McCluggage, W G; Alderdice, J M; Walsh, M Y
Two polypoid submucosal uterine lesions were examined histologically and immunohistochemically with monoclonal antibodies to desmin and alpha smooth muscle actin. One case comprised a leiomyoma and the other a polypoid form of adenomyosis. Both polyps had prolapsed through the external cervical os. The lesions had an ulcerated surface with focal areas of marked increased cellularity and pronounced vascularity throughout, such that they mimicked a low grade endometrial stromal sarcoma infiltrating the myometrium. The cellular areas showed diffuse positivity for desmin and alpha smooth muscle actin, confirming them to be of smooth muscle origin. The changes of marked hypercellularity and pronounced vascularity within polypoid submucosal uterine lesions have not been emphasised in published reports up to now. Pathologists should be aware of these morphological features in order to avoid misdiagnosis of such cases as endometrial stromal sarcomas. The changes described here are likely to be secondary to trauma associated with a polypoid lesion prolapsing through the external cervical os. Images PMID:10605413
Kim, Jihoon; Fazleabas, Asgerally; Walsh, Joseph T.
Endometriosis is one of the most common causes of chronic pelvic pain and infertility and is characterized by the presence of endometrial glands and stroma outside of the uterine cavity. A novel laparoscopic polarization imaging system was designed to detect endometriosis by imaging endometrial lesions. Linearly polarized light with varying incident polarization angles illuminated endometrial lesions. Degree of linear polarization image maps of endometrial lesions were constructed by using remitted polarized light. The image maps were compared with regular laparoscopy image. The degree of linear polarization map contributed to the detection of endometriosis by revealing structures inside the lesion. The utilization of rotating incident polarization angle (IPA) for the linearly polarized light provides extended understanding of endometrial lesions. The developed polarization system with varying IPA and the collected image maps could provide improved characterization of endometrial lesions via higher visibility of the structure of the lesions and thereby improve diagnosis of endometriosis.
Conoscenti, G; Meir, Y J; Fischer-Tamaro, L; Maieron, A; Natale, R; D'Ottavio, G; Rustico, M; Mandruzzato, G
A total of 149 women with postmenopausal bleeding underwent transvaginal sonography, hysteroscopy and dilatation and curettage in order to study the diagnostic accuracy of several ultrasound parameters in assessing endometrial pathology and to determine the most sensitive cut-off value of endometrial thickness for the exclusion of endometrial lesions. In distinguishing pathological from normal endometrium, transvaginal sonography showed a sensitivity of 69.3%, specificity of 82.7%, positive predictive value of 74.1% and negative predictive value of 72.1%. In detecting premalignant and malignant endometrial pathology, transvaginal sonography showed a sensitivity, specificity, positive predictive value and negative predictive value of 55%, 96.1%, 68.7% and 93.2%, respectively. Considering endometrial thickness as a single parameter, the most sensitive cut-off for defining normality was 4 mm; nevertheless, in the group of patients that had an endometrial thickness less than 4 mm, there was one case of malignancy (sensitivity, 95.2%; specificity, 49.4%; positive predictive value, 57.3%; and negative predictive value, 93.5%). Transvaginal sonography combined evaluation (morphology, thickness and color Doppler) showed a poor diagnostic accuracy in detecting endometrial pathology and in differentiating between endometrial benign lesions, endometrial polyps and adenocarcinoma in women with postmenopausal bleeding. Endometrial thickness evaluated with transvaginal sonography was preferable but not sensitive enough to exclude endometrial pathology.
Tangen, Ingvild L; Veneris, Jennifer Taylor; Halle, Mari K; Werner, Henrica M; Trovik, Jone; Akslen, Lars A; Salvesen, Helga B; Conzen, Suzanne D; Fleming, Gini F; Krakstad, Camilla
Glucocorticoid receptor (GR) has emerged as an important steroid nuclear receptor in hormone dependent cancers, however few data are available regarding a potential role of GR in endometrial cancer. The aim of this study was to investigate expression of GR in primary and metastatic endometrial cancer lesions, and to assess the relationship between GR expression and clinical and histopathological variables and survival. Expression of GR was investigated by IHC in 724 primary tumors and 289 metastatic lesions (from 135 patients), and correlations with clinical and histopathological data and survival were explored. Expression of GR was significantly increased in non-endometrioid tumors compared to endometrioid tumors, and was associated with markers of aggressive disease and poor survival both in univariate and multivariate analysis after correcting for age, FIGO stage and histologic grade. Within the subgroups of hormone receptor negative tumors (loss of androgen receptor, estrogen receptor or progesterone receptor) expression of GR was highly significantly associated with poor disease specific survival. There was an overall increase in GR expression from primary to metastatic lesions, and the majority of metastases expressed GR. GR expression in primary endometrial cancer is associated with aggressive disease and poor survival. The majority of metastatic endometrial cancer lesions express GR; therefore GR may represent a therapeutic target in the adjuvant therapy of poor prognosis early-stage as well as metastatic endometrial cancer. Copyright © 2017 Elsevier Inc. All rights reserved.
Jiang, Zhongyong; Xu, Wanqing; Dan, Gang; Liu, Yuan; Xiong, Jie
Background Endometrial lesions are common in obstetrics and gynecology, including endometrial polyps, uterine adenomyosis, and malignant endometrial adenocarcinoma. Endometrial lesions seriously affect women’s health, fertility, quality of life, and life safety. As a pro-apoptosis gene, p53 is considered to be closely related with human tumors. Murine double mimute 2 (MDM2) is an oncogene that can promote tumor occurrence and development. P53 and MDM2 expression and significance in different types of endometrial lesions have not been fully elucidated. Material/Methods Normal endometrium, endometrial polyps, uterine adenomyosis, and endometrial adenocarcinoma tissue samples were collected. Real-time PCR was used to detect p53 and MDM2 mRNA expression. Immunohistochemical staining and Western blot analysis were applied to test p53 and MDM2 protein expression. Their correlation with clinical staging of endometrial adenocarcinoma was analyzed. Results P53 and MDM2 mRNA and protein expression were significantly elevated in the endometrial polyps group and the endometrial adenocarcinoma group compared with the normal control group (P<0.05). Their levels increased more obviously in endometrial adenocarcinoma compared with endometrial polyps (P<0.05). P53 and MDM2 mRNA and protein expression were slightly enhanced in uterine adenomyosis compared with normal controls, but this difference lacked statistical significance (P>0.05). P53 and MDM2 mRNA and protein level showed a positive correlation. Significantly higher expression of p53 or MDM2 was observed in patients with stage III compared to those in patients with stage II. Higher expression was also observed in patients with stage II than in patients with stage I. Conclusions P53 and MDM2 mRNA and protein were elevated in endometrial polyps and endometrial adenocarcinoma and their expressions were correlated with clinical staging of endometrial adenocarcinoma. They can promote cancer occurrence and development, and can
Genc, Mine; Sivrikoz, Oya Nermin; Sahin, Nur; Celik, Esin; Turan, Guluzar Arzu; Guclu, Serkan
The aim of this study was to evaluate the expression of cyclooxygenase 2 (COX-2) and its association with the development of premalignant lesions in gland structures of the endometrium in patients with uterine prolapse, a condition which exposes the uterus to mechanical and infectious stress. The study included 102 patients who underwent hysterectomy to correct grade 3-4 uterine prolapse and 105 patients who underwent hysterectomy for other causes. Endometrial gland structures underwent immunohistochemical staining and COX-2 expression was graded. Grades 0 and 1 represent low expression; grades 2 and 3 correspond to high levels of COX-2 expression. The prevalence of grade 2-3 COX-2 expression was significantly higher in the endometrial gland structures of patients with prolapse and hyperplasia compared to the remaining patients (p = 0.014). Grade 0-1 COX-2 expression was significantly more common in the endometrial gland structures of patients without uterine prolapse or hyperplasia (p = 0.004). Among the patients without endometrial hyperplasia, COX-2 expression was elevated in the endometrial gland structures of those with uterine prolapse compared to those without prolapse. Elevated COX-2 expression may explain the presence of unexpected premalignant lesions of the endometrium in patients with uterine prolapse. © 2015 S. Karger AG, Basel.
Lenci, Marco Antonio; do Nascimento, Vanessa Alessandra Lui; Grandini, Ana Beatriz; Fahmy, Walid Makin; Depes, Daniella de Batista; Baracat, Fausto Farah; Lopes, Reginaldo Guedes Coelho
ABSTRACT Objective: To evaluate the incidence of premalignant lesions and cancer in endometrial polyps, in patients undergoing hysteroscopic polypectomy. Methods: The results of 1,020 pathological examinations of patients submitted to hysteroscopic polypectomy were analyzed, as well as their diagnostic and surgical hysteroscopy findings. As to their menstrual status, 295 (28.9%) patients were in menacme. Of the total, 193 (65.4%) presented abnormal uterine bleeding, and 102 (34.6%) were asymptomatic with altered endometrial echo on transvaginal ultrasound. Out of 725 (71.1%) postmenopausal patients, 171 (23.6%) were symptomatic (abnormal uterine bleeding), and 554 (76.4%) were asymptomatic with endometrial echo >5.0mm. Results: Twenty-one (2.0%) patients presented premalignant lesions in the polyps, 13 had simple glandular hyperplasia, of which 5 had no atypia, and eight presented atypia. Eight polyps presented focal area of complex hyperplasia: 4 with atypia and 4 without lesions. Cancer was diagnosed in 5 (0.5%) polyps. Of the 21 polyps that harbored premalignant lesions, 12 were interpreted as benign in diagnostic and surgical hysteroscopy. Of the polyps with cancer, 4 were also histeroscopically interpreted as normal. Conclusion: Symptomatic polyps in menacme and in all postmenopausal women should be resected and submitted to histopathological examination, since they may have a benign aspect, even when harboring areas of cellular atypia or cancer. PMID:24728240
Feng, Dilu; Menger, Michael D; Wang, Hongbo; Laschke, Matthias W
In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE(+)) and without luminal epithelium (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE(-) fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE(+) fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE(+) lesions compared with LE(-) lesions. In addition, we found that many GFP(+) microvessels grew outside the LE(-) lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.
Mentrikoski, Mark J; Shah, Akeesha A; Hanley, Krisztina Z; Atkins, Kristen A
The effects of increased amounts of progesterone on the endometrium, including such features as eosinophilic cytoplasmic metaplasia, glandular atrophy, and decidualized stroma, are well-known among surgical pathologists. These changes are typically seen as secondary effects of pregnancy or exogenous hormone therapy for birth control purposes or abnormal bleeding. Treatment with progesterone has become a viable alternative to hysterectomy in some patients with complex atypical hyperplasia (CAH) and well-differentiated endometrial carcinoma (WDC), especially those who are poor surgical candidates or those wishing to preserve fertility. To date, only 1 study has specifically examined the effects of progestin therapy on patients with a previous diagnosis of CAH or WDC. That study proposed a classification scheme for the assessment of treated CAH and WDC. The authors concluded that after 6 months of treatment, endometrial biopsy findings of persistent cytologic atypia and architectural abnormalities were associated with treatment failure. This current study aims to assess the previously proposed criteria in a cohort of 30 patients (18 with a diagnosis of CAH and 12 with a diagnosis of WDC), and determine the usefulness of these criteria in clinical practice. Our study confirms that cytologic atypia after 6 months of therapy is strongly associated with treatment failure, and should be an indication to pursue definitive surgical treatment in these patients.
Makris, Georgios-Marios; Pouliakis, Abraham; Siristatidis, Charalampos; Margari, Niki; Terzakis, Emmanouil; Koureas, Nikolaos; Pergialiotis, Vasilios; Papantoniou, Nikolaos; Karakitsos, Petros
This study aims to investigate the efficacy of an Artificial Neural Network based on Multi-Layer Perceptron (ANN-MPL) to discriminate between benign and malignant endometrial nuclei and lesions in cytological specimens. We collected 416 histologically confirmed liquid-based cytological smears from 168 healthy patients, 152 patients with malignancy, 52 with hyperplasia without atypia, 20 with hyperplasia with atypia, and 24 patients with endometrial polyps. The morphometric characteristics of 90 nuclei per case were analyzed using a custom image analysis system; half of them were used to train the MPL-ANN model, which classified each nucleus as benign or malignant. Data from the remaining 50% of cases were used to evaluate the performance and stability of the ANN. The MLP-ANN for the nuclei classification (numeric and percentage classifiers) and the algorithms for the determination of the optimum threshold values were estimated with in-house developed software for the MATLAB v2011b programming environment; the diagnostic accuracy measures were also calculated. The accuracy of the MPL-ANN model for the classification of endometrial nuclei was 81.33%, while specificity was 88.84% and sensitivity 69.38%. For the case classification based on numeric classifier the overall accuracy was 90.87%, the specificity 93.03% and the sensitivity 87.79%; the indices for the percentage classifier were 95.91%, 93.44%, and 99.42%, respectively. Computerized systems based on ANNs can aid the cytological classification of endometrial nuclei and lesions with sufficient sensitivity and specificity. Diagn. Cytopathol. 2017;45:202-211. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Voorwald, Fabiana Azevedo; Marchi, Fabio Albuquerque; Villacis, Rolando Andre Rios; Alves, Carlos Eduardo Fonseca; Toniollo, Gilson Hélio; Amorim, Renee Laufer
Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity. PMID:26222498
Mauland, Karen Klepsland; Wik, Elisabeth; Salvesen, Helga Birgitte
Endometrial carcinoma (EC) is the most common gynecologic cancer in industrialized countries. Traditional prognostic markers include FIGO stage, histologic subtype and histologic grade. DNA ploidy was introduced as a prognostic marker 30 years ago, and the majority of published literature demonstrates significant associations between tumor aneuploidy and poorer prognosis in EC. However, ploidy analysis is not routinely implemented in the clinic. We reviewed the literature on clinical value of ploidy measured by DNA content as a prognostic marker, and its potential role as a predictive marker in EC. PubMed was searched for papers evaluating the prognostic or predictive role of ploidy in EC. Search criteria were "DNA ploidy prognosis/predictive value endometrial cancer/carcinoma". Only articles written in English, published year 2000 or later were included. The majority of the studies demonstrated highly significant correlation between DNA index (DI) and survival, in univariate analysis including stages I-IV, and in subgroup analysis of stage I and stage I-II EC. Several studies also showed significant association between DI and survival in multivariate analysis. Few studies have evaluated DI as a prognostic marker in a prospective setting. No studies evaluating DI as a predictive marker in EC were identified. In other cancer types, ploidy has been linked to prediction of response to hormonal therapy and chemotherapy. Ploidy assessment in EC by DI is a strong prognostic marker. Still, its clinical applicability needs validation in a routine diagnostic, prospective setting with sufficient number of patients, characterized by state of the art histopathological evaluation and surgical staging. © 2014 Clinical Cytometry Society. Copyright © 2014 Clinical Cytometry Society.
Mauland, Karen Klepsland; Wik, Elisabeth; Salvesen, Helga Birgitte
Endometrial carcinoma (EC) is the most common gynecologic cancer in industrialized countries. Traditional prognostic markers include FIGO stage, histologic subtype, and histologic grade. DNA ploidy was introduced as a prognostic marker 30 years ago, and the majority of published literature demonstrates significant associations between tumor aneuploidy and poorer prognosis in EC. However, ploidy analysis is not routinely implemented in the clinic. We reviewed the literature on clinical value of ploidy measured by DNA content as a prognostic marker, and its potential role as a predictive marker in EC. PubMed was searched for papers evaluating the prognostic or predictive role of ploidy in EC. Search criteria were "DNA ploidy prognosis/predictive value endometrial cancer/carcinoma". Only articles written in English, published year 2000 or later were included. The majority of the studies demonstrated highly significant correlation between DNA index (DI) and survival, in univariate analysis including stages I-IV, and in subgroup analysis of stage I and stage I-II EC. Several studies also showed significant association between DI and survival in multivariate analysis. Few studies have evaluated DI as a prognostic marker in a prospective setting. No studies evaluating DI as a predictive marker in EC were identified. In other cancer types, ploidy has been linked to prediction of response to hormonal therapy and chemotherapy. Ploidy assessment in EC by DI is a strong prognostic marker. Still, its clinical applicability needs validation in a routine diagnostic, prospective setting with sufficient number of patients, characterized by state of the art histopathological evaluation and surgical staging. © 2014 Clinical Cytometry Society.
Jeon, Se Jeong; Lee, Jae Il; Kim, Hee Seung; Kim, Jae Weon; Park, Noh Hyun; Song, Yong Sang
Objective To describe the endometrial pathologic lesions in premenopausal breast cancer patients with a history of tamoxifen (TMX) use. Methods We retrospectively reviewed the medical records of 120 premenopausal breast cancer patients with a history of TMX use that had undergone a gynecological examination. Results Among 120 patients, 44.2% (n=53) were asymptomatic with an endometrial thickness ≥5 mm, as assessed by transvaginal ultrasonography. Of the patients that reported abnormal uterine bleeding, 5% (n=6) had an endometrial thickness <5 mm and 20% (n=24) had an endometrial thickness ≥5 mm by transvaginal ultrasonography. The final group of patients were asymptomatic, but showed an abnormal endometrial lesion, such as an endometrial polyp, by transvaginal ultrasonography (30.8%, n=37). Of the 56 benign lesions that were histologically reviewed, 50 (41.7%) were endometrial polyps, 3 (2.5%) were submucosal myomas, 2 (1.7%) were endometrial hyperplasias, and 1 (0.8%) was chronic endometritis. There were 64 (53.3%) other non-pathologic conditions, including secreting, proliferative, and atrophic endometrium, or in some cases, there was insufficient material for diagnosis. In our data, only one case was reported as a complex hyperplasia without atypia arising from an endometrial polyp, and one patient was diagnosed with endometrioid adenocarcinoma. Conclusion For premenopausal breast cancer patients with a history of TMX use, the majority of the patients were asymptomatic, and endometrial polyps were the most common endometrial pathology observed. Therefore, we believe that endometrial assessment before starting TMX treatment, and regular endometrial screening throughout TMX treatment, are reasonable suggestions for premenopausal breast cancer patients. PMID:28217668
Mills, Anne M; Longacre, Teri A
Endometrial hyperplasia is a heterogeneous set of pathologic lesions that range from mild, reversible glandular proliferations to direct cancer precursors. These lesions comprise a continuum of morphologic appearances, with the earliest proliferation represented by crowded glands with simple tubular architecture lined by cells resembling proliferative endometrium, whereas advanced proliferations in this continuum are characterized by crowded glands with complex architecture, often containing cells with nuclear atypia resembling low-grade endometrioid adenocarcinoma. The former "early" proliferations may be isolated to an endometrial polyp, but advanced proliferations are generally more diffusely present throughout the endometrium. There are at least three major classification systems for endometrial carcinoma precursor lesions, each of which trend toward overlap at the complex end of the spectrum. Although some classifications are based on a series of molecular genetic alterations (which may or may not translate into biologically or clinically relevant risk lesions), each classification scheme ultimately uses a series of histologic features, usually a combination of architecture and cytology, to establish a diagnosis of hyperplasia. Because different pathologists may apply different histologic criteria for endometrial hyperplasia depending on the classification system used, this article will provide an overview of the classifications used in current daily practice, present the histologic criteria and relative merits of each classification system, and discuss common and not so common causes of misclassification.
Hysteroscopy-endometrial ablation; Laser thermal ablation; Endometrial ablation-radiofrequency; Endometrial ablation-thermal balloon ablation; Rollerball ablation; Hydrothermal ablation; Novasure ablation
Yilmaz, Ercan; Celik, Onder; Simsek, Yavuz; Turkcuoglu, Ilgin; Celik, Ebru; Gül, Mehmet; Hascalik, Seyma; Aydin, Nasuhi Engin; Aydin, Engin
To evaluate the expression of c-kit (CD117) in endometrial hyperplasia and endometrial cancer. Expression of c-kit in 10 normal endometrium, 18 simple endometrial hyperplasia, 16 complex endometrial hyperplasia (10 cases with atypia and 6 cases without atypia), and 6 endometrial cancer were investigated by immunohistochemistry. c-Kit expression decreased as the lesion progressed to endometrial cancer. Immunostaining was mostly focal and weak in the normal endometrium and was mostly diffuse and strong in the simple and complex endometrial hyperplasia. Simple and complex hyperplastic endometrial tissues express diffuse cytoplasmic staining for c-kit and the expression decreases with the progression of the lesion.
Berg, Anna; Hoivik, Erling A.; Mjøs, Siv; Holst, Frederik; Werner, Henrica M. J.; Tangen, Ingvild L.; Taylor-Weiner, Amaro; Gibson, William J.; Kusonmano, Kanthida; Wik, Elisabeth; Trovik, Jone; Halle, Mari K.; Øyan, Anne M.; Kalland, Karl-Henning; Cherniack, Andrew D.; Beroukhim, Rameen; Stefansson, Ingunn; Mills, Gordon B.; Krakstad, Camilla; Salvesen, Helga B.
Obesity is linked to increased incidence of endometrioid endometrial cancer (EEC) and complex atypical hyperplasia (CAH). We here explore pattern and sequence of molecular alterations characterizing endometrial carcinogenesis in general and related to body mass index (BMI), to improve diagnostic stratification and treatment strategies. We performed molecular characterization of 729 prospectively collected EEC and CAH. Candidate biomarkers were identified in frozen samples by whole-exome and Sanger sequencing, oligonucleotide gene expression and Reverse Phase Protein Arrays (investigation cohort) and further explored in formalin fixed tissues by immunohistochemistry and Fluorescent in Situ Hybridization (validation cohort). We here demonstrate that PIK3CA mutations, PTEN loss, PI3K and KRAS activation are early events in endometrial carcinogenesis. Molecular changes related to KRAS activation and inflammation are more common in obese CAH patients, suggesting different prevention and systemic treatment strategies in obese and non-obese patients. We also found that oncoprotein Stathmin might improve preoperative diagnostic distinction between premalignant and malignant endometrial lesions. PMID:25415225
Leibovitz, Z; Degani, S; Rabia, R; Tal, J; Eibchitz, I; Shapiro, I; Paltieli, Y; Aharoni, A; Steinkuler, M; Ohel, G
A computer program was developed to assess the endometrial echogenicity relative to the myometrial one, based on the gray-level processing of the midsagittal uterine image. The endometrial region of interest was specified within the upper part of the uterine cavity. The adjacent area of the myometrium was used to determine the reference brightness. The endometrial region of interest was analyzed along the anteroposterior uterine axis, as a set of thin strips directed parallelly to the midcavitary line. The endometrial/myometrial relative echogenicity coefficient (E/M REC) was computed for each strip and displayed graphically as a function of the distance from the midcavitary line. The area under the E/M REC curve within the limits of the total endometrial width was defined as total area (TA) and was used as a measure of the endometrial echogenicity. This parameter was assessed in 9 patients during their normal ovulatory cycles and in 29 IVF-treated patients with mechanical infertility. TA has a significant linear increase during the days of the ovulatory cycles. TA was found in high correlation with log(estradiol). TA can be used reliably for sonographic endometrial dating in ovulatory cycles.
Samarnthai, Norasate; Hall, Kevin; Yeh, I-Tien
Molecular profiling of endometrial neoplasms reveals genetic changes in endometrial carcinomas that support the dualistic model, in which type I carcinomas are estrogen-dependent, low grade lesions and type II carcinomas are nonestrogen dependent and high grade. The molecular changes in type I endometrial carcinomas include mutations in PTEN, PIK3CA, KRAS, and β-catenin, along with microsatellite instability, whereas type II endometrial carcinomas are characterized by genetic alterations in p53, HER2/neu, p16, and E-cadherin. For endometrial neoplasms with a malignant mesenchymal component, C-MYC mutations and loss of heterozygosity are frequently seen in carcinosarcomas, and a fusion gene, JAZF1/JJAZ1, is distinctive for endometrial stromal sarcoma. In addition, p53 mutations may play an important role in tumorigenesis of undifferentiated endometrial sarcoma. These molecular changes can help in the diagnosis of endometrial neoplasms, as well as form the basis of molecular targeted therapy. PMID:20368795
Shaw, Eileen; Farris, Megan; McNeil, Jessica; Friedenreich, Christine
Endometrial cancer is the sixth most common cancer in women worldwide and the most common gynecologic malignancy in the developed world. This chapter explores the current epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality. Using body mass index (BMI) as a measure of obesity, we found that obesity (defined as BMI > 30 and < 35 kg/m(2)) was associated with a 2.6-fold increase in endometrial cancer risk, while severe obesity (BMI > 35 kg/m(2)) was associated with a 4.7-fold increase compared to normal-weight women (BMI < 25 kg/m(2)). Increased central adiposity also increased endometrial cancer risk by 1.5- to twofold. Among both healthy and endometrial cancer patient populations, obesity was associated with a roughly twofold increase in endometrial cancer-specific mortality. This risk reduction was also observed for obesity and all-cause mortality among endometrial cancer patients. In the few studies that assessed risk associated with weight change, an increased endometrial cancer risk with weight gain and weight cycling was observed, whereas some evidence for a protective effect of weight loss was found. Furthermore, early-life obesity was associated with a moderately increased risk of endometrial cancer later in life. There are several mechanisms whereby obesity is hypothesized to increase endometrial cancer risk, including increased endogenous sex steroid hormones, insulin resistance, chronic inflammation and adipokines. Further research should focus on histological subtypes or molecular phenotypes of endometrial tumors and population subgroups that could be at an increased risk of obesity-associated endometrial cancer. Additionally, studies on weight gain, loss or cycling and weight loss interventions can provide mechanistic insight into the obesity-endometrial cancer association. Sufficient evidence exists to recommend avoiding obesity to reduce endometrial cancer risk.
Mitamura, Takashi; Todo, Yukiharu; Kato, Tatsuya; Konno, Yosuke; Hosaka, Masayoshi; Sakuragi, Noriaki
Objective According to the International Federation of Gynecology and Obstetrics staging, some surgeons perform lymphadenectomy in all patients with early stage endometrial cancer to enable the accurate staging. However, there are some risks to lymphadenectomy such as lower limb lymphedema. The aim of this study was to investigate whether preoperative assessment is useful to select the patients in whom lymphadenectomy can be safely omitted. Methods We evaluated the risk of lymph node metastasis (LNM) using LNM score (histological grade, tumor volume measured in magnetic resonance imaging [MRI], and serum CA-125), myometrial invasion and extrautrerine spread assessed by MRI. Fifty-six patients of which LNM score was 0 and myometrial invasion was less than 50% were consecutively enrolled in the study in which a lymphadenectomy was initially intended not to perform. We analyzed several histological findings and investigated the recurrence rate and overall survival. Results Fifty-one patients underwent surgery without lymphadenectomy. Five (8.9%) who had obvious myometrial invasion intraoperatively underwent systematic lymphadenectomy. One (1.8%) with endometrial cancer which was considered to arise from adenomyosis had para-aortic LNM. Negative predictive value of deep myometrial invasion was 96.4% (54/56). During the mean follow-up period of 55 months, one patient with deep myometrial invasion who refused an adjuvant therapy had tumor recurrence. The overall survival rate was 100% during the study period. Conclusion This preoperative assessment is useful to select the early stage endometrial cancer patients without risk of LNM and to safely omit lymphadenectomy. PMID:25142623
Gargiulo, T; Giusti, M; Bottero, A; Leo, L; Brokaj, L; Armellino, F; Palladin, L
The aim of the study was to demonstrate the validity of sentinel lymph node (SLN) detection after injection of radioactive isotope and patent blue dye in patients affected by early stage endometrial cancer. The second purpose was to compare radioactive isotope and patent blue dye migration. Between September 2000 and May 2001, 11 patients with endometrial cancer FIGO stage Ib (n=10) and IIa (n=1) underwent laparoscopic SLN detection during laparoscopic assisted vaginal hysterectomy with bilateral salpingo-oophorectomy and pelvic bilateral systematic lymphadenectomy. Radioactive isotope injection was performed 24 ours before surgery and blue dye injection was performed just before surgery in the cervix at 3, 6, 9 and 12 hours. A 350 mm laparoscopic gamma-scintiprobe MR 100 type 11, (99m)Tc setted (Pol.Hi.Tech.), was used intraoperatively for detecting SLN. Seventeen SLN were detected at lymphoscintigraphy (6 bilateral and 5 monolateral). At laparoscopic surgery the same locations were found belonging at internal iliac lymph nodes (the so called "Leveuf-Godard" area, lateral to the inferior vescical artery, ventral to the origin of uterine artery and medial or caudal to the external iliac vein). Fourteen SLN were negative at histological analysis and only 3 positive for micrometastasis (mean SLN sections = 60. All the other pelvic lymph nodes were negative at histological analysis. The same SLN locations detected with g-scintiprobe were observed during laparoscopy after patent blue dye injection. If the sensitivity of the assessment of SLN is confirmed to be 100%, this laparoscopic approach could change the management of early stage endometrial cancer. The clinical validity of this technique must be evaluated prospectively.
Karabuga, Havva; Gultekin, Melis; Tulunay, Gokhan; Yuce, Kunter; Ayhan, Ali; Yuce, Deniz; Yildiz, Ferah
The current study evaluates long-term quality of life (QOL) and sexual function of patients with endometrial cancer who received adjuvant pelvic external beam radiotherapy (EBRT) and/or vaginal brachytherapy (BRT). One hundred forty-four endometrial cancer survivors who were treated between January 2000 and December 2009 in our department were included in this study. Median follow-up was 79 months (range, 31-138 months). Fifty-two patients were treated with 45 to 50.4 Gy EBRT, 76 were with BRT, and 16 were with both EBRT and BRT. Brachytherapy was in the form of vaginal cuff BRT with 5 × 550 cGy high dose rate BRT, prescribed to the first 4 cm and whole wall thickness of vagina. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and subscales from the supplemental 24-item Cervical Cancer Module. Vaginal BRT patients reported better physical functioning (P = 0.01), role functioning (P = 0.03), and sexual enjoyment (P = 0.01) compared to EBRT group. Symptom score (P = 0.01), lymphedema (P = 0.03), pain (P = 0.02), and diarrhea (P = 0.009) scores were also higher with EBRT. Vaginal BRT did not worsen symptom scores or sexual functions when added to EBRT. Obese patients experienced higher rates of lymphedema (P = 0.008). Cognitive and role functioning scores were significantly higher in patients with normal body mass index. External beam radiotherapy negatively affects long-term QOL and sexual functions in endometrial cancer survivors. Vaginal BRT provides higher QOL. Patients with body mass index within normal limits have improved QOL.
Leibovitz, Z; Grinin, V; Rabia, R; Degani, S; Shapiro, I; Tal, J; Eibschitz, I; Harari, O; Paltieli, Y; Aharoni, A; Zeevi, J; Ohel, G
To evaluate the outcome of in vitro fertilization (IVF) treatment in relation to the sonographic parameters of the endometrium. Seventy-five patients with no uterine pathology (age 31.1 +/- 5.4 years) treated in our IVF clinic for various indications were assessed during 75 cycles in which good-quality (grades 1 and 2) embryos were transferred. Controlled ovarian stimulation was achieved by the long protocol (gonadotropin releasing hormone agonist and gonadotropins). The bilayered endometrial thickness (BET), estradiol, luteinizing hormone and progesterone serum levels were measured in 272 tests. A special computer program was used to measure endometrial echogenicity relative to myometrial echogenicity. The gray-level data were analyzed on the basis of the midsagittal sonographic uterine image. Endometrium-myometrium relative echogenicity coefficient (E/M REC) values were computed and displayed graphically along the anteroposterior axis of the endometrial layers in the upper part of the uterine cavity. The area under the E/M REC curve within the BET limits was defined as the relative echogenicity area (REA) and was used as a measure of endometrial echogenicity. Each cycle was sampled in six time segments representing desensitization, follicular and luteal phases. Assigning the day of ovum pick-up as day 0, the time segments of each cycle were: first, day -20 to day -11; second, day -10 to day -6; third, day -5 to day -2; fourth, day 0; fifth, day +7 to day +14; sixth, day +15 to day +21. A total of 276 embryos were transferred (3.68 +/- 1.01 per cycle), of which 223 were of good quality (2.97 +/- 1.51 per cycle). An intrauterine pregnancy was diagnosed in 29 patients. All patients in this study had a BET of > 5 mm in the third and the fourth time segments. There was no significant difference in BET and REA between pregnant and non-pregnant patients tested in the first to the fifth time segments of the IVF cycles. Both BET and REA measured in the sixth time segment
Perino, A; Quartararo, P; Catinella, E; Genova, G; Cittadini, E
The effectiveness of a new levo-norgestrel releasing intrauterine device is assessed in fourteen patients with histologically confirmed hyperplastic lesions of the endometrial mucosa. The morphologic response of the hyperplastic endometria to the action of the levo-norgestrel in this study explains the regression of the cases so treated.
Manners, C V
An immunohistochemical assessment of the endometrium was carried out in a group of IVF patients on stimulated cycles, in order to evaluate this technique against standard histological methods and to consider its application in a clinical situation. Monoclonal antibodies to the two cycle-dependent proteins: pregnancy associated endometrial alpha 2-globulin (alpha 2-PEG) and 24K (a protein originally isolated from an oestrogen-dependent breast tumour line, MCF-7) were used in the experiment. Immunohistochemical results concerning the effect of drug stimulation, age and date of biopsy on the secretory state of the endometrium revealed trends which were consistent with previous histological data, helping to confirm the value of this new technique. In addition, several specimens were found to have a normal, i.e. in phase, histological appearance but to have an atypical pattern of protein secretion. These observations suggest that biochemical monitoring of the uterus should be used in conjunction with routine histological dating.
Li, Xiao-Chao; Song, Wen-Jing
Our study is to determine the presence of endometrial intraepithelial neoplasia (EIN) in endometrial biopsy specimens classified by the 1994 World Health Organization (WHO) criteria for endometrial hyperplasia. Endometrial biopsy specimens that were stained with hematoxylin and eosin (HE) were examined and categorized by the WHO 1994 criteria and for the presence of EIN as defined by the International Endometrial Collaborative Group. β-catenin expression was examined by immunohistochemistry. A total of 474 cases of HE stained endometrial biopsy tissues were reviewed. There were 379 cases of simple endometrial hyperplasia, 16 with simple atypical endometrial hyperplasia, 48 with complex endometrial hyperplasia, and 31 with complex atypical endometrial hyperplasia. Among the 474 endometrial hyperplasia cases, there were 46 (9.7%) that were classified as EIN. Of these 46 cases, 11(2.9%) were classified as simple endometrial hyperplasia, 1 (6.3%) as simple atypical endometrial hyperplasia, 6 (12.5%) as complex endometrial hyperplasia, and 28 (90.3%) as complex atypical endometrial hyperplasia. EIN was associated with a higher rate of β-catenin positivity than endometrium classified as benign hyperplasia (72% vs. 22.5%, respectively, P < 0.001), but a lower rate than endometrial adenocarcinoma (72% vs. 96.2%, respectively, P < 0.001). In benign endometrial hyperplasia, high β-catenin expression was noted in the cell membranes, whereas in EIN and endometrial adenocarcinoma high expression was noted in the cytoplasm. In conclusion, EIN is more accurate than the WHO classification for the diagnosis of precancerous lesions of the endometrium.
Heard, Melissa E; Velarde, Michael C; Giudice, Linda C; Simmen, Frank A; Simmen, Rosalia C M
Krüppel-like Factor (KLF) 13 and the closely related KLF9 are members of the Sp/KLF family of transcription factors that have collectively emerged as essential regulators of tissue development, differentiation, proliferation, and programmed cell death. Steroid hormone-responsive tissues express multiple KLFs that are linked to progesterone receptor (PGR) and estrogen receptor (ESR) actions either as integrators or as coregulators. Endometriosis is a chronic disease characterized by progesterone resistance and dysregulated estradiol signaling; nevertheless, distinct KLF members' contributions to endometriosis remain largely undefined. We previously demonstrated promotion of ectopic lesion establishment by Klf9 null endometrium in a mouse model of endometriosis. Here we evaluated whether KLF13 loss of expression in endometrial cells may equally contribute to lesion formation. KLF13 transcript levels were lower in the eutopic endometria of women with versus women without endometriosis at menstrual midsecretory phase. In wild-type (WT) mouse recipients intraperitoneally administered WT or Klf13 null endometrial fragments, lesion incidence did not differ with donor genotype. No differences were noted for lesion volume, number, proliferation status, and apoptotic index as well. Klf13 null lesions displayed reduced total PGR and ESR1 (RNA and immunoreactive protein) and altered expression of several PGR and ESR1 target genes, relative to WT lesions. Unlike for Klf9 null lesions, changes in transcript levels for PGR-A, ESR1, and Notch/Hedgehog-associated pathway components were not observed for Klf13 null lesions. Results demonstrate lack of a causative relationship between endometrial KLF13 deficiency and lesion establishment in mice, and they support the broader participation of multiple signaling pathways, besides those mediated by steroid receptors, in the pathology of endometriosis.
Clement, Naomi S; Oliver, Thomas R W; Shiwani, Hunain; Saner, Juliane R F; Mulvaney, Caroline A; Atiomo, William
Introduction Endometrial hyperplasia is a precancerous lesion of the endometrium, commonly presenting with uterine bleeding. If managed expectantly, it frequently progresses to endometrial carcinoma, rates of which are increasing dramatically worldwide. However, the established treatment for endometrial hyperplasia (progestogens) involves multiple side effects and leaves the risk of recurrence. Metformin is the most commonly used oral hypoglycaemic agent in type 2 diabetes mellitus. It has also been linked to the reversal of endometrial hyperplasia and may therefore contribute to decreasing the prevalence of endometrial carcinoma without the fertility and side effect consequences of current therapies. However, the efficacy and safety of metformin being used for this therapeutic target is unclear and, therefore, this systematic review will aim to determine this. Methods and analysis We will search the following trials and databases with no language restrictions: Cochrane Gynaecology and Fertility Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; EBSCO Cumulative Index to Nursing and Allied Health Literature; PubMed; Google Scholar; ClinicalTrials.gov; the WHO International Trials Registry Platform portal; OpenGrey and the Latin American and Caribbean Health Sciences Literature (LILACS). We will include randomised controlled trials (RCTs) of use of metformin compared with a placebo or no treatment, conventional medical treatment (eg, progestogens) or any other active intervention. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. Trial authors will be contacted for additional data. The primary review outcome is the regression of endometrial hyperplasia histology towards normal histology. Secondary outcomes include hysterectomy rate; abnormal uterine bleeding; quality of life scores and adverse reactions to treatments. Ethics and dissemination
Yanoh, K; Norimatsu, Y; Hirai, Y; Takeshima, N; Kamimori, A; Nakamura, Y; Shimizu, K; Kobayashi, T K; Murata, T; Shiraishi, T
Objective: The aim of this study was to develop a new reporting format for endometrial cytology that would standardize the diagnostic criteria and the terminology used for reporting. Methods: In previous studies, cytoarchitectural criteria were found to be useful for the cytological assessment of endometrial lesions. To apply these criteria, an appropriate cytological specimen is imperative. In this article, the requirements of an adequate endometrial cytological specimen for the new diagnostic criteria are first discussed. Then, the diagnostic criteria, standardized on a combination of conventional and cytoarchitectural criteria, are presented. Third, terminology that could be used, not only for reporting the histopathological diagnosis, but also for providing better guidance for the gynaecologist to determine further clinical action, is introduced. The proposed reporting format was investigated using endometrial cytology of 58 cases that were cytologically underestimated or overestimated compared to the histopathological diagnosis made on the subsequent endometrial biopsy or surgical specimens. Results: Of the 58 cases, 12 were reassessed as being unsatisfactory for evaluation. Among the remaining 46 cases, 25 of the 27 cases, which had been underestimated and subsequently diagnosed as having endometrial carcinoma or a precursor stage on histopathological examination,were reassessed as recommended for endometrial biopsy. On the other hand, 19 cases overestimated by cytology were all reassessed as not requiring biopsy. Conclusions: The reporting format for endometrial cytology proposed in this article may improve diagnostic accuracy and reduce the number of patients managed inappropriately. PMID:18657157
Grundeken, Maik J; Collet, Carlos; Ishibashi, Yuki; Généreux, Philippe; Muramatsu, Takashi; LaSalle, Laura; Kaplan, Aaron V; Wykrzykowska, Joanna J; Morel, Marie-Angèle; Tijssen, Jan G; de Winter, Robbert J; Onuma, Yoshinobu; Leon, Martin B; Serruys, Patrick W
To compare visual estimation with different quantitative coronary angiography (QCA) methods (single-vessel versus bifurcation software) to assess coronary bifurcation lesions. QCA has been developed to overcome the limitations of visual estimation. Conventional QCA however, developed in "straight vessels," has proved to be inaccurate in bifurcation lesions. Therefore, bifurcation QCA was developed. However, the impact of these different modalities on bifurcation lesion severity classification is yet unknown METHODS: From a randomized controlled trial investigating a novel bifurcation stent (Clinicaltrials.gov NCT01258972), patients with baseline assessment of lesion severity by means of visual estimation, single-vessel QCA, 2D bifurcation QCA and 3D bifurcation QCA were included. We included 113 bifurcations lesions in which all 5 modalities were assessed. The primary end-point was to evaluate how the different modalities affected the classification of bifurcation lesion severity and extent of disease. On visual estimation, 100% of lesions had side-branch diameter stenosis (%DS) >50%, whereas in 83% with single-vessel QCA, 27% with 2D bifurcation QCA and 26% with 3D bifurcation QCA a side-branch %DS >50% was found (P < 0.0001). With regard to the percentage of "true" bifurcation lesions, there was a significant difference between visual estimate (100%), single-vessel QCA (75%) and bifurcation QCA (17% with 2D bifurcation software and 13% with 3D bifurcation software, P < 0.0001). Our study showed that bifurcation lesion complexity was significantly affected when more advanced bifurcation QCA software were used. "True" bifurcation lesion rate was 100% on visual estimation, but as low as 13% when analyzed with dedicated bifurcation QCA software. © 2017 Wiley Periodicals, Inc.
Makker, Annu; Singh, M M
Fertility in humans and other mammalian species depends absolutely on synchronous events that render the developing blastocyst and the receiving uterus competent for implantation. Endometrial receptivity is defined as the period during which the endometrial epithelium acquires functional, but transient, ovarian steroid-dependent status supportive to blastocyst acceptance and implantation. Once inside the uterus, the blastocyst is surrounded by an intact luminal epithelium, which is considered to act as barrier to its attachment, except for this short period of high endometrial receptivity to blastocyst signal(s). Its transport and permeability properties, in conjunction with cellular action of the endometrium and the embryo, have been suggested to influence creation and maintenance of informational and nutritional status of uterine luminal milieu. This period, also termed as the 'window of implantation,' is limited to days 20-24 of menstrual cycle in humans. However, establishment of endometrial receptivity is still a biological mystery that remains unsolved despite marked advances in our understanding of endometrial physiology following extensive research associated with its development and function. This review deals with various structural, biochemical, and molecular events in the endometrium coordinated within the implantation window that constitute essential elements in the repertoire that signifies endometrial receptivity and is aimed to achieve a better understanding of its relationship to fertility, infertility, and for the development of targeted antifertility agents for human use and welfare.
Bergman, L; Beelen, M L; Gallee, M P; Hollema, H; Benraadt, J; van Leeuwen, F E
Tamoxifen increases the risk of endometrial cancer. However, few studies have produced reliable risk estimates by duration, dose, and recency of use, or addressed the prognosis of endometrial cancers in tamoxifen-treated women. We did a nationwide case-control study on the risk and prognosis of endometrial cancer after tamoxifen use for breast cancer. Information on tamoxifen use and other risk factors for endometrial cancer was obtained from 309 women with endometrial cancer after breast cancer (cases), and 860 matched controls with breast cancer but without endometrial cancer. For 276 cases, we obtained tissue blocks of endometrial cancer to review the diagnosis, and used immunohistochemistry to examine hormone-receptor status and overexpression of p53. Tamoxifen had been used by 108 (36.1%) of 299 cases and 245 (28.5%) controls (relative risk 1.5 [95% CI 1.1-2.0]). Risk of endometrial cancer increased with longer duration of tamoxifen use (p < 0.001), with relative risks of 2.0 (1.2-3.2) for 2-5 years and 6.9 (2.4-19.4) for at least 5 years compared with non-users. Endometrial cancers of stage III and IV occurred more frequently in long-term tamoxifen users (> or = 2 years) than in non-users (17.4% vs 5.4%, p=0.006). Long-term users were more likely than non-users to have had malignant mixed mesodermal tumours or sarcomas of the endometrium (15.4% vs 2.9%, p < or = 0.02), p53-positive tumours (31.4% vs 18.2%, p=0.05), and negative oestrogen-receptor concentrations (60.8% vs 26.2%, p < or = 0.001). 3-year endometrial-cancer-specific survival was significantly worse for long-term tamoxifen users than for non-users (76% for > or = 5 years, 85% for 2-5 years vs 94% for non-users, p=0.02). Long-term tamoxifen users have a worse prognosis of endometrial cancers, which seems to be due to less favourable histology and higher stage. However, the benefit of tamoxifen on breast-cancer survival far outweighs the increased mortality from endometrial cancer. Nevertheless, we
Byun, Jung Mi; Jeong, Dae Hoon; Kim, Young Nam; Cho, En Bee; Cha, Ju Eun; Sung, Moon Su; Lee, Kyung Bok
Objective We investigated the features of endometrial hyperplasia with concurrent endometrial cancer that had been diagnosed by endometrial sampling. Further, we attempted to identify an accurate differential diagnostic method. Methods We retrospectively studied 125 patients who underwent a diagnostic endometrial biopsy or were diagnosed after the surgical treatment of other gynecological lesions, such as leiomyoma or polyps. Patients were diagnosed between January 2005 and December 2013 at Busan Paik Hospital. Clinical and histopathological characteristics were compared in patients who had atypical endometrial hyperplasia with and without concurrent endometrial cancer. Results The patients were grouped based on the final pathology reports. One hundred seventeen patients were diagnosed with endometrial hyperplasia and eight patients were diagnosed with endometrioid adenocarcinoma arising from atypical hyperplasia. Of the 26 patients who had been diagnosed with atypical endometrial hyperplasia by office-based endometrial biopsy, eight (30.8%) were subsequently diagnosed with endometrial cancer after they had undergone hysterectomy. The patients with endometrial cancer arising from endometrial hyperplasia were younger (39.1 vs. 47.2 years, P=0.0104) and more obese (body mass index 26.1±9.6 vs. 23.8±2.8 kg/m2, P=0.3560) than the patients with endometrial hyperplasia. The correlation rate between the pathology of the endometrial samples and the final diagnosis of endometrial hyperplasia was 67.3%. Conclusion In patients with atypical endometrial hyperplasia, the detection of endometrial cancer before hysterectomy can decrease the risk of suboptimal treatment. The accuracy of endometrial sampling for the diagnosis of concurrent endometrial carcinoma was much lower than that for atypical endometrial hyperplasia. Therefore, concurrent endometrial carcinoma should be suspected and surgical intervention should be considered in young or obese patients who present with
Proctor, L; Pradhan, M; Leung, S; Cheng, A; Lee, C H; Soslow, R A; Gilks, C B; Talhouk, A; McAlpine, J M; Danielsen, H E; Hoang, L N
We sought to determine whether DNA ploidy correlates with the four molecular subgroups of endometrial carcinoma (EC) as determined using ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). 90 cases of EC previously characterized by clinicopathological parameters, outcomes, and ProMisE molecular subgroup (POLE EDM, MMR-D, p53 wt or p53 abn) were assessed for DNA ploidy using image cytometry. Associations of ploidy with traditional clinicopathological parameters were also tested. Abnormal DNA ploidy status differed amongst the ProMisE groups (p<0.001) and was found in 80.9% (17/21) of p53 abn, 37.0% (10/27) of p53 wt, 28.6% (4/14) of POLE EDM and 14.3% (4/28) of MMR-D. Abnormal DNA content was significantly associated with lower BMI (p=0.034) and grade 3 tumors (p=0.001). In the entire cohort, abnormal DNA content was significantly associated with worse progression free survival (p=0.0094) but not disease specific survival (p=0.249) or overall survival (p=0.187). When examining ploidy within each of the ProMisE groups, abnormal DNA content correlated with worse overall survival (p=0.041) and progression free survival (p=0.011) in the MMR-D group. No statistically significant relationship was seen in the remaining 3 groups. Abnormal DNA ploidy status did correlate with the molecular subgroups of EC; abnormal DNA content was seen in the large majority of p53 abn cases. Abnormal ploidy however was also seen in smaller numbers in the p53 wt, POLE EDM and MMR-D groups; therefore abnormal DNA content was not a specific marker for any one molecular group. The addition of ploidy to the ProMisE molecular categories conferred additional prognostic value within the MMR-D group, which merits further study. Copyright © 2017 Elsevier Inc. All rights reserved.
Zheng, Wenxin; Yi, Xiaofang; Fadare, Oluwole; Liang, Sharon X; Martel, Maritza; Schwartz, Peter E; Jiang, Zhong
universally cytoplasmic, with diffuse staining of strong intensity in serous carcinomas, whereas staining was typically patchy and of moderate or weak intensity in nonserous malignancies. Among the benign endometrial samples, decidualized endometrial stroma showed 100% positivity for IMP3. The remaining samples were negative, with the exception of a few weakly proliferative glands in 3 (5%) of 68 cases that showed focal weak immunoreactivity of IMP3. The trophoblasts in the first trimester chorionic villi were also diffusely positive, which was consistent with previously reported findings. We conclude that expression of IMP3, a newly identified cytoplasmic marker, is closely associated with type II endometrial cancer. It seems that IMP3 expression is associated with an aggressive histologic phenotype among endometrial neoplastic lesions. Strong and diffuse IMP3 expression is highly sensitive for endometrial serous and clear cell carcinomas including their putative precursor lesions. Therefore, IMP3 may be a useful diagnostic marker in the assessment of endometrial cancers and their precursor lesions, particularly when the amount of available tissue material is limited and a concern of type II cancer arises. High frequency of IMP3 expression is present in decidualized endometrial stroma of gestational endometrium and chorionic villi in early pregnancy. Although the significance of the latter finding remains unclear, the differential diagnosis between decidual changes and endometrial serous carcinoma is rarely problematic.
