrea; Zanarini, Mary C.; Winsper, Catherine
Background: Abuse by adults has been reported as a potent predictor of borderline personality disorder (BPD). Unclear is whether victimisation by peers increases the risk of borderline personality symptoms. Method: The Avon Longitudinal Study of Parents and Children (ALSPAC) prospective, longitudinal observation study of 6050 mothers and their…
Frankel-Waldheter, Miriam; Macfie, Jenny; Strimpfel, Jennifer M; Watkins, Christopher D
Several theories propose a relationship between deficits in autonomy and relatedness and the development of borderline personality disorder (BPD). Empirical work supports relationships between maternal BPD and adolescent symptomatology, as well as between maternal autonomy and relatedness and adolescent symptomatology. However, no study has examined how individuals with BPD differ from normative comparisons on autonomy and relatedness, or whether mothers' BPD mediates the relationship between their autonomy and relatedness and their adolescents' symptomatology. We sampled 28 mothers with BPD and their adolescents aged 14-17 years, as well as 28 normative comparisons matched on demographic variables. We assessed BPD as a categorical diagnosis and along a continuum of self-reported borderline features. In a videotaped problem-solving interaction, controlling for current major depressive disorder, mothers with BPD were less likely to promote and more likely to inhibit relatedness, and they were marginally more likely to inhibit but equally likely to promote autonomy with their adolescents. Mothers' total borderline features mediated the relationship between mothers' promotion of autonomy plus relatedness and adolescent internalizing and externalizing symptoms (anxious depression, withdrawn depression, somatic problems, rule breaking, and aggression) and adolescent borderline features (affective instability and self-harm). Mothers' total borderline features also mediated the relationship between mothers' inhibition of autonomy plus relatedness and adolescent internalizing and externalizing symptoms (anxious depression, withdrawn depression, somatic problems, and aggression but not rule breaking) and adolescent borderline features (affective instability and self-harm). We discuss findings in terms of light shed on BPD and the effect of maternal BPD on adolescent development.
Zanarini, Mary C; Frankenburg, Frances R; Reich, D Bradford; Wedig, Michelle M; Conkey, Lindsey C; Fitzmaurice, Garrett M
The purpose of this study was to determine the rate of marriage/sustained cohabitation and parenthood reported by recovered and nonrecovered borderline patients, the age first undertaken, and the stability of these relationships. Borderline patients were interviewed about these topics during their index admission and eight times over 16 years of prospective follow-up. Recovered borderline patients were significantly more likely than nonrecovered borderline patients to have married/lived with an intimate partner and to have become a parent. In addition, they first married/cohabited and became a parent at a significantly older age. They were also significantly less likely to have been divorced or ended a cohabiting relationship. In addition, they were significantly less likely to have given up or lost custody of a child. Taken together, the results of this study suggest that stable functioning as a spouse/partner and as a parent are strongly associated with recovery status for borderline patients.
LEWIS, JUDITH L.
A significant number of patients with the diagnosis of borderline personality disorder have a history of childhood trauma. This article attempts to integrate the treatment approach of Judith Herman to traumatized patients with the psychodynamic approach of Otto Kernberg to borderline patients. To facilitate paradigm shifts between these two approaches, they are presented side by side with one set of terms translated into the other. Aspects of the therapeutic relationship and process are compared and contrasted, and a preliminary attempt is made to integrate these two treatment models. PMID:22700260
Mauricio, Anne Marie; Tein, Jenn-Yun; Lopez, Frederick G
Court-mandated male batterers (n = 192) attending an intervention program completed measures examining adult attachment orientations (anxious and avoidant), personality disorders (borderline and antisocial), type of violence (psychological and physical), and social desirability. Structural equation modeling was used to determine whether there were significant relationships between anxious attachment and physical and psychological violence that are mediated by either borderline or antisocial personality disorders. Social desirability was included in both models as a covariate. Results indicated that personality disorders fully mediated the relationship between avoidant attachment and physical as well as psychological violence. Personality disorders only partially mediated the relationship between anxious attachment and psychological violence. Implications for intervention are discussed.