Krezdorn, N; Limbourg, A; Paprottka, F J; Könneker; Ipaktchi, R; Vogt, P M
Tattoos are on the rise, and so are patients with tattooed burn lesions. A proper assessment with regard to burn depth is often impeded by the tattoo dye. Laser speckle contrast analysis (LASCA) is a technique that evaluates burn lesions via relative perfusion analysis. We assessed the effect of tattoo skin pigmentation on LASCA perfusion imaging in a multicolour tattooed patient. Depth of burn lesions in multi-coloured tattooed and untattooed skin was assessed using LASCA. Relative perfusion was measured in perfusion units (PU) and compared to various pigment colours, then correlated with the clinical evaluation of the lesion. Superficial partial thickness burn (SPTB) lesions showed significantly elevated perfusion units (PU) compared to normal skin; deep partial thickness burns showed decreased PU levels. PU of various tattoo pigments to normal skin showed either significantly lower values (blue, red, pink) or significantly increased values (black) whereas orange and yellow pigment showed values comparable to normal skin. In SPTB, black and blue pigment showed reduced perfusion; yellow pigment was similar to normal SPTB burn. Deep partial thickness burn (DPTB) lesions in tattoos did not show significant differences to normal DPTB lesions for black, green and red. Tattoo pigments alter the results of perfusion patterns assessed with LASCA both in normal and burned skin. Yellow pigments do not seem to interfere with LASCA assessment. However proper determination of burn depth both in SPTB and DPTB by LASCA is limited by the heterogenic alterations of the various pigment colours.
Krezdorn, N.; Limbourg, A.; Paprottka, F.J.; Könneker; Ipaktchi, R.; Vogt, P.M
Summary Tattoos are on the rise, and so are patients with tattooed burn lesions. A proper assessment with regard to burn depth is often impeded by the tattoo dye. Laser speckle contrast analysis (LASCA) is a technique that evaluates burn lesions via relative perfusion analysis. We assessed the effect of tattoo skin pigmentation on LASCA perfusion imaging in a multicolour tattooed patient. Depth of burn lesions in multi-coloured tattooed and untattooed skin was assessed using LASCA. Relative perfusion was measured in perfusion units (PU) and compared to various pigment colours, then correlated with the clinical evaluation of the lesion. Superficial partial thickness burn (SPTB) lesions showed significantly elevated perfusion units (PU) compared to normal skin; deep partial thickness burns showed decreased PU levels. PU of various tattoo pigments to normal skin showed either significantly lower values (blue, red, pink) or significantly increased values (black) whereas orange and yellow pigment showed values comparable to normal skin. In SPTB, black and blue pigment showed reduced perfusion; yellow pigment was similar to normal SPTB burn. Deep partial thickness burn (DPTB) lesions in tattoos did not show significant differences to normal DPTB lesions for black, green and red. Tattoo pigments alter the results of perfusion patterns assessed with LASCA both in normal and burned skin. Yellow pigments do not seem to interfere with LASCA assessment. However proper determination of burn depth both in SPTB and DPTB by LASCA is limited by the heterogenic alterations of the various pigment colours. PMID:28149254
Lee, Robert Chulsung
New, more sophisticated diagnostic tools are needed for the detection and characterization of caries lesions in the early stages of development. It is not sufficient to simply detect caries lesions, methods are needed to assess the activity of the lesion and determine if chemical or surgical intervention is needed. Previous studies have demonstrated that polarization sensitive optical coherence tomography (PS-OCT) can be used to nondestructively image the subsurface lesion structure and measure the thickness of the highly mineralized surface zone. Other studies have demonstrated that the rate of dehydration can be correlated with the lesion activity and that the rate can be measured using optical methods. The main objective of this work was to test the hypothesis that optical methods can be used to assess lesion activity on tooth coronal and root surfaces. Simulated caries models were used to develop and validate an algorithm for detecting and measuring the highly mineralized surface layer using PS-OCT. This work confirmed that the algorithm was capable of estimating the thickness of the highly mineralized surface layer with high accuracy. Near-infrared (NIR) reflectance and thermal imaging methods were used to assess activity of caries lesions by measuring the state of lesion hydration. NIR reflectance imaging performed the best for artificial enamel and natural coronal caries lesion samples, particularly at wavelengths coincident with the water absorption band at 1460-nm. However, thermal imaging performed the best for artificial dentin and natural root caries lesion samples. These novel optical methods outperformed the conventional methods (ICDAS II) in accurately assessing lesion activity of natural coronal and root caries lesions. Infrared-based imaging methods have shown potential for in-vivo applications to objectively assess caries lesion activity in a single examination. It is likely that if future clinical trials are a success, this novel imaging
Teng, Fei; Zhang, Yan-Fang; Wang, Ying-Mei; Yu, Jing; Lang, Xu; Tian, Wen-Yan; Jiang, Chang-Xin; Xue, Feng-Xia
To determine the ability of contrast-enhanced magnetic resonance imaging to predict myometrial invasion, cervical invasion, and pelvic lymph node metastasis in endometrial carcinoma and to analyze factors that lead to errors in this identification. A retrospective study. University general hospital. A total of 167 women diagnosed with endometrial carcinoma. All patients received a preoperative contrast-enhanced magnetic resonance imaging scan. Histopathological findings were used as the definitive diagnosis. The results were compared with histopathological findings, factors that make accurate assessment of myometrial invasion, cervical invasion, and pelvic lymph node metastasis difficult by contrast-enhanced magnetic resonance imaging were analyzed. The sensitivity, specificity, diagnostic accuracy, positive predictive values, and negative predictive values of contrast-enhanced magnetic resonance imaging were 90.9, 91.8, 91.6, 73.2 and 97.6%, respectively, for identifying deep myometrial invasion; 84.2, 96.0, 94.6, 72.7 and 97.9%, respectively, for identifying cervical invasion; and 45.0, 91.2, 85.6, 40.9 and 92.4%, respectively, for identifying pelvic lymph node metastasis. The main causes of error in contrast-enhanced magnetic resonance imaging were myomas, cornual lesions, deep myometrial invasion, large tumor size, non-endometrioid tumor type, and lower tumor grade. Contrast-enhanced magnetic resonance imaging has a high accuracy and a low tendency to produce false-negative predictive values. Gynecological oncologists should combine the imaging data and clinical information to make therapeutic decisions and avoid diagnostic errors. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.
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.
Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma
Phillips, Irene D; Taylor, Jacqueline J; Allen, Andrew L
Reports of spontaneously occurring endometrial polyps in animals are rare and have only involved a few species. This report is intended to advise veterinarians that older African pygmy hedgehogs may develop endometrial polyps and that these lesions can be a cause of bloody vaginal discharge, sometimes interpreted as hematuria.
Abstract Reports of spontaneously occurring endometrial polyps in animals are rare and have only involved a few species. This report is intended to advise veterinarians that older African pygmy hedgehogs may develop endometrial polyps and that these lesions can be a cause of bloody vaginal discharge, sometimes interpreted as hematuria. PMID:16048013
Dowdy, S C; Borah, B J; Bakkum-Gamez, J N; Weaver, A L; McGree, M E; Haas, L R; Keeney, G L; Mariani, A; Podratz, K C
Since 1999, patients with low risk endometrial cancer (EC) as defined by the Mayo criteria have preferably not undergone lymphadenectomy (LND) at our institution. Here we prospectively assess survival, sites of recurrence, morbidity, and cost in this low risk cohort. Cause-specific survival (CSS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Complications were graded per the Accordion Classification. Thirty-day cost analyses were expressed in 2010 Medicare dollars. Among 1393 consecutive surgically managed cases, 385 (27.6%) met inclusion criteria, accounting for 34.1% of type I EC. There were 80 LND and 305 non-LND cases. Complications in the first 30 days were significantly more common in the LND cohort (37.5% vs. 19.3%; P<0.001). The prevalence of lymph node metastasis was 0.3% (1/385). Over a median follow-up of 5.4 years only 5 of 31 deaths were due to disease. The 5-year CSS in LND and non-LND cases was 97.3% and 99.0%, respectively (P=0.32). None of the 11 total recurrences occurred in the pelvic or para-aortic nodal areas. Median 30-day cost of care was $15,678 for LND cases compared to $11,028 for non-LND cases (P<0.001). The estimated cost per up-staged low-risk case was $327,866 to $439,990, adding an additional $1,418,189 if all 305 non-LND cases had undergone LND. Lymphadenectomy dramatically increases morbidity and cost of care without discernible benefits in low-risk EC as defined by the Mayo criteria. In these low-risk patients, hysterectomy with salpingo-oophorectomy alone is appropriate surgical management and should be standard of care. Copyright © 2012. Published by Elsevier Inc.
Interpreting Spontaneous Renal Lesions in Safety and Risk Assessment
Douglas C. Wolf, D.V.M., Ph.D.
Risk assessment is a process whereby the potential adverse health effects from exposure to a xenobiotic are predicted after evaluation of the availab...
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.
... therapy , and chemotherapy . Surgery to remove the uterus ( hysterectomy ) may be done in women with early stage ... uterine; Cancer - endometrial; Uterine corpus cancer Patient Instructions Hysterectomy - abdominal - discharge Hysterectomy - laparoscopic - discharge Hysterectomy - vaginal - discharge ...
... cancer is higher if you are postmenopausal, on Tamoxifen, or have heavy or irregular periods. These factors may increase the risk for endometrial polyps: Obesity Tamoxifen, a treatment for breast cancer Postmenopausal hormone replacement ...
Abdullahi, Y M; Ajani, M A; Iyapo, O; Aramide, K O; Okolo, C A; Akang, Eeu
Endometrium remains the most sensitive indicator of ovarian function and endometrial biopsy is one of the diagnostic procedures in endometrial pathology. The current study was carried out to examine the morphological pattern of endometrial biopsies in Ibadan, South-western Nigeria and compare the results with similar studies. A retrospective study was undertaken to review all cases of endometrial biopsies received in the Department of Pathology, University College Hospital, Ibadan between January 1999 and December 2008. The patients' data were retrieved from the surgical pathology daybooks and Histology Request forms. The neoplastic lesions were classified according to 2003 World Health Organization classification for endometrial neoplasms. A total of 2,444 cases of endometrial biopsies were received during the 10-year study period. The functional endometrial changes were the most common histopathological diagnostic category, accounting for 53.8% (1035) of cases. Other pathological diagnoses included endometritis (7.8%), simple endometrial hyperplasia (5.8%), partial hydatidiform mole (2.3%), complete hydatidiform mole (2.1%) and malignant neoplastic lesions (3.9%). Infertility was the most common (57%) indication for endometrial biopsies followed by uterine bleeding (33%) while the least common clinical indication were the menstrual disorders (10%). The functional endometrial changes account for the highest morphological patterns while malignant lesions account for the least pattern of the endometrial biopsies evaluated for etiological basis of infertility, uterine bleeding and menstrual disorders in Ibadan. Infertility was the commonest indication for endometrial biopsies while the least common clinical indication was menstrual disorders.
Yang, Xue; Li, Gang; Lin, Ling
Multiple diseases such as breast tumor poses a great threat to women's health and life, while the traditional detection method is complex, costly and unsuitable for frequently self-examination, therefore, an inexpensive, convenient and efficient method for tumor self-inspection is needed urgently, and lesion localization is an important step. This paper proposes an self-examination method for positioning of a lesion. The method adopts transillumination to acquire the hyperspectral images and to assess the spatial information of lesion. Firstly, multi-wavelength sources are modulated with frequency division, which is advantageous to separate images of different wavelength, meanwhile, the source serves as fill light to each other to improve the sensitivity in the low-lightlevel imaging. Secondly, the signal-to-noise ratio of transmitted images after demodulation are improved by frame accumulation technology. Next, gray distributions of transmitted images are analyzed. The gray-level differences is constituted by the actual transmitted images and fitting transmitted images of tissue without lesion, which is to rule out individual differences. Due to scattering effect, there will be transition zones between tissue and lesion, and the zone changes with wavelength change, which will help to identify the structure details of lesion. Finally, image segmentation is adopted to extract the lesion and the transition zones, and the spatial features of lesion are confirmed according to the transition zones and the differences of transmitted light intensity distributions. Experiment using flat-shaped tissue as an example shows that the proposed method can extract the space information of lesion.
Portman, David J; Symons, James P; Wilborn, Walter; Kempfert, Nona J
The purpose of this study was to determine the incidence of endometrial hyperplasia in subjects who receive continuous norethindrone acetate and ethinyl estradiol combinations versus unopposed ethinyl estradiol. Nine hundred forty-five postmenopausal women were randomly selected for 12 months of treatment with one of six blinded norethindrone acetate/ethinyl estradiol combinations (milligrams of norethindrone acetate/micrograms of ethinyl estradiol: 0/5, 0.25/5, 1/5, 0/10, 0.5/10, or 1/10) or to open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate. Endometrial hyperplasia and endometrial proliferation were assessed by biopsy at screening, months 6 and 12. Endometrial hyperplasia developed in 26 subjects: Placebo, 0/5 and 0.25/5 (1 subject each) and 0/10 (23 subjects). Significantly less endometrial proliferation was measured in the 1/5 norethindrone acetate/ethinyl estradiol and other norethindrone acetate/ethinyl estradiol combination groups and in the 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate group, than in unopposed ethinyl estradiol groups (6 months: P <.004; 12 months: P <.001). Treatment with 1/5 norethindrone acetate/ethinyl estradiol and with other norethindrone acetate/ethinyl estradiol combinations significantly reduced endometrial proliferation compared with 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (6 and 12 months: P <.02). Norethindrone acetate protects the endometrium from estrogen-induced hyperplasia and changes in proliferative status. In addition, norethindrone acetate/ethinyl estradiol-treated subjects had significantly less endometrial proliferation compared with 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate-treated subjects.
Until the 1930s all meniscal lesions were considered to be of traumatic origin. The efforts of Magnus and his pupils led to a more differentiated medicolegal interpretation of wear and tear of the meniscus and classification of at least some types of meniscal lesions as nontraumatic in the sense of accident insurance. This caused controversy, continuing to the present day, as to whether trauma or degeneration is essential for a meniscal tear. This debate can now be closed. Numerous investigations of meniscus pathology have proved that the isolated, essentially traumatic meniscal tear does not exist. Only if the viscoelastic properties of meniscus tissue are changed may indirect force cause a rupture. There is no longer any reason to follow principles for the assessment of meniscus damage differing from those for tendon or intervertebral disc lesions. Only penetrating joint injuries or joint fractures may lead to a direct meniscal lesion (corresponding to penetrating spine trauma or vertebral body fracture with concomitant disc lesion). Separation of the meniscus from its insertion is the analog of discoligamentous spinal trauma. Post-traumatic meniscus degeneration due to joint instability is equivalent to the instability of the motion segment with intervertebral disc degeneration. Isolated meniscal tears and isolated intervertebral disc ruptures cannot be caused by indirect force. The conventional, inconsistently applied criteria to distinguish traumatic and degenerative meniscal lesions are no longer necessary.
Le, Tien; Menard, Chantal; Samant, Rajiv; Choan, E.; Hopkins, Laura; Faught, Wylam; Fung-Kee-Fung, Michael
Purpose: Adjuvant radiotherapy (RT) is often considered for endometrial cancer. We studied the effect of RT and surgical treatment on patients' quality of life (QOL). Methods and Materials: All patients referred to the gynecologic oncology clinics with biopsy findings showing endometrial cancer were recruited. QOL assessments were performed using the European Organization for Research and Treatment of Cancer QOL questionnaire-C30, version 3. Assessments were obtained at study entry and at regular 3-month intervals for a maximum of 2 years. Open-ended telephone interviews were done every 6 months. Linear mixed regression models were built using QOL domain scores as dependent variables, with the predictors of surgical treatment and adjuvant RT type. Results: A total of 40 patients were recruited; 80% of the surgeries were performed by laparotomy. Significant improvements were seen in most QOL domains with increased time from treatment. Adjuvant RT resulted in significantly more severe bowel symptoms and improvement in insomnia compared with conservative follow-up. No significant adverse effect from adjuvant RT was seen on the overall QOL. Bowel symptoms were significantly increased in patients treated with laparotomy compared with laparoscopy in the patients treated with whole pelvic RT. Qualitatively, about one-half of the patients noted improvements in their overall QOL during follow-up, with easy fatigability the most prevalent. Conclusion: No significant adverse effect was seen on patients' overall QOL with adjuvant pelvic RT after the recovery period. The acute adverse effects on patients' QOL significantly improved with an increasing interval from diagnosis.
Atypical Endometrial Hyperplasia; Endometrial Adenocarcinoma; Recurrent Endometrial Carcinoma; Stage IA Endometrial Carcinoma; Stage IB Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma
Terms, definitions and measurements to describe the sonographic features of the endometrium and intrauterine lesions: a consensus opinion from the International Endometrial Tumor Analysis (IETA) group.
Leone, F P G; Timmerman, D; Bourne, T; Valentin, L; Epstein, E; Goldstein, S R; Marret, H; Parsons, A K; Gull, B; Istre, O; Sepulveda, W; Ferrazzi, E; Van den Bosch, T
The IETA (International Endometrial Tumor Analysis group) statement is a consensus statement on terms, definitions and measurements that may be used to describe the sonographic features of the endometrium and uterine cavity on gray-scale sonography, color flow imaging and sonohysterography. The relationship between the ultrasound features described and the presence or absence of pathology is not known. However, the IETA terms and definitions may form the basis for prospective studies to predict the risk of different endometrial pathologies based on their ultrasound appearance.
Lapensee, L.; Toth, T.L.; Isaacson, K.B.
Objective: A comparison between office hysteroscopy, transvaginal ultrasonography and endometrial biopsy was performed, in terms of detection of intrauterine lesions. A secondary objective was assessment of evaluatory approach in the management of abnormal uterine bleeding in an outpatient setting. Design: Prospective observational study. Material and Methods: A total of 54 women were evaluated for abnormal uterine bleeding. Assessment included performance of an endometrial biopsy, a transvaginal ultra-sound scan followed by office hysteroscopy. Results of hysteroscopy were taken as the gold standard. Sensitivity and specificity of the investigations were assessed. The bleeding pattern was classified as heavy regular, irregular, postmenopausal and heavy or unscheduled bleeding on hormone replacement therapy. Results: The incidence of focal intrauterine lesions in patients presenting with abnormal bleeding was 52% for all ages and 31% for the postmenopausal group. Seventy-five percent of the patients with Hb < 11 gm% and 67% with an enlarged uterus harbored a focal pathology. The incidence of lesions in patients with heavy regular bleeding was 74%. The sensitivity and specificity of transvaginal ultrasound when compared with results of hysteroscopy was 0.60 and 0.88 respectively. A normal endometrial biopsy had a negative predictive value of 51%. The sensitivity and specificity of endometrial biopsy were 0.04 and 0.83, respectively. Conclusion: Both transvaginal ultrasound and endometrial biopsy exhibited poor sensitivity for detection of focal intrauterine lesions. Considering the significantly high incidence of intrauterine lesions in patients presenting with abnormal bleeding, the most cost-effective approach appears to be proceeding with hysteroscopy early in assessment. PMID:9876659
Comparison of Uterine Receptivity between Fertile and Unexplained Infertile Women by Assessment of Endometrial and Subendometrial Perfusion Using Contrast-Enhanced Ultrasound: Which Index is Better--Peak Intensity or Area under the Curve?
Chen, Minxia; He, Yanni; Zhang, Pengjie; Geng, Qiang; Liu, Qiuxiang; Kong, Linghong; Chen, Yihan; Wei, Qingzhu; Liu, Jianghuan; Guo, Suiqun; Liu, Hongmei
The goal of this study was to compare uterine receptivity between women with normal fertility and those with unexplained infertility during natural cycles by assessment of endometrial and subendometrial perfusion using contrast-enhanced ultrasound (CEUS). We wanted to determine the better index: peak intensity (PI) or area under the curve (AUC). Thirty women with unexplained infertility were recruited into the study group, and 30 women with normal fertility were recruited into the control group. All women underwent CEUS during the late proliferative phase, ovulation phase, and implantation window of a menstrual cycle. Endometrial PI, endometrial AUC, subendometrial PI and subendometrial AUC were analyzed. In the late proliferative phase, the control group had a significantly higher endometrial PI (p < 0.001) as well as subendometrial PI (p < 0.001) and AUC (p = 0.004) than the study group. In the ovulation phase, the control group had a significantly higher endometrial PI (p < 0.001) and AUC (p = 0.021), as well as subendometrial PI (p < 0.001) and AUC (p = 0.003). During the implantation window, there were no significant differences between the two groups. Only subendometrial PI underwent a significant periodic change during the menstrual cycle in both groups. This finding was further confirmed by evaluation of the microvessel density of endometria. In conclusion, CEUS can be used to assess endometrial and subendometrial perfusion to evaluate uterine receptivity. Subendometrial PI was the most sensitive index compared with endometrial PI, endometrial AUC and subendometrial AUC.
Dasgupta, Subhankar; Dasgupta, Shyamal; Sharma, Partha Pratim; Mukherjee, Amitabha; Ghosh, Tarun Kumar
To investigate the effect of oral progesterone on the accuracy of imaging studies performed to detect endometrial pathology in comparison to hysteroscopy-guided biopsy in perimenopausal women on progesterone treatment for abnormal uterine bleeding. The study population comprised of women aged 40-55 years with complaints of abnormal uterine bleeding who were also undergoing oral progesterone therapy. Women with a uterus ≥ 12 weeks' gestation size, previous abnormal endometrial biopsy, cervical lesion on speculum examination, abnormal Pap smear, active pelvic infection, adnexal mass on clinical examination or during ultrasound scan and a positive pregnancy test were excluded. A transvaginal ultrasound followed by saline infusion sonography were done. On the following day, a hysteroscopy followed by a guided biopsy of the endometrium or any endometrial lesion was performed. Comparison between the results of the imaging study with the hysteroscopy and guided biopsy was done. The final analysis included 83 patients. For detection of overall pathology, polyp and fibroid transvaginal ultrasound had a positive likelihood ratio of 1.65, 5.45 and 5.4, respectively, and a negative likelihood ratio of 0.47, 0.6 and 0.43, respectively. For detection of overall pathology, polyp and fibroid saline infusion sonography had a positive likelihood ratio of 4.4, 5.35 and 11.8, respectively, and a negative likelihood ratio of 0.3, 0.2 and 0.15, respectively. In perimenopausal women on oral progesterone therapy for abnormal uterine bleeding, imaging studies cannot be considered as an accurate method for diagnosing endometrial pathology when compared to hysteroscopy and guided biopsy. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.
Bruner-Tran, Kaylon L; Osteen, Kevin G; Taylor, Hugh S; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J
Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.
Bartosch, Carla; Monteiro-Reis, Sara; Almeida-Rios, Diogo; Vieira, Renata; Castro, Armando; Moutinho, Manuel; Rodrigues, Marta; Graça, Inês; Lopes, José Manuel; Jerónimo, Carmen
Sirtuins participate in hormone imbalance, metabolism and aging, which are important processes for endometrial cancer (EC) development. Sirtuins mRNA expression (SIRT1 to 7) was determined in 76 ECs (63 Type I, 12 Type II and one mixed EC), and 30 non-neoplastic endometria (NNE) by quantitative real-time PCR. SIRT1 and SIRT7 protein expression was evaluated by immunohistochemistry using Allred score. Compared to NNE, ECs showed SIRT7 (p < 0.001) mRNA overexpression, whereas SIRT1 (p < 0.001), SIRT2 (p < 0.001), SIRT4 (p < 0.001) and SIRT5 (p < 0.001) were underexpressed. No significant differences were observed for SIRT3 and SIRT6. Type II ECs displayed lower SIRT1 (p = 0.032) and SIRT3 (p = 0.016) transcript levels than Type I ECs. Concerning protein expression, SIRT1 immunostaining median score was higher in ECs compared to NNE epithelium (EC = 5 vs. NNE = 2, p < 0.001), while SIRT7 was lower in ECs (EC = 6 vs. NNE = 7, p < 0.001). No significant associations were found between SIRT1/7 immunoexpression and histological subtype, grade, lymphovascular invasion or stage. Our data shows that sirtuins are deregulated in EC. The diversity of expression patterns observed suggests that sirtuins may have distinctive roles in endometrial cancer similarly to what has been described in other cancer models.
Zhang, Yuping; Goodfellow, Renee; Li, Yujun; Yang, Shujie; Winters, Christopher J; Thiel, Kristina W; Leslie, Kimberly K; Yang, Baoli
The PI3K/Akt pathway is frequently dysregulated in endometrial cancer, the most common gynecologic malignancy. Emerging evidence identifies the ubiquitin ligase NEDD4 as a key regulator of the PI3K/Akt pathway via activation of insulin-like growth factor-1 receptor (IGF-1R). Our objective was to understand the role of NEDD4 in endometrial cancer. NEDD4 expression was assessed by immunohistochemistry in a tissue microarray with 77 endometrial lesions ranging from normal benign endometrium to tumor specimens of varying stage and grade. Studies were extended to a panel of eight endometrial cancer cell lines phenotypically representing the most common endometrial patient tumors. Immunohistochemistry demonstrated robust staining of NEDD4 in endometrial tumor specimens, with greater NEDD4 expression in the most aggressive tumors. Expression of NEDD4 was detected in a majority of endometrial cancer cell lines surveyed. Exogenous overexpression of murine Nedd4 in endometrial cancer cell lines with modest endogenous NEDD4 expression resulted in a significant increase in the rate of proliferation. Nedd4 overexpression also promoted an increase in cell surface localization of IGF-1R and activation of Akt. Inhibition of PI3K/Akt signaling reversed the enhanced cell growth in Nedd4-overexpressing endometrial cancer cells. In addition, the expression of NEDD4 in endometrial tumors positively correlated with the Akt downstream effector FoxM1. This study identifies NEDD4 as a putative oncogene in endometrial cancer that may augment activation of the IGF-1R/PI3K/Akt signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.
Kang, Sokbom; Nam, Joo-Hyun; Bae, Duk-Soo; Kim, Jae-Weon; Kim, Moon-Hong; Chen, Xiaojun; No, Jae-Hong; Lee, Jong-Min; Kim, Jae-Hoon; Watari, Hidemich; Kim, Seok Mo; Kim, Sung Hoon; Seong, Seok Ju; Kim, Ki Tae; Kim, Seung Cheol; Kim, Jong-Hyeok; Lim, Myung-Cheol; Lee, Jung-Yun; Ryu, Sang-Young; Yang, Bingyi; Kim, Byoung-Gie
Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed. Eligible patients with histologically confirmed endometrial cancer underwent magnetic resonance imaging (MRI) and serum cancer antigen 125 (CA 125) testing before surgery. The following criteria were used to identify low-risk patients: 1) endometrioid-type cancer, 2) no evidence of deep myometrial invasion on MRI, 3) no enlarged lymph nodes on MRI, 4) no suspicious metastasis out of the uterine corpus, and 5) serum CA 125 levels less than 35 U/mL. Systematic pelvic and/or para-aortic lymphadenectomy was performed for all patients. The primary endpoint was estimation of the negative predictive value (NPV). From January 2012 to December 2014, 529 patients from 20 hospitals in 3 Asian countries were consecutively enrolled. According to our criteria, 272 patients (51.4%) were categorized into the low-risk group. Fifty-three of the 529 patients (10.0%) had lymph node metastases; these patients included 8 (2.9%) falsely categorized as low-risk. The sensitivity and specificity of the criteria were 84.9% and 55.5%, respectively. The NPV of 97.1% was higher than the predefined target endpoint of 96%. The low-risk criteria based on preoperative tests were confirmed to be reliable and accurate for identifying patients at low risk for lymph node metastasis. These criteria may facilitate patient counseling and surgical decision making. Cancer 2017;123:263-272. © 2016 American Cancer Society. © 2016 American Cancer Society.
Hunn, Jessica; Dodson, Mark K; Webb, Joel; Soisson, Andrew P
Endometrial carcinoma is the fourth most common cancer among women in the United States. Surgical pathologic staging has been the standard of care since 1988, which consists of analysis of collected peritoneal fluid, hysterectomy/oophorectomy, and pelvic and para-aortic lymphadenectomy. In 2005, it was further recommended that essentially all women with endometrial cancer who choose to undergo surgery have pelvic and para-aortic lymph node analysis. Despite this recommendation, there still remains controversy as to whether all patients with endometrial cancer should undergo full lymph node dissection. In this review, we assess the evidence surrounding this controversy and conclude that women with endometrial cancer should undergo complete lymphadenectomy at the time of surgery. Furthermore, we evaluate the evidence regarding laparoscopic surgical staging as a safe and effective alternative to the more invasive traditional laparotomy. Finally, for those patients who a gynecologic oncologist is not readily available to perform a complete lymph node dissection, we evaluate the various imaging studies and their utility as preoperative triage modalities.
Rossi, Amerigo; Moadel-Robblee, Alyson; Garber, Carol Ewing; Kuo, Dennis; Goldberg, Gary; Einstein, Mark
Objective To determine the physical activity (PA) behavior, needs and preferences for underserved, ethnically diverse women with a history of endometrial cancer (EC). Methods Women with a history of EC (41 non-Hispanic black, 40 non-Hispanic white, and 18 Hispanic) completed a needs assessment during their regular follow-up appointments at Montefiore Medical Center in Bronx, NY, USA. An 8-week pilot PA intervention based on the results of the needs assessment was conducted with 5 EC survivors. Results Mean body mass index (BMI) among the 99 respondents was 34.1±7.6 kg/m2, and 66% did not exercise regularly. Self-described weight status was significantly lower than actual BMI category (p<0.001). Of the 86% who were interested in joining an exercise program, 95% were willing to attend at least once weekly. The primary motivations were improving health, losing weight, and feeling better physically. Despite the high interest in participation, volunteer rate was very low (8%). However, adherence to the 8-week pilot PA intervention was high (83%), and there were no adverse events. Body weight decreased in all pilot participants. Conclusion These data show that ethnically diverse EC survivors have a great need for, and are highly interested in, PA interventions. However, greater care needs to be taken to assess and identify barriers to increase participation in such programs. PMID:25872894
O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica M J; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B
Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6607 EC cases and 37 925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P=1.86×10(-5)), which was stronger for cancers of endometrioid subtype (P=3.76×10(-6)). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types.
O’Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Dennis, Joe; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Shah, Mitul; Ahmed, Shahana; Healey, Catherine S; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dürst, Matthias; Runnebaum, Ingo; Hillemanns, Peter; Dörk, Thilo; Lambrechts, Diether; Depreeuw, Jeroen; Annibali, Daniela; Amant, Frederic; Zhao, Hui; Goode, Ellen L; Dowdy, Sean C; Fridley, Brooke L; Winham, Stacey J; Salvesen, Helga B; Njølstad, Tormund S; Trovik, Jone; Werner, Henrica MJ; Tham, Emma; Liu, Tao; Mints, Miriam; Bolla, Manjeet K; Michailidou, Kyriaki; Tyrer, Jonathan P; Wang, Qin; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B
Excessive exposure to estrogen is a well-established risk factor for endometrial cancer (EC), particularly for cancers of endometrioid histology. The physiological function of estrogen is primarily mediated by estrogen receptor alpha, encoded by ESR1. Consequently, several studies have investigated whether variation at the ESR1 locus is associated with risk of EC, with conflicting results. We performed comprehensive fine-mapping analyses of 3,633 genotyped and imputed single nucleotide polymorphisms (SNPs) in 6,607 EC cases and 37,925 controls. There was evidence of an EC risk signal located at a potential alternative promoter of the ESR1 gene (lead SNP rs79575945, P = 1.86 × 10−5), which was stronger for cancers of endometrioid subtype (P = 3.76 × 10−6). Bioinformatic analysis suggests that this risk signal is in a functionally important region targeting ESR1, and eQTL analysis found that rs79575945 was associated with expression of SYNE1, a neighbouring gene. In summary, we have identified a single EC risk signal located at ESR1, at study-wide significance. Given SNPs located at this locus have been associated with risk for breast cancer, also a hormonally driven cancer, this study adds weight to the rationale for performing informed candidate fine-scale genetic studies across cancer types. PMID:26330482
Nougaret, Stephanie; Reinhold, Caroline; Alsharif, Shaza S; Addley, Helen; Arceneau, Jocelyne; Molinari, Nicolas; Guiu, Boris; Sala, Evis
To investigate magnetic resonance (MR) volumetry of endometrial tumors and its association with deep myometrial invasion, tumor grade, and lymphovascular invasion and to assess the value of apparent diffusion coefficient (ADC) histographic analysis of the whole tumor volume for prediction of tumor grade and lymphovascular invasion. The institutional review board approved this retrospective study; patient consent was not required. Between May 2010 and May 2012, 70 women (mean age, 64 years; range, 24-91 years) with endometrial cancer underwent preoperative MR imaging, including axial oblique and sagittal T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted imaging. Volumetry of the tumor and uterus was performed during the six sequences, with manual tracing of each section, and the tumor volume ratio (TVR) was calculated. ADC histograms were generated from pixel ADCs from the whole tumor volume. The threshold of TVR associated with myometrial invasion was assessed by using receiver operating characteristic curves. An independent sample Mann Whitney U test was used to compare differences in ADCs, skewness, and kurtosis between tumor grade and the presence of lymphovascular invasion. No significant difference in tumor volume and TVR was found among the six MR imaging sequences (P = .95 and .86, respectively). A TVR greater than or equal to 25% allowed prediction of deep myometrial invasion with sensitivity of 100% and specificity of 93% (area under the curve, 0.96; 95% confidence interval: 0.86, 0.99) at axial oblique diffusion-weighted imaging. A TVR of greater than or equal to 25% was associated with grade 3 tumors (P = .0007) and with lymphovascular invasion (P < .0001). There was no significant difference in the ADCs between grades 1 and 2 tumors (P > .05). The minimum, 10th, 25th, 50th, 75th, and 90th percentile ADCs were significantly lower in grade 3 tumors than in grades 1 and 2 tumors (P < .02). The combination of whole tumor volume and ADC
Reinhold, Caroline; Alsharif, Shaza S.; Addley, Helen; Arceneau, Jocelyne; Molinari, Nicolas; Guiu, Boris; Sala, Evis
Purpose To investigate magnetic resonance (MR) volumetry of endometrial tumors and its association with deep myometrial invasion, tumor grade, and lymphovascular invasion and to assess the value of apparent diffusion coefficient (ADC) histographic analysis of the whole tumor volume for prediction of tumor grade and lymphovascular invasion. Materials and Methods The institutional review board approved this retrospective study; patient consent was not required. Between May 2010 and May 2012, 70 women (mean age, 64 years; range, 24–91 years) with endometrial cancer underwent preoperative MR imaging, including axial oblique and sagittal T2-weighted, dynamic contrast material–enhanced, and diffusion-weighted imaging. Volumetry of the tumor and uterus was performed during the six sequences, with manual tracing of each section, and the tumor volume ratio (TVR) was calculated. ADC histograms were generated from pixel ADCs from the whole tumor volume. The threshold of TVR associated with myometrial invasion was assessed by using receiver operating characteristic curves. An independent sample Mann Whitney U test was used to compare differences in ADCs, skewness, and kurtosis between tumor grade and the presence of lymphovascular invasion. Results No significant difference in tumor volume and TVR was found among the six MR imaging sequences (P = .95 and .86, respectively). A TVR greater than or equal to 25% allowed prediction of deep myometrial invasion with sensitivity of 100% and specificity of 93% (area under the curve, 0.96; 95% confidence interval: 0.86, 0.99) at axial oblique diffusion-weighted imaging. A TVR of greater than or equal to 25% was associated with grade 3 tumors (P = .0007) and with lymphovascular invasion (P < .0001). There was no significant difference in the ADCs between grades 1 and 2 tumors (P > .05). The minimum, 10th, 25th, 50th, 75th, and 90th percentile ADCs were significantly lower in grade 3 tumors than in grades 1 and 2 tumors (P < .02
Seckin, B; Ozgu-Erdinc, A S; Dogan, M; Turker, M; Cicek, M N
The aim of this study was to assess the clinical usefulness of sonographic endometrium thickness measurement in asymptomatic postmenopausal women with endometrial fluid collection. Fifty-two asymptomatic postmenopausal women with endometrial fluid, who underwent endometrial sampling were evaluated. Histopathological findings revealed that 25 (48.1%) women had insufficient tissue, 20 (38.4%) had atrophic endometrium and 7 (13.5%) had endometrial polyps. No case of malignancy was found. There was no statistically significant difference between the various histopathological categories (insufficient tissue, atrophic endometrium and polyp) with regard to the mean single-layer endometrial thickness (1.54 ± 0.87, 2.04 ± 1.76 and 1.79 ± 0.69 mm, respectively, p = 0.436). Out of 44 patients with endometrial thickness of less than 3 mm, 38 (86.4%) had atrophic changes or insufficient tissue and 6 (13.6%) had endometrial polyps. In conclusion, if the endometrial thickness is 3 mm or less, endometrial sampling is not necessary in asymptomatic postmenopausal women with endometrial fluid.
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.
Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo
p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC. PMID:27902476
Yoon, Gun; Koh, Chang Won; Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo
p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC.
Abdullahi, YM; Ajani, MA; Iyapo, O; Aramide, KO; Okolo, CA; Akang, EEU
Background: Endometrium remains the most sensitive indicator of ovarian function and endometrial biopsy is one of the diagnostic procedures in endometrial pathology. The current study was carried out to examine the morphological pattern of endometrial biopsies in Ibadan, South-western Nigeria and compare the results with similar studies. Method: A retrospective study was undertaken to review all cases of endometrial biopsies received in the Department of Pathology, University College Hospital, Ibadan between January 1999 and December 2008. The patients' data were retrieved from the surgical pathology daybooks and Histology Request forms. The neoplastic lesions were classified according to 2003 World Health Organization classification for endometrial neoplasms. Results: A total of 2,444 cases of endometrial biopsies were received during the 10-year study period. The functional endometrial changes were the most common histopathological diagnostic category, accounting for 53.8% (1035) of cases. Other pathological diagnoses included endometritis (7.8%), simple endometrial hyperplasia (5.8%), partial hydatidiform mole (2.3%), complete hydatidiform mole (2.1%) and malignant neoplastic lesions (3.9%). Infertility was the most common (57%) indication for endometrial biopsies followed by uterine bleeding (33%) while the least common clinical indication were the menstrual disorders (10%). Conclusion: The functional endometrial changes account for the highest morphological patterns while malignant lesions account for the least pattern of the endometrial biopsies evaluated for etiological basis of infertility, uterine bleeding and menstrual disorders in Ibadan. Infertility was the commonest indication for endometrial biopsies while the least common clinical indication was menstrual disorders. PMID:28337096
Bruner-Tran, Kaylon L.; Osteen, Kevin G.; Taylor, Hugh S.; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J.
Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10–12 and 18–20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10–30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis. PMID:20844278
Chimbira, T H; Anderson, A B; Turnbull, A c
In 92 women complaining of heavy but regular periods for which no cause was found, the relation was studied between measured menstrual blood loss during two consecutive periods and the patient's subjective assessment of blood loss, the number of days of bleeding, and the number of sanitary pads and tampons used. There was no correlation between menstrual blood loss and these parameters. In many women these parameters are not a reliable indicator of the volume of menstrual blood loss. In 40 of the 92 women, who subsequently had a hysterectomy because of their complaint of menorrhagia, the uterus was weighed and the endometrial surface area measured. The view that menorrhagia is associated with a large uterus or a large endometrial surface area could not be confirmed.
Wang, Lina; Qiao, Jie; Li, Rong; Zhen, Xiumei; Liu, Zhaohui
This is a prospective study of 182 women (38 yrs or younger) undergoing IVF-ET. Endometrial thickness, echo pattern and blood flow on transvaginal ultrasonography were recorded eight hours prior to hCG administration. The patients were divided into three groups: A (n = 10) with undetectable endometrial blood flow; B (n = 82) with sub-endometrial blood flow; C (n = 90) with both endometrial and sub-endometrial blood flow. According to IVF-ET outcomes, all patients were re-divided into three groups: 1 non-pregnancy (n = 92); 2 intrauterine pregnancy with live fetus (n = 70); 3 others (n = 20 including biochemical pregnancy, embryonic diapause, ectopic pregnancy and miscarriage). Intrauterine pregnancy with live fetus in Group C (62.2%) was much higher than that in Group A and B (0% and 17.1%, p less than or equal to 0.001). The implantation rate (33.2%) was much higher than that in Group A and B (0% and 19.90%, p less than or equal to 0.001). The pulsatility index, resistance index, and S/D of endometrial spiral arteries were 0.1 +/- 0.2, 0.6 +/- 0.1 and 2.5 +/- 0.4 in Group 2, which were much lower than those in Group 1 and Group 3 (p1-2 less than 0.001, p2-3 less than 0.05). The patients with detectable endometrial blood flow had higher clinical pregnancy rates and implantation rates.
Bartels, Peter H; Garcia, Francisco AR; Trimble, Cornelia L; Kauderer, James; Curtin, John; Lim, Peter C; Hess, Lisa M; Silverberg, Steven; Zaino, Richard J; Yozwiak, Michael; Bartels, Hubert G; Alberts, David S
Objectives Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). Methods Cases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. Results Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. Conclusions AEH comprises cases which may constitute a low risk group involving <40% of AEH cases. These cases hold a percentage of <20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have >40 % of nuclei of preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. The percentage of nuclei of the preneoplastic phenotype in AEH lesions might serve as criterion for assessment of risk for the development of invasive disease. PMID:22155796
Kang, Sokbom; Todo, Yukiharu; Watari, Hidemichi
Due to advances of radiological imaging and tumor biomarkers, the extent of information provided by preoperative assessment is rapidly growing. The Korean Gynecologic Oncology Group (KGOG) recently proposed new preoperative criteria to identify patients at low risk for lymph node metastasis in endometrial cancer. In the multicenter study, serum carbohydrate antigen 125 levels and three magnetic resonance imaging parameters were found to be independent risk factors for nodal metastasis, and classified 53% of patients as part of a low-risk group. The false-negative predictive value (NPV) was 1.7%, and was 1.4% in the validation set. Furthermore, the KGOG low-risk criteria were validated in 319 Japanese patients with endometrial cancer. The criteria identified 181 of 319 patients as a low-risk group (51%), and three false-negative cases were found (1.9%). These results indicate that we are able to identify low-risk patients with a negligible NPV before surgery. In addition, the low false NPV implies that there is great difficulty in performing a randomized trial to determine the efficacy of routine lymphadenectomy in patients at low risk of lymph node metastasis. Based on these data, the challenges and possible solutions for developing a consensus on the optimized management of low-risk endometrial cancer will be discussed in this review. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.
Lee, Kyung Eun
O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein, the loss of MGMT expression was commonly known due to hypermethylation of CpG islands in its promoter region. Overexpression of p53 protein may be associated with downregulated MGMT expression in brain tumors. The aims of this study were to investigate the role of MGMT expression loss and its correlation with p53 overexpression in endometrial cancers. MGMT and p53 expression was examined in formalin-fixed, paraffin-embedded tissues from 36 endometrial cancer cases using immnunohistochemical staining. The loss of MGMT expression was detected in 11 (30.6%) out of the 36 endometrial cancers and p53 immunoreactivity was detected in 23 (63.9%) out of the 36 endometrial cancers. Ten (90.9%) of the 11 cases with negative MGMT immunoreactivity showed positive p53 expression, so the loss of MGMT expression was significantly associated with the p53 overexpression (P=0.03). These findings suggest that the loss of MGMT expression may be one of factors capable of p53 overexpression in endometrial cancer. Further studies are needed to define the relation between MGMT and p53 for examining the mechanisms of tissue-specific MGMT expression.
Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A
Background This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. Objectives To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. Search methods We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. Selection criteria We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRTor VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Data collection and analysis Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. Main results We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBTwith no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes. EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2
Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A
This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRTor VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBTwith no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes.EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2,965 women; HR 0.99, 95% CI 0.82 to1.20; and dichotomous data: seven trials, 3628 women; RR 0.98, 95
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.
Floriano, I; Bonini, G C; Matos, R; Novaes, T F; Ekstrand, K R; Mendes, F M; Braga, M M
We tested the association between active caries lesions assessed by two different criteria and clinical features of these caries lesions. Three examiners examined forty-nine 3- to 12-year-old children: one examiner used the Nyvad criteria, another examiner used the International Caries Detection and Assessment System with an additional criteria--Lesion Activity Assessment (ICDAS + LAA), and a reference examiner classified lesions regarding plaque stagnation, colour, lustre, cavities, depth and texture. Logistic regressions were used to test associations. For analyses, we grouped sound sites and inactive lesions vs active caries lesions, but also considering only inactive vs active lesions. Active lesions scored by both criteria were similarly associated with different clinical parameters tested, except when the sound sites were excluded from the analysis. In these cases, active lesions according to ICDAS + LAA were associated only with cavitation and texture. Texture was associated with divergences between criteria when differentiating sound or inactive lesions from active ones. Fewer divergences in differentiating active from inactive lesions were observed when lesions present lustre. Most clinical signs associated with active caries lesions were similar, but texture and severity tend to have a greater importance when using ICDAS + LAA for distinguishing caries activity status. Attention should be given to differences due to texture and lustre when using different indices. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A
This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRT or VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBT with no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes.EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2,965 women; HR 0.99, 95% CI 0.82 to 1.20; and dichotomous data: seven trials, 3628 women; RR 0
Burbos, N; Musonda, P; Giarenis, I; Shiner, A M; Giamougiannis, P; Morris, E P; Nieto, J J
Background: This study aimed to show the longitudinal use of routinely collected clinical data from history and ultrasound evaluation of the endometrium in developing an algorithm to predict the risk of endometrial carcinoma for postmenopausal women presenting with vaginal bleeding. Methods: This prospective study collected data from 3047 women presenting with postmenopausal bleeding. Data regarding the presence of risk factors for endometrial cancer was collected and univariate and multivariate analyses were performed. Results: Age distribution ranged from 35 to 97 years with a median of 59 years. A total of 149 women (5% of total) were diagnosed with endometrial carcinoma. Women in the endometrial cancer group were significantly more likely to be older, have higher BMI, recurrent episodes of bleeding, diabetes, hypertension, or a previous history of breast cancer. An investigator best model selection approach was used to select the best predictors of cancer, and using logistic regression analysis we created a model, ‘Norwich DEFAB', which is a clinical prediction rule for endometrial cancer. The calculated Norwich DEFAB score can vary from a value of 0 to 9. A Norwich DEFAB value equal to or greater than 3 has a positive predictive value (PPV) of 7.78% and negative predictive value (NPV) of 98.2%, whereas a score equal to or greater than 5 has a PPV of 11.9% and NPV of 97.8%. Conclusion: The combination of clinical information with our investigation tool for women with postmenopausal vaginal bleeding allows the clinician to calculate a predicted risk of endometrial malignancy and prioritise subsequent clinical investigations. PMID:20354525
Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma
Dwarkasing, Roy S; Verschuuren, Sylvia I; van Leenders, Geert J L H; Braun, Loes M M; Krestin, Gabriel P; Schouten, W Rudolph
The purpose of this study was to assess the a priori chance that primary cystic lesions of the retrorectal space are malignant and to investigate MRI characteristics that indicate malignancy. Patients referred to a center for colorectal surgery were recruited from 2000 to 2014. Lesions were proven by clinical assessment and histopathology. MRI was performed at 1.5 T with examinations evaluated by two radiologists. Interobserver agreement was assessed (Cohen kappa) and differences between malignant and benign lesions calculated (Fisher exact test). Twenty-eight patients (22 women, six men; age range, 18-70 years) with 31 lesions were included. Lesions were categorized as tailgut cysts (n = 16, 52%), teratomas (n = 9, 29%), lesions of colorectal origin (n = 4, 13%), or neurogenic lesions (n = 2, 6%). Five patients (18%) had malignant lesions. Colorectal lesions had the highest percentage of malignancy (3/4, 75%). A solid tissue component was found in all five (100%) malignant lesions and two (8%) of the benign lesions, which were both teratomas (p < 0.05). Sensitivity and specificity for malignancy according to the presence of a solid tissue component was 100% (5/5) and 92% (24/26). For unilocularity, multilocularity, debris, septa, and wall thickening, differences were not significant. Interobserver agreement was excellent (κ = 1) for all characteristics except debris (κ = 0.795). The majority of retrorectal cystic lesions are benign. The presence of a solid tissue component should raise suspicion for malignancy.
Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma
Wareluk, Pawel; Szopinski, Kazimierz T
The aim of this prospective study was to assess the accuracy of modern ultrasonography in diagnostic imaging of meniscal tears. One hundred and sixty menisci were evaluated in 80 patients (42 females, 38 males, mean age=36.2 years, range=16-70 years). Inclusion criteria for the study were twofold: clinical suspicion of meniscal injury and clinical indication for arthroscopy. Knee examination was performed with the Voluson 730 Expert ultrasound system (General Electric). After sonographic examination, all patients underwent arthroscopic procedures within 1-4 days. The final diagnosis of meniscal tears was taken from surgical reports. The overall sensitivity, specificity, positive predictive value and negative predictive value of sonographic examination in the assessment of meniscal tears amounted to 85.4%, 85.7%, 67.3% and 94.4%, respectively. The statistical parameters were not statistically different in medial and lateral menisci. Age, sex, body mass index (BMI), weight, physical activity, mechanism on injury, and time lapse from injury did not have a statistically significant impact on the usefulness of ultrasonography. The highest sensitivity (>90%) was obtained in medial menisci and in patients with a BMI>25. The highest specificity (>90%) was obtained in lateral menisci, in patients after twisting injuries, in sports injuries, and in recent injuries (time lapse from the injury <1 month). The positive predictive value (PPV) of sonographic examination was higher than 90% only in recent injuries (<1 month), however, the negative predictive value of ultrasound is high, being less than 90% in males with lesions of lateral menisci and in sequelae of sports injuries.
Bartels, Peter H; Garcia, Francisco A R; Trimble, Cornelia L; Kauderer, James; Curtin, John; Lim, Peter C; Hess, Lisa M; Silverberg, Steven; Zaino, Richard J; Yozwiak, Michael; Bartels, Hubert G; Alberts, David S
Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). Cases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is the percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. AEH comprises cases which may constitute a low risk group involving <40% of AEH cases. These cases hold a percentage of <20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have >40% of nuclei of preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. The percentage of nuclei of the preneoplastic phenotype in AEH esions might serve as criterion for assessment of risk for the development of invasive disease. Copyright Â© 2011 Elsevier Inc. All rights reserved.
Merritt, Melissa A.; Cramer, Daniel W.
Pregnancy, breastfeeding, and oral contraceptive pill use interrupt menstrual cycles and reduce endometrial and ovarian cancer risk. This suggests the importance of turnover within Mullerian tissues, where the accumulation of mutations in p53 and PTEN has been correlated with number of cycles. The most common type of endometrial cancer (Type I) is endometrioid and molecular abnormalities include mutations in PTEN, KRAS and β-catenin. The Type I precursor is Endometrial lntraepithelial Neoplasia which displays PTEN defects. Type II endometrial cancer (whose precursors are less clear) includes serous and clear cell tumors and the most common alteration is p53 mutation. For ovarian cancer, histopathologic types parallel endometrial cancer and include serous, mucinous, endometrioid, and clear cell; some molecular features are also shared. The most frequent type of ovarian cancer is high grade serous that often displays p53 mutation and its precursor lesions may originate from normal-appearing fallopian tube epithelium that contains a p53 “signature”. Mutations in KRAS, BRAF and PTEN are described in mucinous, endometrioid and low grade serous cancers and these may originate from ovarian cortical inclusion cysts. A consideration of molecular and other pathogenetic features, like epidemiology and histopathology, may provide a bener understanding of endometrial and ovarian cancer. PMID:22112481
Simon, Jacob C.; Darling, Cynthia L.; Fried, Daniel
Bitewing radiography is still considered state-of-the-art diagnostic technology for assessing cavitation within approximal carious dental lesions, even though radiographs cannot resolve cavitated surfaces but instead are used to measure lesion depth in order to predict cavitation. Clinicians need new technologies capable of determining whether approximal carious lesions have become cavitated because not all lesions progress to cavitation. Assessing lesion cavitation from near-infrared (NIR) imaging methods holds great potential due to the high transparency of enamel in the NIR region from λ=1300-1700-nm, which allows direct visualization and quantified measurements of enamel demineralization. The objective of this study was to measure the change in lesion appearance between non-cavitated and cavitated lesions in artificially generated lesions using NIR imaging modalities (two-dimensional) at λ=1300-nm and λ=1450-nm and cross-polarization optical coherence tomography (CP-OCT) (thee-dimensional) λ=1300-nm. Extracted human posterior teeth with sound proximal surfaces were chosen for this study and imaged before and after artificial lesions were made. A high speed dental hand piece was used to create artificial cavitated proximal lesions in sound samples and imaged. The cavitated artificial lesions were then filled with hydroxyapatite powder to simulate non-cavitated proximal lesions.
Simon, Jacob C; Darling, Cynthia L; Fried, Daniel
Bitewing radiography is still considered state-of-the-art diagnostic technology for assessing cavitation within approximal carious dental lesions, even though radiographs cannot resolve cavitated surfaces but instead are used to measure lesion depth in order to predict cavitation. Clinicians need new technologies capable of determining whether approximal carious lesions have become cavitated because not all lesions progress to cavitation. Assessing lesion cavitation from near-infrared (NIR) imaging methods holds great potential due to the high transparency of enamel in the NIR region from λ=1300-1700-nm, which allows direct visualization and quantified measurements of enamel demineralization. The objective of this study was to measure the change in lesion appearance between non-cavitated and cavitated lesions in artificially generated lesions using NIR imaging modalities (two-dimensional) at λ =1300-nm and λ=1450-nm and cross-polarization optical coherence tomography (CP-OCT) (thee-dimensional) λ =1300-nm. Extracted human posterior teeth with sound proximal surfaces were chosen for this study and imaged before and after artificial lesions were made. A high speed dental hand piece was used to create artificial cavitated proximal lesions in sound samples and imaged. The cavitated artificial lesions were then filled with hydroxyapatite powder to simulate non-cavitated proximal lesions.
Background The objective of this study was to perform a systematic review and a meta-analysis in order to estimate the diagnostic accuracy of diffusion weighted imaging (DWI) in the preoperative assessment of deep myometrial invasion in patients with endometrial carcinoma. Methods Studies evaluating DWI for the detection of deep myometrial invasion in patients with endometrial carcinoma were systematically searched for in the MEDLINE, EMBASE, and Cochrane Library from January 1995 to January 2014. Methodologic quality was assessed by using the Quality Assessment of Diagnostic Accuracy Studies tool. Bivariate random-effects meta-analytic methods were used to obtain pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and receiver operating characteristic (ROC) curves. The study also evaluated the clinical utility of DWI in preoperative assessment of deep myometrial invasion. Results Seven studies enrolling a total of 320 individuals met the study inclusion criteria. The summary area under the ROC curve was 0.91. There was no evidence of publication bias (P = 0.90, bias coefficient analysis). Sensitivity and specificity of DWI for detection of deep myometrial invasion across all studies were 0.90 and 0.89, respectively. Positive and negative likelihood ratios with DWI were 8 and 0.11 respectively. In patients with high pre-test probabilities, DWI enabled confirmation of deep myometrial invasion; in patients with low pre-test probabilities, DWI enabled exclusion of deep myometrial invasion. The worst case scenario (pre-test probability, 50%) post-test probabilities were 89% and 10% for positive and negative DWI results, respectively. Conclusion DWI has high sensitivity and specificity for detecting deep myometrial invasion and more importantly can reliably rule out deep myometrial invasion. Therefore, it would be worthwhile to add a DWI sequence to the standard MRI protocols in preoperative evaluation of endometrial cancer in order to detect deep
Davies, Joanna; Kadir, Rezan A
Under normal physiological circumstances menstruation is a highly regulated, complex process that is under strict hormonal control. During normal menstruation, progesterone withdrawal initiates menstruation. The cessation of menstrual bleeding is achieved by endometrial haemostasis via platelet aggregation, fibrin deposition and thrombus formation. Local endocrine, immunological and haemostatic factors interact at a molecular level to control endometrial haemostasis. Tissue factor and thrombin play a key role locally in the cessation of menstrual bleeding through instigation of the coagulation factors. On the other hand, fibrinolysis prevents clot organisation within the uterine cavity while plasminogen activator inhibitors (PAI) and thrombin-activatable fibrinolysis inhibitors control plasminogen activators and plasmin activity. Abnormalities of uterine bleeding can result from imbalance of the haemostatic factors. The most common abnormality of uterine bleeding is heavy menstrual bleeding (HMB). Modern research has shown that an undiagnosed bleeding disorder, in particular von Willebrand disease (VWD) and platelet function disorders, can be an underlying cause of HMB. This has led to a change in the approach to the management of HMB. While full haemostatic assessment is not required for all women presenting with HMB, menstrual score and bleeding score can help to discriminate women who are more likely to have a bleeding disorder and benefit from laboratory haemostatic evaluation. Haemostatic agents (tranexamic acid and DDAVP) enhance systemic and endometrial haemostasis and are effective in reducing menstrual blood loss in women with or without bleeding disorders. Further research is required to enhance our understanding of the complex interactions of haemostatic factors in general, and specifically within the endometrium. This will lead to the development of more targeted interventions for the management of abnormal uterine bleeding in the future.
Putra, Lydia G Johns; Minor, Thomas X; Bolton, Damien M; Appu, Sreevinas; Dowling, Caroline R; Neerhut, Gregory J
To ascertain the potential utility of magnetic resonance imaging in providing additional clarification of those solid renal mass lesions identified at routine antenatal ultrasonography in early pregnancy and influencing the management of such lesions. We present 7 patients in whom magnetic resonance imaging was used to diagnose, stage, and monitor renal lesions detected during pregnancy. Magnetic resonance imaging provided for improved imaging of renal mass lesions identified at antenatal ultrasonography, without the use of ionizing radiation, and permitted management determined by optimal radiographic assessment of such lesions without fetal irradiation. Magnetic resonance imaging is the most appropriate method to further investigate renal masses identified at routine antenatal ultrasonography early in pregnancy.
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.
Bonilla-Musoles, Fernando; Raga, Francisco; Osborne, Newton G; Castillo, Juan Carlos; Bonilla, Francisco
An adequate endometrial receptivity is a crucial factor for embryo implantation. We describe endometrial morphology (endometrial appearance or pattern, endometrial thickness, volume, and delimitation), based on the concepts and possibilities of the new ultrasound modalities (3-dimensional/4-dimensional ultrasound, automatic volume calculation, virtual organ computer-aided analysis, tomographic ultrasound image, inverse mode, and 3-dimensional Doppler angiography) as markers of endometrial receptivity.
Zhao, Jing; Lyu, Chen; Gao, Jian; Du, Li; Shan, Boer; Zhang, Hong; Wang, Hua-Ying; Gao, Ying
Abstract Since body fatness is a convincing risk factor for endometrial cancer, dietary fat intake was speculated to be associated with endometrial cancer risk. However, epidemiological studies are inconclusive. We aimed to conduct a meta-analysis to assess the associations between dietary fat intake and endometrial cancer risk. We searched the PubMed, Embase, and Web of science databases updated to September 2015. In total, 7 cohort and 14 case–control studies were included. Pooled analysis of case–control studies suggested that endometrial cancer risk was significantly increased by 5% per 10% kilocalories from total fat intake (P=0.02) and by 17% per 10 g/1000 kcal of saturated fat intake (P < 0.001). Summary of 3 cohort studies showed significant inverse association between monounsaturated fatty acids and endometrial cancer risk (odds ratio = 0.84, 95% confidence interval = 0.73–0.98) with a total of 524583 participants and 3503 incident cases. No significant associations were found for polyunsaturated fatty acids and linoleic acid. In conclusion, positive associations with endometrial cancer risk were observed for total fat and saturated fat intake in the case–control studies. Results from the cohort studies suggested higher monounsaturated fatty acids intake was significantly associated with lower endometrial cancer risk. PMID:27399120
Singh-Moon, Rajinder P.; Hendon, Christine P.
In non-pharmacological treatment of cardiac arrhythmias such as catheter ablation therapy, long-term treatment effectiveness is related in part to the quality of lesion generation. Superficial lesions may lead to arrhythmia recurrence by allowing recovery along conduction channels for arrhythmic impulses to propagate; conversely transmural lesions inhibit conduction. Conventional techniques rely on measurement of surrogate parameters such as change in bioelectrical impedance, or electrogram amplitude dampening as a qualitative assessment for lesion size. In previous work, we've demonstrated a relationship between lesion dimensions and spectroscopic parameters extracted using an optically-integrated ablation catheter. Though these metrics present some trend, a method to directly assess lesion transmurality maybe better suited. In this work, we report a method for direct recovery of lesion depth in cardiac tissue using diffusely reflected optical measurements and present initial in silico validation. Photon transport throughout a heterogeneous volume was simulated for a series of source-detector pairs and optical properties using a GPU-based Monte Carlo (MC) code. Results were used to generate a multi-dimensional look-up table for each collection geometry for partial to transmural lesions. A genetic algorithm-based two-step inversion method was employed to extract lesion transmurality. MC simulated optical measurements for various lesion sizes were generated using optical properties for ablated and normal cardiac tissue found in literature and were fitted using our algorithm. Recovered lesion depths ranged between 2-10% for lesions less than 3mm and were within 20% for lesions greater than 4mm. These results support the application of this technique for lesion validation for atrial tissue.
Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma
Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Endometrioid Stromal Sarcoma; Recurrent Uterine Corpus Carcinoma
Blesa, David; Ruiz-Alonso, María; Simón, Carlos
The endometrial window of implantation (WOI), the cycle days during which normal embryo implantation can occur, has generally been assumed to begin on cycle day 19 or 20 of an idealized 28 days cycle and last for 4 to 5 days. Noyes et al took the first steps in defining the WOI by establishing a set of morphological criteria to evaluate endometrial development and receptivity, but recent studies have invalidated their use in the routine evaluation of infertility. Based on greater than 10 years of extensive research, our group has developed a molecular diagnostic tool (the endometrial receptivity array [ERA] test) based on the specific transcriptomic signature that identifies the receptive endometrium in natural and artificial (hormonal replacement therapy) cycles. The ERA test has shown that some patients have a delayed WOI, others have an advanced WOI, and others can have unusually short windows of receptivity. This identification and characterization of the WOI allows the personalization of the embryo transfer. In this review, we describe the ERA and our experience with its use in assessment of the endometrial receptivity in patients undergoing assisted reproduction.
Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma
Novetsky, Akiva P; Kuroki, Lindsay M; Massad, L Stewart; Hagemann, Andrea R; Thaker, Premal H; Powell, Matthew A; Mutch, David G; Zighelboim, Israel
To estimate the accuracy of vaginal cytology in postoperative surveillance for detecting recurrent endometrial cancer and to estimate the optimal management of squamous abnormalities detected in this setting. This review included women who underwent hysterectomy for endometrial cancer between January 1, 2006, and December 31, 2010, and had at least one postoperative Pap test. Clinical and demographic data were collected and outcomes including abnormal vaginal cytology, results of colposcopic examination, and endometrial cancer recurrence were assessed. A Cox regression model to estimate the risk of abnormal cytology was created. Sensitivity, specificity, and negative and positive predictive values of detecting vaginal recurrences were calculated. Four hundred thirty-three women contributed 2,378 Pap tests. At least one abnormal cytology result was found during follow-up of 55 (13%) women, representing 3% of all Pap tests. No recurrent endometrial cancers were diagnosed on the basis of isolated abnormal cytology. No cases of recurrent cancer were diagnosed in women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) Pap test results. In multivariable analysis, abnormal cytology was highly associated with prior postoperative radiation therapy (P<.001). The sensitivity, specificity, and positive and negative predictive values of an abnormal Pap test result in detecting a local recurrence are 40%, 87.9%, 7.3%, and 98.4%, respectively. Colposcopy is not needed after a Pap test result read as atypical squamous cells of undetermined significance or LSIL. III.
Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Malignant Uterine Corpus Mixed Epithelial and Mesenchymal Neoplasm; Recurrent Uterine Corpus Carcinoma
Thomas, Michael S. C.; Purser, Harry R. M.; Tomlinson, Simon; Mareschal, Denis
This article presents an investigation of the relationship between lesioning and neuroimaging methods of assessing functional specialisation, using synthetic brain imaging (SBI) and lesioning of a connectionist network of past-tense formation. The model comprised two processing "routes": one was a direct route between layers of input and output…
Thomas, Michael S. C.; Purser, Harry R. M.; Tomlinson, Simon; Mareschal, Denis
This article presents an investigation of the relationship between lesioning and neuroimaging methods of assessing functional specialisation, using synthetic brain imaging (SBI) and lesioning of a connectionist network of past-tense formation. The model comprised two processing "routes": one was a direct route between layers of input and output…
Eriksson, L S E; Lindqvist, P G; Flöter Rådestad, A; Dueholm, M; Fischerova, D; Franchi, D; Jokubkiene, L; Leone, F P; Savelli, L; Sladkevicius, P; Testa, A C; Van den Bosch, T; Ameye, L; Epstein, E
To assess interobserver reproducibility among ultrasound experts and gynecologists in the prediction by transvaginal ultrasound of deep myometrial and cervical stromal invasion in women with endometrial cancer. Sonographic videoclips of the uterine corpus and cervix of 53 women with endometrial cancer, examined preoperatively by the same ultrasound expert, were integrated into a digitalized survey. Nine ultrasound experts and nine gynecologists evaluated presence or absence of deep myometrial and cervical stromal invasion. Histopathology from hysterectomy specimens was used as the gold standard. Compared with gynecologists, ultrasound experts showed higher sensitivity, specificity and agreement with histopathology in the assessment of cervical stromal invasion (42% (95% CI, 31-53%) vs 57% (95% CI, 45-68%), P < 0.01; 83% (95% CI, 78-86%) vs 87% (95% CI, 83-90%), P = 0.02; and kappa, 0.45 (95% CI, 0.40-0.49) vs 0.58 (95% CI, 0.53-0.62), P < 0.001, respectively) but not of deep myometrial invasion (73% (95% CI, 66-79%) vs 73% (95% CI, 66-79%), P = 1.0; 70% (95% CI, 65-75%) vs 69% (95% CI, 63-74%), P = 0.68; and kappa, 0.48 (95% CI, 0.44-0.53) vs 0.52 (95% CI, 0.48-0.57), P = 0.11, respectively). Though interobserver reproducibility (in the context of test proportions 'good' and 'very good', according to kappa) regarding deep myometrial invasion did not differ between the groups (experts, 34% vs gynecologists, 22%, P = 0.13), ultrasound experts assessed cervical stromal invasion with significantly greater interobserver reproducibility than did gynecologists (53% vs 14%, P < 0.001). Preoperative ultrasound assessment of deep myometrial and cervical stromal invasion in endometrial cancer is best performed by ultrasound experts, as, compared with gynecologists, they showed a greater degree of agreement with histopathology and greater interobserver reproducibility in the assessment of cervical stromal invasion. Copyright © 2014 ISUOG
MÉNDEZ-LÓPEZ, LUIS FERNANDO; DÁVILA-RODRÍGUEZ, MARTHA IMELDA; ZAVALA-POMPA, ANGEL; TORRES-LÓPEZ, ERNESTO; GONZÁLEZ-MARTÍNEZ, BLANCA EDELIA; LÓPEZ-CABANILLAS-LOMELÍ, MANUEL
The adipokine leptin plays a critical role in the regulation of reproductive function and there has been growing interest in its potential role in the development of cancers in which obesity is an established risk factor. Serum leptin levels were found to be higher in patients diagnosed with endometrial and ovarian cancer compared to those observed in healthy individuals. This study was conducted to determine the expression of the leptin receptor (Ob-R) in endometrial biopsies of patients diagnosed with endometrial and ovarian cancer. In this preliminary study, immunohistochemistry (IHC) and the color deconvolution method were used to assess the expression levels of the Ob-R protein in three groups of endometrial tissue: one from patients diagnosed with endometrioid endometrial carcinoma, one from patients diagnosed with ovarian cancer and one from individuals without any diagnosed gynecologic disease (control group). Our results demonstrated that the highest expression of Ob-R protein in endometrial biopsies was detected in the ovarian cancer group (P=0.000). This finding suggests that changes in Ob-R expression may be assessed through the measurement of the optical density of endometrial biopsies and may become a useful tool in preventive screening, particularly for ovarian cancer. PMID:24649005
Chen, Baiyu; Ma, Chi; Yu, Zhicong; Leng, Shuai; Yu, Lifeng; McCollough, Cynthia
To perform task-based image quality assessment in CT, it is desirable to have a large number of realistic patient images with known diagnostic truth. One effective way to achieve this objective is to create hybrid images that combine patient images with simulated lesions. Because conventional hybrid images generated in the image-domain fails to reflect the impact of scan and reconstruction parameters on lesion appearance, this study explored a projection-domain approach. Liver lesion models were forward projected according to the geometry of a commercial CT scanner to acquire lesion projections. The lesion projections were then inserted into patient projections (decoded from commercial CT raw data with the assistance of the vendor) and reconstructed to acquire hybrid images. To validate the accuracy of the forward projection geometry, simulated images reconstructed from the forward projections of a digital ACR phantom were compared to physically acquired ACR phantom images. To validate the hybrid images, lesion models were inserted into patient images and visually assessed. Results showed that the simulated phantom images and the physically acquired phantom images had great similarity in terms of HU accuracy and high-contrast resolution. The lesions in the hybrid image had a realistic appearance and merged naturally into the liver background. In addition, the inserted lesion demonstrated reconstruction-parameter-dependent appearance. Compared to conventional image-domain approach, our method enables more realistic hybrid images for image quality assessment.
Lee, Robert C; Darling, Cynthia L; Staninec, Michal; Ragadio, Antonio; Fried, Daniel
The purpose of this study was to evaluate thermal and near-infrared (NIR) reflectance imaging methods for the assessment of the activity of root caries lesions. In addition, changes in the lesion structure were monitored with polarization sensitive optical coherence tomography (PS-OCT). Artificial bovine and natural root caries lesions were imaged with PS-OCT, and their dehydration rate was measured with thermal and NIR cameras. The lesion activity of the natural root caries samples was also assessed by two clinicians by conventional means according to ICDAS II guidelines. The thickness of the highly mineralized transparent surface layer measured using PS-OCT increased and the area enclosed by the time-temperature curve, ΔQ, measured with thermal imaging decreased significantly with longer periods of remineralization in simulated dentin lesions, but the NIR reflectance intensity differences, ΔI, failed to show any significant relationship with the degree of remineralization. The PS-OCT algorithm for the automated assessment of remineralization successfully detected the highly mineralized surface layer on both natural and simulated lesions. Thermal imaging provided the most accurate diagnosis of root caries lesion activity. These results demonstrate that thermal imaging and PS-OCT may be ideally suited for the nondestructive root caries lesion activity during a clinical examination. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Mederos, Michael A; Villafañe, Nicole; Dhingra, Sadhna; Farinas, Carlos; McElhany, Amy; Fisher, William E; Van Buren Ii, George
Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are exceedingly rare lesions that are difficult to diagnose pre-operatively. This report describes the findings in a 43-year-old patient with a recent episode of acute pancreatitis who presented with a large cyst in the tail of the pancreas. Imaging demonstrated a loculated pancreatic cyst, and cyst fluid aspiration revealed an elevated amylase and carcinoembryonic antigen. The patient experienced an interval worsening of abdominal pain, fatigue, diarrhea, and a 15-pound weight loss 3 mo after the initial episode of pancreatitis. With concern for a possible pre-malignant lesion, the patient underwent a laparoscopic distal pancreatectomy with splenectomy, which revealed a 16 cm × 12 cm × 4 cm lesion. Final histopathology was consistent with an intra-pancreatic endometrial cyst. Here we discuss the overlapping imaging and laboratory features of pancreatic endometrial cysts and mucinous cystic neoplasms of the pancreas.
Rackow, Beth W.; Kliman, Harvey J.; Taylor, Hugh S.
Study objective HOXA10 is an essential regulator of endometrial receptivity. To determine the effect of gonadotropin releasing hormone (GnRH) antagonists on endometrial receptivity we assessed endometrial HOXA10 expression in GnRH antagonist, GnRH agonist, and natural cycles. Design Prospective case-control study Setting University academic medical center Patients Nineteen subjects were included: 12 subjects underwent controlled ovarian hyperstimulation (COH) with recombinant follicle stimulating hormone (rFSH) and used either a GnRH antagonist or a GnRH agonist; 7 control subjects underwent natural cycles. Interventions Pipelle endometrial biopsies were obtained 11 days after human chorionic gonadotropin (hCG) administration or spontaneous luteinizing hormone (LH) surge in untreated cycles, respectively. Immunohistochemistry was used to assess HOXA10 protein expression in endometrial glands and stroma. Main outcome measure(s) Endometrial HOXA10 protein expression Results HOXA10 expression was significantly decreased in endometrial stromal cells in GnRH antagonist treated cycles compared with GnRH agonist treated cycles or natural cycle controls. There was no significant difference in glandular cell HOXA10 expression among the three groups. Conclusions Use of GnRH antagonists may be associated with impaired HOXA10 expression in endometrial stromal cells, and thus may affect endometrial receptivity. PMID:18410932
Cogendez, Ebru; Eken, Meryem Kurek; Bakal, Nuray; Gun, Ismet; Kaygusuz, Ecmel Isik; Karateke, Ates
The purpose of this prospective study was to assess the role of power Doppler imaging in the differential diagnosis of benign intrauterine focal lesions such as endometrial polyps and submucous myomas using the characteristics of power Doppler flow mapping. A total of 480 premenopausal patients with abnormal uterine bleeding were evaluated by transvaginal ultrasonography (TVS) searching for intrauterine pathology. Sixty-four patients with a suspicious focal endometrial lesion received saline infusion sonography (SIS) after TVS. Fifty-eight patients with focal endometrial lesions underwent power Doppler ultrasound (PDUS). Three different vascular flow patterns were defined: Single vessel pattern, multiple vessel pattern, and circular flow pattern. Finally, hysteroscopic resection was performed in all cases, and Doppler flow characteristics were then compared with the final histopathological findings. Histopathological results were as follows: endometrial polyp: 40 (69 %), submucous myoma: 18 (31 %). Of the cases with endometrial polyps, 80 % demonstrated a single vessel pattern, 7.5 % a multiple vessel pattern, and 0 % a circular pattern. Vascularization was not observed in 12.5 % of patients with polyps. Of the cases with submucousal myomas, 72.2 % demonstrated a circular flow pattern, 27.8 % a multiple vessel pattern, and none of them showed a single vessel pattern. The sensitivity, specificity, and positive and negative predictive values of the single vessel pattern in diagnosing endometrial polyps were 80, 100, 100, and 69.2 %, respectively; and for the circular pattern in diagnosing submucous myoma, these were 72.2, 100, 100, and 88.9 %, respectively. Power Doppler blood flow mapping is a useful, practical, and noninvasive diagnostic method for the differential diagnosis of benign intrauterine focal lesions. Especially in cases of recurrent abnormal uterine bleeding, recurrent abortion, and infertility, PDUS can be preferred as a first-line diagnostic method.
Schaefferkoetter, Joshua D.; Yan, Jianhua; Townsend, David W.; Conti, Maurizio
In the context of investigating the potential of low-dose PET imaging for screening applications, we developed methods to assess small lesion detectability as a function of the number of counts in the scan. We present here our methods and preliminary validation using tuberculosis cases. FDG-PET data from seventeen patients presenting diffuse hyper-metabolic lung lesions were selected for the study, to include a wide range of lesion sizes and contrasts. Reduced doses were simulated by randomly discarding events in the PET list mode, and ten realizations at each simulated dose were generated and reconstructed. The data were grouped into 9 categories determined by the number of included true events, from >40 M to <250 k counts. The images reconstructed from the original full statistical set were used to identify lung lesions, and each was, at every simulated dose, quantified by 6 parameters: lesion metabolic volume, lesion-to-background contrast, mean lesion tracer uptake, standard deviation of activity measurements (across realizations), lesion signal-to-noise ratio (SNR), and Hotelling observer SNR. Additionally, a lesion-detection task including 550 images was presented to several experienced image readers for qualitative assessment. Human observer performances were ranked using receiver operating characteristic analysis. The observer results were correlated with the lesion image measurements and used to train mathematical observer models. Absolute sensitivities and specificities of the human observers, as well as the area under the ROC curve, showed clustering and performance similarities among images produced from 5 million or greater counts. The results presented here are from a clinically realistic but highly constrained experiment, and more work is needed to validate these findings with a larger patient population.
Lee, Robert C.; Staninec, Michal; Le, Oanh; Fried, Daniel
New diagnostic methods are needed for the accurate assessment of caries lesion activity to establish the need for surgical treatment. Detection of the highly mineralized surface layer that forms near the surface of the lesions as a result of remineralization is important for diagnosis of the lesion activity. Previous studies have demonstrated that novel imaging methods can be used to detect remineralization of artificial enamel caries lesions. In this paper, the activity of natural enamel caries lesions was assessed in-vitro via detection of the surface layer with PS-OCT and dehydration rate measurements with NIR reflectance and thermal imaging modalities. An automated approach for detecting the surface layer with PS-OCT yielded high sensitivity (= 0.79) and high specificity (= 0.93) with moderate correlation (R2 = 0.5920) with histology. Significant differences in dehydration rate measurements were found between the active and the arrested lesions using both the NIR reflectance and thermal imaging modalities. These results demonstrate that these novel imaging methods are ideally suited for nondestructive, noninvasive and quantitative measurement of lesion activity during a single clinical examination in real-time. PMID:27642246
Somerville, Lyndsay E; Willits, Kevin; Johnson, Andrew M; Litchfield, Robert; LeBel, Marie-Eve; Moro, Jaydeep; Bryant, Dianne
Shoulder pain and disability pose a diagnostic challenge for clinicians owing to the numerous causes that exist. Unfortunately, the evidence in support of most clinical tests is weak or absent. To determine the diagnostic validity of physical examination maneuvers for rotator cuff lesions. Cohort study (diagnosis); Level of evidence, 1. Consecutive shoulder patients recruited for this study were referred to 2 tertiary orthopaedic clinics. A surgeon took a thorough history and indicated his or her certainty about each possible diagnosis. A clinician performed the physical examination for diagnoses where uncertainty remained. Arthroscopy was considered the reference standard for patients who underwent surgery, and MRI with arthrogram was considered the reference for patients who did not. The sensitivity, specificity, and likelihood ratios were calculated to investigate whether combinations of the top tests provided stronger predictions of the presence or absence of disease. There were 139 participants. None of the tests were highly sensitive for diagnosing rotator cuff tears or tendinosis. Tests for subscapularis tears were all highly specific. No optimal combination of tests improved the ability to correctly diagnose rotator cuff tears. Closer analysis revealed the internal rotation and lateral rotation lag sign did not improve the ability to diagnose subscapularis or supraspinatus tears, respectively, although the lateral rotation lag sign demonstrated a discriminatory ability for tear size. No test in isolation is sufficient to diagnose a patient with rotator cuff damage. A combination of tests improves the ability to diagnose damage to the rotator cuff. It is recommended that the internal rotation and lateral rotation lag signs be removed from the gamut of physical examination tests for supraspinatus and subscapularis tears. © 2014 The Author(s).
Liu, Ying; Xu, Yi; Cheng, Wen; Liu, Xinghan
The present study aimed to investigate the feasibility of applying contrast-enhanced ultrasonography (CEUS) imaging technology for distinguishing between benign and malignant endometrial lesions, and to screen markers that could be correlated with the pathological results. In this study, endometrial diseases were diagnosed by biopsy under hysteroscopy and CEUS examinations. The intensity and time parameters of the time-intensity curve (TIC) were analyzed. The mean arrival time (AT), time-to-peak (TTP), rise time (RT), washout half-time and clearance half-time of malignant lesions were shorter than those of benign lesions (P<0.05), whereas the average peak intensity (PI) and enhancement intensity (EI) of malignant lesions were higher than those of benign lesions (P<0.05). The receiver operating characteristic curve showed the following cut-off values: PI, 29.2 dB; EI, 21.35 dB; AT, 12.75 sec; TTP, 26.75 sec; RT, 13.2 sec; clearance half-time, 89.3 sec; and washout half-time, 75.45 sec. The lesions with PI, an EI higher than that of the cut-off and lesions with an AT, TTP, RT, half clearing time and washout half-time shorter than the cut-off were considered malignant. The TTP, RT and half clearing time were negatively correlated with microvessel density (MVD), i.e., MVD was higher when the TTP, RT and half clearing time were shorter. Overall, changes in the enhancement and clearing of lesions could be quantitatively analyzed by CEUS TIC and further discriminate benign from malignant lesions. In the present study, CEUS appeared to indirectly reflect blood vessel changes inside the lesions and provided a pre-operative non-invasive fast imaging method for the diagnosis of endometrial disease. PMID:27895728
Yip, Stephen; Jeraj, Robert
Accurate skeleton registration is necessary to match corresponding metastatic bone lesions for response assessment over multiple scans. In articulated registration (ART), whole-body skeletons are registered by auto-segmenting individual bones, then rigidly aligning them. Performance and robustness of the ART in lesion matching were evaluated and compared to other commonly used registration techniques. Sixteen prostate cancer patients were treated either with molecular targeted therapy or chemotherapy. Ten out of the 16 patients underwent the double baseline whole-body [F-18]NaF PET/CT scans for test-retest (TRT) evaluation. Twelve of the 16 patients underwent pre- and mid-treatment [F-18]NaF PET/CT scans. Skeletons at different time points were registered using ART, rigid, and deformable (DR) registration algorithms. The corresponding lesions were contoured and identified on successive PET images based on including the voxels with the standardized uptake value over 15. Each algorithm was evaluated for its ability to accurately align corresponding lesions via skeleton registration. A lesion matching score (MS) was measured for each lesion, which quantified the per cent overlap between the lesion's two corresponding contours. Three separate sensitivity studies were conducted to investigate the robustness of ART in matching: sensitivity of lesion matching to various contouring threshold levels, effects of imperfections in the bone auto-segmentation and sensitivity of mis-registration. The performance of ART (MS = 82% for both datasets, p ≪ 0.001) in lesion matching was significantly better than rigid (MSTRT = 53%, MSResponse = 46%) and DR (MSTRT = 46%, MSResponse = 45%) algorithms. Neither varying threshold levels for lesion contouring nor imperfect bone segmentation had significant (p∼0.10) impact on the ART matching performance as the MS remained unchanged. Despite the mis-registration reduced MS for ART, as low as 67% (p ≪ 0.001), the performance remained to
Saifullina, E I; Iksanova, G R
Modern neurovisualization modalities - CT and MRI with cerebral circulation assessment was used for diagnosis of cerebrovascular disturbances in patients admitted to the Emergency Care Hospital of Ufa. CT and MRI perfusion methods appeared to be highly effective both in diagnosis and treatment efficacy monitoring of acute stroke.
Bailey, M R; Couret, L N; Sapozhnikov, O A; Khokhlova, V A; ter Haar, G; Vaezy, S; Shi, X; Martin, R; Crum, L A
Overpressure--elevated hydrostatic pressure--was used to assess the role of gas or vapor bubbles in distorting the shape and position of a high-intensity focused ultrasound (HIFU) lesion in tissue. The shift from a cigar-shaped lesion to a tadpole-shaped lesion can mean that the wrong area is treated. Overpressure minimizes bubbles and bubble activity by dissolving gas bubbles, restricting bubble oscillation and raising the boiling temperature. Therefore, comparison with and without overpressure is a tool to assess the role of bubbles. Dissolution rates, bubble dynamics and boiling temperatures were determined as functions of pressure. Experiments were made first in a low-overpressure chamber (0.7 MPa maximum) that permitted imaging by B-mode ultrasound (US). Pieces of excised beef liver (8 cm thick) were treated in the chamber with 3.5 MHz for 1 to 7 s (50% duty cycle). In situ intensities (I(SP)) were 600 to 3000 W/cm(2). B-mode US imaging detected a hyperechoic region at the HIFU treatment site. The dissipation of this hyperechoic region following HIFU cessation corresponded well with calculated bubble dissolution rates; thus, suggesting that bubbles were present. Lesion shape was then tested in a high-pressure chamber. Intensities were 1300 and 1750 W/cm(2) ( +/- 20%) at 1 MHz for 30 s. Hydrostatic pressures were 0.1 or 5.6 MPa. At 1300 W/cm(2), lesions were cigar-shaped, and no difference was observed between lesions formed with or without overpressure. At 1750 W/cm(2), lesions formed with no overpressure were tadpole-shaped, but lesions formed with high overpressure (5.6 MPa) remained cigar-shaped. Data support the hypothesis that bubbles contribute to the lesion distortion.
Battal, Bilal; Kocaoglu, Murat; Akgun, Veysel; Karademir, Ibrahim; Deveci, Salih; Guvenc, Inanc; Bulakbasi, Nail
The objective of the study was to assess the value of visual assessment of signal intensities on b800 diffusion-weighted images and apparent diffusion coefficient (ADC) maps in differentiation of benign and malignant focal liver lesions (FLLs). Approval for this retrospective study was obtained from the institutional review board. One hundred forty-three FLLs in 65 patients (38 women, 27 men; mean age, 50.8 years) underwent magnetic resonance (MR) imaging and diffusion-weighted imaging (DWI) with a respiratory-triggered single-shot echo-planar imaging sequence. Focal liver lesions were evaluated visually according to the signal intensities on b800 and ADC map images, and ADC values were also calculated. The conventional MR imaging, follow-up imaging findings, and histopathologic data were regarded as gold standard. Normal distribution was assessed with Kolmogorov-Smirnov test. The accuracies of visual assessment and ADC values in differentiating benign and malignant FLLs were assessed with the Student t test, and threshold values were determined with receiver operating characteristic curve analysis. By using a cutoff value of 1.21 × 10⁻³ mm²/s, ADC had a sensitivity of 100%, a specificity of 89.3%, and an accuracy of 92.3% in the discrimination of malignant FLLs. With the visual assessment of the DWIs and ADC maps, malignant lesions were differentiated from benign ones, with 100% sensitivity, 92.2% specificity, and 94.4% accuracy. Although some benign lesions were interpreted as malignant, no malignant lesion was determined as benign in visual assessment. Most FLLs are benign ones such as hemangiomas and cysts, which can be readily and practically characterized only by using visual assessment of DWIs without requiring time-consuming conventional and dynamic contrast-enhanced imaging sequences. Some benign lesions that are falsely interpreted as malignant can be further characterized by using conventional and contrast-enhanced MR studies.
Nojima, Masanori; Harada, Taku; Maruyama, Reo; Ashida, Masami; Aoki, Hironori; Matsushita, Hiro-o; Yoshikawa, Kenjiro; Harada, Eiji; Tanaka, Yoshihito; Wakita, Shigenori; Niinuma, Takeshi; Kai, Masahiro; Eizuka, Makoto; Sugai, Tamotsu; Suzuki, Hiromu
To clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we assessed the DNA methylation of cancer-associated genes in a cohort of BRAF-mutant precancerous lesions from 94 individuals. We then compared those results with the lesions' clinicopathological features, especially colorectal subsites. The lesions included hyperplastic polyps (n = 16), traditional serrated adenomas (TSAs) (n = 15), TSAs with sessile serrated adenomas (SSAs) (n = 6), SSAs (n = 49) and SSAs with dysplasia (n = 16). The prevalence of lesions exhibiting the CpG island methylator phenotype (CIMP) was lower in the sigmoid colon and rectum than in other bowel subsites, including the cecum, ascending, transverse and descending colon. In addition, several cancer-associated genes showed higher methylation levels within lesions in the proximal to sigmoid colon than in the sigmoid colon and rectum. These results indicate that the methylation status of lesions with BRAF mutation is strongly associated with their location, histological findings and neoplastic pathways. By contrast, no difference in aberrant DNA methylation was observed in normal-appearing background colonic mucosa along the bowel subsites, which may indicate the absence of an epigenetic field defect. PMID:27145369
Gressel, Gregory M; Parkash, Vinita; Pal, Lubna
Definitive management with hysterectomy could be appropriate for some patients with endometrial cancer and its precursor lesions, but poses challenges for those desiring future fertility. To review risk factors for endometrial hyperplasia/cancer among premenopausal women and discuss management options for fertility preservation. A literature search through the PubMed, Ovid, and Cochrane databases was conducted using the terms "endometrial hyperplasia" and "endometrial cancer," cross-referenced with "fertility preservation." All articles published in English between January 1, 2000, and January 1, 2015, were considered if they were readily available online. Articles were analyzed and information was synthesized into a comprehensive review. Chronic anovulation, obesity, polycystic ovarian syndrome, metabolic syndrome, insulin resistance, and type 2 diabetes mellitus must be appreciated as risk factors for endometrial pathology. Providers must exert vigilance in identifying patients at risk and in initiating pre-emptive strategies. Risk reduction with lifestyle modification, weight loss, and glycemic control can improve regression and overall health. Fertility outcomes for these patients are promising, especially with assisted reproductive technology. Conservative management could be appropriate for carefully selected women with complex atypical endometrial hyperplasia or early-stage endometrial cancer who desire future fertility. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Kołodziejczak, Małgorzata; Knapp, Paweł; Kuźmicki, Mariusz; Knapp, Piotr
Endometrial hyperplasia is one of the most frequent reasons of pre- and menopausal bleeding. In recent years, knowledge of biology of hyperplastic endometrium has changed some medical guidelines in a group of patients diagnosed with endometrial lesions. In many cases radical procedures have been replaced with preservative treatment, especially for those women who wished to spare their uterus. Also, in many high-risk surgical procedures there are a number of algorithms which allow to perform non-radical treatment in those cases. Enforcement of those strategy should be linked to precise examination of endometrium morphology Summarizing, a preservative treatment in case of endometrial hyperplasia needs sensitive and specific tests which determine safety limits of the procedure. This paper has presented current possibilities of examination and non-radical treatment of endometrial hyperplasia.
Loose, Jennifer; Harz, Markus T.; Laue, Hendrik; Twellmann, Thorsten; Bick, Ulrich; Rominger, Marga; Hahn, Horst K.; Peitgen, Heinz-Otto
Breast cancer diagnosis based on magnetic resonance images (breast MRI) is increasingly being accepted as an additional diagnostic tool to mammography and ultrasound, with distinct clinical indications.1 Its capability to detect and differentiate lesion types with high sensitivity and specificity is countered by the fact that visual human assessment of breast MRI requires long experience. Moreover, the lack of evaluation standards causes diagnostic results to vary even among experts. The most important MR acquisition technique is dynamic contrast enhanced (DCE) MR imaging since different lesion types accumulate contrast material (CM) differently. The wash-in and wash-out characteristic as well as the morphologic characteristic recorded and assessed from MR images therefore allows to differentiate benign from malignant lesions. In this work, we propose to calculate second order statistical features (Haralick textures) for given lesions based on subtraction and 4D images and on parametermaps. The lesions are classified with a linear classification scheme into probably malignant or probably benign. The method and model was developed on 104 histologically graded lesions (69 malignant and 35 benign). The area under the ROC curve obtained is 0.91 and is already comparable to the performance of a trained radiologist.
Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel
Accurate detection and measurement of the highly mineralized surface layer that forms on caries lesions is important for the diagnosis of lesion activity. Previous studies have demonstrated that optical imaging methods can be used to measure the degree of remineralization on enamel lesions. The purpose of this study was to determine if thermal and near-IR reflectance imaging could be used to assess the remineralization process in simulated dentin lesions. Artificial bovine (n=15) dentin lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for up to 12 days. The samples were dehydrated using an air spray for 30 seconds and imaged using thermal and InGaAs cameras. The area enclosed by the time-temperature curve, ΔQ, from thermal imaging decreased significantly with longer periods of remineralization. However, near-IR reflectance intensity differences, ΔI, before and after dehydration failed to show any significant relationship with the degree of remineralization. This study shows that thermal imaging can be used for the assessment of the remineralization of dentin lesions.
Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel
Accurate detection and measurement of the highly mineralized surface layer that forms on caries lesions is important for the diagnosis of lesion activity. Previous studies have demonstrated that optical imaging methods can be used to measure the degree of remineralization on enamel lesions. The purpose of this study was to determine if thermal and near-IR reflectance imaging could be used to assess the remineralization process in simulated dentin lesions. Artificial bovine (n=15) dentin lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for up to 12 days. The samples were dehydrated using an air spray for 30 seconds and imaged using thermal and InGaAs cameras. The area enclosed by the time-temperature curve, ΔQ, from thermal imaging decreased significantly with longer periods of remineralization. However, near-IR reflectance intensity differences, ΔI, before and after dehydration failed to show any significant relationship with the degree of remineralization. This study shows that thermal imaging can be used for the assessment of the remineralization of dentin lesions. PMID:27006522
Liao, Chung-Min; Lin, Tzu-Ling; Hsieh, Nan-Hung; Chen, Wei-Yu
The purpose of this study was to assess the potential risk of children skin lesions from arsenic-contaminated rice (Oryza sativa) consumption in West Bengal (India). Published age- and gender-specific skin lesions data in West Bengal were reanalyzed and incorporated into a Weibull dose-response model to predict children skin lesion prevalence. Monomethylarsonous acid (MMA(III)) levels in urine was used as a biomarker that could be predicted from a human physiologically based pharmacokinetic (PBPK) model. This study integrated arsenic contents in irrigation water, bioaccumulation factors of paddy soil, cooking methods, and arsenic bioavailability of cooked rice in gastrointestinal tract into a probabilistic risk model. Results indicated that children aged between 13 and 18 years might pose a relative higher potential risk of skin lesions to arsenic-contaminated cooked rice (odds ratios (ORs)=1.18 (95% CI 1.12-2.15)) than those of 1-6 years children (ORs=0.98 (0.85-1.40)). This study revealed the need to consider the relationships between cooking method and arsenic in cooked rice when assessing the risk associated with children skin lesions from rice consumption. This study suggested that arsenic-associated skin lesions risk from arsenic-contaminated rice consumption would be reduced significantly by adopting traditional rice cooking method (wash until clean; rice:water=1:6; discard excess water) as followed in West Bengal (India) and using water containing lower arsenic (e.g., <10 microg L(-1)) for cooking.
The endometrium is one of the most fascinating tissues in the human body. Its sole purpose is to enable implantation of an embryo during a relatively short window of opportunity in the menstrual cycle. It is becoming clear that overcoming the current bottleneck in improvements to assisted reproductive techniques will require a closer look at the interface between uterus and embryo. Indeed, embryo implantation requires a cross talk with a receptive endometrium. Using sonography, hysteroscopy and endometrial biopsy we can learn about anatomical and functional markers of endometrial receptivity. This article reviews the factors which might cause defective endometrial receptivity. These include uterine polyps, septa, leiomyomata and adhesions. The effect of thin endometrium, endometriosis and hydrosalpinx is also described. Finally contemporary investigation of molecular markers of endometrial receptivity is described. Improving embryo implantation by a closer look inside the uterus is the key to increasing pregnancy rates in IVF.
... Transvaginal ultrasound Endometrial sampling Tests are used to screen for different types of cancer. Some screening tests ... endometrium by inserting a brush, curette , or thin, flexible tube through the cervix and into the uterus. ...
Sanders, Barry H.
Endometrial ablation is a relatively new treatment for patients with persistent menorrhagia. The procedure can be performed by either laser photocoagulation or electrocoagulation; both have a very low risk of complication. Generally, less than 24 hours of hospitalization is required and return to normal activities, including work, is almost immediate. Endometrial ablation is likely to become a mainstay of treatment for menorrhagia as the technology and training become more readily available. PMID:21229128
Boldrick, Jennifer C; Layton, Christle J; Nguyen, Josephine; Swetter, Susan M
Digital dermoscopy systems employ computer-based algorithms to quantitate features of pigmented skin lesions (PSLs) and provide an assessment of malignancy risk. We evaluated interobserver concordance of PSL malignancy risk between a pigmented lesion specialist and an artificial neural network (ANN)-based automated digital dermoscopy system. While digital dermoscopy provides a reliable means of image capture, storage, and comparison of PSLs over time, the ANN algorithm requires further training and validation before the malignancy risk assessment feature can be widely used in clinical practice.
Haouzi, Delphine; Dechaud, Hervé; Assou, Said; De Vos, John; Hamamah, Samir
The appreciation of endometrial receptivity is a crucial step in assisted reproductive technology as implantation failures are thought to result, in large part, from abnormal endometrial receptivity. Using emerging omics technologies, investigators have begun to define both molecular signatures and specific biomarkers of receptive endometrium. The aim of this review was to analyse the new perspectives brought to the appreciation of endometrial receptivity by transcriptomic and proteomic technologies, involving the analysis of gene- or protein-expression-profile shifts between the pre-receptive and receptive secretory stages and how they might lead to new strategies for endometrial receptivity assessments. The use of omics as molecular tools to determine the effects of stimulation protocols on endometrial gene expression and clinical outcomes has also been investigated.
Kruse, Casper; Spin-Neto, Rubens; Reibel, Jesper; Wenzel, Ann; Kirkevang, Lise-Lotte
Traditionally, healing after surgical endodontic retreatment (SER); i.e. apicectomy with or without a retrograde filling, is assessed in periapical radiographs (PR). Recently, the use of Cone Beam CT (CBCT) has increased within endodontics. Generally, CBCT detects more periapical lesions than PR, but basic research on the true nature of these lesions is missing. The objective was to assess the diagnostic validity of PR and CBCT for determining inflammation in SER-cases that were re-operated (SER-R) due to unsuccessful healing, using histology of the periapical lesion as reference for inflammation. Records from 149 patients, receiving SER 2004-10, were screened. In total 108 patients (119 teeth) were recalled for clinical follow-up examination, PR and CBCT, of which 74 patients (83 teeth) participated. Three observers assessed PR and CBCT as "successful healing" or "unsuccessful healing" using Rud and Molven´s criteria. SER-R was offered to all non-healed teeth with expected favorable prognosis for subsequent functional retention. During SER-R, biopsy was performed and histopathology verified whether or not inflammation was present. All re-operated cases were assessed non-healed in CBCT while 11 of these were assessed successfully healed in PR. Nineteen biopsies were examined. Histopathologic diagnosis revealed 42% (teeth=8) without periapical inflammation, 16% (teeth=3) with mild inflammation, and 42% (teeth=8) with moderate to intense inflammation. A correct diagnosis was obtained in 58% with CBCT (true positives) and 63% with PR (true positives+true negatives). Of the re-operated teeth, 42% had no periapical inflammatory lesion, and hence no benefit from SER-R. Not all lesions observed in CBCT represented periapical inflammatory lesions.
Tam, Wilson; Lee, Robert C.; Lin, Brent; Simon, Jacob C.; Fried, Daniel
Previous studies have demonstrated that the structural changes on enamel due to demineralization and remineralization can be exploited through optical imaging methods such as QLF, thermal and NIR imaging. The purpose of this study is to investigate whether PS-OCT and NIR reflectance imaging can be utilized to assess lesion structure in artificial enamel lesions on the smooth surfaces of primary teeth exposed to fluoride. The smooth coronal surfaces of primary teeth (n=25) were divided into 4 windows: sound, demineralization, demineralization with remineralization and APF with demineralization. Windows were treated with either acidulated phosphate fluoride (APF) for 1 minute, a demineralization solution for 4 days, and/or an acidic remineralization solution for 12 days. The samples were imaged using PS-OCT, QLF and NIR reflectance at 1400-1700 nm wavelengths. This study demonstrated that both PS-OCT and NIR reflectance imaging were suitable for assessing lesion structure in the smooth surfaces of primary dentition.
Tam, Wilson; Lee, Robert C.; Lin, Brent; Simon, Jacob C.; Fried, Daniel
Previous studies have demonstrated that the structural changes on enamel due to demineralization and remineralization can be exploited through optical imaging methods such as QLF, thermal and NIR imaging. The purpose of this study is to investigate whether PS-OCT and NIR reflectance imaging can be utilized to assess lesion structure in artificial enamel lesions on the smooth surfaces of primary teeth exposed to fluoride. The smooth coronal surfaces of primary teeth (n=25) were divided into 4 windows: sound, demineralization, demineralization with remineralization and APF with demineralization. Windows were treated with either acidulated phosphate fluoride (APF) for 1 minute, a demineralization solution for 4 days, and/or an acidic remineralization solution for 12 days. The samples were imaged using PS-OCT, QLF and NIR reflectance at 1400–1700 nm wavelengths. This study demonstrated that both PS-OCT and NIR reflectance imaging were suitable for assessing lesion structure in the smooth surfaces of primary dentition. PMID:26997743
The WHO 1994 classification for endometrial hyperplasias is based on the morphologic features of the lesions. This system characterizes the nuclear cytologic morphology as typical or atypical and describes the glandular architectural pattern as simple or complex. The main problem of this classification is the poor reproducibility. Although the predictive value of the atypical category is high, there are many typical hyperplasia cases with cancer progression. Modern molecular data related to endometrial tumorigenesis and precise computerized morphometric analysis have identified the lesion that may be considered as a precursor of endometrioid adenocarcinoma. By definition, this endometrial intraepithelial neoplasia (EIN) is a clonal proliferation of architecturally and cytologically altered endometrial glands which are prone to malignant transformation to endometrioid (type I) endometrial adenocarcinoma. The morphometric basis of EIN diagnosis is the D-score (DS), which is a logical combination of three morphometric features that represent the glandular complexity, glandular volume and cytological alterations. PTEN inactivation and K-ras mutation are the earliest genetic changes that can be revealed in these lesions. Hyperplasia cases that do not fit into the EIN categories are considered as benign or hormonal endometrial hyperplasia. This is the theoretical basis of a new classification system in premalignant endometrial diseases. Retrospective clinical data proved the high predictive value of the EIN scheme, so the decision on therapy can be more established. The reproducibility is excellent with application of precise definitions and PTEN immunohistochemistry. In the "Blue book" published in 2003 the WHO introduces the new morphometric- and molecular-based EIN system, and recommends it as an alternative classification method.