Obeyesekere, Manoj N; Leong-Sit, Peter; Gula, Lorne J; Yee, Raymond; Skanes, Allan C; Klein, George J; Krahn, Andrew D
QT prolongation on resting electrocardiography (ECG) is common, and the clinician is often challenged by the dilemma of excluding acquired causes and recognizing potential congenital long QT syndrome (LQTS). The hallmark of LQTS is an abnormally long QT interval. However, a normal or borderline long QT interval may be observed in up to 50% of patients with LQTS because of the intermittent nature of QT prolongation. This review presents an approach to evaluating the asymptomatic patient with a borderline long QT interval, which incorporates a comprehensive clinical assessment, rest and provocative ECG testing, and genetic testing when appropriate.
Fischer-Kern, Melitta; Doering, Stephan; Taubner, Svenja; Hörz, Susanne; Zimmermann, Johannes; Rentrop, Michael; Schuster, Peter; Buchheim, Peter; Buchheim, Anna
Borderline personality disorder is associated with deficits in personality functioning and mentalisation. In a randomised controlled trial 104 people with borderline personality disorder received either transference-focused psychotherapy (TFP) or treatment by experienced community therapists. Among other outcome variables, mentalisation was assessed by means of the Reflective Functioning Scale (RF Scale). Findings revealed only significant improvements in reflective function in the TFP group within 1 year of treatment. The between-group effect was of medium size (d = 0.45). Improvements in reflective function were significantly correlated with improvements in personality organisation.
Goodman, Marianne; Patil, Uday; Triebwasser, Joseph; Hoffman, Perry; Weinstein, Zachary A; New, Antonia
To identify aspects of parental burden associated with borderline personality disorder (BPD), an anonymous internet survey linked to BPD support websites was developed for parents to complete on their BPD offspring and unaffected siblings. The questions cover aspects of the child's life from pregnancy through young adulthood, and query about the impact of the child's BPD on six domains of the parent's life, including physical and emotional health, marriage, job, standard of living, social life, and career trajectory. Additionally, financial burden was assessed with questions pertaining to insurance and out-of pocket costs associated with the BPD disorder. BPD offspring were identified by meeting diagnostic criteria embedded within the survey and having been given a diagnosis of BPD by a professional at some point in their life. We report on 233 female offspring meeting strict criteria for BPD. Parents of daughters with BPD endorsed varying levels of impact on the six domains comprising burden with the largest impact on emotional health which was impacted in over 88% of the respondents. Over 50% of parents endorsed four or greater of the six burden items. Particular aspects of the offspring's BPD symptom profile correlated with intensity of parental burden included including problems in adolescence with acting out behavior (p < .000), property destruction (.003), delusional symptoms (.007), and hallucinatory symptoms (.008). A subgroup of respondents provided data on specific financial expenses. The average and median out-of-pocket expense was $60,087, and $10,000. Insurance costs totaled an average of $108,251 with a mean of $20,000. The average cost per year after diagnosis was $14,606 out-of-pocket and $45,573 billed to insurance. The median cost per year after diagnosis was $3,667 out-of-pocket, and $12,500 billed to insurance. After adjusting for household income, a female proband who had been raped incurred roughly $40,000 more in BPD-related costs, while a
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Burke, Jeffrey D.; Stepp, Stephanie D.
Very few studies have prospective information, especially regarding males, on the prediction of Borderline Personality Disorder (BPD) in adulthood from psychiatric disorders in childhood. Certain childhood disorders, however, have notably similar features in common with BPD. In particular, the affective dysfunction, hostility and interpersonal…
Draper, Matthew R.; Faulkner, Ginger E.
This case study examines the dynamics and challenges associated with counseling a client experiencing borderline personality disorder in the small college institutional context. The work of counseling centers at small private institutions has been relatively unexplored in the extant college counseling literature. To help fill this gap, the current…
Hines, Denise A.
Although research has consistently shown that men and women use intimate partner aggression (IPA) at approximately equal rates, there is little empirical research on whether the predictors of IPA are the same for men and women. The current study investigated whether borderline personality (BP) differentially predicted the use of IPA for men and…
Grilo, Carlos M.; Sanislow, Charles A.; Gunderson, John G.; Pagano, Maria E.; Yen, Shirley; Zanarini, Mary C.; Shea, Tracie M.; Skodol, Andrew E.; Stout, Robert L.; Morey, Leslie C.; McGlashan, Thomas H.
The authors examined the stability of schizotypal (STPD), borderline (BPD), avoidant (AVPD) and obsessive-compulsive (OCPD) personality disorders (PDs) over 2 years of prospective multiwave follow-up. Six hundred thirty-three participants recruited at 4 collaborating sites who met cri