Lakshmanan, Manu N; Kapadia, Anuj J
We present a quantitative analysis of the image quality obtained using filtered back-projection (FBP) with Ram-Lak filtering and maximum likelihood-expectation maximization (ML-EM)-with no post-reconstruction filtering in either case-in neutron stimulated emission computed tomography (NSECT) imaging using Monte Carlo simulations in the context of clinically relevant models of liver iron overload. The ratios of pixel intensities for several regions of interest and lesion shape detection using an active-contours segmentation algorithm are assessed for accuracy across different scanning configurations and reconstruction algorithms. The modulation transfer functions (MTFs) are also computed for the cases under study and are applied to determine a minimum detectable lesion spacing as a form of sensitivity analysis. The accuracy of NSECT imaging in measuring relative tissue concentration is presented for simulated clinical liver cases. When using the 15th iteration, ML-EM provides at least 25% better resolution than FBP and proves to be highly robust under low-signal high-noise conditions prevalent in NSECT. However, FBP gives more accurate lesion pixel intensity ratios and size estimates in some cases; due to advantages provided by both reconstruction algorithms, it is worth exploring the development of an algorithm that is a hybrid of the two. We also show that NSECT imaging can be used to accurately detect 3-cm lesions in backgrounds that are a significant fraction (one-quarter) of the concentration of the lesion, down to a 4-cm spacing between lesions.
Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma
Wan, Qi; Deng, Ying-Shi; Zhou, Jia-Xuan; Yu, Yu-Dong; Bao, Ying-Ying; Lei, Qiang; Chen, Hou-Jin; Peng, Ya-Hui; Mei, Ying-Jie; Zeng, Qing-Si; Li, Xin-Chun
This study aimed to investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in assessing solitary pulmonary lesions (SPLs). Sixty-two patients with pathologically confirmed SPLs, including 51 and 11 cases of malignant and benign lesions, respectively, were assessed. Diffusion weighted imaging (DWI) with 13 b values was used to derive apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Our results showed that, there was an excellent inter-observer agreement on the measurements of D and ADC between observers (inter-class correlation coefficient, ICC = 0.902 and 0.884, respectively). Meanwhile, f and D* showed good and substantial reproducibility (ICC = 0.787 and 0.623, respectively). D and ADC of malignant lesions were significantly lower than those of benign lesions (both P ≤ 0.001), while similar values were obtained in both groups for D* and f (both P > 0.05). In receiver operating characteristic (ROC) analysis, D showed the highest area under curve (AUC) for distinguishing malignant from benign lesions, followed by ADC. Accompanying signs of SPLs have specific features on IVIM maps. In conclusion, IVIM provides functional information in characterizing SPLs which is helpful to differential diagnosis. D and ADC have a significantly higher diagnostic value than f and D*. PMID:28225064
Wan, Qi; Deng, Ying-Shi; Zhou, Jia-Xuan; Yu, Yu-Dong; Bao, Ying-Ying; Lei, Qiang; Chen, Hou-Jin; Peng, Ya-Hui; Mei, Ying-Jie; Zeng, Qing-Si; Li, Xin-Chun
This study aimed to investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in assessing solitary pulmonary lesions (SPLs). Sixty-two patients with pathologically confirmed SPLs, including 51 and 11 cases of malignant and benign lesions, respectively, were assessed. Diffusion weighted imaging (DWI) with 13 b values was used to derive apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f). Our results showed that, there was an excellent inter-observer agreement on the measurements of D and ADC between observers (inter-class correlation coefficient, ICC = 0.902 and 0.884, respectively). Meanwhile, f and D* showed good and substantial reproducibility (ICC = 0.787 and 0.623, respectively). D and ADC of malignant lesions were significantly lower than those of benign lesions (both P ≤ 0.001), while similar values were obtained in both groups for D* and f (both P > 0.05). In receiver operating characteristic (ROC) analysis, D showed the highest area under curve (AUC) for distinguishing malignant from benign lesions, followed by ADC. Accompanying signs of SPLs have specific features on IVIM maps. In conclusion, IVIM provides functional information in characterizing SPLs which is helpful to differential diagnosis. D and ADC have a significantly higher diagnostic value than f and D*.
Baba, Tsukasa; Mandai, Masaki; Yamanishi, Yukio; Suzuki, Ayako; Kang, Hyun Sook; Konishi, Ikuo
Several reports have documented adenocarcinoma arising from endometriotic implants within cesarean section (C-S) scars on the serosal surface of the uterus; however, endometrial cancer invading the C-S scar from the uterine cavity has not been described. We report a case of a grade 1 endometrioid adenocarcinoma 'drop' lesion invading a previous C-S scar with resultant cervical stromal invasion. Using both MR images and a thorough review of the pathology, the tumor at the C-S scar was determined to be an implant derived from a primary lesion at the uterine fundus. With increases in the incidence of both endometrial cancer and births by C-S, it is likely we will encounter more cases of iatrogenic implants of endometrial cancers in C-S scars.
Michoux, Nicolas; Guillet, Alain; Rommel, Denis; Mazzamuto, Giosué; Sindic, Christian; Duprez, Thierry
Brain blood barrier breakdown as assessed by contrast-enhanced (CE) T1-weighted MR imaging is currently the standard radiological marker of inflammatory activity in multiple sclerosis (MS) patients. Our objective was to evaluate the performance of an alternative model assessing the inflammatory activity of MS lesions by texture analysis of T2-weighted MR images. Twenty-one patients with definite MS were examined on the same 3.0T MR system by T2-weighted, FLAIR, diffusion-weighted and CE-T1 sequences. Lesions and mirrored contralateral areas within the normal appearing white matter (NAWM) were characterized by texture parameters computed from the gray level co-occurrence and run length matrices, and by the apparent diffusion coefficient (ADC). Statistical differences between MS lesions and NAWM were analyzed. ROC analysis and leave-one-out cross-validation were performed to evaluate the performance of individual parameters, and multi-parametric models using linear discriminant analysis (LDA), partial least squares (PLS) and logistic regression (LR) in the identification of CE lesions. ADC and all but one texture parameter were significantly different within white matter lesions compared to within NAWM (p < 0.0167). Using LDA, an 8-texture parameter model identified CE lesions with a sensitivity Se = 70% and a specificity Sp = 76%. Using LR, a 10-texture parameter model performed better with Se = 86% / Sp = 84%. Using PLS, a 6-texture parameter model achieved the highest accuracy with Se = 88% / Sp = 81%. Texture parameter from T2-weighted images can assess brain inflammatory activity with sufficient accuracy to be considered as a potential alternative to enhancement on CE T1-weighted images. PMID:26693908
Cytological Study of Grade 3 Endometrioid Adenocarcinoma of Endometrial Origin: Cytoarchitecture and Features of Cell Clusters Assessed With Endometrial Brushing Cytology--Focusing on a comparison with endometrioid adenocarcinoma Grade 1, 2.
Matsui, Naruaki; Kajiwara, Hiroshi; Morishita, Akihiro; Tsukada, Hitomi; Nakazawa, Kazumi; Miyazawa, Masaki; Mikami, Mikio; Nakamura, Naoya; Sato, Shinkichi
Aim of study was to clarify the cytological characteristics of grade 3 endometrioid adenocarcinoma of endometrial origin (G3 EA) by endometrial brushing cytology. The subjects were 11 patients in whom G3 EA was diagnosed by review of preoperative cytological specimens obtained at our hospital and related institutions between 2000 and 2010. These patients were investigated with respect to the preoperative cytological diagnosis, background changes, cell cluster patterns, and individual cellular findings. Background changes were classified as inflammatory or tumorous, while cell clusters were classified as overlapping cell cluster, sheet-like cell cluster, clump of high dense gland, papillary, or other cell cluster. Cellular findings were investigated by comparing the incidence of squamous and clear cell metaplasia, the nuclear rounding rate, and the nuclear area with the findings in a control group (35 patients with G1-2 EA). Background changes were classified as inflammatory in 63.6% and necrotic in 36.4%. The cell clusters were classified as overlapping cell cluster in 44.8%, cell cluster in 21.7%, clump of high dense gland in 10.0%, papillary in 4.0%, and other cell cluster in 19.5%. The incidence of squamous and clear cell metaplasia was 27.2% and 18.1%, respectively. The mean nuclear rounding rate was 0.97, and the mean nuclear area was 55.98 µm2. Investigation of the cytoarchitecture of G3 EA with endometrial brushing cytology revealed overlapping cell cluster and tumor cells of a relatively uniform size. These findings suggest that it is necessary to recognize that there are differences between the cytological findings of G3 EA and the usual features of G1-2 EA.
van Hanegem, Nehalennia; Prins, Marileen M C; Bongers, Marlies Y; Opmeer, Brent C; Sahota, Daljit Singh; Mol, Ben Willem J; Timmermans, Anne
Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and endometrial disease (endometrial pathology, including benign polyps). We systematically searched the literature for studies comparing the results of endometrial sampling in women with postmenopausal bleeding with two different reference standards: blind dilatation and curettage (D&C) and hysteroscopy with histology. We assessed the quality of the detected studies by the QUADAS-2 tool. For each included study, we calculated the fraction of women in whom endometrial sampling failed. Furthermore, we extracted numbers of cases of endometrial cancer, atypical hyperplasia and endometrial disease that were identified or missed by endometrial sampling. We detected 12 studies reporting on 1029 women with postmenopausal bleeding: five studies with dilatation and curettage (D&C) and seven studies with hysteroscopy as a reference test. The weighted sensitivity of endometrial sampling with D&C as a reference for the diagnosis of endometrial cancer was 100% (range 100-100%) and 92% (71-100) for the diagnosis of atypical hyperplasia. Only one study reported sensitivity for endometrial disease, which was 76%. When hysteroscopy was used as a reference, weighted sensitivities of endometrial sampling were 90% (range 50-100), 82% (range 56-94) and 39% (21-69) for the diagnosis of endometrial cancer, atypical hyperplasia and endometrial disease, respectively. For all diagnosis studied and the reference test used, specificity was 98-100%. The weighted failure rate of endometrial sampling was 11% (range 1-53%), while insufficient samples were found in 31% (range 7-76%). In these women with insufficient or failed samples, an endometrial (pre) cancer was found in 7% (range 0-18%). In women with
Lefringhouse, Jason R; Elder, Jeffrey W; Baldwin, Lauren A; Miller, Rachel W; DeSimone, Chris P; van Nagell, John R; Samoyoa, Luis M; West, Dava S; Dressler, Emily V; Liu, Meng; Ueland, Frederick R
Prospectively validate an intraoperative surgical staging algorithm to stratify patients with early endometrial cancer by risk of lymph node metastasis. Subjects with endometrial cancer clinically confined to the uterus were prospectively enrolled at an academic cancer center between Jan 2012 and Jun 2015. Study participants were stratified intraoperatively into two groups based on risk of nodal involvement using cell type, tumor grade, myometrial invasion, and tumor size in accordance with an established protocol from the Mayo Clinic. Low risk (LR) subjects received extrafascial hysterectomy with bilateral salpingo-oophorectomy; high risk (HR) patients received complete surgical staging including bilateral pelvic and para-aortic lymphadenectomy. Of the 200 subjects enrolled, 194 were eligible for analysis. The algorithm identified 132 (68%) HR and 62 (32%) LR cancers. Of the HR subjects, 126 had lymphadenectomy performed with 14 (11%) positive for nodal metastases. Five HR subjects experienced disease recurrence. Of the 62 LR cancers, two patients developed disease recurrence. Ten LR cancers were upgraded to HR on final pathology due to lesion size (6) and grade (4). None of these patients experienced disease recurrence. The algorithm demonstrated 90% sensitivity (18/20) and 36% specificity (62/174) as determined by positive lymph nodes and/or disease recurrence. Intraoperative assessment of early endometrial cancer can be used to determine the extent of surgical staging. The studied algorithm has low specificity and modifications are necessary to better match the surgical procedure to the risk of metastatic cancer. Published by Elsevier Inc.
Abnormal mismatch repair and other clinicopathologic predictors of poor response to progestin treatment in young women with endometrial complex atypical hyperplasia and well-differentiated endometrial adenocarcinoma: a consecutive case series.
Zakhour, M; Cohen, J G; Gibson, A; Walts, A E; Karimian, B; Baltayan, A; Aoyama, C; Garcia, L; Dhaliwal, S K; Elashoff, D; Amneus, M; Walsh, C
To report the response to progestin therapy in young women with endometrial complex atypical hyperplasia (CAH) or FIGO grade 1 endometrial adenocarcinoma (FIGO 1 EAC) based on clinicopathologic features, including abnormal DNA mismatch repair (MMR) by immunohistochemistry (IHC). Consecutive case series. Olive View-UCLA Medical Center in Sylmar, CA, USA, and Cedars-Sinai Medical Center in Los Angeles, CA, USA. Women ≤55 years old with CAH or FIGO 1 EAC. Response to progestin therapy in 84 consecutive patients was assessed based on clinicopathologic factors, including age, body mass index (BMI), initial histology, and IHC staining for MMR proteins. Rates of abnormal MMR protein expression and response to progestin therapy were determined. Six (7%) patients had abnormal IHC staining, of whom five (83%) had FIGO 1 EAC at initial diagnosis. Following progestin treatment, none of the endometrial lesions in patients with abnormal IHC for MMR proteins had resolution of hyperplasia or malignancy, in contrast to 41 (53%) with normal staining (P = 0.028). Age ≤40 years and initial lesion (CAH versus FIGO 1 EAC) were predictors of response to progestin; BMI was not. In this cohort, 7% of women ≤55 years of age with CAH or FIGO 1 EAC had loss of MMR proteins by IHC. These patients had a higher incidence of invasive cancer and a lower incidence of resolution with progestin therapy. Abnormal MMR protein expression predicts poor response to progestins in young women with CAH or FIGO 1 EAC. © 2017 Royal College of Obstetricians and Gynaecologists.
REED, Susan D.; NEWTON, Katherine M.; CLINTON, Walter L.; EPPLEIN, Meira; GARCIA, Rochelle; ALLISON, Kimberly; VOIGT, Lynda F.; Weiss, Noel S.
Objective Estimate age-specific incidence of endometrial hyperplasia: simple, complex, and atypical, in order of increasing likelihood of progression to carcinoma. Study design Women ages 18–90 years with endometrial pathology specimens (1985–2003) at a large integrated health plan were identified using automated data. Incidence rates were obtained by dividing the number of cases by the estimated number of female health plan enrollees who retained a uterus. Results Endometrial hyperplasia peak incidence was: simple-142/100,000 woman-years, complex-213/100,000 woman-years, both in the early 50s; and atypical-56/100,000 woman-years in the early 60s. Age-adjusted incidence decreased over the study period, especially for atypical hyperplasia. Conclusions Endometrial hyperplasia incidence without and with atypia peaks in the early postmenopausal years and in the early 60s, respectively. Given that some cases of endometrial hyperplasia likely go undiagnosed, the figures provided should be viewed as minimum estimates of the true incidence. PMID:19393600
Andrade, Ticianne de Sousa de Oliveira Mota; Sousa, Debora Batista Pinheiro; Dantas, Janaina Gomes; Castro, Jonatas da Silva; Neta, Raimunda Nonata Fortes Carvalho
This study used oxidative stress enzyme (Glutathione S-Transferase and Catalase), histopathological lesions (Branchial lesions) and biometric data in the freshwater fish tambaqui, Colossoma macropomum, to assess environmental impacts in an Environmental Protection Area at São Luis, Brazil. Fish were sampled from two locations (A1 = contaminated area and A2 = reference site) within the protected area on four occasions. The activity of catalase (CAT) and glutathione S-transferase (GST) in C. macropomum was compared with biometric data and histopathological lesions. Results have shown that biometric data decreased significantly in fish (p<0.05) at the contaminated site. The activity of CAT was higher in fish specifically caught in A1. A significant difference was observed in the GST activity in the liver of C. macropomum when comparing fish from the contaminated site and those from the reference site (p<0.05).
Senneby, Anna; Elfvin, Margareta; Stebring-Franzon, Christina; Rohlin, Madeleine
To design and pilot a novel classification system for the assessment of caries lesion progression in bitewing radiography and to report rater agreement of the system. A classification system with drawings and text was designed to assess caries lesion progression. Guidelines for Reporting Reliability and Agreement Studies were used to study and report rater agreement. Pairs of posterior bitewing radiographs (baseline and 1-year follow-up) with different status concerning caries lesion progression were selected from files from public dental health clinics. 10 raters, 5 general dental practitioners and 5 specialists in oral and maxillofacial radiology were asked to assess the radiographs with the aid of the classification system. Seven raters repeated their assessments. Rater agreement was expressed as percentage of agreement and kappa. Kappa for the interrater agreement of 10 raters assessing progression was 0.61, indicating substantial agreement. Agreement was moderate for progression in the outer half of the dentine (kappa 0.55) and within enamel (kappa 0.44). Pairwise interrater agreement varied (range 69-92%; kappa 0.42-0.84). For about half of the pairs of raters, kappa was substantial (≥0.61). Intrarater agreement assessing progression was substantial (kappa 0.66-0.82). We demonstrated the applicability of the proposed classification system on caries lesion progression with respect to rater agreement. This system can provide a common framework for clinical decision-making on caries interventional methods and patient visiting intervals. Scientifically, this system allows for a comparative analysis of different methods of prevention and treatment of caries as well as of different caries risk assessment methods.
Elfvin, Margareta; Stebring-Franzon, Christina; Rohlin, Madeleine
Objectives: To design and pilot a novel classification system for the assessment of caries lesion progression in bitewing radiography and to report rater agreement of the system. Methods: A classification system with drawings and text was designed to assess caries lesion progression. Guidelines for Reporting Reliability and Agreement Studies were used to study and report rater agreement. Pairs of posterior bitewing radiographs (baseline and 1-year follow-up) with different status concerning caries lesion progression were selected from files from public dental health clinics. 10 raters, 5 general dental practitioners and 5 specialists in oral and maxillofacial radiology were asked to assess the radiographs with the aid of the classification system. Seven raters repeated their assessments. Rater agreement was expressed as percentage of agreement and kappa. Results: Kappa for the interrater agreement of 10 raters assessing progression was 0.61, indicating substantial agreement. Agreement was moderate for progression in the outer half of the dentine (kappa 0.55) and within enamel (kappa 0.44). Pairwise interrater agreement varied (range 69–92%; kappa 0.42–0.84). For about half of the pairs of raters, kappa was substantial (≥0.61). Intrarater agreement assessing progression was substantial (kappa 0.66–0.82). Conclusions: We demonstrated the applicability of the proposed classification system on caries lesion progression with respect to rater agreement. This system can provide a common framework for clinical decision-making on caries interventional methods and patient visiting intervals. Scientifically, this system allows for a comparative analysis of different methods of prevention and treatment of caries as well as of different caries risk assessment methods. PMID:27043978
Lee, Wen-Ling; Lee, Fa-Kung; Su, Wen-Hsiang; Tsui, Kuan-Hao; Kuo, Cheng-Deng; Hsieh, Shie-Liang Edmond; Wang, Peng-Hui
The relationship between hormones and endometrial cancer is well known because disease states, such as chronic anovulation and endogenous estrogen production from hormone-secreting tumors (for example, granulosa cell tumor of the ovary), are related to excess estrogen, and unopposed estrogen use might lead to endometrial overgrowth, hyperplasia, and subsequent development of endometrial carcinoma. Therefore, the possibility of using antihormone therapy in endometrial carcinoma and/or its precancer lesions, such as simple hyperplasia with and without atypia and complex hyperplasia with and without atypia, is always supposed, as in the management of breast cancer. In addition, if women in whom endometrial cancer is diagnosed are very young, some critical issues should be considered, including the possibility of ovary preservation-partial preservation of fertility and the possibility of both ovary and uterus preservation-complete preservation of fertility. Other factors are also important to consider and include oncologic risk, appropriateness of candidates for treatment, type of hormone use, response rate of hormonal therapy, appropriate surveillance, and additional counseling for issues such as anxiety about relapse and metastasis, distress about side effects, advice of the family, advice of the medical staff, and economic burden. This review will be focused on updated information and recent knowledge of the use of hormones in the management of younger women with endometrial cancer who want fertility preservation.
Lee, Robert C.; Darling, Cynthia L.; Fried, Daniel
Previous studies have demonstrated that near-IR imaging can be used to nondestructively monitor the severity of enamel lesions. Arrested lesions typically have a highly mineralized surface layer that reduces permeability and limits diffusion into the lesion. The purpose of this study was to investigate whether the rate of water loss correlates with the degree of remineralization using near-IR reflectance imaging. Artificial bovine (n=15) enamel lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for different periods. The samples were dehydrated using an air spray for 30 seconds and surfaces were imaged using an InGaAs camera at 1300-1700 nm wavelengths. Near-IR reflectance intensity differences before and after dehydration decreased with longer periods of remineralization. This study demonstrated that near-IR reflectance imaging was suitable for the detection of remineralization in simulated caries lesions and near-IR wavelengths longer than 1400 nm are well suited for the assessment of remineralization.
Ando, Masatoshi; Ferreira-Zandoná, Andrea G.; Eckert, George J.; Zero, Domenick T.; Stookey, George K.
This study aimed to evaluate the ability of quantitative light-induced fluorescence (QLF) to assess caries lesion activity using visual examination (VE) as the gold standard. Twenty-four visible white spot lesions on buccal surfaces were examined from 23 children, ages 9 to 14 years. At baseline, the surface was hydrated with water, and thereafter, it was dehydrated with continuous compressed air during image acquisition. QLF images were acquired at 0 (baseline), 5, and 15 s. QLF variables [QLFV: fluorescence loss (ΔF), lesion size (S), ΔQ: ΔF×S] was recorded. Changes-in-QLFV per second (ΔQLFV) were determined: ΔQLFV=(QLFVN-QLF/N), where N indicates dehydration time. One experienced dentist conducted VE independently using a dental unit's light, compressed air, and explorer. QLFV and ΔQLFV of the active group (n=11) were compared with those of the inactive group (n=13) using two-sample t-tests. As the surface was dehydrated, S and ΔQ values of the active group increased, whereas QLFV of the inactive group showed only a small change. ΔQLFV of the active group were larger than those of the inactive group; however, the difference did not reach statistical significance (p>0.11). Within the limitations of this study, QLF data indicated increments for lesions designated as active and minimal change for lesions defined as inactive.
Abdel-Wahed, Nagla'a; Abo-Taleb, Noha Saleh Mahmoud
Purpose The purpose of this study was to assess cone-beam computed (CBCT) sialography imaging in the detection of different changes associated with lesions of salivary glands. Materials and Methods This study consisted of 8 cases with signs and symptoms from salivary gland lesions. Conventional sialography using digital panoramic and lateral oblique radiographs and CBCT sialography were performed for each subject. The radiographs were evaluated by 3 radiologists independently of each other. The results were compared between conventional sialography and CBCT sialography in the evaluation of various lesions associated with the salivary glands. Results There was an agreement between the radiologists in interpreting the lesions that affected salivary glands with both techniques. The detection of the presence of stones or filling defects, stenosis, ductal evagination, dilatation, and space occupying lesions was 83% for conventional sialography compared with CBCT sialography. CBCT sialography was superior to conventional sialography in revealing stones, stenosis, and strictures, especially in the second and third order branches. Conclusion It would be advisable to perform CBCT sialography in cases of obstructive salivary gland diseases for better demonstration of the ductal system of the gland. PMID:23524990
Lee, Robert C; Darling, Cynthia L; Fried, Daniel
Previous studies have demonstrated that near-IR imaging can be used to nondestructively monitor the severity of enamel lesions. Arrested lesions typically have a highly mineralized surface layer that reduces permeability and limits diffusion into the lesion. The purpose of this study was to investigate whether the rate of water loss correlates with the degree of remineralization using near-IR reflectance imaging. Artificial bovine (n=15) enamel lesions were prepared by immersion in a demineralization solution for 24 hours and they were subsequently placed in an acidic remineralization solution for different periods. The samples were dehydrated using an air spray for 30 seconds and surfaces were imaged using an InGaAs camera at 1300-1700 nm wavelengths. Near-IR reflectance intensity differences before and after dehydration decreased with longer periods of remineralization. This study demonstrated that near-IR reflectance imaging was suitable for the detection of remineralization in simulated caries lesions and near-IR wavelengths longer than 1400 nm are well suited for the assessment of remineralization.
You, Changjun; Dai, Xiaoxia; Yuan, Bifeng; Wang, Jin; Wang, Jianshuang; Brooks, Philip J; Niedernhofer, Laura J; Wang, Yinsheng
Most mammalian cells in nature are quiescent but actively transcribing mRNA for normal physiological processes; thus, it is important to investigate how endogenous and exogenous DNA damage compromises transcription in cells. Here we describe a new competitive transcription and adduct bypass (CTAB) assay to determine the effects of DNA lesions on the fidelity and efficiency of transcription. Using this strategy, we demonstrate that the oxidatively induced lesions 8,5'-cyclo-2'-deoxyadenosine (cdA) and 8,5'-cyclo-2'-deoxyguanosine (cdG) and the methylglyoxal-induced lesion N(2)-(1-carboxyethyl)-2'-deoxyguanosine (N(2)-CEdG) strongly inhibited transcription in vitro and in mammalian cells. In addition, cdA and cdG, but not N(2)-CEdG, induced transcriptional mutagenesis in vitro and in vivo. Furthermore, when located on the template DNA strand, all examined lesions were primarily repaired by transcription-coupled nucleotide excision repair in mammalian cells. This newly developed CTAB assay should be generally applicable for quantitatively assessing how other DNA lesions affect DNA transcription in vitro and in cells.
Franasiak, Jason M.; Holoch, Kristin J.; Yuan, Lingwen; Schammel, David P.; Young, Steven L.; Lessey, Bruce A.
Objective To evaluate endometrial leukemia inhibitor factor (LIF) expression as a marker of endometrial receptivity in women with unexplained infertility (UI). Design Prospective case-control study. Setting University-associated infertility clinics. Patient(s) Women with UI for more than 1 year and healthy control women. Intervention(s) Endometrial biopsy. Main Outcome Measure(s) Time to pregnancy was compared between patients with UI who were evaluated for endometrial LIF protein as well as ανβ3 integrin expression. Endometrium was evaluated using immunohistochemistry (IHC) and messenger RNA by real time reverse transcriptase–polymerase chain reaction (PCR) (quantitative real-time reverse transcriptase–PCR) in samples from women with UI as well as healthy control women. Result(s) Leukemia inhibitor factor was expressed in epithelial cells in a cyclic fashion in controls, and overall expression in the secretory phase was similar between controls and women with UI, whereas ανβ3 integrin expression was reduced. However, using quantitative real-time PCR, LIF messenger RNA abundance was 4.4-fold lower in women with low levels of ανβ3 integrin expression compared with samples with normal integrins. By immunohistochemistry, ανβ3 integrin expression was always lacking when the histology was out of phase, whereas LIF expression was only negative in a subset of those samples. Reduced endometrial LIF expression was strongly associated with poor reproductive outcomes. Conclusion(s) Endometrial LIF expression peaks in the midsecretory phase and is reduced in some women with UI. The use of LIF in combination with ανβ3 integrin as biomarkers appears to be superior to integrin testing alone when evaluating endometrial receptivity, primarily because of its earlier pattern of expression during the secretory phase. PMID:24690239
Hwang, Jason T K; Gu, Ying R; Dickson, Benjamin J; Shen, Mi; Ralhan, Ranju; Walfish, Paul G; Mock, David; Pritzker, Kenneth P H
Straticyte™ was previously shown to be a more effective prognostic assessment than the current standard of care, histopathological dysplasia grading, to assess progression risk of oral epithelial dysplasia to invasive cancer [Hwang JT, Gu YR, Shen M, Ralhan R, Walfish PG, Pritzker KP, et al. Individualized five-year risk assessment for oral premalignant lesion progression to cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123:374-81]. In this follow-up study, our aim is to confirm the prognostic value of Straticyte using an independent cohort of oral biopsy cases previously assessed as epithelial dysplasia of various grades. Using Visiopharm image analysis system, we analyzed an independent retrospective cohort of 51 oral biopsy samples with known outcomes and a follow-up history of up to 12years, to verify Straticyte, an individualized 5-year risk assessment for progression of oral potentially malignant lesions to invasive squamous cell carcinoma. Straticyte classified the lesions more accurately than histopathological oral epithelial dysplasia grading for risk for progression to cancer over five years. The sensitivity of low-risk vs. non-low-risk Straticyte groups was 100% compared to 68% for mild vs. non-mild dysplasia. The sensitivity of high-risk vs. non-high-risk Straticyte was 71% compared to 3% for severe vs. non-severe dysplasia. Furthermore, the Negative Predictive Value (NPV) for Straticyte was 100% for low-risk vs. non-low-risk, whereas the NPV for mild vs. non-mild dysplasia was 38%. In this cohort, Straticyte ascertains as a more useful assessment for risk of cancer progression in oral potentially malignant lesions than oral epithelial dysplasia grade. Copyright © 2017 Elsevier Ltd. All rights reserved.
Background Gastric ulcers in fattening pigs from intensive pork production can cause sudden deaths on farm and the grinding intensity of the diet appears to be among the risk factors. The objective of this work is to adopt the latest laboratory tests and thresholds for the ulcerogenic risk assessment of diets from experimental reports and verify the class of risk in relation to gastric lesion prevalence in reared finishers. Results Specificity and accuracy of feed safety tests based on the ulcerogenic risk of feed associated with the particle size distribution of diets were calculated on the occurrence of gastric lesions observed at a slaughterhouse: 41 lard-type hogs, fed with two diets [pelleted (n = 21 pigs) vs. mixed meal (n = 20 pigs)], analyzed at the laboratory of our Institute, were involved. Gross inspection at the abattoir allowed the identification of the development of macroscopic gastric lesions in the pigs (13/21) fed with a pelleted complete diet, ranked in Class 1 (high ulcerogenic risk) on laboratory assessment. Breakdown of gastric lesion severity: hyperkeratosis (13/13), mucosal erosions (11/13) and bleeding ulcers (2/13). This occurrence was compared to the morphology of stomach mucosa from 20 finishers fed with a mixed meal diet, ranked in Class 3 (low ulcerogenic risk), in which no gastric lesions were observed. Very fine particle (VFP) mass (<0.4 mm) according to cut off thresholds (>36%) for the safety ranking of diets, showed: 100% positive predictive value (PPV); 100% specificity; 88.1% accuracy; 72.2% sensitivity. Conclusions Three factors emerged: the elevated mass (42.6%) of <0.4 mm particles in the pelleted complete diet confirmed the associated risk rank in Class 1 assessed by laboratory procedures, as gastric lesions were selectively observed in 61.9% of finishers fed with the high risk diet; in these animals, macroscopic gastric lesions occurred within four weeks and showed a sub-clinical course, independently of severity
Gertych, Arkadiusz; Wong, Alexis; Sangnil, Alan; Liu, Brent J.
Multiple sclerosis (MS) is a frequently encountered neurological disease with a progressive but variable course affecting the central nervous system. Outline-based lesion quantification in the assessment of lesion load (LL) performed on magnetic resonance (MR) images is clinically useful and provides information about the development and change reflecting overall disease burden. Methods of LL assessment that rely on human input are tedious, have higher intra- and inter-observer variability and are more time-consuming than computerized automatic (CAD) techniques. At present it seems that methods based on human lesion identification preceded by non-interactive outlining by CAD are the best LL quantification strategies. We have developed a CAD that automatically quantifies MS lesions, displays 3-D lesion map and appends radiological findings to original images according to current DICOM standard. CAD is also capable to display and track changes and make comparison between patient's separate MRI studies to determine disease progression. The findings are exported to a separate imaging tool for review and final approval by expert. Capturing and standardized archiving of manual contours is also implemented. Similarity coefficients calculated from quantities of LL in collected exams show a good correlation of CAD-derived results vs. those incorporated as expert's reading. Combining the CAD approach with an expert interaction may impact to the diagnostic work-up of MS patients because of improved reproducibility in LL assessment and reduced time for single MR or comparative exams reading. Inclusion of CAD-generated outlines as DICOM-compliant overlays into the image data can serve as a better reference in MS progression tracking.
Meireles, Cinthia G; Pereira, Sidney A; Valadares, Luciana P; Rêgo, Daniela F; Simeoni, Luiz A; Guerra, Eliete N S; Lofrano-Porto, Adriana
Endometrial cancer is one of the most common gynecological cancers, which is frequently preceded by atypical endometrial hyperplasia, a premalignant lesion. Metformin, an antidiabetic drug, has emerged as a new adjunctive strategy for different cancer types, including endometrial cancer. This systematic review and meta-analysis aimed to evaluate the effects of metformin in atypical endometrial hyperplasia and endometrial cancer patients. The search was conducted on January 2017 and the articles were collected in Cochrane, LILACS, PubMed, Scopus and Web of Science. A grey literature search was undertaken using Google SCHOLAR, ProQuest and Open Grey. Nineteen studies were included, which contained information about the following outcomes: reversal of atypical endometrial hyperplasia, cellular proliferation biomarkers expression and overall survival in metformin-users compared to non-users. Metformin was associated with reversion of atypical endometrial hyperplasia to a normal endometrial, and with decreased cell proliferation biomarkers staining, from 51.94% (CI=36.23% to 67.46%) to 34.47% (CI=18.55% to 52.43%). However, there is a high heterogeneity among studies. Metformin-users endometrial cancer patients had a higher overall survival compared to non-metformin users and non-diabetic patients (HR=0.82; CI: 0.70-0.95; p=0.09, I(2)=40%). Regardless the high heterogeneity of the analyzed studies, the present review suggests that adjunct metformin treatment may assist in the reversal of atypical endometrial hyperplasia to normal endometrial histology, in the reduction of cell proliferation biomarkers implicated in tumor progression, and in the improvement of overall survival in endometrial cancer. Further work on prospective controlled trials designed to address the effects of adjunct metformin on clinical outcomes is necessary for definite conclusions. Copyright © 2017 Elsevier Inc. All rights reserved.
Ianculescu, Victor; Ciolovan, Laura Maria; Dunant, Ariane; Vielh, Philippe; Mazouni, Chafika; Delaloge, Suzette; Dromain, Clarisse; Blidaru, Alexandru; Balleyguier, Corinne
To determine the diagnostic performance of Acoustic Radiation Force Impulse (ARFI) Virtual Touch IQ shear wave elastography in the discrimination of benign and malignant breast lesions. Conventional B-mode and elasticity imaging were used to evaluate 110 breast lesions. Elastographic assessment of breast tissue abnormalities was done using a shear wave based technique, Virtual Touch IQ (VTIQ), implemented on a Siemens Acuson S3000 ultrasound machine. Tissue mechanical properties were interpreted as two-dimensional qualitative and quantitative colour maps displaying relative shear wave velocity. Wave speed measurements in m/s were possible at operator defined regions of interest. The pathologic diagnosis was established on samples obtained by ultrasound guided core biopsy or fine needle aspiration. BIRADS based B-mode evaluation of the 48 benign and 62 malignant lesions achieved 92% sensitivity and 62.5% specificity. Subsequently performed VTIQ elastography relying on visual interpretation of the colour overlay displaying relative shear wave velocities managed similar standalone diagnostic performance with 92% sensitivity and 64.6% specificity. Lesion and surrounding tissue shear wave speed values were calculated and a significant difference was found between the benign and malignant populations (Mann-Whitney U test, p<0.0001). By selecting a lesion cut-off value of 3.31m/s we achieved 80.4% sensitivity and 73% specificity. Applying this threshold only to BIRADS 4a masses, we reached overall levels of 92% sensitivity and 72.9% specificity. VTIQ qualitative and quantitative elastography has the potential to further characterise B-mode detected breast lesions, increasing specificity and reducing the number of unnecessary biopsies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Tica, Andrei Adrian; Tica, Oana Sorina; Georgescu, Claudia Valentina; Pirici, Daniel; Bogdan, Maria; Ciurea, Tudorel; Mogoantă, Stelian ŞtefăniŢă; Georgescu, Corneliu Cristian; Comănescu, Alexandru Cristian; Bălşeanu, Tudor Adrian; Ciurea, Raluca Niculina; Osiac, Eugen; Buga, Ana Maria; Ciurea, Marius Eugen
G-protein coupled estrogen receptor 1 (GPER), a particular extranuclear estrogen receptor (ER), seems not to be significantly involved in normal female phenotype development but especially associated with severe genital malignancies. This study investigated the GPER expression in different types of normal and abnormal proliferative endometrium, and the correlation with the presence of ERα. GPER was much highly expressed in cytoplasm (than onto cell membrane), contrary to ERα, which was almost exclusively located in the nucleus. Both ERs' densities were higher in columnar epithelial then in stromal cells, according with higher estrogen-sensitivity of epithelial cells. GPER and ERα density decreased as follows: complex endometrial hyperplasia (CEH) > simple endometrial hyperplasia (SHE) > normal proliferative endometrium (NPE) > atypical endometrial hyperplasia (AEH), ERα' density being constantly higher. In endometrial adenocarcinomas, both ERs were significant lower expressed, and widely varied, but GPER÷ERα ratio was significantly increased in high-grade lesions. The nuclear ERα is responsible for the genomic (the most important) mechanism of action of estrogens, involved in cell growth and multiplication. In normal and benign proliferations, ERα expression is increased as an evidence of its effects on cells with conserved architecture, in atypical and especially in malignant cells ERα's (and GPER's) density being much lower. Cytoplasmic GPER probably interfere with different tyrosine÷protein kinases signaling pathways, also involved in cell growth and proliferation. In benign endometrial lesions, GPER's presence is, at least partially, the result of an inductor effect of ERα on GPER gene transcription. In high-grade lesions, GPER÷ERα ratio was increased, demonstrating that GPER is involved per se in malignant endometrial proliferations.
Otis, Colombe; Guillot, Martin; Moreau, Maxim; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Beaudry, Francis; Troncy, Eric
Characterising the temporal evolution of changes observed in pain functional assessment, spinal neuropeptides and cartilage lesions of the joint after chemical osteoarthritis (OA) induction in rats. On day (D) 0, OA was induced by an IA injection of monosodium iodoacetate (MIA). Rats receiving 2mg MIA were temporally assessed at D3, D7, D14 and D21 for the total spinal cord concentration of substance P (SP), calcitonin gene related-peptide (CGRP), bradykinin (BK) and somatostatin (STT), and for severity of cartilage lesions. At D21, the same outcomes were compared with the IA 1mg MIA, IA 2mg MIA associated with punctual IA injection of lidocaine at D7, D14 and D21, sham (sterile saline) and naïve groups. Tactile allodynia was sequentially assessed using a von Frey anaesthesiometer. Non-parametric and mixed models were applied for statistical analysis. Tactile allodynia developed in the 2mg MIA group as soon as D3 and was maintained up to D21. Punctual IA treatment with lidocaine counteracted it at D7 and D14. Compared to naïve, [STT], [BK] and [CGRP] reached a maximum as early as D7, which plateaued up to D21. For [SP], the increase was delayed up to D14 and maintained at D21. No difference in levels of neuropeptides was observed between MIA doses, except for higher [STT] in the 2mg MIA group (P=0.029). Neuropeptides SP and BK were responsive to lidocaine treatment. The increase in severity of cartilage lesions was significant only in the 2mg MIA groups (P=0.01). In the MIA OA pain model, neuropeptide modulation appears early, and confirms the central nervous system to be an attractive target for OA pain quantification. The relationship of neuropeptide release with severity of cartilage lesions and functional assessment are promising and need further validation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Seppälä, M; Julkunen, M; Riittinen, L; Koistinen, R
Uterine factors influence reproduction at the macro-anatomy level, and the effects of hormonal steroids on endometrial morphology are well recognized in the histopathological diagnosis of dysfunctional bleeding and infertility. During the past decade, attention has been paid to endometrial protein synthesis and secretion with respect to endocrine stimuli and implantation, and to the paracrine/autocrine effects of endometrial peptide growth factors, their binding proteins and other factors. The emphasis of this presentation is on protein secretion of the secretory endometrium, in which progesterone plays a pivotal role. Insulin-like growth factors have receptors on the endometrium, and IGF-binding proteins, stimulated by progesterone, modulate the effects of IGFs locally. Also other protein products of the secretory endometrium have been reviewed in this communication, with special emphasis on studies of a progesterone-associated endometrial protein which has many names in the literature, such as PEP, PP14, alpha 2-PEG and AUP. Extensive studies are ongoing in many laboratories to elucidate the regulation, function, interplay at tissue and cellular levels, and clinical significance of these proteins.
Rashidnasab, A.; Elangovan, P.; Yip, M.; Diaz, O.; Dance, D. R.; Young, K. C.; Wells, K.
A new method of generating realistic three dimensional simulated breast lesions known as diffusion limited aggregation (DLA) is presented, and compared with the random walk (RW) method. Both methods of lesion simulation utilize a physics-based method for inserting these simulated lesions into 2D clinical mammogram images that takes into account the polychromatic x-ray spectrum, local glandularity and scatter. DLA and RW masses were assessed for realism via a receiver operating characteristic (ROC) study with nine observers. The study comprised 150 images of which 50 were real pathology proven mammograms, 50 were normal mammograms with RW inserted masses and 50 were normal mammograms with DLA inserted masses. The average area under the ROC curve for the DLA method was 0.55 (95% confidence interval 0.51-0.59) compared to 0.60 (95% confidence interval 0.56-0.63) for the RW method. The observer study results suggest that the DLA method produced more realistic masses with more variability in shape compared to the RW method. DLA generated lesions can overcome the lack of complexity in structure and shape in many current methods of mass simulation.
Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma
Okadome, Masao; Saito, Toshiaki; Nishiyama, Naoko; Ariyoshi, Kazuya; Shimamoto, Kumi; Shimada, Takako; Kodama, Keisuke; Imamura, Shogo; Nishiyama, Ken-ichi; Taguchi, Kenichi
Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC. Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest. For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002). Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.
Yaginuma, Y; Fujita, M; Saitoh, S; Hayakawa, K; Kuzumaki, N; Ishikawa, M
Monoclonal antibody rp-28 directed against the ras gene product p21 has been used to evaluate ras p21 expression in endometrial lesions. Endometrial cancer showed a variable reactivity according to histological type: in well differentiated adenocarcinoma 63% were positive (12/19); in moderately differentiated adenocarcinoma 53% were positive (8/15); in poorly differentiated adenocarcinoma 40% were positive (2/5). The staining intensity of ras p21 seemed to be stronger in the more differentiated types of endometrial carcinoma. In endometrial carcinoma with premenopausal women, 27% were positive (3/11), and with postmenopausal women 71% were positive (20/28). The difference between premenopausal and postmenopausal groups was statistically significant (Mantel-Haenszel procedure, M-H chi 2 = 6.765, P < 0.01). The results suggest the existence of different carcinogenetic mechanisms in these two groups of endometrial cancer.
Fujiwara, Hiroyuki; Takahashi, Yoshifumi; Takano, Masashi; Miyamoto, Morikazu; Nakamura, Kazuto; Kaneta, Yoshibumi; Hanaoka, Tatsuya; Ohwada, Michitaka; Sakamoto, Takanori; Hirakawa, Takashi; Fujiwara, Keiichi; Suzuki, Mitsuaki
Endometrial cytology by direct intrauterine sampling is the most common test for an initial evaluation of the endometrium in Japan. However, its diagnostic value for endometrial cancer remains unknown. Here, we assess the correlation between cytopathology and histopathology to evaluate the diagnostic value of cytology for endometrial cancer. Patients with histologically confirmed endometrial cancer and controls with a normal endometrium confirmed by hysterectomy had all undergone preoperative endometrial cytology between 2001 and 2010 at our eight institutions and were retrospectively analyzed. The cytological results were compared by clinical stage, histological type, differentiation, and sampling instrument. We analyzed 1,441 endometrial cancer and 1,361 control cases. Endometrial cytology detected cancer in 1,279 (916 positive and 363 suspicious) cases with a sensitivity (positive plus suspicious cases) of 88.8% and a specificity of 98.5%. The positive rate was high in advanced-stage, nonendometrioid, and undifferentiated cases, but there was no significant difference in sensitivity between these clinical conditions. Endometrial cytology shows a relatively high sensitivity and specificity for endometrial cancer, and neither statistical measure is significantly affected by clinical stage, histological type, differentiation, sample numbers, or sampling instrument. These findings form a superior dataset for evaluating the efficacy of endometrial cytology. © 2014 S. Karger AG, Basel.
Liao, Chung-Min; Lin, Tzu-Ling; Chen, Szu-Chieh
Chronic arsenic exposure and skin lesions (keratosis and hyperpigmentation) are inextricably linked. This paper was to quantify the children skin lesions risks and to further recommend safe drinking water arsenic standard based on reported arsenic epidemiological data. We linked the Weibull dose-response function and a physiologically based pharmacokinetic (PBPK) model to estimate safe drinking water arsenic concentrations and to perform the risk characterization. We calculated odds ratios (ORs) to assess the relative magnitude of the effect of the arsenic exposure on the likelihood of the prevalence of children skin lesions by calculating proposed Weibull-based prevalence ratios of exposed to control groups associated with the age group-specific PBPK model predicted dimethylarsinite (MMA(III)) levels in urine. Positive relationships between arsenic exposures and cumulative prevalence ratios of skin lesions were found using Weibull dose-response model (r2=0.91-0.96). We reported that the safe drinking water arsenic standards were recommended to be 2.2 and 1 microg/L for male and 6 and 2.8 microg/L for female in 0-6 and 7-18 years age groups, respectively, based on hyperpigmentation with an excess risk of 10(-3) for a 75 years lifetime exposure. Risk predictions indicate that estimated ORs have 95% confidence intervals of 1.33-5.12, 1.74-19.15, and 2.81-19.27 based on mean drinking water arsenic contents of 283.19, 282.65, and 468.81 microg/L, respectively, in West Bengal, India, Bangladesh, and southwestern Taiwan. Our findings also suggest that increasing urinary monomethylarsonic acid (MMA) levels are associated with an increase in risks of arsenic-induced children skin lesions.
Purposes 1. To determine the optimal pelvic nodal clinical target volume for post-operative treatment of endometrial cancer. 2. To compare the DVH of different treatment planning techniques applied to this new CTV and the surrounding tissues. Methods and Materials Based on the literature, we selected a methodology to delineate nodal target volume to define a NEW-CTV and NEW-PTV. Conventional 2D fields, 3D fields based on anatomic guidelines per RTOG 0418, 3D fields based on our guidelines, and IMRT based on our guidelines were assessed for coverage of NEW-CTV, NEW-PTV, and surrounding structures. CT scans of 10 patients with gynecologic malignancies after TAH/BSO were used. DVHs were compared. Results For NEW-PTV, mean V45Gy were 50% and 69% for 2D and RTOG 0418-3DCRT vs. 98% and 97% for NEW-3DCRT and NEW-IMRT (p < 0.0009). Mean V45Gy small bowel were 24% and 20% for 2D and RTOG 0418-3DCRT, increased to 32% with NEW-3DCRT, and decreased to 14% with IMRT (p = 0.005, 0.138, 0.002). Mean V45Gy rectum were 26%, 35%, and 52% for 2D, RTOG 0418-3DCRT, and NEW-3DCRT, and decreased to 26% with NEW-IMRT (p < 0.05). Mean V45Gy bladder were 83%, 51%, and 73% for 2D, RTOG 0418-3DCRT, and NEW-3DCRT, and decreased to 30% with NEW-IMRT (p < 0.002). Conclusions Conventional 2D and RTOG 0418-based 3DCRT plans cover only a fraction of our comprehensive PTV. A 3DCRT plan covers this PTV with high doses to normal tissues, whereas IMRT covers the PTV while delivering lower normal tissue doses. Re-consideration of what specifically the pelvic target encompasses is warranted. PMID:20579393
Guo, Susan; Ennis, Ronald D; Bhatia, Stephen; Trichter, Frieda; Bashist, Benjamin; Shah, Jinesh; Chadha, Manjeet
1. To determine the optimal pelvic nodal clinical target volume for post-operative treatment of endometrial cancer. 2. To compare the DVH of different treatment planning techniques applied to this new CTV and the surrounding tissues. Based on the literature, we selected a methodology to delineate nodal target volume to define a NEW-CTV and NEW-PTV. Conventional 2D fields, 3D fields based on anatomic guidelines per RTOG 0418, 3D fields based on our guidelines, and IMRT based on our guidelines were assessed for coverage of NEW-CTV, NEW-PTV, and surrounding structures. CT scans of 10 patients with gynecologic malignancies after TAH/BSO were used. DVHs were compared. For NEW-PTV, mean V45Gy were 50% and 69% for 2D and RTOG 0418-3DCRT vs. 98% and 97% for NEW-3DCRT and NEW-IMRT (p < 0.0009). Mean V45Gy small bowel were 24% and 20% for 2D and RTOG 0418-3DCRT, increased to 32% with NEW-3DCRT, and decreased to 14% with IMRT (p = 0.005, 0.138, 0.002). Mean V45Gy rectum were 26%, 35%, and 52% for 2D, RTOG 0418-3DCRT, and NEW-3DCRT, and decreased to 26% with NEW-IMRT (p < 0.05). Mean V45Gy bladder were 83%, 51%, and 73% for 2D, RTOG 0418-3DCRT, and NEW-3DCRT, and decreased to 30% with NEW-IMRT (p < 0.002). Conventional 2D and RTOG 0418-based 3DCRT plans cover only a fraction of our comprehensive PTV. A 3DCRT plan covers this PTV with high doses to normal tissues, whereas IMRT covers the PTV while delivering lower normal tissue doses. Re-consideration of what specifically the pelvic target encompasses is warranted.
Siemonsen, S; Fitting, T; Thomalla, G; Krützelmann, A; Fiehler, J
Few magnetic resonance imaging (MRI) studies of stroke have evaluated the value of visual assessment of perfusion/diffusion mismatch, which is crucial for routine application. In this study an attempt was made to visually assess perfusion lesions resembling the acute clinical situation and identify parameters with the highest interobserver reliability when used to define a perfusion/diffusion mismatch and the highest accuracy for prediction of infarct growth. Magnetic resonance imaging was performed within 6 h of symptom onset and again 1-11 days thereafter in 86 consecutive stroke patients who received intravenous thrombolytic therapy. The MRI protocol included diffusion-weighted imaging apparent diffusion coefficient (DWI/ADC), fluid-attenuated inversion recovery (FLAIR) and perfusion imaging (PI). Maps for different perfusion parameters, e.g. cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) were calculated. Areas of perfusion deficits of all perfusion parameters were visually compared to corresponding ADCs and final infarct size by two independent observers. The final infarct size was overestimated by TTP (in 81/83 patients by raters 1 and 2, respectively), MTT (82/83) and CBF (65/74) lesions. The ADC lesions were rated smaller than the final infarct size in 43/38 cases by raters 1 and 2 and the CBV decrease was rated to underestimate final infarct size in 40/31 cases. The only significantly increased OR of 3.883 (95 % CI 1.466-10.819, p = 0.004, rater 1)/5.142 (95 % CI 1.828-15.142, p = 0.001, rater 2) for predicting infarct growth was observed for the presence of a CBV > ADC mismatch, which also showed the highest kappa value of 0.407. All mismatch patterns were prone to high interrater variability when assessed under conditions resembling the clinical setting. Of all tested mismatch patterns the CBV > ADC mismatch was the strongest predictor of lesion growth while visual assessment of TTP and CBF generally
Nicolae, Alina; Preda, Ovidiu; Nogales, Francisco F
Endometrial metaplasias and changes (EMCs) are conditions frequently overlooked and misdiagnosed. The aim of this review is to update current issues and provide a classification with a practical clinicopathological approach. Hormonal or irritative stimuli are the main inducing factors of EMCs, although some metaplasias have a mutational origin. EMCs vary from reactive, degenerative lesions to those able to associate with malignancy or those having a preneoplastic potential. The most common types of EMCs are ciliated tubal metaplasia (CTM) and mucinous metaplasia (MM), which occur in simple and complex glands, and possibly these architectural changes hold the same prognostic significance as they do in hyperplastic endometrioid lesions. Immunohistochemically, CTM is positive for LhS28, bcl-2, PAX2 and p16(INK4A). Complex CTM is likely to be a precursor of ciliated endometrioid-type carcinomas. MMs should be evaluated architecturally, taking into account that their atypicality is minimal. The differentiation between complex MM and mucinous carcinoma may be extremely difficult. Surface complex, papillary MM in endometrial polyps can be considered as benign. Intestinal-type endometrial MM is rare and its presence should prompt further investigation of associated lesions in the endocervix. Endometrial squamous metaplasia (ESS) is often linked to chronic irritative situations. It should be differentiated from secondary involvement by a human papilomavirus-related cervical lesion. Morular metaplasia is a mutational phenomenon with a distinct phenotype that helps to differentiate it from ESS. Morules are benign, hormonally inert structures that are often markers of complex endometrioid glandular architecture, and they are associated with an attenuated malignancy. Endometrial reactive changes are commonly associated with desquamation or hormonal imbalance. The frequent, p16(INK4A) positive, benign surface papillary syncytial change may be misdiagnosed, in some cases, as
Freiman, M.; Lamash, Y.; Gilboa, G.; Nickisch, H.; Prevrhal, S.; Schmitt, H.; Vembar, M.; Goshen, L.
The determination of hemodynamic significance of coronary artery lesions from cardiac computed tomography angiography (CCTA) based on blood flow simulations has the potential to improve CCTA's specificity, thus resulting in improved clinical decision making. Accurate coronary lumen segmentation required for flow simulation is challenging due to several factors. Specifically, the partial-volume effect (PVE) in small-diameter lumina may result in overestimation of the lumen diameter that can lead to an erroneous hemodynamic significance assessment. In this work, we present a coronary artery segmentation algorithm tailored specifically for flow simulations by accounting for the PVE. Our algorithm detects lumen regions that may be subject to the PVE by analyzing the intensity values along the coronary centerline and integrates this information into a machine-learning based graph min-cut segmentation framework to obtain accurate coronary lumen segmentations. We demonstrate the improvement in hemodynamic significance assessment achieved by accounting for the PVE in the automatic segmentation of 91 coronary artery lesions from 85 patients. We compare hemodynamic significance assessments by means of fractional flow reserve (FFR) resulting from simulations on 3D models generated by our segmentation algorithm with and without accounting for the PVE. By accounting for the PVE we improved the area under the ROC curve for detecting hemodynamically significant CAD by 29% (N=91, 0.85 vs. 0.66, p<0.05, Delong's test) with invasive FFR threshold of 0.8 as the reference standard. Our algorithm has the potential to facilitate non-invasive hemodynamic significance assessment of coronary lesions.
Tran, Arthur-Quan; Gehrig, Paola
Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer. PMID:28184290
Gargett, Caroline E.; Schwab, Kjiana E.; Deane, James A.
's syndrome. Endometrial MSCs (eMSCs) and menstrual blood stromal fibroblasts are an attractive source of MSCs for regenerative medicine because of their relative ease of acquisition with minimal morbidity. Their homologous and non-homologous use as autologous and allogeneic cells for therapeutic purposes is currently being assessed in preclinical animal models of pelvic organ prolapse and phase I/II clinical trials for cardiac failure. eMSCs and stromal fibroblasts also exhibit non-stem cell-associated immunomodulatory and anti-inflammatory properties, further emphasizing their desirable properties for cell-based therapies. CONCLUSIONS Much has been learnt about endometrial stem/progenitor cells in the 10 years since their discovery, although several unresolved issues remain. These include rationalizing the terminology and diagnostic characteristics used for distinguishing perivascular stem/progenitor cells from stromal fibroblasts, which also have considerable differentiation potential. The hierarchical relationship between clonogenic epithelial progenitor cells, endometrial and decidual SP cells, CD146+PDGFR-β+ and SUSD2+ cells and menstrual blood stromal fibroblasts still needs to be resolved. Developing more genetic animal models for investigating the role of endometrial stem/progenitor cells in endometrial disorders is required, as well as elucidating which bone marrow cells contribute to endometrial tissue. Deep sequencing and epigenetic profiling of enriched populations of endometrial stem/progenitor cells and their differentiated progeny at the population and single-cell level will shed new light on the regulation and function of endometrial stem/progenitor cells. PMID:26552890
Gargett, Caroline E; Schwab, Kjiana E; Deane, James A
. Endometrial MSCs (eMSCs) and menstrual blood stromal fibroblasts are an attractive source of MSCs for regenerative medicine because of their relative ease of acquisition with minimal morbidity. Their homologous and non-homologous use as autologous and allogeneic cells for therapeutic purposes is currently being assessed in preclinical animal models of pelvic organ prolapse and phase I/II clinical trials for cardiac failure. eMSCs and stromal fibroblasts also exhibit non-stem cell-associated immunomodulatory and anti-inflammatory properties, further emphasizing their desirable properties for cell-based therapies. Much has been learnt about endometrial stem/progenitor cells in the 10 years since their discovery, although several unresolved issues remain. These include rationalizing the terminology and diagnostic characteristics used for distinguishing perivascular stem/progenitor cells from stromal fibroblasts, which also have considerable differentiation potential. The hierarchical relationship between clonogenic epithelial progenitor cells, endometrial and decidual SP cells, CD146(+)PDGFR-β(+) and SUSD2(+) cells and menstrual blood stromal fibroblasts still needs to be resolved. Developing more genetic animal models for investigating the role of endometrial stem/progenitor cells in endometrial disorders is required, as well as elucidating which bone marrow cells contribute to endometrial tissue. Deep sequencing and epigenetic profiling of enriched populations of endometrial stem/progenitor cells and their differentiated progeny at the population and single-cell level will shed new light on the regulation and function of endometrial stem/progenitor cells. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
Gabre, Pia; Birring, Eva; Gahnberg, Lars
Epidemiological data reveal that the prevalence of dental caries in western countries has decreased in recent decades. The aim of this study was to investigate how dentists and dental hygienists assess dental caries lesions in bite-wing radiographs between 1983 and 2003. All dentists and dental hygienists in Public Dental Health in Uppsala County were offered to take part in the study. The participants assessed manifest and initial caries lesions in eight bite-wing radiographs from three patients individually. An X-ray viewer and binoculars were used. The assessments were repeated in the same radiographs every five years, a total of five times, between 1983 and 2003. In the different test occasions 80-103 dentists and 11-48 dental hygienists participated. The registration of dental caries changed between 1983 and 2003. The number of manifest lesions registered by dentists decreased between 1983 and 1988, but were stable after 1988. Dental hygienists showed no changes in the registration of manifest lesions during the study. Initial lesions registered by dentists and dental hygienists increased between 1988 and 1998. Assessments of initial caries lesions displayed a wider range than manifest lesions. Increasing age and more years in the profession resulted in fewer registered initial caries lesions. Dental hygienists had a tendency to register less caries than dentists. In conclusion, the result of the study indicate that inclusion of initial caries lesions in epidemiological reports should lead to a reduction in reliability. The changes in assessments of manifest caries lesions that took place in the 19805s should be considered when epidemiological data are evaluated.
Di Benedetto, Luisa; Giovanale, Valentina; Caserta, Donatella
Introduction: Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre and post-menopausal women. Previous studies have suggested an increased prevalence of endometrial diseases after treatment with tamoxifen. Case presentation: The authors report a case of 38-year-old woman with diagnosis of endometrial polyp and tubal metaplasia, during puerperium and after micropapillary ductal breast cancer surgery, 5 years of tamoxifen treatment, spontaneous pregnancy without complications and full-term vaginal delivery. Conclusion: Tamoxifen is a safe and reliable treatment of breast cancer, but data suggest an association with endometrial polyps, hyperplasia, metaplasia and carcinoma. One of the most common types of endometrial metaplasia is ciliated tubal metaplasia. It is generally known that endometrial tubal metaplasia is a benign disease. However studies propose endometrial tubal metaplasia to be a potential premalignant endometrial lesion and its association with endometrial hyperplasia and well-differentiated endometrioid carcinoma. We propose close monitoring of patients taking tamoxifen and prompt evaluation of any uterine bleeding or pelvic complaint or abnormal TVUS images. PMID:26261678
Liquid-Based Endometrial Cytology Using SurePath™ Is Not Inferior to Suction Endometrial Tissue Biopsy in Clinical Performance for Detecting Endometrial Cancer Including Atypical Endometrial Hyperplasia.
Yanaki, Fumiko; Hirai, Yasuo; Hanada, Azusa; Ishitani, Ken; Matsui, Hideo
We evaluated the clinical performance of liquid-based endometrial cytology (SurePath™) for detecting endometrial malignancies by comparison with the performance of suction endometrial tissue biopsy. From November 2011 to May 2013, we consecutively collected 1,118 liquid-based endometrial cytology specimens and 674 suction endometrial tissue biopsy specimens. The rate of nonpositive final histology in nonpositive liquid-based endometrial cytology (98.2%) was higher than the rate of nonpositive final histology in nonpositive suction endometrial tissue biopsy (97.0%). None of the clinical performance values of liquid-based endometrial cytology for detecting the endometrial malignancies were statistically inferior to those of the suction endometrial tissue biopsy. When the positivity threshold was more than "atypical endometrial cells of undetermined significance," the rate of positive liquid-based endometrial cytology from cases with a positive final histology (84.5%) was higher than the rate of positive suction endometrial tissue biopsy from cases with a positive final histology (69.8%). However, there were still no significant differences among all the performance values. Our liquid-based endometrial cytology would be more appropriate in various clinical situations as the initial detection tool for endometrial malignancies, rather than suction endometrial tissue biopsy. In addition, it could be used in screening for endometrial malignancies on a broader scale. © 2017 S. Karger AG, Basel.
Baram, A; Ron, I; Kupferminc, M; Inbar, M
Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately.
Paradisi, Roberto; Rossi, Stefania; Scifo, Maria Cristina; Dall'O', Francesca; Battaglia, Cesare; Venturoli, Stefano
To estimate the recurrence rate of patients with endometrial polyps and to evaluate whether the recurrence can be correlated with the histopathologic features of the polyp. Two hundred and eighty-two women with endometrial polyps in both pre- or postmenopausal period and suffering from abnormal uterine bleeding or not were treated by resectoscopic surgery in a tertiary university hospital and were subsequently followed to check for polyp recurrence. Polyp recurrence rate after hysteroscopic surgery and correlation between recurrence and main demographic, hysteroscopic and histopathologic characteristics were analyzed. During mean ± SD follow-up period of 26.3 ± 19.7 months, the overall recurrence rate was high (13.3%) and did not vary (p = NS) with age, parity, weight or other demographic characteristics of the patients or with the hysteroscopic appearance. On the contrary, the histopathologic features showed significant differences between patients with and without polyp recurrence. Recurrence rate was higher (p < 0.001) in women with histopathologically hyperplastic polyps without atypia and lower (p < 0.001) in women with benign polyps. The study shows that after resectoscopic polypectomy, the recurrence rate of endometrial polyps is high (13.3%). Moreover, the hyperplastic polyps without atypia recur more frequently than benign ones. © 2014 S. Karger AG, Basel.
Higgins, Laura M.; Pierce, Mark C.
A compact handpiece combining high resolution fluorescence (HRF) imaging with optical coherence tomography (OCT) was developed to provide real-time assessment of oral lesions. This multimodal imaging device simultaneously captures coregistered en face images with subcellular detail alongside cross-sectional images of tissue microstructure. The HRF imaging acquires a 712×594 μm2 field-of-view at the sample with a spatial resolution of 3.5 μm. The OCT images were acquired to a depth of 1.5 mm with axial and lateral resolutions of 9.3 and 8.0 μm, respectively. HRF and OCT images are simultaneously displayed at 25 fps. The handheld device was used to image a healthy volunteer, demonstrating the potential for in vivo assessment of the epithelial surface for dysplastic and neoplastic changes at the cellular level, while simultaneously evaluating submucosal involvement. We anticipate potential applications in real-time assessment of oral lesions for improved surveillance and surgical guidance.
Higgins, Laura M.; Pierce, Mark C.
Abstract. A compact handpiece combining high resolution fluorescence (HRF) imaging with optical coherence tomography (OCT) was developed to provide real-time assessment of oral lesions. This multimodal imaging device simultaneously captures coregistered en face images with subcellular detail alongside cross-sectional images of tissue microstructure. The HRF imaging acquires a 712×594 μm2 field-of-view at the sample with a spatial resolution of 3.5 μm. The OCT images were acquired to a depth of 1.5 mm with axial and lateral resolutions of 9.3 and 8.0 μm, respectively. HRF and OCT images are simultaneously displayed at 25 fps. The handheld device was used to image a healthy volunteer, demonstrating the potential for in vivo assessment of the epithelial surface for dysplastic and neoplastic changes at the cellular level, while simultaneously evaluating submucosal involvement. We anticipate potential applications in real-time assessment of oral lesions for improved surveillance and surgical guidance. PMID:25104410
Robertson, Keith E; Hennigan, Barry; Berry, Colin; Oldroyd, Keith G
Coronary angiography alone cannot accurately identify the haemodynamic impact of a coronary artery stenosis. Current international guidelines for myocardial revascularization recommend that inducible ischaemia should be demonstrated before the consideration of percutaneous coronary intervention. Invasive physiological assessment of coronary stenosis severity has increasingly been utilized for this purpose and use of the best validated technique, fractional flow reserve (FFR), has been shown to improve clinical outcomes in patients with stable and unstable coronary artery disease. This has led to the use of FFR being recommended in international revascularization guidelines, despite which, clinical uptake has been limited. One potential reason for slow adoption has been the requirement for maximal hyperaemia at the time of FFR measurement, usually achieved by the administration of pharmacological vasodilators such as adenosine. In some healthcare systems, adenosine is expensive and, in addition, its use can be associated with significant, albeit transient, adverse effects that patients (and some operators) find uncomfortable. Consequently, several methods of nonhyperaemic lesion assessment and their potential role in decision making have been reported. In this review we will review and discuss the current evidence for hyperaemic and nonhyperaemic methods of lesion assessment. We will also look at hybrid strategies that utilize both hyperaemic and nonhyperaemic methods as a means of potentially maintaining diagnostic accuracy while minimizing the requirement for adenosine administration and discuss whether or not they represent viable clinical alternatives.
Yang, Dong Hyun; Kim, Namkug; Park, Seung Il; Kim, Dong Kwan; Kim, Ellen Ai-Rhan
Objective We wanted to evaluate the resistance to collateral ventilation in congenital hyperlucent lung lesions and to correlate that with the anatomic findings on xenon-enhanced dynamic dual-energy CT. Materials and Methods Xenon-enhanced dynamic dual-energy CT was successfully and safely performed in eight children (median age: 5.5 years, 4 boys and 4 girls) with congenital hyperlucent lung lesions. Functional assessment of the lung lesions on the xenon map was done, including performing a time-xenon value curve analysis and assessing the amplitude of xenon enhancement (A) value, the rate of xenon enhancement (K) value and the time of arrival value. Based on the A value, the lung lesions were categorized into high or low (A value > 10 Hounsfield unit [HU]) resistance to collateral ventilation. In addition, the morphologic CT findings of the lung lesions, including cyst, mucocele and an accessory or incomplete fissure, were assessed on the weighted-average CT images. The xenon-enhanced CT radiation dose was estimated. Results Five of the eight lung lesions were categorized into the high resistance group and three lesions were categorized into the low resistance group. The A and K values in the normal lung were higher than those in the low resistance group. The time of arrival values were delayed in the low resistance group. Cysts were identified in five lesions, mucocele in four, accessory fissure in three and incomplete fissure in two. Either cyst or an accessory fissure was seen in four of the five lesions showing high resistance to collateral ventilation. The xenon-enhanced CT radiation dose was 2.3 ± 0.6 mSv. Conclusion Xenon-enhanced dynamic dual-energy CT can help visualize and quantitate various degrees of collateral ventilation to congenital hyperlucent lung lesions in addition to assessing the anatomic details of the lung. PMID:21228937
Musin, É Kh; Roman'ko, N A; Makarov, I Iu; Kutsenko, K I
This paper reports the results of analysis of the data obtained in experimental studies and practical expert assessments of body injuries inflicted by rubber balls for traumatic weapons. The causes accounting for the polymorphism of such injuries and the mechanisms of their development were elucidated by means of damage simulation taking into consideration the physical and dynamic properties of elastic ball-type destructive agents and the morphological structure of different anatomical regions of the human body. The results of the study may be of interest for differential diagnostics of gunshot lesions caused by elastic destructive agents.
Nevadunsky, Nicole S; Van Arsdale, Anne; Strickler, Howard D; Moadel, Alyson; Kaur, Gurpreet; Levitt, Joshua; Girda, Eugenia; Goldfinger, Mendel; Goldberg, Gary L; Einstein, Mark H
Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis. A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R=0.049, P<.001). This association persisted after multivariable adjustment (R=0.181, P<.02). A linear association between BMI and age of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis. II.
Yoo, Heon Jong; Lim, Myong Cheol; Son, Yedong; Seo, Sang-Soo; Kang, Sokbom; Kim, Sun Ho; Yoo, Chong Woo; Park, Sang-Yoon
A familial history of ovarian cancer/breast cancer is considered a significant prognostic factor for ovarian cancer. We investigated hereditary factors by examining the incidence of synchronous malignancy in patients with endometrial cancer, and assessed the prognostic role of heredity in endometrial cancer. We retrospectively evaluated patients with endometrial cancer who underwent surgery from January 2001 to April 2011. A hereditary background in this study was defined as double primary cancer, that is, endometrial cancer accompanied by colon, ovarian, or breast cancer suggestive of Lynch syndrome, hereditary breast ovarian cancer syndrome, or Cowden syndrome, respectively. Among 282 patients with endometrial cancer in the study population, 20 patients (7.1%) had a hereditary predisposition: 10 patients (3.5%) had ovarian cancer, six patients (2.1%) had breast cancer, and four patients (1.4%) had colon cancer. Age and lower uterine segment involvement were not statistically different between the hereditary and nonhereditary groups. The majority of the women in the hereditary group presented with Stage I cancer; however, there were no significant differences in Stage I cancer between the hereditary group and the sporadic endometrial cancer group (85% and 77%, respectively, p = 0.561). The median follow-up period was 60 months. A 5-year overall survival rate was not different between the two groups (95% and 95%, respectively, p = 0.659). Among a subgroup of patients with Stage I endometrial cancer, the 5-year overall survival rate was lower in the endometrial cancer with a hereditary predisposition group compared with the sporadic endometrial cancer group (94% and 98%, respectively, p = 0.027). Seven percent of the women with endometrial cancer in our study had other malignancies such as ovarian, colon, or breast cancer synchronously. Among a subgroup of patients with Stage I cancer in the endometrial cancer with a hereditary predisposition group, the 5-year
Polanski, Lukasz T; Baumgarten, Miriam N; Brosens, Jan J; Quenby, Siobhan M; Campbell, Bruce K; Martins, Wellington P; Raine-Fenning, Nick J
Our aim in the study described here was to assess the feasibility of spatiotemporal image correlation power Doppler quantification of the endometrium with two techniques: spherical samples and whole tissue. We scanned 51 women in the midluteal phase of the menstrual cycle: STIC assessment of the whole endometrium was not possible in 10% of cases, whereas spherical analysis was possible in all. The time taken for data set analysis was much longer for the whole endometrium compared with spherical analysis (1478.9 ± 291 s vs. 266.8 ± 39.3 s, p < 0.05). Intra-class correlation coefficients for the vascularization flow index (VFI) were similar for both methods. Volumetric vascularity indices were higher when spherical sampling was conducted. Significant cycle-to-cycle variability in the vascularity indices was present, with coefficients of variation exceeding 20% for both techniques. We found that STIC power Doppler quantification of the whole endometrium is possible in the majority of cases, however, it is time consuming and limited by significant cycle-to-cycle variability. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
Li, S C; Liebling, M S; Haines, K A; Weiss, J E; Prann, A
To evaluate the construct validity of 2 proposed measures (the Ultrasound Disease Activity [U-DA] and the Tissue Thickness Score [TTS]) for evaluating sonographic differences in juvenile localized scleroderma skin lesions. We conducted a retrospective review of juvenile localized scleroderma patients who had ultrasound scans of their skin lesions between October 2005 and February 2009. Imaged lesions were classified as active or inactive based upon clinical assessment. Lesions had to have been imaged within 1 month of a clinic visit or have the same clinical assessment during both the visit before and the visit after the scan. Two physicians scored the scans using the U-DA, which scores for differences in lesion echogenicity and vascularity compared with normal tissue. Tissue thickness differences were evaluated by percent differences and by using the TTS. Wilcoxon's rank sum test was performed to assess differences. We studied 52 scans from 21 patients, 32 scans of active skin lesions and 20 scans of inactive skin lesions. Features reported by clinicians as indicative of active disease included erythema, warmth, violaceous color, new lesion, expansion of lesion, and induration. The U-DA was significantly different between active and inactive skin lesions (P = 0.0010) with significant differences found for the parameters of total echogenicity, hypodermis echogenicity, and deep tissue layer vascularity (P = 0.0014, P = 0.0023, and P = 0.0374, respectively). No significant differences were found for tissue layer thickness or TTS. The U-DA may be a useful tool in the identification of localized scleroderma activity. Further study is needed to prospectively evaluate the validity, reliability, and sensitivity of this potential monitoring tool. Copyright © 2011 by the American College of Rheumatology.
Mederos, Michael A; Villafañe, Nicole; Dhingra, Sadhna; Farinas, Carlos; McElhany, Amy; Fisher, William E; Van Buren II, George
Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are exceedingly rare lesions that are difficult to diagnose pre-operatively. This report describes the findings in a 43-year-old patient with a recent episode of acute pancreatitis who presented with a large cyst in the tail of the pancreas. Imaging demonstrated a loculated pancreatic cyst, and cyst fluid aspiration revealed an elevated amylase and carcinoembryonic antigen. The patient experienced an interval worsening of abdominal pain, fatigue, diarrhea, and a 15-pound weight loss 3 mo after the initial episode of pancreatitis. With concern for a possible pre-malignant lesion, the patient underwent a laparoscopic distal pancreatectomy with splenectomy, which revealed a 16 cm × 12 cm × 4 cm lesion. Final histopathology was consistent with an intra-pancreatic endometrial cyst. Here we discuss the overlapping imaging and laboratory features of pancreatic endometrial cysts and mucinous cystic neoplasms of the pancreas. PMID:28246486
Düzgüner, Soner; Ozkan, Mehmet Burak; Küçüközkan, Tuncay; Ozkaya, Enis; Kara, Fadıl; Balın, Ipek Nur; Korkmaz, Vakkas; Karslı, Mehmet Fatih; Gültekin, Burak
The purpose of this study was to determine the value of endometrial blood flow assessment in predicting type 2 endometrial carcinoma. Sixty-five consecutive post-menopoausal women who had vaginal bleeding were enrolled in the study. All subjects were directed to transvaginal sonography to determine endometrial blood flow and underwent endometrial biopsy. Doppler findings were analysed to predict endometrial pathology. Subjects with unsatisfactory Doppler analyses were excluded from the study. Mean age of the study population was 50.1±6.9 years (42-73). Mean endometrial thickness was 10.1±2.9 mm (4-15 mm) and mean cancer antigen 125 (CA125) level was 20.1±17.4 U/mL (3-92). Histopathological evaluation revealed 14 cases of type 2 endometrial cancer and 18 cases of endometrial hyperplasia without atypia, while the other 33 cases had normal endometrial tissue. CA125 (Area under curve (AUC)=0.853, p=0.000), spiral artery resistance index (AUC=0.905, p=0.000), and spiral artery peak systolic velocity (AUC=0.822, p=0.000) were significant predictors for the type 2 endometrial cancer cases. Endometrial thickness did not significantly predict pathologic cases (p>0.05). Hyperplasia cases were not predicted by any of these diagnostic modalities (p>0.05). In patients with postmenopausal bleeding, spiral artery Doppler ultrasound, could play a role in refining the diagnosis of type 2 endometrial carcinoma; however, its predictive value should be evaluated with further studies.
Drukker, K.; Giger, M. L.
We developed a self-assessment method in which the CADx system provided a confidence level for its lesion segmentations. The self-assessment was performed by a fuzzy-inference system based on 4 computer-extracted features of the computer-segmented lesions in a leave-one-case-out evaluation protocol. In instances where the initial segmentation received a low assessment rating, lesions were re-segmented using the same segmentation method but based on a user-defined region-of-interest. A total of 542 cases with 1133 lesions were collected in this study, and we focused here on the 97 normal lymph nodes in this dataset since these pose challenges for automated segmentation due to their inhomogeneous appearance. The percentage of all lesions with satisfactory segmentation (i.e., normalized overlap with the radiologist-delineated lesion >=0.3) was 85%. For normal lymph nodes, however, this percentage was only 36%. Of the lymph nodes, 53 received a low confidence rating (<0.3) for their initial segmentation. When those lymph nodes were re-segmented, the percentage with a satisfactory segmentation improved to 80.0%. Computerassessed confidence levels demonstrated potential to 1) help radiologists decide whether to use or disregard CADx output, and 2) provide a guide for improvement of lesion segmentation.
Liang, Lusha W.; Perez, Alexendar R.; Cangemi, Nicholas A.; Zhou, Qin; Iasonos, Alexia; Abu-Rustum, Nadeem; Alektiar, Kaled M.; Makker, Vicky
Objective To determine clinical outcomes in patients with stage IA polyp-limited versus endometrium-limited high-grade (type II) endometrial carcinoma (EC). Methods We identified all cases of stage IA polyp-limited or endometrium-limited high-grade EC (FIGO Grade 3 endometrioid, Serous, Clear Cell, or Mixed) who underwent simple hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and paraaortic lymph node dissection and received adjuvant treatment at our institution from 10/1995–11/2012. Progression-free survival (PFS) and overall survival (OS) by histology, adjuvant therapy, and polyp-limited vs endometrium-limited disease status were determined using log-rank test. We analyzed three treatment groups: patients who received chemotherapy with or without Radiation Therapy (RT) (intravaginal or pelvic); patients who received RT (intravaginal RT or pelvic RT) alone; and patients who received no adjuvant treatment. Results In all, 85 women underwent hysterectomy/salpingo-oophorectomy; all were surgically staged with lymph node assessment and had stage IA EC with no lymphovascular or myometrial invasion. Median follow-up for survivors was 46.5 months (range, 1.98–188.8 months). Forty-nine patients (57.6%) had polyp-limited disease and 36 (42.4%) had endometrium-limited disease. There were no significant differences in clinicopathologic characteristics between patients within the three treatment groups with regards to age at diagnosis, mean BMI, ECOG performance status, polyp-limited, endometrium-limited disease, diabetes, or race. The 3-year PFS rate was 94.9% and the 3-year OS rate was 98.8%. Univariate PFS and OS analysis revealed that age was a relevant prognostic factor [(PFS:HR (95%CI):1.13(1.02–1.25); P=0.022 and OS HR (95%CI):1.19(1.02–1.38); P=0.03]. Adjuvant treatment did not impact outcomes. Conclusions Clinical outcomes of surgical stage IA, type II polyp- or endometrium-limited high-grade epithelial EC are
Zhou, Qian; Cheng Tang; Zhao, Ke-Wei; Xiong, Yan-Li; Chen, Shu; Xu, Wen-Jing; Lei, Xin
OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I–III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range. PMID:26872078
Zhou, Qian; Tang, Cheng; Zhao, Ke-Wei; Xiong, Yan-Li; Chen, Shu; Xu, Wen-Jing; Lei, Xin
The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.
Moreno, Inmaculada; Franasiak, Jason M
Detection of bacteria with molecular techniques has enabled the study of low biomass microbiomes in tissues and organs previously considered sterile, such as the endometrium. Subsequently, an abnormal endometrial microbiota has been associated with implantation failure, pregnancy loss, and other gynecological and obstetrical conditions. Further investigation of the reproductive tract microbiome will allow for a better understanding of bacterial communities' role in both physiology and pathophysiology, which in turn impacts the ability to achieve pregnancy and maintain a healthy pregnancy. Here we review the current literature that surrounds the endometrial microbiome and highlight the importance of assessing it as a future tool for improving reproductive outcomes in infertile patients. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Rubinacci, A; Tresoldi, D; Villa, I; Rizzo, G; Gaudio, D; De Angelis, D; Gibelli, D; Cattaneo, C
Peripheral quantitative computed tomography (pQCT) has found new fields of application in bone medicine, but none of them concerns the forensic practice. This study exposes the potential of pQCT applied to a penetrating lesion in a vertebral body. A pQCT scanner was used for the measurements (XCT Research SA+; Stratec Medizintechnik GmbH, Pforzheim, Germany). A more precise reconstruction of the path of the lesion within the trabecular bone was reached, with more details concerning the morphological characteristics of the lesion inside the vertebral body, and the elaboration of a 3D model was created, which allowed the operator to define the volume of the lack of tissues related to the lesion. The application of pQCT scan proved to be a potentially useful tool for the assessment of bone lesions, although further studies are needed in order to verify its applicability to forensic context.
Chapados, Catherine; Petrides, Michael
The Frontal Assessment Battery is a set of six subtests that is used widely to assess frontal cortical executive dysfunction. Performance on the Frontal Assessment Battery has been shown to be sensitive to various neurodegenerative diseases, but it has never been shown to be sensitive to damage restricted to the frontal cortex. Thus, despite its wide use, it has never been validated on an appropriate population of patients with frontal lesions. The present study shows that, of the six subtests that comprise the Frontal Assessment Battery, only performance on the verbal fluency subtest (mental flexibility) was specifically sensitive to injury restricted to the frontal cortex. Performance of patients with damage to the dorsal part of the medial frontal region in the language-dominant left hemisphere was impaired. None of these patients was aphasic at the time of testing. The critical region in the dorsomedial frontal cortex includes the supplementary speech zone but is not restricted to it: it extends into the cingulate motor region and the paracingulate cortex as well as the medial prefrontal areas 8 and 9. The results indicate that the Frontal Assessment Battery is not a sensitive measure of prefrontal cortical dysfunction, except for the verbal fluency subtest.
Kasasbeh, Aimen S; Christensen, Søren; Straka, Matus; Mishra, Nishant; Mlynash, Michael; Bammer, Roland; Albers, Gregory W; Lansberg, Maarten G
The minimal scan duration needed to obtain reliable lesion volumes with computed tomographic perfusion (CTP) has not been well established in the literature. We retrospectively assessed the impact of gradual truncation of the scan duration on acute ischemic lesion volume measurements. For each scan, we identified its optimal scan time, defined as the shortest scan duration that yields measurements of the ischemic lesion volumes similar to those obtained with longer scanning, and the relative height of the fitted venous output function at its optimal scan time. We analyzed 70 computed tomographic perfusion scans of acute stroke patients. An optimal scan time could not be determined in 11 scans (16%). For the other 59 scans, the median optimal scan time was 32.7 seconds (90th percentile 52.6 seconds; 100th percentile 68.9 seconds), and the median relative height of the fitted venous output function at the optimal scan times was 0.39 (90th percentile 0.02; 100th percentile 0.00). On the basis of a linear model, the optimal scan time was T0 plus 1.6 times the width of the venous output function (P<0.001; R(2)=0.49). This study shows how the optimal duration of a computed tomographic perfusion scan relates to the arrival time and width of the contrast bolus. This knowledge can be used to optimize computed tomographic perfusion scan protocols and to determine whether a scan is of sufficient duration. Provided a baseline (T0) of 10 seconds, a total scan duration of 60 to 70 seconds, which includes the entire downslope of the venous output function in most patients, is recommended. © 2016 American Heart Association, Inc.
Espigares, Jorge; Sadr, Alireza; Hamba, Hidenori; Shimada, Yasushi; Otsuki, Masayuki; Tagami, Junji; Sumi, Yasunori
Abstract. A technology to characterize early enamel lesions is needed in dentistry. Optical coherence tomography (OCT) is a noninvasive method that provides high-resolution cross-sectional images. The aim of this study is to compare OCT with microfocus x-ray computed tomography (μCT) for assessment of natural enamel lesions in vitro. Ten human teeth with visible white spot-like changes on the enamel smooth surface and no cavitation (ICDAS code 2) were subjected to imaging by μCT (SMX-100CT, Shimadzu) and 1300-nm swept-source OCT (Dental SS-OCT, Panasonic Health Care). In μCT, the lesions appeared as radiolucent dark areas, while in SS-OCT, they appeared as areas of increased signal intensity beneath the surface. An SS-OCT attenuation coefficient based on Beer–Lambert law could discriminate lesions from sound enamel. Lesion depth ranged from 175 to 606 μm in SS-OCT. A correlation between μCT and SS-OCT was found regarding lesion depth (R=0.81, p<0.001) and also surface layer thickness (R=0.76, p<0.005). The images obtained clinically in real time using the dental SS-OCT system are suitable for the assessment of natural subsurface lesions and their surface layer, providing comparable images to a laboratory high-resolution μCT without the use of x-ray. PMID:26158079
Espigares, Jorge; Sadr, Alireza; Hamba, Hidenori; Shimada, Yasushi; Otsuki, Masayuki; Tagami, Junji; Sumi, Yasunori
A technology to characterize early enamel lesions is needed in dentistry. Optical coherence tomography (OCT) is a noninvasive method that provides high-resolution cross-sectional images. The aim of this study is to compare OCT with microfocus x-ray computed tomography ([Formula: see text]) for assessment of natural enamel lesions in vitro. Ten human teeth with visible white spot-like changes on the enamel smooth surface and no cavitation (ICDAS code 2) were subjected to imaging by μCT (SMX-100CT, Shimadzu) and 1300-nm swept-source OCT (Dental SS-OCT, Panasonic Health Care). In [Formula: see text], the lesions appeared as radiolucent dark areas, while in SS-OCT, they appeared as areas of increased signal intensity beneath the surface. An SS-OCT attenuation coefficient based on Beer-Lambert law could discriminate lesions from sound enamel. Lesion depth ranged from 175 to [Formula: see text] in SS-OCT. A correlation between [Formula: see text] and SS-OCT was found regarding lesion depth ([Formula: see text], [Formula: see text]) and also surface layer thickness ([Formula: see text], [Formula: see text]). The images obtained clinically in real time using the dental SS-OCT system are suitable for the assessment of natural subsurface lesions and their surface layer, providing comparable images to a laboratory high-resolution [Formula: see text] without the use of x-ray.
Seo, InSeok; Bargo, Paulo R; Kollias, Nikiforos
We present a simple and cost-effective optical technique for the simultaneous assessment of pulsating and total blood noninvasively in an inflammatory skin lesion. Acquisitions of diffuse reflectance spectra in the visible range at 6 Hz are used to trace the oscillating components of reflectance. Measurements on erythematous lesions from a UV insult show slow changing signal at about 0.1 Hz and heart-driven regular oscillations at about 1 Hz simultaneously. The results demonstrate the potential of the technique in monitoring both pulsating and steady components of the blood in inflammatory lesions of the skin.
Billingsley, Caroline C; Kenne, Kimberly A; Cansino, Catherine D; Backes, Floor J; Cohn, David E; O'Malley, David M; Copeland, Larry J; Fowler, Jeffrey M; Salani, Ritu
To determine the use of the transvaginal ultrasound (TVUS) in postmenopausal women with type II endometrial cancer. A retrospective review was conducted for 173 women with pathology proven type II endometrial cancer at a single institution. Those who underwent preoperative TVUS were included, and the following data were obtained: endometrial stripe (EMS) measurement, uterine and/or adnexal findings, and uterine size/volume. Clinicopathologic factors were abstracted. Descriptive and regression analyses were performed. Fifty-eight women comprised the cohort, and the median age was 66.5 years (50-85 years). The most commonly reported symptom was postmenopausal bleeding in 53 patients (91.4%). The EMS was reported as thin (≤ 5 mm) or indistinct in 16 patients (27.5%). Approximately 60% of patients had 1 or more ultrasound abnormalities: intracavitary mass (31%), intracavitary fluid (12.1%), myometrial lesion (31.03%), and adnexal mass (12.1%). Poorly differentiated endometrioid cancer (53.45%) represented the predominant histology. Of the 16 (27.5%) women with a thin/indistinct EMS, 5 women (8.6%) did not have any abnormal ultrasound findings whatsoever. Women with type II endometrial cancer had a thin/indistinct EMS on TVUS in approximately 25% of cases. Lack of any ultrasound abnormality, including a thickened EMS, was noted in approximately 10% of patients. The use of TVUS, which has been of value in type I cancer, is limited in type II endometrial cancer. Therefore, endometrial sampling should be included in the evaluation of all women with postmenopausal bleeding, regardless of EMS thickness.
Chan, Heang-Ping; Goodsitt, Mitchell M; Helvie, Mark A; Hadjiiski, Lubomir M; Lydick, Justin T; Roubidoux, Marilyn A; Bailey, Janet E; Nees, Alexis; Blane, Caroline E; Sahiner, Berkman
An observer performance study was conducted to evaluate the usefulness of assessing breast lesion characteristics with stereomammography. Stereoscopic image pairs of 158 breast biopsy tissue specimens were acquired with a GE Senographe 2000D full field digital mammography system using a 1.8x magnification geometry. A phantom-shift method equivalent to a stereo shift angle of +/- 3 degrees relative to a central axis perpendicular to the detector was used. For each specimen, two pairs of stereo images were taken at approximately orthogonal orientations. The specimens contained either a mass, microcalcifications, both, or normal tissue. Based on pathological analysis, 39.9% of the specimens were found to contain malignancy. The digital specimen radiographs were displayed on a high resolution MegaScan CRT monitor driven by a DOME stereo display board using in-house developed software. Five MQSA radiologists participated as observers. Each observer read the 316 specimen stereo image pairs in a randomized order. For each case, the observer first read the monoscopic image and entered his/her confidence ratings on the presence of microcalcifications and/or masses, margin status, BI-RADS assessment, and the likelihood of malignancy. The corresponding stereoscopic images were then displayed on the same monitor and were viewed through stereoscopic LCD glasses. The observer was free to change the ratings in every category after stereoscopic reading. The ratings of the observers were analyzed by ROC methodology. For the 5 MQSA radiologists, the average Az value for estimation of the likelihood of malignancy of the lesions improved from 0.70 for monoscopic reading to 0.72 (p=0.04) after stereoscopic reading, and the average Az value for the presence of microcalcifications improved from 0.95 to 0.96 (p=0.02). The Az value for the presence of masses improved from 0.80 to 0.82 after stereoscopic reading, but the difference fell short of statistical significance (p=0.08). The visual
Matsumoto, Simone Ferreira Borges; Motta, Lara Jansiski; Alfaya, Thays Almeida; Guedes, Carolina Cardoso; Fernandes, Kristianne Porta Santos; Bussadori, Sandra Kalil
Chemomechanical removal of carious lesions consists of the dissolution of carious tissue by the application of a natural or synthetic agent, followed by atraumatic mechanical removal. The aim of the present study was to assess the effectiveness of Papacarie Duo ® gel in the chemomechanical removal of carious lesions in primary teeth in comparison to the traditional method (low-speed bur). A randomized clinical trial was conducted with 20 children between 5 and 8 years of age. Two teeth were treated in each child (split-mouth design), with the randomization of two methods: Group 1 - chemomechanical caries removal with Papacarie Duo™; and Group 2 - removal of carious dentin tissue using a low-speed bur. Both methods involved restoration with glass ionomer cement and follow up. The following aspects were evaluated: time required for the procedure; pain (face evaluation scale); retention of the restorative material in the cavity; and the presence of secondary caries after 30 days. Chi-squared test, Student's t-test, and Wilcoxon test. No statistically significant differences between methods were found regarding time required for the procedure (P = 0.13), the occurrence of pain (P = 0.585), or restoration status at the 30-day clinical evaluation (P = 0.713). The findings of the present study demonstrate that the two methods achieve similar results. The advantages of minimally invasive treatment, such as chemomechanical caries removal with Papacarie Duo™, are its ease of use, patient comfort, and the fact that it causes less damage to dental tissue.
Pickering, J G; Boughner, D R
Reliable histologic methods for gauging the maturity of fibrotic lesions are limited, making interventions in the healing process difficult to assess. As collagen ages there is enhanced birefringence due to increased molecular and fibrillar organization. The purpose of this study was to develop a microscopal technique to quantify this process and to determine its ability to distinguish scars of varying ages. Fibrosis in the rat gracilis muscle was studied 5 to 63 days after superficial injury. Sections were stained with picrosirius red and illuminated with monochromatic, polarized light. The microscope fields were digitized using a computer-video system yielding an image in which noncollagenous material was dark (gray level 0) and collagen was depicted by grey levels 1 to 255. In the fibrosis model used, the collagen area fraction plateaued at 80% by day 21. The median collagen grey level increased progressively as the scar aged. It is concluded that this histologic, nondestructive technique can reliably quantify age-related optical properties of fibrotic collagen and that this could be used to determine the maturity of fibrotic lesions.
Vaziri, Sana; Lafontaine, Marisa; Olson, Beck; Crane, Jason C.; Chang, Susan; Lupo, Janine; Nelson, Sarah J.
The increasing interest in enhancing the RANO criteria by using quantitative assessments of changes in lesion size and image intensities has highlighted the need for rapid, easy-to-use tools that provide DICOM compatible outputs for evaluation of patients with glioma. To evaluate the performance of the SmartBrush software (Brainlab AG), which provides computer-assisted definitions of regions of interest (ROIs), a cohort of 20 patients with glioma (equal number having high and low grade and treated and un-treated) were scanned using a 3T whole-body MR system prior to surgical resection. The T2-weighted FLAIR, pre- and post-contrast T1-weighted gradient echo DICOM images were pushed from the scanner to an offline workstation where analysis of lesion volumes was performed using SmartBrush. Volumes of the T2Ls ranged from 7.9 to 110.2cm3 and the volumes of the CELs was 0.1 to 28.5 cm3 with 19/20 of the subjects having CELs and all 20 having T2Ls. the computer-assisted analysis was performed rapidly and efficiently, with the mean time for defining both lesions per subject was 5.77 (range 3.5 to 7.5) minutes. Prior analysis of ROIS with the SLICER package (www.slicer.org) took approximately 30 minutes/subject. SmartBrush provides lesion volumes and cross-sectional diameter as a PDF report, which can be stored in DICOM. The ROIs were also saved as DICOM objects and transferred to other packages for performing histogram analysis from ADC or other functional parameter maps. Ongoing studies that will be reported in this presentation are performing a similar analysis with multiple users in order to compare the relative intra- and inter-operator variations in terms of both the speed of analysis and the ROIs that are identified. Acknowledgements: The authors would like to acknowledge Rowena Thomson and Natalie Wright from Brainlab for helping to set up this study.
Papafaklis, Michail I; Mavrogiannis, Michail C; Siogkas, Panagiotis K; Lakkas, Lampros S; Katsouras, Christos S; Fotiadis, Dimitrios I; Michalis, Lampros K
Hemodynamic indices derived from measurements with the pressure wire (primarily fractional flow reserve [FFR]) have been established as a reliable tool for assessing coronary stenoses and improving clinical decision making. However, the use of the pressure wire constitutes a hurdle for the universal adoption of physiology-guided patient management. Technological advancements have enabled the large-scale application of blood flow simulation (computational fluid dynamics [CFD]) to medical imaging, thereby enabling the virtual assessment of coronary physiology. Areas covered: This review summarizes the stand-alone non-invasive (coronary computed tomographic imaging) and invasive (coronary angiography) imaging approaches which were initially used for predicting FFR, and focuses on the use of blood flow modeling for functional assessment of coronary lesions in clinical practice. Expert commentary: Validation studies of CFD-derived methodologies for functional assessment have shown that virtual indices correlate well and have good diagnostic accuracy compared to pressure wire-FFR despite inherent limitations of spatial resolution and assumptions regarding boundary conditions in flow modeling. Beyond point-to-point agreement with FFR, further studies are needed to demonstrate the clinical safety/efficacy of these computational tools regarding patient outcomes. Such evidence base could support the incorporation of these methodologies into routine patient management for decision making and reliable risk stratification.
Gundreddy, Rohith Reddy; Tan, Maxine; Qiu, Yuchen; Cheng, Samuel; Liu, Hong; Zheng, Bin
To develop a new computer-aided diagnosis (CAD) scheme using a content-based image retrieval (CBIR) approach for classification between the malignant and benign breast lesions depicted on the digital mammograms and assess CAD performance and reproducibility. An image dataset including 820 regions of interest (ROIs) was used. Among them, 431 ROIs depict malignant lesions and 389 depict benign lesions. After applying an image preprocessing process to define the lesion center, two image features were computed from each ROI. The first feature is an average pixel value of a mapped region generated using a watershed algorithm. The second feature is an average pixel value difference between a ROI's center region and the rest of the image. A two-step CBIR approach uses these two features sequentially to search for ten most similar reference ROIs for each queried ROI. A similarity based classification score was then computed to predict the likelihood of the queried ROI depicting a malignant lesion. To assess the reproducibility of the CAD scheme, we selected another independent testing dataset of 100 ROIs. For each ROI in the testing dataset, we added four randomly queried lesion center pixels and examined the variation of the classification scores. The area under the ROC curve (AUC) = 0.962 ± 0.006 was obtained when applying a leave-one-out validation method to 820 ROIs. Using the independent testing dataset, the initial AUC value was 0.832 ± 0.040, and using the median classification score of each ROI with five queried seeds, AUC value increased to 0.878 ± 0.035. The authors demonstrated that (1) a simple and efficient CBIR scheme using two lesion density distribution related features achieved high performance in classifying breast lesions without actual lesion segmentation and (2) similar to the conventional CAD schemes using global optimization approaches, improving reproducibility is also one of the challenges in developing CAD schemes using a CBIR based regional
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.
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.
Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Stage III Uterine Corpus Cancer
Sun, Z; Wang, Y; Ji, S; Wang, K; Zhao, Y
Body surface area is important in determining the severity of psoriasis. However, objective, reliable, and practical method is still in need for this purpose. We performed a computer image analysis (CIA) of psoriatic area using the image J freeware to determine whether this method could be used for objective evaluation of psoriatic area. Fifteen psoriasis patients were randomized to be treated with adalimumab or placebo in a clinical trial. At each visit, the psoriasis area of each body site was estimated by two physicians (E-method), and standard photographs were taken. The psoriasis area in the pictures was assessed with CIA using semi-automatic threshold selection (T-method), or manual selection (M-method, gold standard). The results assessed by the three methods were analyzed with reliability and affecting factors evaluated. Both T- and E-method correlated strongly with M-method, and T-method had a slightly stronger correlation with M-method. Both T- and E-methods had a good consistency between the evaluators. All the three methods were able to detect the change in the psoriatic area after treatment, while the E-method tends to overestimate. The CIA with image J freeware is reliable and practicable in quantitatively assessing the lesional of psoriasis area. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
McGrath, Monica; Lee, I-Min; Buring, Julie; De Vivo, Immaculata
Objective The insulin-like growth factor (IGF) pathway plays a critical role in the growth and development of the uterus and is believed to function as a mediator of steroid hormone actions in the endometrium. The local expression of genes encoding IGFs and IGF-binding proteins (IGFBPs) are important in determining IGF bioactivity in the uterus. Genetic variation in key genes within the IGF pathway may influence the rate of cellular proliferation and differentiation in the uterus and ultimately affect the risk of endometrial cancer. Our hypothesis is that variant alleles in key genes involved in the IGF pathway will influence the development of endometrial cancer. Methods We conducted a case-control study nested within the Nurses’ Health Study (NHS) and the Women's Health Study (WHS) to investigate the association between forty-four polymorphisms within IGFI, IGFII, IGFBP-1, and IGFBP-3 with endometrial cancer risk using 692 invasive endometrial cancer cases and 1723 matched controls. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the risk of endometrial cancer. Results We observed an inverse association with IGFII rs3741211 and endometrial cancer risk (OR = 0.79 (95% CI: 0.63, 0.99)) and IGFII rs1004446 and endometrial cancer risk (OR = 0.80 (95% CI: 0.68, 0.94)). We also observed an inverse association with IGFBP-3 rs2453839 and endometrial cancer risk (OR= 0.81 (95%CI: 0.67, 0.98). However, we did not observe any statistically significant associations with the polymorphisms in IGFI and IGFBP1 and endometrial cancer risk. Conclusions Genetic variation with IGFII and IGFBP-3 may influence endometrial cancer risk in Caucasians. Polymorphisms in IGFI and IGFBP-1 were not associated with endometrial cancer risk, but further research is needed. PMID:21078522
Babayev, Samir N; Park, Chan Woo; Keller, Patrick W; Carr, Bruce R; Word, Ruth A; Bukulmez, Orhan
Androgenic compounds have been implicated in induction of endometrial atrophy yet the mechanisms of androgen effects on human endometrium have not been well studied. We hypothesized that androgens may promote their endometrial effects via modulation of progesterone receptor (PR) expression. Proliferative phase endometrial samples were collected at the time of hysterectomy. We evaluated the effect of the potent androgen 5α-dihydrotestosterone (DHT) on endometrial PR expression by treating human endometrial explants, endometrial stromal cells, and Ishikawa cells with DHT. Ishikawa cells were also treated with DHT ± the androgen receptor (AR) blocker flutamide. The PR-B, total PR messenger RNA (mRNA), and PR protein expression were assessed. Expression of cyclin D1 and D2 was checked as markers of cell proliferation. As expected, estradiol induced PR expression in isolated stromal cells, endometrial epithelial cells, and tissue explants. The DHT treatment also resulted in increased PR expression in endometrial explants and Ishikawa cells but not in stromal cells. Further, protein levels of both nuclear PR isoforms (PR-A and PR-B) were induced with the DHT treatment. Although flutamide treatment alone did not affect PR expression, flutamide diminished androgen-induced upregulation of PR in both endometrial explants and Ishikawa cells. Although estradiol induced both cyclin D1 and cyclin D2 mRNA, DHT did not induce these markers of cell proliferation. Androgens may mediate endometrial effects through upregulation of PR gene and protein expression. Endometrial PR upregulation by androgens is mediated, at least in part, through AR.
Yatabe, Salete; Pereira, Ana Maria Gomes; Takeda, Gilberto Kendi; Depes, Daniela de Baptista; Lopes, Reginaldo Guedes Coelho
To assess the value of diagnostic hysteroscopy with biopsy in the preoperative preparation for endometrial ablation. It was a prospective non-randomized study conducted at the division of Gynecologic Endoscopy of Hospital do Servidor Público Estadual "Francisco Morato de Oliveira" from March 2007 to May 2009. A total of 45 patients with abnormal uterine bleeding, and referred to endometrial ablation were included. All women underwent a diagnostic hysteroscopy, and were treated with a GnRH analogous - goserelin - 10.8 mg before surgery. The endometrial ablation was performed with a surgical resectoscope. Patients were submitted to one directed endometrial biopsy, one guided endometrial biopsy with Novak curette, and to endometrial ablation, which was considered as reference for pathological examination with samples from the biopsies. Data were analyze using the SPSS-v16 software, and considered significance at p = 0.05. The mean age of women was 44.20 years (33-56), parity of 2.67 (0-9), uterus size of 139.99 calculated in cc (42-278), and the mean duration of symptoms was 3.68 years (0.5-15). The guided endometrial biopsy showed sensitivity of 80% for endometrium without atypia, and the directed endometrial biopsy had sensitivity of 60%. For proliferative endometrium the directed endometrial biopsy showed sensitivity of 76 and 100% for secretory endometrium, which was higher than the guided endometrial biopsy with 53 and 50%, respectively. The directed biopsy before endometrial ablation had lower sensitivity than guided biopsy for endometrium without atypia, however it was higher for proliferative and secretory endometrium.
Park, Jin-Young; Noh, Young-Min; Chung, Seok-Won; Moon, Sung-Gyn; Ha, Dae-Ho; Lee, Ki-Sun; Chung, Seok Won
The purpose of this study was to evaluate the characteristics of Bennett lesions in baseball players compared with those without a Bennett lesion and to identify other possible factors associated with Bennett lesions on magnetic resonance imaging (MRI). We investigated 388 male baseball players with a career >1 year. Demographic factors and a routine physical examination, including glenohumeral internal rotation difference, scapular dyskinesis, and various pathologic changes, were reviewed on MRI to identify relative factors for Bennett lesions. Of the 388 patients evaluated, 125 (32.2%) were diagnosed with Bennett lesions of the shoulder. No significant differences were observed between the groups in demographic factors, physical examination results, visual analog scale score, American Shoulder and Elbow Surgeons score, or prevalence of concomitant diseases. However, players with Bennett lesions had played baseball longer than those without the lesions (P < .001). An association was found between Bennett lesions and the length of time that a patient with a Bennett lesion had played baseball. The prevalence of pathologic lesions detected on MRI and the physical examination results were not different between players with and without Bennett lesions. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.
Wagemakers, Harry P; Luijsterburg, Pim A; Boks, Simone S; Heintjes, Edith M; Berger, Marjolein Y; Verhaar, Jan A; Koes, Bart W; Bierma-Zeinstra, Sita M
To assess the diagnostic accuracy of history taking and physical examination for assessing anterior cruciate ligament (ACL) lesions in primary care. Cross-sectional diagnostic study. Primary care. Patients (N=134; age, 18-65y) who consulted their general practitioner (GP) within 5 weeks after injury. Not applicable. Index tests were obtained with a questionnaire and physical examination. Magnetic resonance imaging (MRI) was used as the reference test. Logistic regression analysis was used to determine associations with ACL lesions. Diagnostic accuracy was determined by calculating sensitivity (Se), specificity (Sp), predictive values, and likelihood ratio (LR). MRI showed an ACL lesion in 28 of 134 included patients. "Effusion," "popping sensation," "giving way," and "anterior drawer test (ADT)" showed associations with an ACL lesion (P<.05). Popping sensation showed Se, Sp, positive predictive value (PPV), and positive LR (LR(+)) of .63, .73, .39, and 2.3, respectively. Combining determinants from history taking (2 of 3 positive results regarding effusion, popping sensation, and giving way) improved diagnostic accuracy (Se, .71; Sp, .71; PPV, .42; and LR(+), 2.5). The ADT added diagnostic accuracy to these combinations (Se, .63; Sp, .85; PPV, .52; and LR(+), 4.2). ACL lesions are seen frequently. Based on history taking (effusion, popping sensation, and/or giving way) and physical examination (ADT), GPs can screen for ACL lesions in primary care.
Gliem, Michael; Panayotopoulos, Dimitris; Feindt, Peter; Heikaus, Sebastian; Fleisch, Markus C.; Seitz, Rüdiger J.
We report a 66-year-old woman with slowly progressive ataxia due to cerebellar atrophy. Imaging studies revealed multiple lesions in both the lungs and dorsal subpleural space. A biopsy identified the lesions as metastases of a low-grade endometrial stromal sarcoma containing sex-cord elements. The histological appearance was identical to a uterine tumor the patient was treated for with hysterectomy 16 years before. The metastases were removed surgically, and after 3 months ataxia had regressed. We conclude that the presenting cerebellar degeneration in this patient resulted from the metastatic recurrence of the endometrial tumor. PMID:21490714
Zeichner, S.J.; Ruttimann, U.E.; Webber, R.L.
In this investigation the efficacy of dental radiography for the detection of occult intraosseous lesions of the face and jaws was evaluated. An analysis of 30 million health insurance records indicated that the period prevalence of malignant lesions was less than 5 cases/million/year, and for benign lesions approximately 100 cases/million/year. Data from a controlled observer-performance study showed that radiographic sensitivities ranged between 50% and 80%. The cost per true-positive finding was estimated to be +8.6 million per malignant case and +430,000 per benign case. An assessment of the dosimetric literature indicated that the benefits of radiographic screening as a means for early detection of a malignancy appear to be counterbalanced by the risk of causing a radiation-induced malignancy. Taken together, these data demonstrate that dental radiography is not efficacious for the purpose of detecting occult lesions.
Chandra, Vishal; Kim, Jong Joo; Benbrook, Doris Mangiaracina; Dwivedi, Anila; Rai, Rajani
Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.
Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH. PMID:26463434
... Transvaginal ultrasound Endometrial sampling Tests are used to screen for different types of cancer. Some screening tests ... endometrium by inserting a brush, curette , or thin, flexible tube through the cervix and into the uterus. ...
This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.
Kalatzis-Sousa, N G; Spin-Neto, R; Wenzel, A; Tanomaru-Filho, M; Faria, G
This systematic review aimed to review the literature on the acquisition-, reconstruction-, and analysis parameters of micro-computed tomography (micro-CT) for the assessment of periapical lesions in rats and mice, and to illustrate the effect of variation in these parameters. The PubMed database was searched from 2000 to January 2015 (English-language publications) for reports on the use of micro-CT to evaluate periapical lesions in rats and mice. QUADAS criteria were used to rate the quality of the studies. To illustrate the effect of variations in acquisition-, reconstruction-, and analysis parameters on images of periapical lesions, micro-CT examination of two hemi-mandibles of mice, with periapical lesions around the first molar was undertaken. Twenty-one studies were identified, which analyzed periapical lesions in rats or mice using micro-CT. According to the QUADAS, no study was classified as high-, seven were classified as moderate-, and 14 as low quality. The effect of variation in parameters was that voxel size may interfere with image sharpness, reconstruction may interfere with image sharpness and contrast, and inadequate plane orientation may alter the size of the periapical lesion. Non-personalized ROIs resulted in areas that were not part of the periapical lesion. Changing the limits of the threshold for bone-tissue visualization increased lesion size. There is no defined protocol for acquiring and analyzing micro-CT images of periapical lesions in rats and mice. Further, acquisition-, reconstruction-, and analysis parameters are not adequately explained, which may compromise the scientific impact of the studies. This article is protected by copyright. All rights reserved.
Sowter, M C; Lethaby, A; Singla, A A
Group search strategy (see Review Group details) was used to identify randomised trials that had compared the use of these drugs with either each other, or placebo, or no pre-operative treatment. An updated search was performed in 2001-2002 to identify new trials. Trials were included if they compared the effects of these agents with each other, or with placebo or no treatment on relevant intra-operative and post-operative treatment outcomes. Only randomised studies were included in this review. Twelve studies met the inclusion criteria for this review. Five studies compared goserelin (a GnRH analogue) with no treatment or placebo and one study compared decapeptyl (a GnRH analogue) with no treatment. Three studies compared goserelin with danazol. Two studies compared progestogens, danazol and triptorelin or nasal spray nafarelin (both GnRH analogues) with no treatment. Only one study comparing triptorelin with no treatment assessed outcomes after balloon ablation and no studies assessing endometrial thinning agents prior to other second generation ablation techniques were identified. One study assessed the effects of progestogens compared to no treatment. Data were extracted independently by two reviewers. A third reviewer checked data extraction for accuracy and wrote to authors where relevant data was missing or unclear. Intra-operative parameters included endometrial thickness, duration of surgery, ease of surgery, distension medium absorption and complication rate. Post-operative outcomes included the proportion of women with amenorrhoea, post-operative menstrual loss and dysmenorrhoea, and the need for further surgery. Data on side-effects were also recorded. When compared with no treatment, GnRH analogues are associated with a shorter duration of surgery, greater ease of surgery and a higher rate of post-operative amenorrhoea at 12 months with hysteroscopic resection or ablation. Post-operative dysmenorrhoea also appears to be reduced. The use of GnRH analogues
Braga, Juliana Casagrande Tavoloni; Scope, Alon; Klaz, Itay; Mecca, Patricia; González, Salvador; Rabinovitz, Harold; Marghoob, Ashfaq A
Solitary pink lesions often manifest nondescript clinical and dermatoscopic primary morphologic features. The differential diagnosis for pink lesions tends, therefore, to be broad, ranging from inflammatory processes to malignancy. In vivo reflectance confocal microscopy (RCM) may help in the evaluation of pink lesions. We sought to demonstrate the use of RCM as an adjunct to the bedside diagnosis of pink lesions. We describe a series of patients with clinically and dermatoscopically equivocal pink lesions for which RCM examination allowed for a rapid and accurate diagnosis. All lesions were excised for histopathologic evaluation. Integrating the findings in the case series with a literature review, we present RCM diagnostic criteria for pink lesions. Lesions included basal cell carcinoma, squamous cell carcinoma, amelanotic melanoma, and inflamed seborrheic keratosis. RCM shows distinctive findings for each diagnostic entity when stratified by anatomic level into suprabasal epidermis, dermoepidermal junction, and papillary dermis. In the cases presented RCM allowed for a rapid and accurate noninvasive diagnosis. The study is descriptive and does not test accuracy of RCM criteria in a prospective series of pink lesions. RCM may add useful diagnostic features to the clinical evaluation of solitary pink lesions.
Wollenweber, Scott D.; Kinahan, Paul E.; Alessio, Adam M.
The early detection of abnormal regions with increased tracer uptake in positron emission tomography (PET) is a key driver of imaging system design and optimization as well as choice of imaging protocols. Detectability, however, remains difficult to assess due to the need for realistic objects mimicking the clinical scene, multiple lesion-present and lesion-absent images and multiple observers. Fillable phantoms, with tradeoffs between complexity and utility, provide a means to quantitatively test and compare imaging systems under truth-known conditions. These phantoms, however, often focus on quantification rather than detectability. This work presents extensions to a novel phantom design and analysis techniques to evaluate detectability in the context of realistic, non-piecewise constant backgrounds. The design consists of a phantom filled with small solid plastic balls and a radionuclide solution to mimic heterogeneous background uptake. A set of 3D-printed regular dodecahedral `features' were included at user-defined locations within the phantom to create `holes' within the matrix of chaotically-packed balls. These features fill at approximately 3:1 contrast to the lumpy background. A series of signal-known-present (SP) and signal-known-absent (SA) sub-images were generated and used as input for observer studies. This design was imaged in a head-like 20 cm diameter, 20 cm long cylinder and in a body-like 36 cm wide by 21 cm tall by 40 cm long tank. A series of model observer detectability indices were compared across scan conditions (count levels, number of scan replicates), PET image reconstruction methods (with/without TOF and PSF) and between PET/CT scanner system designs using the same phantom imaged on multiple systems. The detectability index was further compared to the noise-equivalent count (NEC) level to characterize the relationship between NEC and observer SNR.
Chai, Ning-Li; Ling-Hu, En-Qiang; Morita, Yoshinori; Obata, Daisuke; Toyonaga, Takashi; Azuma, Takeshi; Wu, Ben-Yan
Any prognosis of gastrointestinal (GI) cancer is closely related to the stage of the disease at diagnosis. Endoscopic submucosal dissection (ESD) and en bloc endoscopic mucosal resection (EMR) have been performed as curative treatments for many early-stage GI lesions in recent years. The technologies have been widely accepted in many Asian countries because they are minimally invasive and supply thorough histopathologic evaluation of the specimens. However, before engaging in endoscopic therapy, an accurate diagnosis is a precondition to effecting the complete cure of the underlying malignancy or carcinoma in situ. For the past few years, many new types of endoscopic techniques, including magnifying endoscopy with narrow-band imaging (ME-NBI), have emerged in many countries because these methods provide a strong indication of early lesions and are very useful in determining treatment options before ESD or EMR. However, to date, there is no comparable classification equivalent to “Kudo’s Pit Pattern Classification in the colon”, for the upper GI, there is still no clear internationally accepted classification system of magnifying endoscopy. Therefore, in order to help unify some viewpoints, here we will review the defining optical imaging characteristics and the current representative classifications of microvascular and microsurface patterns in the upper GI tract under ME-NBI, describe the accurate relationship between them and the pathological diagnosis, and their clinical applications prior to ESD or en bloc EMR. We will also discuss assessing the differentiation and depth of invasion, defying the lateral spread of involvement and targeting biopsy in real time. PMID:22493543
Bohîlțea, RE; Ancăr, V; Rădoi, V; Furtunescu, F; Bohîlțea, LC
Rationale: Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania. Since 2013, an increased trend of endometrial cancer occurrence has been registered in urban areas as compared with rural ones. Unfortunately, most of the cancer cases are diagnosed too late, in an advanced stage of the disease, resulting into diminished lifetime expectancy. The first part of the article concentrated on issues such as: the description of the study, results, and discussions regarding the study, definitions and terms, risk factors specific for endometrial carcinomas, presentation of the activities of the Program, etc. Objective: Drafting a national program that will serve as an early diagnosis method of endometrial cancer. This second part of the study continues with the presentation of the activities of the Program, analyzes the human resources and materials needed to implement the Program, presents the strategies and the indicators specific for the implementation of the project. Methods and Results: A standardization of the diagnostic steps was proposed and the focus was on 4 key elements for the early diagnosis of endometrial cancer: The first steps were approached in the first part of the study and the second part of the study investigated the proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Discussion: Improving medical practice based on diagnostic algorithms and programs improves and increases the lifetime expectancy, due to the fact that endometrial cancer is early diagnosed and treated before it causes serious health problems or even death. Abbreviations: ASCCP = American Society for Colposcopy and Cervical Pathology, CT = Computerized Tomography, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, MSI = Microsatellites instability, MSI-H/ MSI-L = high (positive test)/ low (negative test
Romero-Pérez, Laura; López-García, M Ángeles; Díaz-Martín, Juan; Biscuola, Michele; Castilla, M Ángeles; Tafe, Laura J; Garg, Karuna; Oliva, Esther; Matias-Guiu, Xavier; Soslow, Robert A; Palacios, José
Undifferentiated endometrial carcinomas are very aggressive high-grade endometrial carcinomas that are frequently under-recognized. This study aimed to analyze the molecular alterations underlying the development of these endometrial carcinomas, focusing on those related to dedifferentiation. We assessed a series of 120 tumors: 57 grade 1 and 2 endometrioid endometrial carcinomas, 15 grade 3 endometrioid endometrial carcinomas, 27 endometrial serous carcinomas, and 21 undifferentiated endometrial carcinomas. We found a high frequency of DNA mismatch repair deficiency (38%) and moderate rate of p53 overexpression (∼33%) in undifferentiated carcinomas. In contrast to the characteristic endometrioid phenotype, there was a dramatic downregulation of E-cadherin expression in the undifferentiated subtype. Quantitative methylation studies dismissed CDH1 promoter hypermethylation as the mechanism responsible for this change in gene expression, while immunohistochemistry revealed that the E-cadherin repressor ZEB1 was frequently overexpressed (62%) in undifferentiated endometrial carcinomas. This finding was accompanied by a sharp downregulation in the expression of the miR-200 family of microRNAs, well-known targets of ZEB1. Furthermore, there was enhanced expression of epithelial-to-mesenchymal transition markers in undifferentiated endometrial carcinomas, such as N-cadherin, cytoplasmic p120, and osteonectin. In addition, HMGA2, a regulator of epithelial-to-mesenchymal transition that is expressed in aggressive endometrial tumors, such as endometrial serous carcinomas and carcinosarcomas, was expressed in >20% of undifferentiated carcinomas. These results suggest that ZEB1 overexpression, associated with E-cadherin and miR-200s downregulation, and the expression of mesenchymal markers might enhance the metastatic potential of undifferentiated endometrial carcinomas, leading to a poor prognosis. In addition, our observations suggest that the immnohistochemical analysis
Apostolou, G; Apostolou, N; Moulos, P; Chatzipantelis, P
To investigate the different identity and biological behaviour of endometrial benign epithelial and endometrial adenocarcinoma cell categories. For this study, the imprint smears from three groups, 10 cases of disordered proliferative/benign hyperplastic endometrium, 21 cases of low-grade and eight cases of high-grade endometrial adenocarcinoma, were examined using image analysis and the Ki-67 biomarker. The plastic stem cell model was also applied. Among the examined groups, the nuclear area major axis ranged statistically different in the digitally measured Ki-67 positive endometrial epithelial and adenocarcinoma cells (P<.0001). Moreover, higher values of the cycling nuclear area major axis were observed in high-grade, as compared with the low-grade endometrial adenocarcinomas (P<.0001) and the cases of disordered/benign hyperplastic endometrium (P<.0001). Additionally, a Ki-67 increase pathway was observed in the benign endometrial lesions, and a relatively stable pathway was noticed in low- and high-grade endometrial adenocarcinomas. The different range of the nuclear area major axis among cycling endometrial epithelial and adenocarcinoma cells may correlate with their specific identity and biological behaviour. The different values of the cycling nuclear area major dimension may also be connected with the biological behaviour of the three examined groups. Moreover, the endometrial epithelial cells may follow a Ki-67 increase pathway, instead of the relatively stable pathway which the rapidly proliferating adenocarcinoma cells may use. Finally, the studied cell categories may exhibit different biology, because their stem cells may reside in different states of stemness. © 2017 John Wiley & Sons Ltd.
Shan, Weiwei; Wang, Chao; Zhang, Zhenbo; Luo, Xuezhen; Ning, Chengcheng; Yu, Yinhua; Feng, Youji; Gu, Chao; Chen, Xiaojun
The purpose of the study was to explore the role and mechanism of ataxia-telangiectasia mutated (ATM) protein in endometrial carcinogenesis. A reverse-phase protein array (RPPA) was used to analyze the expression of ATM signal pathway proteins in Ishikawa and progesterone-insensitive Ishikawa. ATM expression was detected in endometrium specimens by immunohistochemistry, including 8 cases with proliferative endometrium, 6 cases with secretory endometrium, 10 cases with simple hyperplasia (SH), 13 cases of complex hyperplasia (CH), 11 cases of endometrial atypical hyperplasia (EAH), and 83 cases with type I endometrial cancer. The relationship between ATM expression and other clinicopathological indicators was also examined in type I endometrial cancer patients. The mechanisms of ATM were explored in vitro with the endometrial cell lines Ishikawa and RL95-2. A cell counting kit-8 (CCK-8) test and Western blot analysis were performed to test proliferation and protein expression. Statistical analysis was performed with SPSS19.0. The significance level was set at 0.05. ATM was increased with medroxyprogesterone acetate (MPA) stimulation in Ishikawa in RPPA. ATM expression gradually decreased in endometrial hyperplasic lesions compared with the normal proliferative and secretory endometrium and was the lowest in type I endometrial cancer. ATM expression was negatively correlated with pathological grades in type I endometrial cancer. In vitro, ATM silencing retarded proliferation inhibition in Ishikawa and RL95-2 treated with MPA. ATM silencing could down-regulate the MPA-stimulated signal proteins, including Chk2, P53, and caspase-3 in vitro. MPA might exert its role through activating the ATM-associated pathway, ATM-Chk2-P53-caspase-3 (active), preserving normal endometrium and protecting it from malignancies. ATM might be a promising indicator for endometrial hyperplasia and cancer.
Krupinski, Elizabeth A; Chao, Joseph; Hofmann-Wellenhof, Rainer; Morrison, Lynne; Curiel-Lewandrowski, Clara
The goal of this investigation was to explore the feasibility of characterizing the visual search characteristics of dermatologists evaluating images corresponding to single pigmented skin lesions (PSLs) (close-ups and dermoscopy) as a venue to improve training programs for dermoscopy. Two Board-certified dermatologists and two dermatology residents participated in a phased study. In phase I, they viewed a series of 20 PSL cases ranging from benign nevi to melanoma. The close-up and dermoscopy images of the PSL were evaluated sequentially and rated individually as benign or malignant, while eye position was recorded. Subsequently, the participating subjects completed an online dermoscopy training module that included a pre- and post-test assessing their dermoscopy skills (phase 2). Three months later, the subjects repeated their assessment on the 20 PSLs presented during phase I of the study. Significant differences in viewing time and eye-position parameters were observed as a function of level of expertise. Dermatologists overall have more efficient search than residents generating fewer fixations with shorter dwells. Fixations and dwells associated with decisions changing from benign to malignant or vice versa from photo to dermatoscopic viewing were longer than any other decision, indicating increased visual processing for those decisions. These differences in visual search may have implications for developing tools to teach dermatologists and residents about how to better utilize dermoscopy in clinical practice.
Silva, M J B; Caliari, M V; Sobrinho, A P R; Vieira, L Q; Arantes, R M E
To design and validate a rat molar model of furcal perforation to allow investigation of the biological phenomena that follow and to explore its potential for evaluating repair materials under standardized conditions. Eighteen male Wistar rats were used. Surgical aseptic procedures were carried out in order to open the pulp chamber of a first molar tooth. A cavity was prepared on the floor of the pulp chamber using a (1/4) round bur that created a communication between the furcation and the periodontal tissues. Six animals for each time point were sacrificed on days 14, 21 and 28 to assay morphological changes at the furcation region of molars. Maxillary bone was processed, removed and sectioned. Cellular infiltration, collagen deposition and bone resorption were assessed by histological analysis. Cellularity in the lesion area was determined by morphometric analysis. Data were analysed using parametric Student's t-test. A furcal perforation model was standardized in which both radiological outcome and periodontal tissue reactions could be assessed through evaluation of cellularity, osteoclast activity and collagen deposition. The morphometric analysis revealed a greater number of cells 21 day post-surgery when compared with 14 days. This animal model was suitable for radiological and histological evaluation of the processes that accompany surgical furcal perforation.
Golatta, Michael; Schweitzer-Martin, Mirjam; Harcos, Aba; Schott, Sarah; Gomez, Christina; Stieber, Anne; Rauch, Geraldine; Domschke, Christoph; Rom, Joachim; Schütz, Florian; Sohn, Christof; Heil, Jörg
To evaluate virtual touch tissue imaging quantification (VTIQ) as a new elastography method concerning its intra- and interexaminer reliability and its ability to differentiate benign from malignant breast lesions in comparison to and in combination with ultrasound (US) B-mode breast imaging reporting and data system (BI-RADS) assessment. US and VTIQ were performed by two examiners in 103 women with 104 lesions. Intra- and interexaminer reliability of VTIQ was assessed. The area under the receiver operating curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of BIRADS, VTIQ, and combined data were compared. Fifty-four of 104 lesions were malignant. Intraexaminer reliability was consistent, and interexaminer agreement showed a strong positive correlation (r = 0.93). The mean VTIQ values in malignant lesions were significantly higher than those in benign (7.73 m/s ± 1.02 versus 4.46 m/s ± 1.87; P < 0.0001). The combination of US-BIRADS with the optimal cut-off for clinical decision making of 5.18 m/s yielded a sensitivity of 98%, specificity of 82%, PPV of 86%, and NPV of 98%. The combination of BIRADS and VTIQ led to improved test validity. VTIQ is highly reliable and reproducible. There is a significant difference regarding the mean maximum velocity of benign and malignant lesions. Adding VTIQ to BIRADS assessment improves the specificity.
Depta, Jeremiah P; Patel, Jayendrakumar S; Novak, Eric; Gage, Brian F; Masrani, Shriti K; Raymer, David; Facey, Gabrielle; Patel, Yogesh; Zajarias, Alan; Lasala, John M; Amin, Amit P; Kurz, Howard I; Singh, Jasvindar; Bach, Richard G
Although lesions deferred revascularization following fractional flow reserve (FFR) assessment have a low risk of adverse cardiac events, variability in risk for deferred lesion intervention (DLI) has not been previously evaluated. The aim of this study was to develop a prediction model to estimate 1-year risk of DLI for coronary lesions where revascularization was not performed following FFR assessment. A prediction model for DLI was developed from a cohort of 721 patients with 882 coronary lesions where revascularization was deferred based on FFR between 10/2002 and 7/2010. Deferred lesion intervention was defined as any revascularization of a lesion previously deferred following FFR. The final DLI model was developed using stepwise Cox regression and validated using bootstrapping techniques. An algorithm was constructed to predict the 1-year risk of DLI. During a mean (±SD) follow-up period of 4.0 ± 2.3 years, 18% of lesions deferred after FFR underwent DLI; the 1-year incidence of DLI was 5.3%, while the predicted risk of DLI varied from 1 to 40%. The final Cox model included the FFR value, age, current or former smoking, history of coronary artery disease (CAD) or prior percutaneous coronary intervention, multi-vessel CAD, and serum creatinine. The c statistic for the DLI prediction model was 0.66 (95% confidence interval, CI: 0.61-0.70). Patients deferred revascularization based on FFR have variation in their risk for DLI. A clinical prediction model consisting of five clinical variables and the FFR value can help predict the risk of DLI in the first year following FFR assessment. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: email@example.com.
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.
Hosford, S; Elliott, J; Ma, Z-W; Majeste, R; Dubeshter, B
The objective of this paper is to evaluate the relationship between CD44 expression and the clinicopathologic features of papillary serous endometrial cancer. CD44 expression was assessed in 32 cases of papillary serous endometrial carcinoma by standard immunohistochemical staining techniques. Clinicopathologic features including myometrial invasion, nodal metastases, tumor spread, stage, and the shedding of malignant cells on cervical cytology were reviewed. The Chi-square test was used for statistical analysis. CD44 was not expressed in 81% of patients with papillary serous endometrial carcinoma. Malignant cells were seen on cervical cytology in 68% of all cases with significantly more in the CD44-negative group (78% vs. 33%, P 0.05). CD44 expression was not related to stage, myometrial invasion, nodal involvement, or intraperitoneal spread. We conclude that the cell adhesion molecule CD44 is expressed infrequently in papillary serous endometrial carcinoma. Shedding of malignant cells on cervical cytology is common in papillary serous endometrial cancer and occurs more frequently in CD44-negative cases. CD44 expression doesn't appear to be related to known prognostic features such as nodal metastases or stage. The biologic aggressiveness of this tumor type may, in part, be related to its lack of CD44 expression.
Konstantinos, Kosmas; Marios, Stamoulas; Anna, Marouga; Nikolaos, Kavantzas; Efstratios, Patsouris; Paulina, Athanassiadou
The aims of this study were to determine the expression of Ki-67 in type I and type II endometrial adenocarcinomas as well as normal endometrium in imprint smears and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. During a 29-month period, 255 patients were evaluated with entometrial imprint cytology. Endometrial samples freshly resected from women who underwent total abdominal hysterectomy were studied. One hundred twenty-six patients had endometrial carcinoma and 129 cases were diagnosed as normal endometrium. The expression of Ki-67 was assessed by immunocytochemistry. Positive staining was correlated with increased stage, grade and lymph node metastases. High expression was more frequent in type II than type I endometrial adenocarcinoma and high-grade endometrial carcinoma had higher proportions of Ki-67 positive immunostaining compared with low-grade carcinoma. Proliferative endometrium showed high Ki-67 expression level, even higher than those of grade 1 and type I. On the other hand, secretory endometrium Ki-67 positive cells were markedly diminished and even disappeared. Completely negative staining was found to be related to atrophic endometrium. Immunocytochemical findings from Ki-67 stain, in addition to cytomorphologic features, appeared to be useful for the diagnosis of endometrial carcinoma in endometrial cytology with imprint smears. High Ki-67 expression correlates with morphologic features of aggressiveness and the expression pattern of Ki-67 correspond to the expected cyclic/atrophic pattern in normal endometrium.
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.
Yang, H P; Cook, L S; Weiderpass, E; Adami, H-O; Anderson, K E; Cai, H; Cerhan, J R; Clendenen, T V; Felix, A S; Friedenreich, C M; Garcia-Closas, M; Goodman, M T; Liang, X; Lissowska, J; Lu, L; Magliocco, A M; McCann, S E; Moysich, K B; Olson, S H; Petruzella, S; Pike, M C; Polidoro, S; Ricceri, F; Risch, H A; Sacerdote, C; Setiawan, V W; Shu, X O; Spurdle, A B; Trabert, B; Webb, P M; Wentzensen, N; Xiang, Y-B; Xu, Y; Yu, H; Zeleniuch-Jacquotte, A; Brinton, L A
Background: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. Methods: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59–1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13–1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. Conclusions: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters. PMID:25688738
Stubert, J; Gerber, B
Endometrial carcinoma is the most common carcinoma of the female genital tract. Its most important clinical sign is postmenopausal bleeding. An endometrial biopsy is essential for diagnosis. Treatment decisions are governed by tumour risk assessment and patient comorbidity, which is often present. Pelvic and paraaortic lymph node dissection is unnecessary in low risk cases (definition: pT1 a, G1/2) and adjuvant radiotherapy and systemic treatments are usually avoidable. Treatment of high-risk patients (G3 and/or pT1b) and palliative cases is difficult and not well standardised. New molecular-based subtype classification may help treatment decision making in future.
Eyerly, Stephanie A.; Hsu, Stephen J.; Agashe, Shruti H.; Trahey, Gregg E.; Li, Yang; Wolf, Patrick D.
Introduction Lesion placement and transmurality are critical factors in the success of cardiac transcatheter radiofrequency ablation (RFA) treatments for supraventricular arrhythmias. This study investigated the capabilities of catheter transducer based acoustic radiation force impulse (ARFI) ultrasound imaging for quantifying ablation lesion dimensions. Methods and Results RFA lesions were created in vitro in porcine ventricular myocardium and imaged with an intracardiac ultrasound catheter transducer capable of acquiring spatially registered B-mode and ARFI images. The myocardium was sliced along the imaging plane and photographed. The maximum ARFI-induced displacement images of the lesion were normalized and spatially registered with the photograph by matching the surfaces of the tissue in the B-mode and photographic images. The lesion dimensions determined by a manual segmentation of the photographed lesion based on the visible discoloration of the tissue were compared to automatic segmentations of the ARFI image using two different calculated thresholds. ARFI imaging accurately localized and sized the lesions within the myocardium. Differences in the maximum lateral and axial dimensions were statistically below 2 mm and 1 mm respectively for the two thresholding methods, with mean percent overlap of 68.7±5.21% and 66.3±8.4% for the two thresholds used. Conclusion ARFI imaging is capable of visualizing myocardial RFA lesion dimensions to within 2 mm in vitro. Visualizing lesions during transcatheter cardiac ablation procedures could improve the success of the treatment by imaging lesion line discontinuity and potentially reducing the required number of ablation lesions and procedure time. PMID:20021518
Yu, Mei; Yang, Jia-xin; Wu, Ming; Lang, Jing-he; Huo, Zhen; Shen, Keng
A retrospective study on 25 women (8 with endometrial carcinoma, 17 with severe endometrial atypical hyperplasia) under 35 years treated with progestin showed that six cases (75%) in the endometrial carcinoma (EC) group and 17 (100%) in the atypical hyperplasia (AH) group responded to the treatment, and among the 14 complete responders, 4 (40%) patients with AH had 7 pregnancies and 3 healthy deliveries. Given accurate pretreatment assessment, progestin therapy is a feasible management option to preserve fertility for young women with well-differentiated endometrial carcinoma or severe atypical hyperplasia of endometrium.
Tadir, Yona; Tromberg, Bruce J.; Krasieva, Tatiana B.; Berns, Michael W.
Potential applications of photodynamic therapy for endometrial disease are discussed. Experimental models that may lead to diagnosis and treatment of endometriosis as well as selective endometrial ablation are summarized.
Fishman, A; Altaras, M; Bernheim, J; Cohen, I; Beyth, Y; Tepper, R
To evaluate the diagnostic accuracy of preoperative transvaginal sonography (TVS) in the detection of deep myometrial invasion in endometrial cancer cases classified by the grade of disease, and in comparison to frozen section analysis in grade 1 cases. In a prospective study, 91 patients with confirmed endometrial carcinoma underwent preoperative TVS for evaluation of myoinvasion. Sonographic results were categorized as superficial (less than or equal to 1/2 myometrial depth) and deep invasion (greater than 1/2 myometrial depth). TAH-BSO followed by retroperitoneal lymph node sampling were performed in all patients with grade 2-3 tumors. In patients with grade 1 disease, the surgical specimen was intraoperatively evaluated by frozen section, and lymph node sampling was carried out if deep invasion was determined. The preoperative sonographic findings and the frozen section results were compared to the final histopathology report of myoinvasion. In 77 of the 91 (84.6%) patients, the sonographic assessment of the depth of myoinvasion was in accord with the final histopathologic findings. TVS demonstrated a sensitivity of 87.8% and a specificity of 82.7% in detecting deep invasion in the entire study group (grade 1-3), with positive and negative predictive values (PPV, NPV) of 74.3% and 92.3%, respectively. TVS in grade 1 cases (n=47) showed a sensitivity of 77.7%, a specificity of 79%, PPV of 46.6% and NPV of 93.7%. TVS in cases with grade 2-3 tumors (n=44) showed a sensitivity of 90%, specificity of 91.6%, PPV of 90% and NPV of 91.6%. Thus, the accuracy of TVS in grade 2-3 cases was superior to that achieved in grade 1 cases (91% vs 78.7%; p=.002). The myometrial invasion was assessed by frozen section in 41 out of 47 patients with grade 1 disease and demonstrated a sensitivity of 85.7%, a specificity of 100%, PPV of 100% and NPV of 97.1%. The specificity (100%) and accuracy (97.5%) of the frozen section were found to be superior compared to that of the TVS (79
Torwane, Nilesh Arjun; Hongal, Sudhir; Goel, Pankaj; Chandrashekar, Byarakele; Saxena, Vrinda
The present cross-sectional study following the STROBE guidelines was conducted to assess the prevalence of oral mucosal lesions among males, females, and eunuchs residing in Bhopal city, Madhya Pradesh India. Based on convenient non-probability snowball sampling technique, all the self-identified eunuchs residing in the city of Bhopal who were present at the time of examination and who fulfilled the selection criteria were examined. A cross section of the general population (males and females) residing in the same locality where these eunuchs live was also examined. The World Health Organization (WHO) oral health assessment proforma (1997) was used to collect the information on oral mucosal lesions. All the obtained data were analyzed by using a Statistical Package for Social Sciences version 20. Overall prevalence of oral mucosal lesions was 127 (19.9%) among the study subjects. Fifty-nine (28.5%) eunuchs, 56 (25.7%) males, and 12 (5.6%) females were observed to have some oral mucosal lesions. Oral submucous fibrosis (6.4%), leukoplakia (5.5%), and traumatic ulceration (4.2%) were the major oral mucosal conditions observed. The information presented in this study adds to our understanding of the common oral mucosal lesions occurring in the eunuch population. Efforts to increase patient awareness of the oral effects of tobacco use and to eliminate the habit are needed to improve the oral and general health of eunuchs.
Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage III Endometrial Carcinoma; Stage IV Endometrial Carcinoma
Laberge, Philippe; Leyland, Nicholas; Murji, Ally; Fortin, Claude; Martyn, Paul; Vilos, George; Leyland, Nicholas; Wolfman, Wendy; Allaire, Catherine; Awadalla, Alaa; Dunn, Sheila; Heywood, Mark; Lemyre, Madeleine; Marcoux, Violaine; Potestio, Frank; Rittenberg, David; Singh, Sukhbir; Yeung, Grace
Abnormal uterine bleeding (AUB) is the direct cause of a significant health care burden for women, their families, and society as a whole. Up to 30% of women will seek medical assistance for the problem during their reproductive years. To provide current evidence-based guidelines on the techniques and technologies used in endometrial ablation (EA), a minimally invasive technique for the management of AUB of benign origin. Members of the guideline committee were selected on the basis of individual expertise to represent a range of practical and academic experience in terms of both location in Canada and type of practice, as well as subspecialty expertise and general background in gynaecology. The committee reviewed all available evidence in the English medical literature, including published guidelines, and evaluated surgical and patient outcomes for the various EA techniques. Recommendations were established by consensus. Published literature was retrieved through searches of MEDLINE and The Cochrane Library in 2013 and 2014 using appropriate controlled vocabulary and key words (endometrial ablation, hysteroscopy, menorrhagia, heavy menstrual bleeding, AUB, hysterectomy). RESULTS were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English from January 2000 to November 2014. Searches were updated on a regular basis and incorporated in the guideline to December 2014. Grey (unpublished) literature was identifies through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). This document reviews the evidence regarding the available techniques and technologies for EA
Collier, F I; Heath, M R; Lynch, E; Beighton, D
The microflora of root carious lesions (n = 151) and sound root surfaces (n = 30) in 22 institutionalized, older patients was investigated using a standardized method of sampling. Material was removed using a sterile excavator and the numbers of bacteria in each sample were determined using conventional culturing techniques and by rapid (2 h) fluorogenic enzyme assay. Correlation between bacterial counts and enzyme assay result was 0.873 (p < 0.001). The numbers of bacteria and fluorogenic enzyme assay values were significantly (p < 0.001) greater from soft lesions than from leathery lesions while hard lesions and sound root surfaces had significantly (p < 0.001) lower values than the other lesion types and were not different from each other. A similar trend was apparent when these values were correlated with treatment needs. The fluorogenic enzyme assay may provide a rapid, objective measure of root caries severity which might be used in the monitoring and comparison of treatment protocols.
Tavel, Laurette; Fontana, Francesca; Garcia Manteiga, Josè Manuel; Mari, Silvia; Mariani, Elisabetta; Caneva, Enrico; Sitia, Roberto; Camnasio, Francesco; Marcatti, Magda; Cenci, Simone; Musco, Giovanna
Multiple myeloma (MM) is a malignancy of plasma cells characterized by multifocal osteolytic bone lesions. Macroscopic and genetic heterogeneity has been documented within MM lesions. Understanding the bases of such heterogeneity may unveil relevant features of MM pathobiology. To this aim, we deployed unbiased 1H high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) metabolomics to analyze multiple biopsy specimens of osteolytic lesions from one case of pathological fracture caused by MM. Multivariate analyses on normalized metabolite peak integrals allowed clusterization of samples in accordance with a posteriori histological findings. We investigated the relationship between morphological and NMR features by merging morphological data and metabolite profiling into a single correlation matrix. Data-merging addressed tissue heterogeneity, and greatly facilitated the mapping of lesions and nearby healthy tissues. Our proof-of-principle study reveals integrated metabolomics and histomorphology as a promising approach for the targeted study of osteolytic lesions. PMID:27809247
Cai, Jin-Zan; Zhang, Yao-Jun; Xu, Tian; Zhu, Yong-Xiang; Mao, Chen-Yu; Bourantas, Christos V.; Crake, Tom; Chen, Shao-Liang
Abstract The DEFINITION (Impact of the complexity of bifurcation lesions treated with drug-eluting stents) study has provided a novel classification to evaluate the complexity of coronary bifurcation lesion according to coronary angiography, but angiographic imaging due to its low resolution and inherited limitation may result in an inaccurate adjudication. We used optical coherence tomography (OCT) to further evaluate the coronary characteristics in a patient with “simple” bifurcation lesion which was classified by the DEFINITION criteria. However, a “complex” bifurcation lesion was defined and confirmed according to the OCT results. A double kissing Crush stenting approach was adopted to treat this “complex” case finally. The immediate and long-term angiographic and OCT results were excellent. OCT may be useful imaging modality to classify complexity of coronary bifurcation lesion and subsequently guide its treatment strategy. PMID:28072714
Huhdanpaa, Hannu; Hwang, Darryl H; Gasparian, Gregory G; Booker, Michael T; Cen, Yong; Lerner, Alexander; Boyko, Orest B; Go, John L; Kim, Paul E; Rajamohan, Anandh; Law, Meng; Shiroishi, Mark S
The quantitative, multiparametric assessment of brain lesions requires coregistering different parameters derived from MRI sequences. This will be followed by analysis of the voxel values of the ROI within the sequences and calculated parametric maps, and deriving multiparametric models to classify imaging data. There is a need for an intuitive, automated quantitative processing framework that is generalized and adaptable to different clinical and research questions. As such flexible frameworks have not been previously described, we proceeded to construct a quantitative post-processing framework with commonly available software components. Matlab was chosen as the programming/integration environment, and SPM was chosen as the coregistration component. Matlab routines were created to extract and concatenate the coregistration transforms, take the coregistered MRI sequences as inputs to the process, allow specification of the ROI, and store the voxel values to the database for statistical analysis. The functionality of the framework was validated using brain tumor MRI cases. The implementation of this quantitative post-processing framework enables intuitive creation of multiple parameters for each voxel, facilitating near real-time in-depth voxel-wise analysis. Our initial empirical evaluation of the framework is an increased usage of analysis requiring post-processing and increased number of simultaneous research activities by clinicians and researchers with non-technical backgrounds. We show that common software components can be utilized to implement an intuitive real-time quantitative post-processing framework, resulting in improved scalability and increased adoption of post-processing needed to answer important diagnostic questions.
Gluhovschi, G H; Gadalean, Florica; Gluhovschi, Cristina; Velciov, Silvia; Petrica, Ligia; Timar, R; Anastasiu, D; Gluhovschi, A
The paper highlights the importance of tubular lesions of the solitary kidney (SK), identified and monitored by means of urinary biomarkers, mainly N-acetyl-beta-D-glucosaminidase (NAG), albumin, alpha 1-, and beta 2-microglobulin. It is considered that the assessment of a SK should be performed with four and not three parameters as it was usually done until recently: renal function, proteinuria and blood pressure (BP), to which biomarkers should be added. The solitary kidney can result after nephrectomy for kidney transplantation. In some countries living kidney donors represent the only option for performing kidney transplantation. The SK in living donors has generally a good evolution, although sometimes renal injury manifested by proteinuria, arterial hypertension (AH), or diminution of renal function does occur. Therefore, living donors require attentive monitoring. The SK is considered to have a good evolution (even in donors), in spite of alterations of the above-mentioned clinical and biological parameters. The very infrequent cases who evolve progressively towards renal failure are not predictable, which requires monitoring of all persons with a SK. The SK represents a special situation in case of association with a disease affecting the kidney, such as urinary tract infection (UTI), diabetes mellitus, or systemic lupus erythematosus (SLE). Pregnancy occurring in a person with a SK also needs attentive follow-up. Pregnancy associated diseases, such as preeclampsia occurring in patients with a SK, impose appropriate therapeutic behaviour. The SK remains a particular entity in nephrology which needs to be carefully monitored.
Nighoghossian, N; Berthezene, Y; Adeleine, P; Wiart, M; Damien, J; Derex, L; Itti, R; Froment, J C; Trouillas, P
A simultaneous decrease of cerebral blood volume (CBV) and cerebral blood flow (CBF) has been described after subcortical stroke with positron emission tomography. However, this imaging modality cannot be applied routinely to stroke patients. Dynamic susceptibility contrast-enhanced MRI techniques (DSC-MRI) might be interesting in the assessment of these effects. Dynamic T2-weighted echo planar imaging was used to produce DSC-MR images during an intravenous bolus injection of gadopentetate dimeglumine in 9 patients who experienced a subcortical stroke involving thalamus or basal ganglia and in 8 control subjects. A series of 50 consecutive images at 1-second intervals was acquired at the anatomic level of the centrum semiovale quite distant from the subcortical lesion, rCBF and rCBV were determined over frontal and parietal regions of interest and through the entire cortical mantle. DSC-MRI enabled the detection of hemodynamic changes induced by subcortical stroke. Analysis of rCBV and rCBF values showed that the hemodynamic parameters were significantly decreased on the affected side. In controls mean rCBF and rCBV values recorded over the whole cortical mantle of each hemisphere showed no significant interhemispheric asymmetry.
Boone, M A L M; Suppa, M; Dhaenens, F; Miyamoto, M; Marneffe, A; Jemec, G B E; Del Marmol, V; Nebosis, R
One of the most challenging problems in clinical dermatology is the early detection of melanoma. Reflectance confocal microscopy (RCM) is an added tool to dermoscopy improving considerably diagnostic accuracy. However, diagnosis strongly depends on the experience of physicians. High-definition optical coherence tomography (HD-OCT) appears to offer additional structural and cellular information on melanocytic lesions complementary to that of RCM. However, the diagnostic potential of HD-OCT seems to be not high enough for ruling out the diagnosis of melanoma if based on morphology analysis. The aim of this paper is first to quantify in vivo optical properties such as light attenuation in melanocytic lesions by HD-OCT. The second objective is to determine the best critical value of these optical properties for melanoma diagnosis. The technique of semi-log plot whereby an exponential function becomes a straight line has been implemented on HD-OCT signals coming from four successive skin layers (epidermis, upper papillary dermis, deeper papillary dermis and superficial reticular dermis). This permitted the HD-OCT in vivo measurement of skin entrance signal (SES), relative attenuation factor normalized for the skin entrance signal (µ raf1) and half value layer (z 1/2). The diagnostic accuracy of HD-OCT for melanoma detection based on the optical properties, µ raf1 , SES and z 1/2 was high (95.6, 82.2 and 88.9 %, respectively). High negative predictive values could be found for these optical properties (96.7, 89.3 and 96.3 %, respectively) compared to morphologic assessment alone (89.9 %), reducing the risk of mistreating a malignant lesion to a more acceptable level (3.3 % instead of 11.1 %). HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with in vivo analysis of optical properties of tissue scatterers in melanocytic lesions. In vivo HD-OCT analysis of optical properties permits melanoma
Van Gorp, Toon; Neven, Patrick
Unopposed estrogens for treating menopausal symptoms were extensively used when epidemiological findings associated them with an increased endometrial cancer risk. Adding progestogens reverse this side effect efficiently but patient, dose, type and especially time during which the progestogen is administered are important. Long-term uterine safety of the long cycle HRT with administration of the progestogen every 3 months remains unclear. Because regular bleeding lowers compliance, continuous combined estrogen-progestogen treatment has become popular. Many different regimens are now available using oral, transdermal, subcutaneous, intravaginal or intra-uterine application of the estrogen and/or progestogen. Available but inadequate studies seem to point towards a slightly decreased endometrial cancer risk with continuous combined preparations compared with non-HRT-users and an increased risk with long-term oral but not vaginal treatment with low-potency estrogen formulations such as estriol. Newer compounds for menopausal health such as tibolone and raloxifene seem to be safe. As for any women with abnormal vaginal bleeding, those on HRT must have an intra-uterine evaluation. Transvaginal ultrasound (TVU) is very accurate in predicting a normal uterine cavity but inaccurate in predicting endometrial pathology because of a low specificity and positive predictive value of a thick echogenic endometrium. In all such cases a three-dimensional visualisation of intra-uterine lesions is more accurate. Periodic examination with TVU and/or endometrial biopsy of HRT exposed endometrium in asymptomatic women is not cost-effective. The available limited data on the use of HRT in hysterectomised women for early stage endometrial cancer show little evidence in terms of recurrence.
Cheng, Renxiang; Shao, Jiaojiao; Gao, Xiaoxiang; Tao, Chao; Ge, Jiuyu; Liu, Xiaojun
Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro-structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion.
Cheng, Renxiang; Shao, Jiaojiao; Gao, Xiaoxiang; Tao, Chao; Ge, Jiuyu; Liu, Xiaojun
Dental hard tissue lesions, including caries, cracked-tooth, etc., are the most prevalent diseases of people worldwide. Dental lesions and correlative diseases greatly decrease the life quality of patients throughout their lifetime. It is still hard to noninvasively detect these dental lesions in their early stages. Photoacoustic imaging is an emerging hybrid technology combining the high spatial resolution of ultrasound in deep tissue with the rich optical contrasts. In this study, a dual-contrast photoacoustic tomography is applied to detect the early dental lesions. One contrast, named B-mode, is related to the optical absorption. It is good at providing the sharp image about the morphological and macro-structural features of the teeth. Another contrast, named S-mode, is associated with the micro-structural and mechanical properties of the hard tissue. It is sensitive to the change of tissue properties induced by the early dental lesions. Experiments show that the comprehensive analysis of dual-contrast information can provide reliable information of the early dental lesions. Moreover, the imaging parameter of S-mode is device-independent and it could measure tissue properties quantitatively. We expect that the proposed scheme could be beneficial for improving safety, accuracy and sensitivity of the clinical diagnosis of the dental lesion. PMID:26902394
Bretschi, Maren; Fränzle, Andrea; Merz, Maximilian; Hillengass, Jens; Semmler, Wolfhard; Bendl, Rolf; Bäuerle, Tobias
Aim of the study was to compare between volumetric and unidimensional approaches for treatment response monitoring in a nude rat model of experimental bone metastases. For the volumetric approach, an automated segmentation algorithm of osteolytic lesions was introduced and compared to manual volumetry. Nude rats bearing osteolytic metastases were treated with zoledronate and sunitinib and compared to controls. Treatment response was assessed longitudinally in vivo using flat-panel volumetric computed tomography at days 30, 35, 45, and 55 after tumor cell inoculation. The mean sizes and volumes of osteolytic lesions were determined according to response evaluation criteria in solid tumors (RECIST) and by automated and manual volumetry (software: MITK [The Medical Imaging Interaction Toolkit, Heidelberg, Germany] and VIRTUOS, Heidelberg, Germany). In contrary to RECIST, the manual volumetric approach indicated a significant decrease in osteolytic lesion volume in response to treatment. The presented automatic segmentation algorithm for treatment monitoring identified bone metastases adequately and assessed changes in the osteolytic lesion volume over time according to manual volumetry. In an animal model, volumetric treatment response assessment of osteolytic bone metastases is superior to unidimensional measurements, and automated volumetric segmentation may be a valuable alternative to manual volume determination. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.
Sugita, Iori; Nakashima, Syozi; Ikeda, Asaomi; Burrow, Michael F; Nikaido, Toru; Kubo, Shisei; Tagami, Junji; Sumi, Yasunori
This longitudinal pilot study aimed to morphologically and quantitatively investigate the progress of non-carious cervical lesions (NCCLs) by using swept-source optical coherence tomography (SS-OCT). The samples examined comprised sets of NCCL epoxy resin replicas obtained from 10 lesions in 6 patients who attended annual dental visits over 4 or 5 years. SS-OCT images of the replicas were analyzed in terms of the maximum depth (Dmax) and corresponding vertical width (VW) - using an image analyzer to estimate progression of the NCCLs over time. It was found that differences between wedge- and saucer-shaped lesions were morphologically distinguished well by the OCT images. There were significant differences in dimensions among Dmax, VW and horizontal width (HW). HW was the largest and Dmax was the smallest. Although no significant differences in absolute values of annual progression rates were found among Dmax, VW and HW, the percentage increase in Dmax was significantly greater compared to VW and HW. The ratios of Dmax to corresponding VW ranged from 0.49 to 1.01 for the wedge-shaped lesions and from 0.13 to 0.44 for saucer-shaped lesions, respectively. The dimensional analysis demonstrated notable progression with large variations. The wedge-shaped lesions appeared to show greater Dmax values compared to the saucer-shaped lesions. With respect to the depth, the wedge-shaped lesions may progress at a greater rate compared to the saucer-shaped lesions. Copyright © 2016 Elsevier Ltd. All rights reserved.
To provide clear guidelines for the safe and effective performance of endometrial ablation. Representatives of American, Australian, British, and Canadian hysteroscopists were brought together to produce a consensus document of good practice in endometrial ablation. The guidelines were produced after researching the literature, combining the extensive experience of the group, and debating the relevant issues. Endometrial ablation is a new procedure. Correct patient selection is essential in producing good results. Patients must be counseled carefully about the advantages, disadvantages, and potential complications of this approach to the management of menstrual disorders. The main indication for endometrial ablation is heavy menstrual loss in the absence of organic disease. Excessive uterine size, the presence of active pelvic infection, and evidence of malignant and premalignant endometrium are absolute contraindications. Ablation can be produced by electrosurgical resection, rollerball or rollerbarrel ablation and Nd-YAG laser ablation. Severe complications can occur, and techniques should be adopted to avoid uterine perforation, hemorrhage, and excessive fluid absorption. In skilled hands, endometrial ablation can be a safe and effective treatment for menorrhagia.
Gundreddy, Rohith Reddy; Tan, Maxine; Qiu, Yuchen; Cheng, Samuel; Liu, Hong; Zheng, Bin
Purpose: To develop a new computer-aided diagnosis (CAD) scheme using a content-based image retrieval (CBIR) approach for classification between the malignant and benign breast lesions depicted on the digital mammograms and assess CAD performance and reproducibility. Methods: An image dataset including 820 regions of interest (ROIs) was used. Among them, 431 ROIs depict malignant lesions and 389 depict benign lesions. After applying an image preprocessing process to define the lesion center, two image features were computed from each ROI. The first feature is an average pixel value of a mapped region generated using a watershed algorithm. The second feature is an average pixel value difference between a ROI’s center region and the rest of the image. A two-step CBIR approach uses these two features sequentially to search for ten most similar reference ROIs for each queried ROI. A similarity based classification score was then computed to predict the likelihood of the queried ROI depicting a malignant lesion. To assess the reproducibility of the CAD scheme, we selected another independent testing dataset of 100 ROIs. For each ROI in the testing dataset, we added four randomly queried lesion center pixels and examined the variation of the classification scores. Results: The area under the ROC curve (AUC) = 0.962 ± 0.006 was obtained when applying a leave-one-out validation method to 820 ROIs. Using the independent testing dataset, the initial AUC value was 0.832 ± 0.040, and using the median classification score of each ROI with five queried seeds, AUC value increased to 0.878 ± 0.035. Conclusions: The authors demonstrated that (1) a simple and efficient CBIR scheme using two lesion density distribution related features achieved high performance in classifying breast lesions without actual lesion segmentation and (2) similar to the conventional CAD schemes using global optimization approaches, improving reproducibility is also one of the challenges in developing
Hinz, Torsten; Ehler, Lin-Kristin; Voth, Harald; Fortmeier, Ines; Hoeller, Tobias; Hornung, Thorsten; Schmid-Wendtner, Monika-Hildegard
Accurate assessment of vertical tumor size is important for surgical treatment planning of melanocytic skin lesions. High-frequency ultrasound (HFUS) is frequently used for this purpose, but overestimation of tumor thickness is known as a problem especially in thin melanocytic lesions. Optical coherence tomography (OCT) as a new imaging technique might be a promising alternative. To evaluate the ability of OCT to accurately determine the vertical tumor thickness of melanocytic skin lesions and to compare it with HFUS and histopathology in order to improve surgical planning. In this single-center study, 26 melanocytic lesions were imaged by OCT and HFUS. Vertical lesion dimensions of both methods were compared with histopathological measurements. Bland-Altman plots for OCT and histopathology as well as for HFUS and histopathology revealed better agreement for OCT and histopathology concerning tumor thickness measurements. Tumor thickness values for the melanocytic lesions measured by OCT presented a median tumor thickness of 0.31 mm (range 0.10-0.77) compared to a median tumor thickness of 0.25 mm (range 0.06-1.5) measured by histopathology. The median tumor thickness of HFUS was 0.44 mm (range 0.23-1.1). A Spearman correlation procedure including the correlation coefficient (r) showed a stronger relationship between OCT and histopathology (r = 0.734) compared to HFUS and histopathology (r = 0.390). On the basis of this smaller study cohort, OCT seems to be more exact than HFUS as far as thickness determination of thin melanocytic skin lesions is concerned. Copyright © 2011 S. Karger AG, Basel.
Karageorgi, Stalo; Gates, Margaret A.; Hankinson, Susan E.; De Vivo, Immaculata
Background Several studies have reported a positive association between perineal use of talcum powder among adult women and ovarian cancer risk. However, the relationship between talcum powder use and other gynecologic malignancies such as endometrial cancer has not been examined, and little information is available on non-hormonal risk factors for endometrial cancer. Methods Perineal use of talcum powder was assessed in 1982 in the Nurses’ Health Study. Approximately 40% of women who responded to the questions about perineal use of talcum powder reported ever use. Cox proportional hazards models were used to estimate the incidence rate ratio of endometrial cancer and 95% confidence interval (CI), adjusted for body mass index and other potential confounders. We evaluated the relationship among all women and stratified by menopausal status. Results Our analysis included 66,028 women with 599 incident cases of invasive endometrial adenocarcinoma diagnosed between 1982 and 2004. Although no association was observed overall, the association varied by menopausal status (p-interaction=0.02) and a positive association was observed among postmenopausal women; ever use of talcum powder was associated with a 21% increase in risk of endometrial cancer (95% CI: 1.02, 1.44), while regular use (≥once/week) was associated with a 24% increase in risk (95% CI: 1.03, 1.48). In addition, we observed a borderline increase in risk with increasing frequency of use (p-trend=0.04). Conclusions Our results suggest that perineal talcum powder use increases the risk of endometrial cancer, particularly among postmenopausal women. Impact Future and larger studies are needed to confirm this association and investigate potential mechanisms. PMID:20406962
Dewdney, Summer B; Rimel, B J; Thaker, Premal H; Thompson, Dominic M; Schmidt, Amy; Huettner, Phyllis; Mutch, David G; Gao, Feng; Goodfellow, Paul J
Effective treatments for advanced endometrial cancer are lacking. Novel therapies that target specific pathways hold promise for better treatment outcomes with less toxicity. Mutation activation of the FGFR2/RAS/ERK pathway is important in endometrial tumorigenesis. RPS6KA6 (RSK4) is a putative tumor suppressor gene and is a target of the ERK signaling pathway. We explored the role of RSK4 in endometrial cancer. We showed that RSK4 is expressed in normal endometrial tissue and is absent or much reduced in endometrial cancer. On the basis of previous reports on methylation in other cancers, we hypothesized that the absence of RSK4 transcript is associated with epigenetic silencing rather than mutation. We determined the methylation and expression status of RSK4 in primary endometrial cancers and cell lines and the effects of treatment with a demethylating agent. The relationship between RSK4 methylation and clinicopathologic features was assessed. RSK4 is frequently hypermethylated in endometrial cancer cells lines and in primary endometrial cancer compared with normal endometrial tissue. RSK4 methylation was significantly associated with tumor grade, with higher grade tumors having lower levels of methylation (P = 0.03). RSK4 methylation levels were not associated with other clinical variables. We did find that RSK4 methylation was significantly correlated with expression in primary endometrial tumors and in cell lines. Reactivation of RSK4 by 5-azacytidine was successfully performed showing 8- to more than 1,200-fold increases in transcript levels. RSK4 appears to be epigenetically silenced in endometrial cancer as evidenced by hypermethylation. Its role as a suppressor in endometrial cancer, however, remains uncertain. ©2011 AACR.
Dewdney, Summer B.; Rimel, BJ; Thaker, Premal H.; Thompson, Dominic M.; Schmidt, Amy; Huettner, Phyllis; Mutch, David G.; Gao, Feng; Goodfellow, Paul J.
Purpose Effective treatments for advanced endometrial cancer are lacking. Novel therapies that target specific pathways hold promise for better treatment outcomes with less toxicity. Mutation activation of the FGFR2/RAS/ERK pathway is important in endometrial tumorigenesis. RPS6KA6 (Rsk4) is a putative tumor suppressor gene and is a target of the ERK signaling pathway. We explored the role of RSK4 in endometrial cancer. Experimental design We showed that RSK4 is expressed in normal endometrial tissue and is absent or much reduced in endometrial cancer. Based on previously reports on methylation in other cancers we hypothesized that the absence of RSK4 transcript is associated with epigenetic silencing rather than mutation. We determined the methylation and expression status of RSK4 in primary endometrial cancers and cell lines and the effects of treatment with a demethylating agent. The relationship between RSK4 methylation and clinicopathologic was assessed. Results RSK4 is frequently hypermethylated in endometrial cancer cells lines and in primary endometrial cancer compared to normal endometrial tissue. RSK4 methylation was significantly associated with tumor grade, with higher grade tumors having lower levels of methylation (p=0.03). RSK4 methylation levels were not associated with other clinical variables. We did find that RSK4 methylation was significantly correlated with expression in primary endometrial tumors and in cell lines. Re-activation of RSK4 by 5-azacytidine was successfully performed showing 8 to >1,200 fold increases in transcript levels. Conclusion RSK4 appears to be epigenetically silenced in endometrial cancer as evidenced by hypermethylation. Its role as suppressor in endometrial cancer, however, remains uncertain. PMID:21372219
Escalona, Manuel; Delivet-Mongrain, Hugo; Kundu, Aritra; Gossard, Jean-Pierre; Rossignol, Serge
After lesions of the CNS, locomotor abilities of animals (mainly cats) are often assessed on a simple flat treadmill (FTM), which imposes little demands on supraspinal structures as is the case when walking on targets. Therefore, the aims of the present work were as follows: (1) to develop a treadmill allowing the assessment of locomotion of intact cats required to place the paws on the rungs of a moving ladder treadmill (LTM); (2) to assess the capability of cats after a unilateral spinal hemisection at T10 to cope with such a demanding locomotor task; and (3) to regularly train cats for 6 weeks on the LTM to determine whether such regular training improves locomotor recovery on the FTM. A significant improvement would indicate that LTM training maximizes the contribution of spinal locomotor circuits as well as remnant supraspinal inputs. Together, we used 9 cats (7 females, 2 males). Six were used to compare the EMG and kinematic locomotor characteristics during walking on the FTM and LTM. We found that the swing phase during LTM walking was slightly enhanced as well as some specific activity of knee flexor muscles. Fore-hindlimb coupling favored a more stable diagonal coupling. These 6 cats were then hemispinalized and trained for 6 weeks on the LTM, whereas the 3 other cats were hemispinalized and trained solely on the FTM to compare the two training regimens. Intensive LTM training after hemisection was found to change features of locomotion, such as the foot trajectory as well as diminished paw drag often observed after hemisection.SIGNIFICANCE STATEMENT This paper introduces a method (ladder treadmill [LTM]) to study the locomotor ability of cats with an intact spinal cord or after a unilateral hemisection to walk with a precise foot placement on the rungs fixed to an ordinary flat treadmill (FTM). Because cats are compared in various conditions (intact or hemisected at different time points) in the same enclosure on the FTM and the LTM, the changes in
Holub, Z; Shomani, A
Endometrial cancer in malformation of the urogenital system is a rare lesion. A correct diagnosis in these cases may be difficult to make due to urogenital anomalies or the unrecognised presence of a second uterine cavity. Proper diagnosis is very important for corresponding treatment.
Hryhorczuk, Anastasia L; Strouse, Peter J; Biermann, J Sybil
CT-guided percutaneous core needle biopsy has been shown in adults to be an effective diagnostic tool for a large number of musculoskeletal malignancies. To characterize our experience with CT-guided percutaneous core needle biopsy of pediatric bone lesions and determine its utility in diagnosing pediatric osseous lesions, in a population where such lesions are commonly benign. From 2000 to 2009, 61 children underwent 63 CT-guided percutaneous biopsies. Radiological, pathological and clinical records were reviewed. Fourteen biopsies (22%) were performed on malignant lesions, while 49 biopsies (78%) were performed on benign lesions. Forty-nine of the 63 biopsies (78%) were adequate; these children underwent no further tissue sampling. Fourteen of the 63 biopsies (22%) were inadequate or non-conclusive. Of these patients, 12 underwent open biopsy. Retrospective analysis of percutaneous biopsies in these patients demonstrates that 9/12 provided clinically relevant information, and 4/12 patients received final diagnoses that confirmed initial core biopsy findings. No malignancies were diagnosed as benign on percutaneous biopsy. Overall, percutaneous core needle biopsy provided accurate diagnostic information in 84% (53/63) of biopsies. Our results demonstrate that CT-guided percutaneous biopsy is safe and beneficial in children. This study supports the use of CT-guided percutaneous core needle biopsy for primary diagnosis of pediatric bone lesions.
Eslamipour, Faezeh; Shahmoradi, Majid; Farhadi, Vashnad
White spot lesions (WSLs) are common adverse effect of orthodontic treatment, which can be prevented and treated by orthodontists. This study was conducted to assess Iranian orthodontists' practice regarding the prevention and treatment of WSLs in their patients. In this cross-sectional study, 109 Iranian orthodontists were selected from the Iranian Association of Orthodontists' directory by cluster sampling. For data collection, a questionnaire was designed and its validity and reliability was confirmed (Cronbach's α =0.85). The questionnaire included eight general questions and eight questions about practice with regard to the prevention and treatment of WSL. Data were analyzed by descriptive tests, ANOVA test, and t-test in SPSS 20 software. P < 0.05 was considered statistically significant. The mean score of orthodontists' practice was 7.62 (range: 0-8), and 94.4% of the participants were rated as good, while 3.7% and 1.9% were rated as moderate and weak, respectively. Women's score was significantly higher than that of men (P = 0.001). With increasing participants' age, their practice has been improved (P = 0.001), but there was no significant relation between years of experience and their practice (P = 0.230). Nearly 94.4% of the orthodontists prescribed fluoride products. Toothpastes and fluoride mouth rinses were the most common prescribed products (34%). With regard to Iranian orthodontists' practice, it was fortunate to note that majority of the respondents were taking care of their patients with regarding to the prevention and treatment of WSLs. For enhancing their competencies, it is recommended to plan educational courses which are useful for promoting their knowledge and practice about new products and procedures used for the prevention and treatment of WSLs.
Obara, Toshimasa; Hasegawa, Hiroshi; Wachi, Yoshitaka; Tanaka, Masamichi; Sato, Michiko; Kobayashi, Yoshio; Koshiba, Hitomi; Nagai, Kumiko; Yamada, Yukiko; Matsui, Toshifumi; Kozaki, Koichi
Vascular dementia may be referred to as "treatable dementia" because its development and progress can be inhibited by intervention in the early stage. In particular, cerebral white matter lesions are readily encountered the clinical setting. In this study, we aimed to clarify the phenomenon and symptoms of patients with mild cognitive impairment (MCI) with cerebral white matter lesions prior to the onset of dementia. The subjects included 181 cases diagnosed with MCI among 643 consecutive new patients of the Center for Comprehensive Care on Memory Disorder at Kyorin University Hospital from January 1, 2013 to January 31, 2014. Patients with particular diseases were excluded. An interview, physical examination, comprehensive geriatric assessment, brain MRI and SPECT were performed for all subjects. The cerebral white matter lesions were evaluated using the modified Fazekas scale. We defined Grades 0 and 1 as the group without apparent cerebral white matter lesions and Grades 2 and 3 as the group with apparent cerebral white matter lesions. We compared the laboratory findings and outcomes of these two groups. The age of the group with apparent cerebral white matter lesions was significantly higher than the group without apparent cerebral white matter lesions (P<0.05). No significant difference was observed regarding gender, MMSE, or "vegetable" term retrieval. A significant difference was observed in the total score and the subordinate component of the 21-item fall risk index and geriatric depression scale between the groups (P<0.05). Additionally, a significant difference was observed regarding the subordinate component of the instrumental ADL, the Dementia Behavior Disturbance Scale and the Zarit Care Burden Scale between the groups (P<0.05). Our results suggest that the presence of white matter lesions at the stage of MCI has a significant relationship to care burden due to the deterioration of ADL, risk of falling, and the presence of depression and behavior
Svirydenka, Hanna; Delso, Gaspar; De Galiza Barbosa, Felipe; Huellner, Martin; Davison, Helen; Fanti, Stefano; Veit-Haibach, Patrick; Ter Voert, Edwin E G W
Metalic implants may affect attenuation correction (AC) in PET/MR imaging. The purpose of this study was to evaluate the effect of susceptibility artifacts related to metallic implants on adjacent metabolically active lesions in clinical simultaneous PET/MR scanning for both time-of-flight (TOF) and non-TOF reconstructed PET images. Methods: We included 27 patients without implants but with confirmed (18)F-FDG-avid lesions adjacent to common implant locations. In all patients, a clinically indicated whole-body (18)F-FDG PET/MR scan was acquired. Baseline non-TOF and TOF PET images were reconstructed. Reconstruction was repeated after the introduction of artificial signal voids in the AC map to simulate metallic implants in standard anatomic areas. All reconstructed images were qualitatively and quantitatively assessed and compared with the baseline images. Results: In total, 51 lesions were assessed. In 40 and 50 of these cases (non-TOF and TOF, respectively), the detectability of the lesions did not change; in 9 and 1 cases, the detectability changed; and in 2 non-TOF cases, the lesions were no longer visible after the introduction of metallic artifacts. The inclusion of TOF information significantly reduced artifacts due to simulated implants in the femoral head, sternum, and spine (P = 0.01, 0.01, and 0.03, respectively). It also improved image quality in these locations (P = 0.02, 0.01, and 0.01, respectively). The mean percentage error was -3.5% for TOF and -4.8% for non-TOF reconstructions, meaning that the inclusion of TOF information reduced the percentage error in SUVmax by 28.5% (P < 0.01). Conclusion: Qualitatively, there was a significant reduction of artifacts in the femoral head, sternum, and spine. There was also a significant qualitative improvement in image quality in these locations. Furthermore, our study indicated that simulated susceptibility artifacts related to metallic implants have a significant effect on small, moderately (18)F
Sobirov, Zh G; Bakhritdinov, F Sh
The present study was aimed at working out a methodology combining clinical, haemodynamic, and functional parameters of lesions of arterial basins in patients presenting with concomitant lesions of the aortic arch branches and arteries of lower extremities. The authors retrospectively investigated the results of examining a total of 181 patients operated on for concomitant atherosclerotic lesions of the aortic arch branches, terminal portion of the abdominal aorta, and lower limb arteries. In patients subjected as the first stage to interventions on the aortic arch branches (Group 1), the index of severity of the lesion of the aortic arch branches (Cs) was higher than in those from Groups 2 and 3. In Group 2 patients who as the first stage underwent reconstruction of the terminal portion of the abdominal aorta and lower-limb arteries, the index of severity of lesions of lower limb arteries (Ls) turned out to be higher as compared with patients from Groups 1 and 3. The mean value of the Ls/Cs ratio for Group 1 patients amounted to 1.07, for Group 2 patients to 2.7, and for Group 3 subjects to 1.96. The proposed methodology makes it possible to determine the degree of the lesion of arterial basins in patients suffering from multifocal atherosclerosis and may objectively reflect severity of the lesion thereof. The comparative retrospective analysis has demonstrated that with the Ls/Cs ratio equaling 1.0, the first stage consisted in carrying out an intervention on the aortic arch branches, in the Ls/Cs ratio varying from 2.5 to 3.0, the first stage performed was reconstruction of the terminal portion of the abdominal aorta and arteries of the lower limbs, and cases associated with the Ls/Cs ratio equaling 2 involved simultaneous interventions. A possibility of wide application of the method warrants further investigation.
Inoue, Osamu; Hamatani, Toshio; Susumu, Nobuyuki; Yamagami, Wataru; Ogawa, Seiji; Takemoto, Takashi; Hirasawa, Akira; Banno, Kouji; Kuji, Naoaki; Tanaka, Mamoru; Aoki, Daisuke
Patients hoping to preserve their fertility receive conservative treatment with high-dose medroxyprogesterone acetate (MPA) for well-differentiated endometrioid adenocarcinoma (EC) or atypical endometrial hyperplasia (AEH) . Such treatment generally involves frequent intrauterine operations, including dilation and curettage (D&C) and endometrial biopsy (EMB), which could result in endometritis, endometrial thinning, or intrauterine adhesion. In turn, any of these outcomes could adversely affect implantation and pregnancy development. The current study thus aimed to identify factors that might affect pregnancy following conservative treatment by MPA. We compared a pregnancy group (45 patients) with a non-pregnancy group (53 patients) of MPA-treated patients to evaluate the factors affecting clinical pregnancy establishment. We undertook a multivariate logistic regression analysis based on factors shown by univariate analysis to be significantly different between the groups. Univariate analysis identified number of D&C, endometrial thickness, duration of MPA administration, age of pregnancy permission (the age at which a patient was first allowed to attempt pregnancy after disappearance of the lesion), period of disappearance of lesions, and recurrence as independent variables. The odds ratios (95 % confidence interval) of multivariate analysis for disease recurrence, endometrial thickness during ovulation, and age of pregnancy permission were 0.283 (0.102-0.785), 1.677 (1.251-2.248), and 0.889 (0.792-0.998), respectively. There was no significant difference in the other independent variables between groups. We identified three factors considered to affect pregnancy establishment following conservative treatment with MPA: recurrence, endometrial thickness during ovulation, and the age of the pregnancy permission. Introduction of infertility treatment including assisted reproductive technology (ART) soon after achieving tumor disappearance by MPA would therefore be
Beurmann, Silvia; Runyon, Christina M; Videau, Patrick; Callahan, Sean M; Aeby, Greta S
Coral colonies in Kāne'ohe Bay, Hawai'i (USA), are afflicted with the tissue loss disease chronic Montipora white syndrome (cMWS). Here we show that removal of chronic disease lesions is a potential method to slow the progression of cMWS in M. capitata. Over the 24 wk observation period, treatment colonies lost almost half the amount of tissue that was lost by control colonies. The percentage of tissue loss at each sampling interval (mean ± SEM; treatment: 1.17 ± 0.47%, control: 2.25 ± 0.63%) and the rate of tissue loss per day (treatment: 0.13 ± 0.04%, control: 0.27 ± 0.08%) were both significantly lower on treated colonies than control colonies. While lesion removal stopped tissue loss at the initial infection site, which allowed colony healing, it did not prevent re-infection; in all but one of the treated colonies, new cMWS lesions appeared in other areas of the colony but not around the treatment margins. Additionally, the rate of new infections was similar between treatment and control colonies, indicating that physical injury from lesion removal did not appear to increase cMWS susceptibility. These results indicate that lesion removal reduced morbidity in M. capitata exhibiting cMWS but did not stop the disease.
Anquez, Jeremie; Corréas, Jean-Michel; Criton, Aline; Lacoste, François; Yon, Sylvain
The aim of this work was to evaluate Shear Wave Elastography (SWE) as a tool to visualize HIFU lesions in an acute in-vivo setting. Extracorporeal HIFU sonications of liver were performed on 14 rabbits in 19 consecutive, adjacent pulses, with in situ energies between 75 J and 228 J. A set of images of the sonicated area was acquired prior and post HIFU ablation: 2 orthogonal SWE images (transverse and sagittal) and contrast enhanced CT scan. SWE images were acquired with theAixplorer® device (SuperSonic Imagine, Aix, France). Prior to the treatment, the liver elasticity appeared homogeneous, with a elasticity comprised between 5 and 11 kPa. The lesion extents were manually segmented on post-treatment SWE images and their areas A(SWE)T (transverse) and A(SWE)S (sagittal) were computed. On 3D CT the lesions were segmented as a hypo intense (devascularized) region on 3D CT images, and considered as "ground truth". The transverse and sagittal planes passing by their centers of mass were extracted. The lesion areas were computed for each plane, respectively A(CT)T and A(CT)S. The ratios A(CT)T/A(SWE)T and A(CT)S/A(SWE)S were computed for all the 14 cases. SWE appear to underestimate the lesion extent in the sagittal orientation with respect to CT images, while a good matching is obtained in the transverse orientation.
Zhao, Jing; Lyu, Chen; Gao, Jian; Du, Li; Shan, Boer; Zhang, Hong; Wang, Hua-Ying; Gao, Ying
Since body fatness is a convincing risk factor for endometrial cancer, dietary fat intake was speculated to be associated with endometrial cancer risk. However, epidemiological studies are inconclusive. We aimed to conduct a meta-analysis to assess the associations between dietary fat intake and endometrial cancer risk. We searched the PubMed, Embase, and Web of science databases updated to September 2015. In total, 7 cohort and 14 case-control studies were included. Pooled analysis of case-control studies suggested that endometrial cancer risk was significantly increased by 5% per 10% kilocalories from total fat intake (P=0.02) and by 17% per 10 g/1000 kcal of saturated fat intake (P < 0.001). Summary of 3 cohort studies showed significant inverse association between monounsaturated fatty acids and endometrial cancer risk (odds ratio = 0.84, 95% confidence interval = 0.73-0.98) with a total of 524583 participants and 3503 incident cases. No significant associations were found for polyunsaturated fatty acids and linoleic acid. In conclusion, positive associations with endometrial cancer risk were observed for total fat and saturated fat intake in the case-control studies. Results from the cohort studies suggested higher monounsaturated fatty acids intake was significantly associated with lower endometrial cancer risk.
GLUT-1 Expression in Proliferative Endometrium, Endometrial Hyperplasia, Endometrial Adenocarcinoma and the Relationship Between GLUT-1 Expression and Prognostic Parameters in Endometrial Adenocarcinoma.
Canpolat, Tuba; Ersöz, Canan; Uğuz, Aysun; Vardar, Mehmet Ali; Altintaş, Aytekin
Malignant cells show increased glucose uptake in in vitro and in vivo studies. This uptake is mediated by glucose transporter proteins. GLUT-1 is the most common transporter protein, and its expression is reported to be increase in many human cancers. The aim of this study is to determine the GLUT-1 overexpression in benign, hyperplastic, and malignant endometrial tissues, to evaluate the usefulness of GLUT-1 expression in endometrial hyperplasia, and to determine its role in the neoplastic progression to endometrioid type adenocarcinoma. We also aimed to analyze prognostic clinical parameters, predict prognosis, and survival. We examined immunohistochemical expression of GLUT-1 in 91 cases of endometrial hyperplasia, 100 cases of endometrioid type adenocarcinoma, and 10 proliferative endometrial tissues. The percentage of positive cells and staining intensity were assessed in a semi quantitative fashion and scored (1+ to 3+). GLUT-1 immunoreactivity was not present in proliferative endometrium. Twenty-nine (31.9%) of 91 endometrial hyperplasia cases showed positive immunoreactivity, of which only six were cases of hyperplasia without atypia while 23 of them were cases with atypia. We found GLUT-1 positivity of 95% in endometrioid type adenocarcinoma. GLUT-1 overexpression was not significantly correlated with any of the clinicopathological parameters except histological grade in endometrioid adenocarcinoma; the survival was not found to be correlated with GLUT-1 expression. GLUT-1 immunostaining may be useful in distinguishing hyperplasia without atypia from hyperplasia with atypia; GLUT-1 overexpression is a consistent feature of endometrioid adenocarcinoma. A correlation between GLUT -1 expression and tumor grade has been found, although other prognostic parameters and survival has no meaningful correlation.
Moreno, Inmaculada; Codoñer, Francisco M; Vilella, Felipe; Valbuena, Diana; Martinez-Blanch, Juan F; Jimenez-Almazán, Jorge; Alonso, Roberto; Alamá, Pilar; Remohí, Jose; Pellicer, Antonio; Ramon, Daniel; Simon, Carlos
Bacterial cells in the human body account for 1-3% of total body weight and are at least equal in number to human cells. Recent research has focused on understanding how the different bacterial communities in the body (eg, gut, respiratory, skin, and vaginal microbiomes) predispose to health and disease. The microbiota of the reproductive tract has been inferred from the vaginal bacterial communities, and the uterus has been classically considered a sterile cavity. However, while the vaginal microbiota has been investigated in depth, there is a paucity of consistent data regarding the existence of an endometrial microbiota and its possible impact in reproductive function. This study sought to test the existence of an endometrial microbiota that differs from that in the vagina, assess its hormonal regulation, and analyze the impact of the endometrial microbial community on reproductive outcome in infertile patients undergoing in vitro fertilization. To identify the existence of an endometrial microbiota, paired samples of endometrial fluid and vaginal aspirates were obtained simultaneously from 13 fertile women in prereceptive and receptive phases within the same menstrual cycle (total samples analyzed n = 52). To investigate the hormonal regulation of the endometrial microbiota during the acquisition of endometrial receptivity, endometrial fluid was collected at prereceptive and receptive phases within the same cycle from 22 fertile women (n = 44). Finally, the reproductive impact of an altered endometrial microbiota in endometrial fluid was assessed by implantation, ongoing pregnancy, and live birth rates in 35 infertile patients undergoing in vitro fertilization (total samples n = 41) with a receptive endometrium diagnosed using the endometrial receptivity array. Genomic DNA was obtained either from endometrial fluid or vaginal aspirate and sequenced by 454 pyrosequencing of the V3-V5 region of the 16S ribosomal RNA (rRNA) gene; the resulting sequences were
Kim, Christine H.; Khoury-Collado, Fady; Barber, Emma L.; Soslow, Robert A.; Makker, Vicky; Leitao, Mario M.; Sonoda, Yukio; Alektiar, Kaled M.; Barakat, Richard R.; Abu-Rustum, Nadeem R.
Objective To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging. Methods All patients from 9/2005-12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with <50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells. Results Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology—13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion. Conclusions Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases. PMID:24099838
Zeidenberg, Joshua; Burks, S Shelby; Jose, Jean; Subhawong, Ty K; Levi, Allan D
Ultrasound technology continues to improve with better image resolution and availability. Its use in evaluating peripheral nerve lesions is increasing. The current review focuses on the utility of ultrasound in traumatic injuries. In this report, the authors present 4 illustrative cases in which high-resolution ultrasound dramatically enhanced the anatomical understanding and surgical planning of traumatic peripheral nerve lesions. Cases include a lacerating injury of the sciatic nerve at the popliteal fossa, a femoral nerve injury from a pseudoaneurysm, an ulnar nerve neuroma after attempted repair with a conduit, and, finally, a spinal accessory nerve injury after biopsy of a supraclavicular fossa lesion. Preoperative ultrasound images and intraoperative pictures are presented with a focus on how ultrasound aided with surgical decision making. These cases are set into context with a review of the literature on peripheral nerve ultrasound and a comparison between ultrasound and MRI modalities.
Modica, Ippolito; Soslow, Robert A; Black, Destin; Tornos, Carmen; Kauff, Noah; Shia, Jinru
Identification of the microsatellite instability (MSI) phenotype in endometrial carcinoma is important given that such tumors are the most common noncolorectal tumors to occur in hereditary nonpolyposis colorectal cancer syndrome, and may bear prognostic relevance. The objective of this study was to assess the utility of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI in endometrial carcinoma. The study subjects consisted of 90 endometrial carcinoma patients with equal representation of MSI-high (MSI-H) and non-MSI-H tumors. MSI was tested using the standard polymerase chain reaction-based method and the 5 NCI-recommended markers. Overall, IHC with MLH1 and MSH2 antibodies detected 69% of MSI-H tumors with a specificity of 100%. Adding PMS2 and MSH6 to the antibody panel increased the sensitivity to 91% but decreased the specificity to 83%. The most common IHC abnormality in MSI tumors was concurrent loss of MLH1/PMS2. Assessment of staining was straightforward in most cases but not in all. Staining inadequacies existed. Five stains (4 MLH1 and 1 MSH6) were not interpretable because of the lack of any internal positive control. Two percent to 10% of the cases (depending on the antibody assessed) had only focal weak staining; the highest frequency (10%) occurred with MLH1 antibody. PMS2 staining detected 7 MLH1-staining present MSI-H cases, thus partly accounting for the increased sensitivity with the 4-antibody panel. MSH6 staining identified 9 cases with loss of MSH6 alone, 6 of 9 were non-MSI-H, thus partly accounting for the decreased specificity with the 4-antibody panel. In conclusion, our results suggest that IHC is useful in detecting MSI in endometrial carcinoma. Although IHC has a lower sensitivity with more apparent staining inadequacies in detecting MSI in endometrial carcinoma than it does in colorectal carcinoma, its use in endometrial carcinoma may be an important adjunct when screening for hereditary cases. In the future, as
Kokka, Fani; Brockbank, Elly; Oram, David; Gallagher, Chris; Bryant, Andrew
Background Endometrial cancer is a cancer of the lining of the womb and worldwide is the seventh most common cancer in women. Treatment with hormones is thought to be beneficial in patients with endometrial cancer. Objectives To assess the indications, effectiveness and safety of hormone therapy for advanced or recurrent epithelial endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE up to May 2009 and and CENTRAL (Issue 2, 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies, and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that studied hormonal therapy in adult women diagnosed with advanced or recurrent endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Comparisons were restricted to single-trial analyses so we did not synthesise data in meta-analyses. Main results We found six trials (542 participants) that met our inclusion criteria. These trials assessed the effectiveness of hormonal therapy in women with advanced or recurrent endometrial cancer as a single agent, as part of combination therapy and as low versus high dose. All comparisons were restricted to single-trial analyses, where we found no evidence that hormonal therapy as a single agent or as a combination treatment prolonged overall or five-year disease-free survival of women with advanced or recurrent endometrial cancer. However, low-dose hormonal therapy may have had a benefit in terms of overall and progression-free survival (PFS) compared to high-dose hormonal therapy (HR 1.31, 95% CI 1.04 to 1.66 and HR 1.35, 95% CI 1.07 to 1.71 for overall and PFS, respectively). Authors’ conclusions We found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy improves the survival of patients with advanced or
DeVita, Robert; Barr, Richard G
To evaluate the effect of precompression on power Doppler visualization of blood flow in breast masses. This Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study evaluated 30 patients with breast masses (16 benign and 14 malignant) undergoing ultrasound-guided breast biopsy. A computational mathematics program was used to calculate the number of color pixels in a region of interest at various degrees of compression of the breast by the transducer. The amount of precompression was calculated as previously described. The percentage of color pixels compared to minimal compression was plotted against the percentage of precompression. The amount of precompression needed to decrease the number of color pixels by 50% and 100% was calculated. The differences between benign and malignant lesions were compared. The mean percentages of precompression ± SD needed to decrease the number of color voxels by 50% in were 15.9% ± 6.43% (range, 8%-30%) for benign lesions and 14.0% ± 4.17% (range, 8%-20%) for malignant lesions (P = .35). The percentages of precompression needed to decrease the number of color pixels by 100% in were 34.7% ± 12.33% (range, 23%-62%) for benign lesions and for malignant lesions 26.7% ± 3.89% (range, 18%-31%), which were statistically significant (P = .027). The amount of precompression normally used when obtaining B-mode images can substantially decrease the number of color voxels on power Doppler sonography. When performing quantitative work on Doppler evaluation of breast lesions, precompression needs to be controlled. © 2016 by the American Institute of Ultrasound in Medicine.
Sprenger, Till; Seifert, Christian L; Valet, Michael; Andreou, Anna P; Foerschler, Annette; Zimmer, Claus; Collins, D Louis; Goadsby, Peter J; Tölle, Thomas R; Chakravarty, M Mallar
Central post-stroke pain of thalamic origin is an extremely distressing and often refractory disorder. There are no well-established predictors for pain development after thalamic stroke, and the role of different thalamic nuclei is unclear. Here, we used structural magnetic resonance imaging to identify the thalamic nuclei, specifically implicated in the generation of central post-stroke pain of thalamic origin. Lesions of 10 patients with central post-stroke pain of thalamic origin and 10 control patients with thalamic strokes without pain were identified as volumes of interest on magnetic resonance imaging data. Non-linear deformations were estimated to match each image with a high-resolution template and were applied to each volume of interest. By using a digital atlas of the thalamus, we elucidated the involvement of different nuclei with respect to each lesion. Patient and control volumes of interest were summed separately to identify unique areas of involvement. Voxelwise odds ratio maps were calculated to localize the anatomical site where lesions put patients at risk of developing central post-stroke pain of thalamic origin. In the patients with pain, mainly lateral and posterior thalamic nuclei were affected, whereas a more anterior-medial lesion pattern was evident in the controls. The lesions of 9 of 10 pain patients overlapped at the border of the ventral posterior nucleus and the pulvinar, coinciding with the ventrocaudalis portae nucleus. The lesions of this area showed an odds ratio of 81 in favour of developing thalamic pain. The high odds ratio at the ventral posterior nucleus-pulvinar border zone indicates that this area is crucial in the pathogenesis of thalamic pain and demonstrates the feasibility of identifying patients at risk of developing central post-stroke pain of thalamic origin early after thalamic insults. This provides a basis for pre-emptive treatment studies.
de Azevedo, Julia Marques da Rocha; de Azevedo, Ligia Marques da Rocha; Freitas, Fernando; Wender, Maria Celeste Osorio
To determine the prevalence of malignant and premalignant endometrial polyps and to investigate the association of malignancy with specific factors. This is a retrospective study of women submitted to hysteroscopic resection of endometrial polyps between January 2005 and July 2013 at a university hospital in southern Brazil. Data regarding clinical characteristics and pathology findings were collected from patient charts. Of 359 patients, 87.2% had benign polyps and 9.9% had hyperplasia without atypia. Atypical hyperplasia was found in 2.6% of the sample. Endometrial adenocarcinoma was found in one woman (0.3%). A correlation was observed between malignant/premalignant polyps and patient age, menopausal status, and uterine bleeding. All patients with malignancies/premalignancies had abnormal uterine bleeding. Higher frequency of malignant polyps was observed in tamoxifen users, however, without statistical significance (p = 0.059%). Malignancy was not correlated with arterial hypertension, diabetes mellitus, obesity, hormone therapy, endometrial thickness, and polyp diameter. Malignant/premalignant findings had low prevalence and were absent in asymptomatic patients. From the data of this retrospective study, it is unclear whether routine polypectomy should be performed in asymptomatic patients. Further prospective studies including larger numbers of patients are required to guide treatment recommendations.
Xiao, Wei; Dong, Xiujuan; Zhao, Honghui; Han, Shiyu; Nie, Ruixue; Zhang, Xiahua; An, Ruifang
The aim of the present study was to investigate the expression of c-erbB-2 and macrophage migration inhibitory factor (MIF) in endometrial cancer and to elucidate the significance of the early diagnosis and prognosis of endometrial cancer. The gene copy number of c‑erbB‑2 and MIF was characterized by reverse transcription quantitative polymerase chain reaction and the reactivity was assessed by immunohistochemistry in 70 patients using a polyclonal antibody, and evaluated semiquantitatively according to the percentage of cells demonstrating membranous or diffuse cytoplasmic staining. A correlation between age, tumor stage, grade, myometrial invasion and lymph node metastasis was observed. The mRNA expression of c‑erbB‑2 and MIF was high in endometrial carcinoma. The positive expression rate of MIF protein in normal endometrium, atypical hyperplasia and endometrial carcinoma significantly increased along with the degree of aggravation of the disease by 20 (3/15), 45 (9/20) and 70% (35/50), respectively. The positive expression of MIF and c‑erbB‑2 was highest in endometrial cancer and a significantly higher level of protein was observed in tumors at stage I, stage G1, with a depth of myometrial invasion <0.4 cm and no lymph node metastasis. The protein expression of c‑erbB‑2 in endometrial cancer was higher in tumors at the G2‑3 phase, clinical stage III‑IV, lymph node metastasis, and had no association with the depth of myometrial invasion and age. MIF and c‑erbB‑2 were correlated with the occurrence and the development of endometrial cancer, and thus can be used for the early diagnosis and prognosis of endometrial cancer. The present study laid the foundation for identifying new treatments for endometrial cancer.
Acrylamide has been associated with carcinogenicity in experimental animals, but potential health risks of dietary acrylamide intake and endometrial cancer in human are inconclusive. Thus, a meta-analysis of prospective cohort studies was conducted to provide a quantitative assessment of the association between dietary acrylamide intake and endometrial cancer risk. PubMed database was used to identify prospective cohort studies on dietary acrylamide intake and endometrial cancer risk published up to June 2014. Since smoking is an important source of acrylamide and is inversely associated with endometrial cancer risk, the association was examined in women who never smoked as well. Multivariable relative risks (RR) adjusting for potential confounders were combined using random effects models. Four large prospective cohort studies were identified, which included 453,355 female participants and 2,019 endometrial cancer cases. There was no association between dietary acrylamide intake and endometrial cancer risk overall [pooled RR for high vs. low intake = 1.10; 95% confidence interval (CI) 0.91-1.34]. High acrylamide intake, however, was significantly associated with increased risk of endometrial cancer among women who never smoked (pooled RR for high vs. low intake = 1.39; 95% CI 1.09-1.77). In dose-response analyses, pooled RRs for an increase of 10 µg/day were 1.04 (95% CI 0.97-1.11) among all women and 1.11 (95% CI 1.04-1.19) among never-smoking women. Endometrial cancer risk was not associated with dietary acrylamide intake overall. Among women who never smoked, however, there was a significantly increased endometrial cancer risk in women who consumed high dietary acrylamide.
Nead, Kevin T.; Sharp, Stephen J.; Thompson, Deborah J.; Painter, Jodie N.; Savage, David B.; Semple, Robert K.; Barker, Adam; Perry, John R. B.; Attia, John; Dunning, Alison M.; Easton, Douglas F.; Holliday, Elizabeth; Lotta, Luca A.; O’Mara, Tracy; McEvoy, Mark; Pharoah, Paul D. P.; Scott, Rodney J.; Spurdle, Amanda B.; Langenberg, Claudia; Wareham, Nicholas J.
Background: Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. Methods: We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. Results: Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10-6). Conclusion: This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk. PMID:26134033
Nead, Kevin T; Sharp, Stephen J; Thompson, Deborah J; Painter, Jodie N; Savage, David B; Semple, Robert K; Barker, Adam; Perry, John R B; Attia, John; Dunning, Alison M; Easton, Douglas F; Holliday, Elizabeth; Lotta, Luca A; O'Mara, Tracy; McEvoy, Mark; Pharoah, Paul D P; Scott, Rodney J; Spurdle, Amanda B; Langenberg, Claudia; Wareham, Nicholas J; Scott, Robert A
Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10(-6)). This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk. © The Author 2015. Published by Oxford University Press.
Lemetre, Christophe; Vieites, Begoña; Ng, Charlotte K Y; Piscuoglio, Salvatore; Schultheis, Anne M; Marchiò, Caterina; Murali, Rajmohan; Lopez-García, Maria A; Palacios, Jose C; Jungbluth, Achim A; Terracciano, Luigi M; Reis-Filho, Jorge S; Weigelt, Britta
Endometrial carcinoma comprises a group of tumours with distinct histologic and molecular features and clinical behaviour. Here, we sought to define the biological processes that govern the clinical behaviour of endometrial cancers. Sixteen prototype genes representative of different biological processes that would likely play a role in endometrial and other hormone-driven cancers were defined. RNA-sequencing gene expression data from 323 endometrial cancers from The Cancer Genome Atlas (TCGA) were used to determine the transcription module of each prototype gene. The expression of prototype genes and modules and their association with outcome was assessed in univariate and multivariate survival analyses. The association of MSH6 expression with outcome was validated in an independent cohort of 243 primary endometrial cancers using immunohistochemistry. We observed that the clinical behaviour of endometrial cancers as a group was associated with hormone receptor signalling, PI3K pathway signalling and DNA mismatch repair processes. When analysed separately, in endometrioid carcinomas, hormone receptor, PI3K and DNA mismatch repair modules were significantly associated with outcome in univariate analysis, whereas the clinical behaviour of serous cancers was likely governed by apoptosis and Wnt signalling. Multivariate survival analysis revealed that MSH6 gene expression was associated with outcome of endometrial cancer patients independently from traditional prognostic clinicopathologic parameters, which was confirmed in an independent cohort at the protein level. Endometrioid and serous endometrial cancers are underpinned by distinct molecular pathways. MSH6 expression levels may be associated with outcome in endometrial cancers as a group. Copyright © 2016 Elsevier Ltd. All rights reserved.
Chambers, Ba; Laksito, Ma; Long, F; Yates, Gd
A 9-year-old bitch was presented because of lethargy and abdominal distension. Abdominal ultrasound revealed an enlarged, fluid-filled uterus and associated mass. Subsequent exploratory laparotomy revealed unilateral uterine torsion involving the mass. Recovery following ovariohysterectomy was uneventful and the histopathological diagnosis was of a benign endometrial inflammatory polyp. Reports of uterine torsion in the English-language literature are reviewed to identify factors associated with the incidence of uterine torsion. The aetiology of the cystic endometrial hyperplasia/pyometra complex and its possible role in the development of inflammatory polypoid lesions in the bitch is also discussed.
Purpose: The goal of this study was to perform a retrospective analysis of the ultrasonographic findings associated with low-grade endometrial stromal sarcoma. Methods: Ten pathologically confirmed cases of low-grade endometrial stromal sarcoma at our institution from January 2007 to April 2014 were retrospectively reviewed. All patients underwent a preoperative transvaginal ultrasound. Two radiologists came to a consensus regarding the location, size, margin, and echogenicity of the tumor, as well as the presence of intratumoral cystic degeneration and its extent and configuration. Results: Low-grade endometrial stromal sarcoma manifested as an intramural mass protruding into the endometrial cavity (n=6) or as a purely intramural mass (n=4). The maximal diameter of the lesion ranged from 4 to 9.1 cm (mean, 6.2 cm). The imaging features of low-grade endometrial stromal sarcoma were variable: six cases involved predominantly solid masses containing cystic degeneration, one was a predominantly unilocular cystic mass, two were ill-defined infiltrative solid masses, and one was a well-defined solid mass. Among the seven cases with internal cystic degeneration, five patients showed a multiseptated cystic area or a cystic area with multiple small clusters, while a unilocular cystic area within the tumor was found in two patients. Conclusion: Low-grade endometrial stromal sarcoma is associated with variable ultrasonographic findings with regard to the location, margin, and configuration of the lesion. Multiseptated cystic areas and multiple small areas of cystic degeneration are common. PMID:26537303
Shon, Kilhwan; Sung, Kyung Rim
To evaluate patterns of macular retinal ganglion cell (RGC) loss measured by spectral domain optical coherence tomography in patients with neurologic lesions mimicking glaucoma. We evaluated four patients with neurological lesions who showed characteristic patterns of RGC loss, as determined by ganglion cell thickness (GCT) mapping. Case 1 was a 30-year-old man who had been treated with glaucoma medication. A left homonymous vertical pattern of RGC loss was observed in his GCT map and a past brain magnetic resonance imaging (MRI) revealed a hemorrhagic lesion around the right optic radiation. Case 2 was a 72-year-old man with a pituitary adenoma who had a binasal vertical pattern of RGC loss that corresponded with bitemporal hemianopsia. Case 3 was a 77-year-old man treated for suspected glaucoma. His GCT map showed a right inferior quadratic pattern of loss, indicating a right superior homonymous quadranopsia in his visual field (VF). His brain MRI revealed a left posterior cerebral artery territory infarct. Case 4 was a 38-year-old woman with an unreliable VF who was referred for suspected glaucoma. Her GCT map revealed a left homonymous vertical pattern of RGC loss, which may have been related to a previous head trauma. Evaluation of the patterns of macular RGC loss may be helpful in the differential diagnosis of RGC-related diseases, including glaucoma and neurologic lesions. When a patient's VF is unavailable, this method may be an effective tool for diagnosing and monitoring transneuronal retrograde degeneration-related structural changes.
Churchley, David; Lynch, Richard J. M.; Lippert, Frank; O'Bryan Eder, Jennifer Susan; Alton, Jesse; Gonzalez-Cabezas, Carlos
We compare terahertz-pulsed imaging (TPI) with transverse microradiography (TMR) and microindentation to measure remineralization of artificial caries lesions. Lesions are formed in bovine enamel using a solution of 0.1 M lactic acid/0.2% Carbopol C907 and 50% saturated with hydroxyapatite adjusted to pH 5.0. The 20-day experimental protocol consists of four 1 min treatment periods with dentifrices containing 10, 675, 1385, and 2700 ppm fluoride, a 4-h/day acid challenge, and, for the remaining time, specimens are stored in a 50:50 pooled human/artificial saliva mixture. Each specimen is imaged at the focal point of the terahertz beam (data-point spacing = 50 μm). The time-domain data are used to calculate the refractive index volume percent profile throughout the lesion, and the differences in the integrated areas between the baseline and post-treatment profiles are used to calculate ΔΔZ(THz). In addition, the change from baseline in both the lesion depth and the intensity of the reflected pulse from the air/enamel interface is determined. Statistically significant Pearson correlation coefficients are observed between TPI and TMR/microindentation (P < 0.05). We demonstrate that TPI has potential as a research tool for hard tissue imaging.
Zhuo, Zhihong; Wang, Aiming; Yu, Huimin
Metformin is the most prescribed anti-diabetic medication worldwide because of its proven efficacy and limited side effects. In this study, the significant anticancer effect of metformin was investigated in both endometrial carcinoma and progesterone-resistant endometrial carcinoma cells. We tested the growth inhibition assay using MTT cell proliferation, cell cycle assay, apoptosis assessment with flow cytometry using propidium iodide and Annexin V, and autophagy protein expression with western blot analysis. Metformin inhibited the growth of cancer cells with different concentrations in a dose- and time-dependent manner. Moreover, the inhibition properties observed as a function of increased concentrations of metformin were markedly augmented when the medication was administered in the progesterone-resistant Ishikawa cells, even with a dose as low as 10 mM. The early and late phases of apoptosis were enhanced in the metformin-treated tumour cells that were analyzed. For the Ishikawa cells, the expression of p-AMPK, LC-3, and beclin1 was upregulated after treatment, whereas the AMPK levels were not modulated. Furthermore, for the Ishikawa-PR cells, the protein levels were similarly upregulated. Finally, we observed that the three proteins showed much more variability in Ishikawa-PR cells than in Ishikawa cells. The application of metformin to target autophagy in endometrial cancer cells provides a new potential treatment for progesterone-resistant endometrial carcinoma.
Sanz-Chávez, Tania L N; Vilar-Compte, Diana; de Nicola-Delfín, Luigina; Meneses-García, Abelardo
in postmenopausal women, the excess of fat has been associated with an increased risk of endometrial cancer. The aim of the study was to determine the prevalence of overweight, obesity, diabetes and hypertension in patients with endometrial cancer. we collected demographic, clinical, laboratory and histopathological information from the electronic records of patients diagnosed with endometrial cancer in the period from January 2009 to July 2011. Subsequently descriptive analysis of the information was done. a total of 274 records. The average age of patients was 54 years. The 50.4 % were postmenopausal. At the time of diagnosis, 112 cases (48.6 %) were in clinical stage I. Of all patients, 104 (37.9 %) had diabetes mellitus, 122 (44.5 %) hypertension, 194 (72.6 %) were overweight or obese, and 24 cases were registered with the metabolic syndrome. in regards to this diagnosis the results show a higher incidence of overweight and obesity compared with other countries. It is necessary to conduct further studies to assess the relationship of excess fat as a risk factor for endometrial cancer.
Introduction The aim of this study was to determine the incidence rates of endometrial hyperplasia (EH) and endometrial cancer (EC) in the Republic of Korea using national insurance claim data generated from 2009 to 2012. Materials and Methods Data that were generated from 2009 to 2012 were sourced from the Korean Health Insurance Review and Assessment Service-National Inpatients Sample database. The data from women who were assigned diagnosis codes representing EH or EC within 1 month of being assigned codes that corresponded to procedures that included endometrial biopsies and several types of gynecologic surgeries to obtain endometrial pathology samples, were selected for analysis. Results Data from 2,477,424 women were entered into the database between 2009 and 2012, and the data from 1,868 women with EH and 868 women with EC were extracted for analysis. The mean ages of the patients were 44.1 ± 0.4 years for those with EH and 52.7 ± 0.6 years for those with EC. The EH and EC incidence rates were 37 per 100,000 woman-years and 8 per 100,000 woman-years, respectively. The EH and EC incidence rates peaked when the women were in their late forties and fifties, respectively. Conclusions The EH and EC incidence rates determined in this study were somewhat lower than those determined from previous studies. Further studies are required that adjust the data for race, menopausal hormone therapy, and obesity. PMID:27635340
Jafarabadi, Mina; Salehnia, Mojdeh; Sadafi, Rana
Background: The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. Objective: In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. Materials and Methods: The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN) and matrix metalloproteinase 2 (MMP2) genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. Results: The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03). Conclusion: Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments. PMID:28280797
Luo, J; Beresford, S; Chen, C; Chlebowski, R; Garcia, L; Kuller, L; Regier, M; Wactawski-Wende, J; Margolis, K L
A growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI). A total of 88 107 postmenopausal women aged 50-79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer. Over a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13-1.85 for diabetes, HR=1.57, 95% CI: 1.19-2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08-1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer
McCormick, Betsy A; Wilburn, Rochelle D; Thomas, Michael A; Williams, Daniel B; Maxwell, Rose; Aubuchon, Mira
Body mass index is predictive of sonographic endometrial stripe thickness, which in turn is predictive of endometrial hyperplasia in patients with polycystic ovary syndrome. For every 1-mm increase in endometrial stripe, the odds ratio of hyperplasia increased by 1.48 (95% confidence interval, 1.04-2.10).
Development and Progression of Breast Cancer From Benign Breast Lesions PRINCIPAL INVESTIGATOR: Maria J...Population Based Assessment of MHC Class I Antigens Down Regulation as Marker 5a. CONTRACT NUMBER of Increased Risk for Development and...interaction with other epidemiological risk factors that can serve as risk indicators for subsequent development of breast cancer from precancerous lesions
Caslowitz, P.L.; Labs, J.D.; Fishman, E.K.; Siegelman, S.S. )
Fifty-nine cases of nontraumatic splenic disease were reviewed to evaluate the roles of clinical findings, computed tomography, ultrasound, and radionuclide scanning in diagnosis and management. Patient groups included lymphoma (30 patients), infarct (11 patients), abscess (9 patients), cyst (5 patients), hemangioma (3 patients), and hamartoma (1 patient). In no case were clinical findings alone sufficient to diagnose a splenic lesion. Clinical and laboratory manifestations were nonspecific in all groups. Moreover, no radiologic study reliably diagnosed splenic lymphoma or leukemia. All other focal splenic lesions were consistently diagnosed noninvasively. Cross-sectional imaging was more useful than radioisotope scanning, and often provided adjunctive diagnosis of extrasplenic pathology. The superior detail, spatial resolution, and sensitivity of computed tomography made it the single most valuable diagnostic modality.
Tan, Yu Hwee; Lethaby, Anne
registered trials; citation indexes; conference abstracts in the Web of Knowledge; the LILACS database for trials from the Portuguese- and Spanish-speaking world; PubMed; and the OpenSIGLE database and Google for grey literature.All searches were performed in consultation with the MDSG Trials Search Co-ordinator. Randomised controlled trials (RCTs) were included if they compared the effects of these agents with one other, or with placebo or no treatment, on relevant intraoperative and postoperative treatment outcomes. Selection of trials was carried out independently by two review authors. Two review authors independently assessed studies for risk of bias and extracted data on surgical outcomes, effectiveness outcomes, proportion of women requiring further surgical therapy during follow-up, endometrial outcome measures, acceptability of use outcomes and quality of life. Data were analysed on an intention-to-treat basis. Dichotomous data were combined for meta-analysis with RevMan software using the Mantel-Haenszel method to estimate pooled risk ratios (RRs). Continuous data were combined for meta-analysis with RevMan software using an inverse variance method to estimate the pooled mean difference (MD) with 95% confidence interval (CI). The overall quality of evidence for the main findings was assessed with the use of GRADE working group methods. Twenty studies with 1969 women were included in this review. These studies compared GnRHa, danazol and progestogens versus placebo or no treatment; GnRHa versus danazol, progestogens, GnRH antagonists or dilatation & curettage; and danazol versus progestogens. Four studies performed more than one comparison.When compared with no treatment, GnRHa used before hysteroscopic resection were associated with a higher rate of postoperative amenorrhoea at 12 months (RR 1.6, 95% CI 1.2 to 2.0, 7 RCTs, 605 women, moderate heterogeneity; I(2) = 40%) and at 24 months (RR 1.62, 95% CI 1.04 to 2.52, 2 RCTs, 357 women, no heterogeneity; I(2) = 0
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.
Afroz, Nishat; Singh, Mamta; Verma, Manju; Bansal, Vandana
Female infertility can be categorised into those who fail to ovulate (anovulatory infertility) because of some defect at hypothalamic-pituitary-ovarian axis and those who are ovulatory (ovulatory infertility), but are infertile because of some lesion present in genital tract. The role of vaginal hormonal cytology, endometrial biopsy and endocrinological evaluation in the detection of ovulation and various ovulatory dysfunction was studied in 42 infertile female patients. On the basis of cytological findings, of the 42 patients, 14 were found to be ovulatory, 26 anovulatory (which include 5 cases of atrophic changes) and 2 inconsistent due to inflammatory changes. Endometrial biopsy showed evidence of ovulation in 15, anovulation in 27 cases. Hormonal evaluation indicated some sort of endocrinological disorders in 15 patients, which may underlie anovulatory infertility in these patients, while results were within normal range in the rest 27 patients. Results of vaginal cytology and endometrial biopsy showed correlation in respect to ovulation in 93.33% of the cases.
Henseler, Ilona; Regenbrecht, Frank; Obrig, Hellmuth
indicate that: (i) Aachen Aphasia Test-based syndrome allocation allows for an unexpectedly concise differentiation between 'Broca's' and 'Wernicke's' aphasia corresponding to non-overlapping anterior and posterior lesion sites; whereas (ii) analyses for modalities and specific symptoms yielded more circumscribed but partially overlapping lesion foci, often cutting across the above syndrome territories; and (iii) especially for lexico-semantic capacities more specialized clinical test-batteries are required to delineate precise lesion patterns at this linguistic level. In sum this is the first report on a successful lesion-delineation of syndrome-based aphasia classification highlighting the relevance of vascular distribution for the syndrome level while confirming and extending a number of more linguistically motivated differentiations, based on clinically used tests. We consider such a comprehensive view reaching from the syndrome to a fine-grained symptom-oriented assessment mandatory to converge neurolinguistic, patholinguistic and clinical-therapeutic knowledge on language-competence and impairment.
Zhang, Guo-Qiang; Chen, Jin-Liang; Liu, Qin; Zhang, Yong; Zeng, Huan; Zhao, Yong
Abstract Epidemiologic studies reporting the effect of soy intake on endometrial cancer risk conveyed conflicting results. We systematically reviewed the literature to investigate whether there was an inverse relation between dietary soy intake and endometrial cancer risk. PubMed, EMBASE, the Cochrane Library, and 4 main Chinese literature databases were searched from their inception to August 25, 2015 for both case–control studies and cohort studies that assessed the effect of soy intake on endometrial cancer risk. Study-specific most-adjusted odds ratios (ORs) or relative risks (RRs) were combined by using fixed-effects or random-effects model to calculate pooled risk estimates (REs). A total of 10 epidemiologic studies were included in this meta-analysis, including 8 case–control studies and 2 prospective cohort studies. Dietary soy intake was inversely associated with endometrial cancer risk with an overall RE of 0.81 (95% CI: 0.72, 0.91). In subgroup analyses, a statistically significant protective effect of soy intake was found for unfermented soy food (RE: 0.81, 95% CI: 0.67, 0.97), postmenopausal women (RE: 0.76, 95% CI: 0.61, 0.95), and Asian (RE: 0.79, 95% CI: 0.66, 0.95) and non-Asian population (RE: 0.83, 95% CI: 0.71, 0.96). Current evidence indicates that soy food intake is associated with lower endometrial cancer risk. Further larger cohort studies are warranted to fully clarify such an association. PMID:26683956
Androutsopoulos, Georgios; Adonakis, Georgios; Liava, Anna; Ravazoula, Panagiota; Decavalas, Georgios
Endometrial cancer is the most common malignancy of the female genital tract. Based on clinical and pathological features, endometrial cancer is classified into two types. The aim of our study was to describe the expression and the potential clinical role of ErbB receptors in Greek patients with type II endometrial cancer. Between 1991 and 2008, 10 women with histologically confirmed type II endometrial cancer were referred to the Department of Gynecologic Oncology of the University of Patras Medical School. Tissue specimens from endometrial lesions were immunostained for EGFR, ErbB-2, ErbB-3 and ErbB-4. For EGFR, 5 cases were positive (50%) and 5 cases were negative. For ErbB-2, 9 cases were positive (90%) and 1 case was negative. For ErbB-3, all cases were positive. For ErbB-4, 7 cases were positive (70%) and 3 cases were negative. Also for all ErbB receptors, 5 cases were positive (50%). During follow up, 3 patients died from their disease. All of them had papillary serous endometrial cancer and 2 of them were positive for all ErbB receptors. Although our study was based on a small number of cases, it is obvious that we had high expression levels of ErbB receptors in patients with type II endometrial cancer. Also the majority of patients with dismal outcome were positive for all ErbB receptors. This is very important, as ErbB-targeted therapies may be clinically active as adjuvant therapy in well-defined subgroups of type II EC patients with EGFR and ErbB-2 overexpression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Reed, SD; Voigt, LF; Newton, KM; Garcia, R; Allison, HK; Epplein, M; Jordan, D; Swisher, E; Weiss, NS
Precis Complex hyperplasia regression is common with and without progestin therapy, and the likelihood of atypical hyperplasia regression is greater with progestin therapy than without. Objective To assess likelihood of histologic persistence/progression of complex hyperplasia and atypical hyperplasia among women treated with progestin compared to those not treated, with attention to type, dose and duration. Methods This was a cohort study of women at an integrated health plan, ages 18-85 years, with complex or atypical hyperplasia on independent pathology review with a second endometrial specimen in the 2-6 months following the index diagnosis. Progestin therapy between index diagnosis and follow-up biopsy was determined from the pharmacy database. Medical record abstraction was performed. Relative risks (RR), adjusted for age and body mass index, were calculated. Results Among 185 women, average age 55.9 years, follow-up 16.1 weeks, 115 women had complex and 70 had atypical hyperplasia. Among women with complex hyperplasia 28.4% of women treated with progestin and 30.0% of those not treated had persistence/progression (RR 1.20, 95% confidence interval (CI) 0.53-2.72). Among women with atypical hyperplasia, 26.9% of those treated with progestin and 66.7% of those not treated had persistence/progression (RR 0.39, 95% CI 0.21-0.70); there was a suggestion that use of at least a medium dose, or a duration of at least 3 months, was associated with a particularly low probability of persistence/progression. Conclusion While progestin treatment of women with atypical hyperplasia was associated with a substantial increase in the likelihood of regression of the lesion during the ensuing 2-6 months, persistence/progression was nonetheless present in more than one-quarter of treated women. Regression of complex hyperplasia without atypia was common whether progestin had or had not been used. PMID:19300331
Gonthier, C; Trefoux-Bourdet, A; Luton, D; Koskas, M
The fertility sparing management of endometrial cancer and atypical hyperplasia concern women in childbearing age with stage 1, grade 1, endometrioid adenocarcinoma confined to endometrium or atypical hyperplasia (simple or complex). These pathologies affecting more frequently postmenopausal women, the number of people involved is relatively low. The main risk factor is hyperestrogenism and these patients often present a history of infertility with a desire for pregnancy. The recommendations for this conservative management are scarce and unclear. The national observatory in the gynecology and obstetrics department of Bichat hospital gives expert advice to help doctors and patients concerned. We present a type of conservative management based on the expertise of the national observatory. Rigorous pre-therapeutic assessment must first be made to avoid missing a more advanced lesion. Hormone therapy is then started to obtain complete remission. In case of remission, fast achieving pregnancy is advised, and the use of assisted reproductive therapy is possible if necessary. Monitoring by hysteroscopy and histological examination is essential during the treatment. Hysterectomy is the last time the conservative management. It is motivated by the risk of recurrence and progression. The probability of remission after conservative treatment is estimated at 78.0 % at 12 months, the probability of recurrence at 29.2 % at 24 months, and the risk of progression at 15 % (stage 1A with myometrial invasion or more on the hysterectomy specimen). In terms of fertility, 32 % of women get at least one pregnancy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Balthazar, Patricia; Shinagare, Atul B; Tirumani, Sree Harsha; Jagannathan, Jyothi P; Ramaiya, Nikhil H; Khorasani, Ramin
To evaluate the impact of contrast agent selection on radiologists' confidence in assessing liver lesions on follow-up magnetic resonance imaging (MRI) studies in patients with neuroendocrine tumors. This Institutional Review Board-approved, retrospective study performed at a tertiary cancer center and a quaternary care urban academic hospital included all 694 follow-up abdominal MRI studies from 179 patients with gastroenteropancreatic neuroendocrine tumor performed from 01/01/2010 to 05/31/2015. Primary outcome measure was radiologists' confidence in assessing liver lesions on follow-up MRI. MRI reports were reviewed to abstract radiologists' confidence, classified as "equivocal" if any equivocal connotation (mention of limitation due to differences in contrast agent or follow-up recommendation with specific contrast agent) was present; or "unequivocal" if a precise, confident comparison to prior was documented without the use of ambiguous terms. A fellowship-trained radiologist separately evaluated 100 randomly selected reports and images to calculate interobserver agreement with the report classification (equivocal vs. unequivocal) and with the original MRI report, respectively. Chi-square test was used to compare the proportion of equivocal reports when "same" or "different" contrast agent was used for successive examinations. Rates of equivocal reports were higher when different contrast agents were used for successive examinations compared to examinations with same contrast agent (13.2% [21/159] vs. 1.8% [10/535]; p < 0.0001). There was very good interobserver agreement for assessment of radiologist confidence (κ = 0.92 for report review, κ = 0.82 for image review). Consistent use of contrast agent for follow-up MRIs allows more confident assessment of liver lesions in patients with neuroendocrine tumors.
Fonager, Randi F; Zacho, Helle D; Albertsen, Signe; Fledelius, Joan; Ejlersen, June A; Christensen, Mette H; Aleksyniene, Ramune; Biurrun Manresa, José A; Petersen, Lars J
The aim of this study was to assess observer agreement on the evaluation of treatment responses of bone metastases by bone scintigraphy (BS) using different scoring methods in prostate cancer patients. Sixty-three paired BS from 55 patients were included. BS was performed before and after more than 12 weeks of anticancer treatment. A panel of experienced nuclear medicine physicians from several institutions evaluated treatment response using three different methods: (a) standard clinical assessment, (b) MD Anderson criteria, and (c) Prostate Cancer Working Group 2 (PCWG-2) criteria. All methods were based on the evaluation of paired before-after bone scans. Readers were able to classify the presence of bone metastases at baseline with a high level of agreement [Cohen's κ=0.94, 95% confidence interval (CI) 0.82-1.00]. Observer agreement on bone response by PCWG-2 criteria showed considerable agreement (Cohen's κ=0.84, 95% CI: 0.69-0.99). Evaluation using standard clinical assessment and MD Anderson criteria showed moderate agreement (0.52, 95% CI: 0.36-0.69 and 0.64, 95% CI: 0.48-0.79, respectively). There was considerable variation among readers for regional lesion count on individual scans, with limits of agreement of -10 to 10 lesions or more for the majority of anatomical regions, including the thorax, spine, and pelvis. Observer agreement on treatment response by BS varied notably across methods. Optimal agreement was achieved by the PCWG-2 criteria. Variation in the classification of treatment response of bone metastases may have a significant impact on clinical decision-making, emphasizing the need for a uniform approach, including during clinical practice. Response assessment by lesion counting on repeated BS without access to previous scans cannot be recommended.
Salem, Shahenda; Houseni, Mohamed; Zidan, Lamiaa; Kandil, Ahmed
The liver hosts a variety of benign and malignant tumors. Accurate diagnosis can be challenging in certain cases, especially in patients with a history of malignancy or in those with underlying liver pathology, such as cirrhosis. To evaluate the added clinical value of multi-modality liver imaging utilizing PET/Ce-CT/DW-MRI for characterization of hepatic focal lesions (HFL) and compare it with each diagnostic modality when interpreted alone. The study included 35 patients with HFL. They were 7 females & 28 males; their age ranged from 41 to 78years, all patients underwent PET/Ce-CT and DW-MRI scans. Ce-CT, PET and DW-MR images were reviewed independently, and then combined PET/Ce-CT, PET/DW-MRI and PET/Ce-CT/DW-MRI scans were analyzed. The results were correlated with histopathology or clinical/imaging follow-up. The 35 patients had 98 focal lesions. Fifty-three lesions were finally diagnosed as primary hepatocellular carcinoma, 18 lesions were metastases, 7 lesions were lymphoma and 20 lesions were benign. On a patient based analysis; the sensitivity, specificity, PPV, NPV and accuracy were 100%, 67%, 94%, 100% and 94% for PET/Ce-CT compared to 97%, 83%, 97%, 83% and 94 % for DW-MRI, respectively. Combined PET/Ce-CT/DW-MR scans raise those parameters up to 100%. On a lesion based analysis; the sensitivity, specificity, PPV, NPV and accuracy were 94%, 75%, 94%, 75%, 90% for PET/Ce-CT compared to 94%, 95%, 99%, 97% and 94 % for DW-MRI, respectively. All these parameters were 100 % with PET/Ce-CT/DW-MRI. The addition of DW-MRI to PET/Ce-CT is valuable in the characterization of hepatic focal lesions. Copyright © 2015 Elsevier Inc. All rights reserved.
Chandavarkar, Uma; Kuperman, Julie M; Muderspach, Laila I; Opper, Neisha; Felix, Juan C; Roman, Lynda
To determine the preoperative pelvic ultrasonographic characteristics of postmenopausal women diagnosed with endometrial cancer (EC) at our institution. Postmenopausal women with EC who underwent preoperative transvaginal pelvic ultrasound from 1999-2009 were identified from our institutional database. The histologic diagnosis was based on pathologic findings in the hysterectomy specimen. Endometrial echo complex (EEC) thickness was abstracted from ultrasound reports. In all instances, ultrasound preceded the biopsy by a maximum of 3 months. Means with standard deviations were calculated for all categorical data. Differences between type 1 and type 2 ECs were determined using Mann-Whitney U tests and Chi squared/Fisher's exact tests, as appropriate. A p-value of <0.05 was considered statistically significant. Among 250 patients with postmenopausal EC, 156 had type 1 EC while 94 had type 2 EC. Thirty-six percent of the cohort had an EEC ≤ 4 mm, including 37% of patients with type 1 EC and 34% of patients with type 2 EC (p=0.63). There were no significant differences between type 1 and type 2 ECs in any demographic characteristic, other than likelihood of postmenopausal bleeding. Current expert opinion recommends no further diagnostic procedure in a woman with postmenopausal bleeding and an EEC ≤ 4 mm. These results indicate that a sizable proportion of women with EC have EECs ≤ 4 mm during their initial evaluation. An EEC ≤ 4 mm does not completely rule out endometrial cancer and cannot supplant histologic evaluation. © 2013.
Jadhav, Meenal V.; Phatke, Anjali S.; Kadgi, Nalini Vinayak; Rane, Sharda R.; Kulkarni, Kalpana K.
Context: Endometrial aspiration is not a popular modality for the study of the endometrium despite its simplicity and potential utility. Aim: The present study was aimed at evaluating the utility of endometrial aspiration in various gynecological disorders. Materials and Methods: In this diagnostic accuracy study, 55 prospectively registered women with various gynecological disorders were evaluated clinically and subjected to endometrial aspiration cytology and study of endometrial histology. Endometrial aspiration was performed by infant feeding tube in 10 cases and intra cath cannula in 45 cases. The slides were stained with rapid Papanicolaou (PAP) stain and Leishman stain. Results: Endometrial aspiration cytology showed 90% and 94.6% sampling adequacy with infant feeding tube and intra cath cannula, respectively. Intra cath cannula was very convenient to handle and superior to infant feeding tube in aspirating the endometrium. Of the two stains used, rapid PAP stain was less time-consuming and superior to Leishman stain in studying the nuclear details. Leishman stain was helpful in detecting cytoplasmic vacuoles of secretory endometrium. Overall diagnostic accuracy of endometrial cytology was 90.4% while that for morphological hormonal evaluation was 97.6%. It enjoyed a sensitivity of 91.66%, a specificity of 88.23%, positive predictive value of 94.28%, and negative predictive value of 83.33%. Conclusion: Intra cath cannula emerged as an inexpensive, effective, and convenient device for endometrial aspiration. Endometrial aspiration proved to be a fairly effective, simple, and informative diagnostic modality. PMID:27011435
Hirasawa, Akira; Makita, Kazuya; Akahane, Tomoko; Yokota, Megumi; Yamagami, Wataru; Banno, Kouji; Susumu, Nobuyuki; Aoki, Daisuke
Objective Previous studies have reported an association between endometrial cancer and the risk of metabolic syndrome; however, the pattern of endometrial cancer-associated dyslipidemia is not well understood. The standard therapy for endometrial cancer is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Premenopausal bilateral salpingo-oophorectomy may cause adverse events, including dyslipidemia. Gynecologists have to care dyslipidemia in endometrial cancer survivors at cancer follow-up clinic. Methods This study included 693 patients who had undergone bilateral salpingo-oophorectomy, and included 412 women with incident endometrial cancer and 281 controls. We divided the patients into two categories according to whether they had a premenopausal or postmenopausal bilateral oophorectomy. Serum lipid levels were measured and statistically analyzed. Results Hypertriglyceridemia was statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy both before and after menopause than in the corresponding non-endometrial cancer controls. High levels of low-density lipoprotein cholesterol and a high low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy before menopause than in non-endometrial cancer controls. Conclusions Our report highlights the importance of the relationship between endometrial cancer and lipid metabolism, which may aid in preventing cerebrovascular or cardiovascular diseases due to dyslipidemia and improving the quality of life in endometrial cancer survivors. PMID:23999769
Kim, Tae Hoon; Yoo, Jung-Yoon; Jeong, Jae-Wook
Endometrial cancer is a frequently occurring gynecological disorder. Estrogen-dependent endometrioid carcinoma is the most common type of gynecological cancer. One of the major pathologic phenomena of endometrial cancer is the loss of estrogen (E2) and progesterone (P4) control over uterine epithelial cell proliferation. P4 antagonizes the growth-promoting properties of E2 in the uterus. P4 prevents the development of endometrial cancer associated with unopposed E2 by blocking E2 actions. Mitogen inducible gene 6 (Mig-6, Errfi1, RALT, or gene 33) is an immediate early response gene that can be induced by various mitogens and common chronic stress stimuli. Mig-6 has been identified as an important component of P4-mediated inhibition of E2 signaling in the uterus. Decreased expression of MIG-6 is observed in human endometrial carcinomas. Transgenic mice with Mig-6 ablation in the uterus develop endometrial hyperplasia and E2-dependent endometrial cancer. Thus, MIG-6 has a tumor suppressor function in endometrial tumorigenesis. The following discussion summarizes our current knowledge of Mig-6 mouse models and their role in understanding the molecular mechanisms of endometrial tumorigenesis and in the development of therapeutic approaches for endometrial cancer.
... and pipette, or catheter. This device is used to study endometrial cytology (cells). (b... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean...
... and pipette, or catheter. This device is used to study endometrial cytology (cells). (b... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean...
Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A
Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data
Franchello, Alessandro; Fronda, Gianruggero; Deiro, Giacomo; Fiore, Alessia; Cassine, Davide; Molinaro, Luca; Chiusa, Luigi; Galati, Sara; Resegotti, Andrea; Silvestri, Stefano
Endometrial carcinoma is the most common neoplasia of female genital tract. The prognosis of early stage disease (FIGO I and FIGO II) is excellent: recurrence after surgery is less than 15%, most of which are reported within 3 years after primary treatment. Herein we report a case of late rectal recurrence from FIGO Ib endometrial adenocarcinoma. Patient had also familiar and personal history of colonic adenocarcinoma and previous findings of microsatellite instability (MSI); molecular analysis evidenced heterozygotic somatic mutation in MLH1 gene. Twenty-eight years after hysterectomy and bilateral salpingoovariectomy, a rectal wall mass was detected during routine colonoscopy. Patients underwent CT scan, pelvic MRI, and rectal EUS with FNA: histopathological and immunohistochemical analysis revealed differentiated carcinoma cells of endometrial origin. No neoadjuvant treatment was planned and low rectal anterior resection with protective colostomy was performed; histology confirmed rectal lesion as metastasis from endometrial carcinoma. Recurrence of early stage endometrial carcinoma after a long period from primary surgery is possible. It is important to keep in mind this possibility in order to set a correct diagnostic and therapeutic algorithm, including preoperative immunohistochemical staining, and to plan a prolonged follow-up program. PMID:26783488
Wallbillich, John J; Josyula, Srirama; Saini, Uksha; Zingarelli, Roman A; Dorayappan, Kalpana Deepa Priya; Riley, Maria K; Wanner, Ross A; Cohn, David E; Selvendiran, Karuppaiyah
STAT3 is over-expressed in endometrial cancer, and diabetes is a risk factor for the development of type 1 endometrial cancer. We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin. In Ishikawa (grade 1) endometrial cancer cells subjected to media with low, normal, or high concentrations of glucose, expression of STAT3 and its target proteins was evaluated by real-time quantitative PCR (qPCR). Ishikawa cells were treated with metformin and assessed with cell proliferation, survival, migration, and ubiquitin assays, as well as Western blot and qPCR. Expression of apoptosis proteins was evaluated with Western blot in Ishikawa cells transfected with a STAT3 overexpression plasmid and treated with metformin. A xenograft tumor model was used for studying the in vivo efficacy of metformin. Expression of STAT3 and its target proteins was increased in Ishikawa cells cultured in high glucose media. In vitro, metformin inhibited cell proliferation, survival and migration but induced apoptosis. Metformin reduced expression levels of pSTAT3 ser727, total STAT3, and its associated cell survival and anti-apoptotic proteins. Additionally, metformin treatment was associated with increased degradation of pSTAT3 ser727. No change in apoptotic protein expression was noticed with STAT3 overexpression in Ishikawa cells. In vivo, metformin treatment led to a decrease in tumor weight as well as reductions of STAT3, pSTAT3 ser727, its target proteins. These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin.
Uysal, Selda; Özbay, Elif Pelin Özün; Ekinci, Tekin; Aksüt, Hayri; Karasu, Şebnem; Işık, Ahmet Zeki; Soylu, Ferit
Objective Uterine perfusion, particularly the endometrial blood flow, may have an important role in endometrial receptivity. In order to assess the contribution of sub endometrial blood flow in the etiopathogenesis of unexplained infertility mid luteal- peri-implantation period spiral artery transvaginal color Doppler parameters were measured and compared with fertile controls. Material and Methods Forty-two consecutive patients admitted to Izmir Katip Celebi University Ataturk Training and Research Hospital, Department of Obstetric and Gynecology with the diagnosis of unexplained infertility after standard diagnostic work up constituted the study group and they were compared with a fertile control group admitted to hospital with non specific gynecological complaints or for check-up in the same period. Mid luteal transvaginal color Doppler ultrasonography was applied to each patient by the same radiologist who was blind to the diagnosis of the particular patient and, RI (resistance index) and PI (pulsatility index) values were calculated. Results There were no significant differences between the two groups, in respect to age, body mass index, basal hormonal and mid luteal progesterone levels (p>0.05). For the fertile control group, mid luteal-peri-implantation phase endometrial spiral artery mean RI values were calculated as 0.48±0.08 SD and mean PI values as 0.65±0.18 SD. For the study group, mean RI values were calculated as 0.54±0.07 SD, PI values were calculated as 0.80±0.16 SD. The differences for RI (p=0.009) and PI (p=0.004) were statistically significant. Conclusion According to Doppler parameters, unexplained infertility patients have high impedance blood flow in spiral arteries which means that peri-implantation blood flow in these patient is lower than fertile controls. These findings suggest that endometrial perfusion may have an important contribution to etiopathogenesis of unexplained infertility. PMID:24592032
Uysal, Selda; Ozbay, Elif Pelin Özün; Ekinci, Tekin; Aksüt, Hayri; Karasu, Sebnem; Işık, Ahmet Zeki; Soylu, Ferit
Uterine perfusion, particularly the endometrial blood flow, may have an important role in endometrial receptivity. In order to assess the contribution of sub endometrial blood flow in the etiopathogenesis of unexplained infertility mid luteal- peri-implantation period spiral artery transvaginal color Doppler parameters were measured and compared with fertile controls. Forty-two consecutive patients admitted to Izmir Katip Celebi University Ataturk Training and Research Hospital, Department of Obstetric and Gynecology with the diagnosis of unexplained infertility after standard diagnostic work up constituted the study group and they were compared with a fertile control group admitted to hospital with non specific gynecological complaints or for check-up in the same period. Mid luteal transvaginal color Doppler ultrasonography was applied to each patient by the same radiologist who was blind to the diagnosis of the particular patient and, RI (resistance index) and PI (pulsatility index) values were calculated. There were no significant differences between the two groups, in respect to age, body mass index, basal hormonal and mid luteal progesterone levels (p>0.05). For the fertile control group, mid luteal-peri-implantation phase endometrial spiral artery mean RI values were calculated as 0.48±0.08 SD and mean PI values as 0.65±0.18 SD. For the study group, mean RI values were calculated as 0.54±0.07 SD, PI values were calculated as 0.80±0.16 SD. The differences for RI (p=0.009) and PI (p=0.004) were statistically significant. According to Doppler parameters, unexplained infertility patients have high impedance blood flow in spiral arteries which means that peri-implantation blood flow in these patient is lower than fertile controls. These findings suggest that endometrial perfusion may have an important contribution to etiopathogenesis of unexplained infertility.
Wallbillich, John J.; Josyula, Srirama; Saini, Uksha; Zingarelli, Roman A.; Dorayappan, Kalpana Deepa Priya; Riley, Maria K.; Wanner, Ross A.; Cohn, David E.; Selvendiran, Karuppaiyah
Objectives STAT3 is over-expressed in endometrial cancer, and diabetes is a risk factor for the development of type 1 endometrial cancer. We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin. Methods In Ishikawa (grade 1) endometrial cancer cells subjected to media with low, normal, or high concentrations of glucose, expression of STAT3 and its target proteins was evaluated by real-time quantitative PCR (qPCR). Ishikawa cells were treated with metformin and assessed with cell proliferation, survival, migration, and ubiquitin assays, as well as Western blot and qPCR. Expression of apoptosis proteins was evaluated with Western blot in Ishikawa cells transfected with a STAT3 overexpression plasmid and treated with metformin. A xenograft tumor model was used for studying the in vivo efficacy of metformin. Results Expression of STAT3 and its target proteins was increased in Ishikawa cells cultured in high glucose media. In vitro, metformin inhibited cell proliferation, survival and migration but induced apoptosis. Metformin reduced expression levels of pSTAT3 ser727, total STAT3, and its associated cell survival and anti-apoptotic proteins. Additionally, metformin treatment was associated with increased degradation of pSTAT3 ser727. No change in apoptotic protein expression was noticed with STAT3 overexpression in Ishikawa cells. In vivo, metformin treatment led to a decrease in tumor weight as well as reductions of STAT3, pSTAT3 ser727, its target proteins. Conclusions These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin. PMID:28114390
The destruction of the endometrium in women with heavy menstrual bleeding has been employed for well over a century and the various techniques of delivering forms of thermal energy have been modified over the years to assure a safe and effective treatment approach. Today, six non-resectoscopic devices are approved for use in the United States in addition to resectoscopic techniques that rely on skillful use of the operative hysteroscope. Regardless of the technique employed, endometrial ablation uniformly reduces menstrual blood loss, improves general and menstrual related quality of life and prevents hysterectomy in four out of five women who undergo the procedure. When patients are appropriately selected, outcomes are optimized and risks of serious complications are minimized. This article reviews the literature with singular reference to non-resectoscopic endometrial ablation procedures including historical background, appropriate patient selection, clinical outcomes data, complication and special or unique considerations. Copyright © 2017. Published by Elsevier Inc.
Mikaelian, Igor; Reavill, Drury R; Practice, Avian
Fifteen captive female African hedgehogs (Atelerix albiventris), 3- to 5-yr-old, were diagnosed with proliferative uterine lesions (n = 28). Lesions were associated with vaginal bleeding in all cases, hematuria in 11 of 13 cases, and weight loss in 7 of 12 cases. Lesions were multiple in eight cases and single in seven cases. The lesions identified were 13 adenosarcomas, 7 endometrial stromal sarcomas, 6 endometrial polyps, 1 adenoleiomyosarcoma, and 1 adenoleiomyoma. In one animal with adenosarcoma, peritoneal seeding was detected at the time of hysterectomy. Mean survival time was 303 days (n = 10). Ovariohysterectomy allows prolonged survival of hedgehogs with uterine tumors.
Zhang, Kai; Xia, Chun-Chao; Yue, Qiang; Guo, Tao; Peng, Wan-Lin; Li, Yu-Ming; Li, Lei; Zhao, Fei; Pu, Jin; Leng, Qi; Li, Zhen-Lin
To explore the clinical value of readout-segmented echo planar imaging (Rs-EPI) sequence in the assessment of intracranial mass lesions compared to the standard single-shot EPI (Ss-EPI) sequence. We included 21 patients with intracranial mass lesions who underwent both Ss-EPI diffusion weighted imaging (DWI) and Rs-EPI DWI at 3.0T MR scanner with a twenty-channel head-neck coil. The quality of images was assessed by two experienced radiologists independently. The differences in image quality between two sequences were analyzed using Wilcoxon signed-rank test. Inter-observer agreements were analyzed using interclass correlation coefficient (ICC) and Kappa test. All objectives were completed on 3.0T MR. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in Rs-EPI DWI were higher than those in Ss-EPI DWI (130.46±49.10 vs. 71.58±30.43, P=0.000; 33.22±18.86 vs. 17.92±18.72, P=0.003). The scores of overall image quality, ghost artifact where next to the paranasal sinuses, mastoid air cells and frontal sinus of Rs-EPI DWI were significantly higher than those of Ss-EPI DWI. Meanwhile, the geometric distortion of anatomical structures of Rs-EPI DWI were significantly lower compared to Ss-EPI DWI sequence (0.016±0.021 vs. 0.037±0.069, P=0.00). The inter-reader and intra-reader agreements for the assessment of qualitative parameters were good [0.74≤Kappa value or ICC≤0.92]. Rs-EPI DWI sequence is a potential technique to improve the imaging quality in the diagnosis of intracranial mass lesions.
Ngonzi, Joseph; Bajunirwe, Francis; Wistrand, Charlotte; Mayanja, Ronald; Altman, Daniel; Thorsell, Malin; Wikström Shemer, Elisabeth Andrea
This study aimed to determine if criterion standard colposcopy could be provided by a pocket-sized battery-driven colposcope, the Gynocular. The study was a randomized, crossover, pilot clinical trial for evaluating agreement of diagnosis of cervical lesions by colposcopy using a standard colposcope and a pocket-sized battery-driven colposcope, the Gynocular, in 69 women positive for visual inspection with acetic acid. Swede scores were used at the time of colposcopy and compared with the final histological diagnosis after directed cervical biopsy. To test the level of agreement between the colposcopy and Gynocular, we calculated the percentage agreement and the κ statistic. We calculated the detection rates of cervical lesions of the Gynocular and a standard colposcope using biopsy results as criterion standards. All included patients also underwent a Pap smear. The level of agreement of Swede score between the Gynocular and colposcope was 70.1% and the κ statistic was 0.65 (p < .001). Biopsy identified 4 women (6.7%) with cervical intraepithelial neoplasia 1 (CIN 1) and 1 woman (1.7%) with CIN 2; 2 women (3.4%) had CIN 3, and 2 women had invasive cervical cancer (CIN 3+). Pap smear detected 2 women (3.1%) with CIN 1 but did not identify any high-grade cervical lesion. Cervicitis was present in 17 (27.4%) of the Pap smears and in 34 (57.6%) of the biopsies. The study shows that in visual inspection with acetic acid-positive women, a battery-driven, pocket-sized colposcope has a significant level of agreement with stationary colposcopy in assessing cervical lesions.
Franklin, M E; Conner-Kerr, T; Chamness, M; Chenier, T C; Kelly, R R; Hodge, T
The Cyriax selective tension assessment paradigm is commonly used by clinicians for the diagnosis of soft tissue lesions; however, studies have not demonstrated that it is a valid method. The purpose of this study was to examine the construct validity of the active motion, passive motion, resisted movement, and palpation components of the Cyriax selective tension diagnosis paradigm in subjects with an exercise-induced minor hamstring muscle lesion. Nine female subjects with a mean age of 23.6 years (SD = 4.7) and a mass of 57.3 kg (SD = 10.7) performed two sets of 20 maximal eccentric isokinetic knee flexor contractions designed to induce a minor muscle lesion of the hamstrings. Active range of motion, passive range of motion, knee extension end-feel pain relative to resistance sequence, knee flexor isometric strength, pain perception during knee flexor resisted movement testing, and palpation pain of the hamstrings were assessed at 0, 5, 2, 12, 24, 48, and 72 hours postexercise and compared with Cyriax's hypothesized selective tension paradigm results. Consistent with Cyriax's paradigm, passive range of motion remained unchanged, and perceived pain of the hamstrings increased with resistance testing at 12, 24, 48, and 72 hours postexercise when compared with baseline. In addition, palpation pain of the hamstrings was significantly elevated at 48 and 72 hours after exercise (p < 0.05). In contrast of Cyriax's paradigm, active range of motion was significantly reduced over time (p < 0.05), with the least amount of motion compared to baseline (85%) occurring at 48 hours postexercise. Further, resisted movement testing found significant knee flexor isometric strength reductions over time (p < 0.05), with the greatest reductions (33%) occurring at 48 hours postexercise. According to Cyriax, when a minor muscle lesion is tested, it should be strong and painful; however, none of the postexercise time frames exhibited results that were strong and painful. This study
Unlu, Cihat; Celik, Onder; Celik, Nilufer; Otlu, Baris
This study was designed to investigate whether endometrial receptivity genes are altered in infertile patients with intramural leiomyomas (IM) not distorting the endometrial cavity undergoing myomectomy. We measured endometrial HOXA-10, HOXA-11, LIF, ITGB3, and ITGAV messenger RNA (mRNA) expressions levels before and after myomectomy/metroplasty during mid-luteal phase in participants with IM, submucosal leiomyomas (SM), and septate uterus and fertile participants without fibroids. Initial endometrial sampling was obtained at the time of surgery, and second sampling was obtained 3 months after myomectomy/metroplasty. Expressions of each gene were evaluated using real-time reverse transcriptase polymerase chain reaction (RT-PCR). A trend toward decreased endometrial HOXA-10, HOXA-11, and ITGAV mRNA expression was detected in both SM and IM groups before myomectomy when compared to both fertile group and septate uterus. However, the differences failed to show statistical significance. After myomectomy of IM, we have detected 12.8-fold increase in endometrial HOXA-10 mRNA expression and 9.0-fold increase in endometrial HOXA-11 mRNA expression. This increase in endometrial HOXA-10 and 11 mRNA expression was significant. Accordingly, 2 patients having intramural fibroids greater than 5 cm were able to remain pregnant after myomectomy. Conversely, submucosal myomectomy did not cause any significant effect on endometrial receptivity markers. Likewise, all markers of endometrial receptivity remained unchanged after metroplasty. Myomectomy of IM have favorable effect on endometrial HOXA-10 and 11 mRNA expression.
Peker, Elif; Öğütlü, Faruk; Karaca, İnci Rana; Gültekin, Elif Sibel; Çakır, Merve
Introduction: The jaw can be affected by several lesions that manifest in the oral cavity, but little is known about their distribution patterns in various populations. Aims and Objectives: This study presents the frequency and distribution of biopsied jaw lesions recorded in Faculty of Dentistry and gathers the information including provisional and final diagnosis of the lesions. Material and Methods: Biopsy of 1938 lesions (2008–2013) was reviewed and 1473 lesions were included in this study. The provisional diagnosis and histopathological validations of lesions were compared. Data on the location of the lesion, as well as patient demographics, were also evaluated. The lesions were divided into three major groups as 1 - developmental/reactive and inflammatory lesions of the jaw, 2 - cystic lesion and 3 - tumor and tumor-like lesions. Statistical Analysis: The variables were recorded and analysed using descriptive statistics. Results and Observations: Three hundred and ninety-six lesions were in Group 1 and periapical granuloma was the most frequent diagnosis. Seven hundred and eighty-nine lesions were in Group 2 and the radicular cyst was the most frequent diagnosis. Two hundred and eighty-eight lesions were in Group 3 and the keratocystic odontogenic tumor was the most frequent. Two hundred and ninety-one biopsied lesions were in disagreement with respect to the diagnoses on clinical and histopathological examination. Conclusion: Consequently, a provisional diagnosis of some of the malignant lesions was reactive, inflammatory, cystic or benign lesions, therefore the importance of evaluation of the specimen is emphasized. PMID:27194866
Haist, Verena; Hirschfeld, Simon Gonzales; Mallig, Carolin; Fehr, Michael; Baumgärtner, Wolfgang
This case report describes the clinical, pathomorphological and histopathological findings in a 12-year-old female pet rabbit with a pathologic fracture of the femur due to a metastasising endometrial adenocarcinoma. The animal was presented due to a history of right hindlimb lameness and inappetence. A fracture of the right femur with adjacent lyric bone lesions was detected by clinical and X-ray examination. Necropsy and histopathology revealed an endometrial adenocarcinoma with metastasis to the right femoral bone, resulting in the pathologic fracture. In both locations, tumour cells were immunohistochemically positive for pan-cytokeratin. Additionally, the animal suffered from an Encephalitozoon cuniculi infection which manifested itself in a multifocal granulomatous encephalitis and bilateral chronic inflammatory lesions in the kidneys.The report shows that in case of bone fractures in female pet rabbits the possibility of a pathologic fracture due to metastasising endometrial adenocarcinoma has to be considered.
Blikslager, A T; Tate, L P; Weinstock, D
Effects of neodymium:yttrium aluminum garnet (Nd:YAG) laser irradiation on equine endometrium were evaluated in vitro and in six mares with endometrial cysts. The Nd:YAG laser was applied to six endometrial sites, in each of five uterine specimens, with power densities of 5659 to 33,954 J/cm2. Depth of tissue ablation was measured and graded on histologic sections of the tissue lesions. Power density had a significant effect on the depth of tissue ablation (p < .001). Grade 3 lesions (full-thickness ablation of the endometrium) were created with energy densities of 16,977 to 33,954 J/cm2. Six mares had endometrial cysts treated by photoablation. Two of the four mares that were reproductively sound but barren, despite appropriate breeding, produced foals after treatment. One mare remained reproductively unsound after treatment, and another mare that was treated postpartum was bred successfully.
Anderson, G. L.; Sarto, G. E.; Haque, R.; Runowicz, C. D.; Aragaki, A. K.; Thomson, C. A.; Howard, B. V.; Wactawski-Wende, J.; Chen, C.; Rohan, T. E.; Simon, M. S.; Reed, S. D.; Manson, J. E.
Background: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women’s Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. Methods: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. Results: After 5.6 years’ median intervention and 13 years’ median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). Conclusion: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence. PMID:26668177
Sinistrero, G; Sismondi, P; Zola, P; Gribaudo, S; Danese, S; Bellora, M G
444 endometrial carcinomas were retrospectively reviewed. Disease-free survival (DFS) was 83.6% at five years and 80.5% at ten years. 349 T1 cancers were treated by TAH-BSO and post-operative irradiation; 22.6% of them were over-staged. DFS ranged from 100% to 91% in 270 low-risk T1 patients, dropping to 84% in intermediate risk patients and to 44% in high-risk patients. DFS was 93% and 66% in the patients overstaged as pT2 and pT3, respectively; it was 82% for ovarian spread and 45% for pelvic peritoneum/parametrium invasion. T2-T3 patients were treated with preoperative irradiation and bilateral hysterectomy. DFS was 90.5% vs. 72.2% and 2/2 vs. 3/7 when the lesion was understaged. The results of irradiation were similar to literature data, but 53% of patients (all in poor general conditions and/or very old) died from associated diseases. Relapses were observed in 13.6% of cases (62/444 patients); 29 (6%) were local recurrences and 33 (7.6%) were distant metastases, which correlated well with recurrences and 33 (7.6%) were distant metastases, which correlated well with risk factors. Severe complication (G3) were observed in 6.3% of cases.
Tang, Wenru; He, Xinggang; Chan, Ying; Luo, Ying
It has been suggested that the p53 tumor suppressor gene Arg72Pro polymorphism is associated with endometrial cancer. However, results have been inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and endometrial cancer. An electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and the association was assessed by pooled odds ratios (ORs) with 95% confidence intervals (CIs). Nine published studies, including 829 endometrial cancer cases and 1387 controls, were identified. The overall results suggested that the variant genotypes were not associated with the endometrial cancer risk in all genetic models (additive model: OR 1.027, 95% CI 0.893-1.18, P=0.71; recessive model: OR 1.099, 95% CI 0.802-1.507, P=0.556; dominant model: OR 1.013, 95% CI 0.842-1.219 P=0.89). Similarly, the results were negative in subgroup analyses for ethnicity (Caucasian, Asian). This meta-analysis suggests that p53 codon 72 polymorphism is not associated with increased risk of endometrial cancer, especially in Caucasians and Asians. To validate the association between this polymorphism and endometrial cancer, further studies with larger numbers of participants worldwide are needed. Copyright © 2012 Elsevier Ltd. All rights reserved.
Coleman, Helen G; Kitahara, Cari M; Murray, Liam J; Dodd, Kevin W; Black, Amanda; Stolzenberg-Solomon, Rachael Z; Cantwell, Marie M
Endometrial cancer risk has been directly associated with glycemic load. However, few studies have investigated this link, and the etiological role of specific dietary carbohydrate components remains unclear. Our aim was to investigate associations of carbohydrate intake, glycemic index, and glycemic load with endometrial cancer risk in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Recruitment took place in 1993-2001. Over a median of 9.0 years of follow-up through 2009, 386 women developed endometrial cancer among 36,115 considered in the analysis. Dietary intakes were assessed using a 124-item diet history questionnaire. Cox proportional hazards models were applied to calculate hazard ratios and 95% confidence intervals. Significant inverse associations were detected between endometrial cancer risk and total available carbohydrate intake (hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.49, 0.90), total sugars intake (HR = 0.71, 95% CI: 0.52, 0.96), and glycemic load (HR = 0.63, 95% CI: 0.46, 0.84) when women in the highest quartile of intake were compared with those in the lowest. These inverse associations were strongest among overweight and obese women. No associations with endometrial cancer risk were observed for glycemic index or dietary fiber. Our findings contrast with previous evidence and suggest that high carbohydrate intakes and glycemic loads are protective against endometrial cancer development. Further clarification of these associations is warranted.
Katzorke, N; Vilella, F; Ruiz, M; Krüssel, J-S; Simón, C
Over the last decade, research to improve success rates in reproductive medicine has focused predominantly on the understanding and optimization of embryo quality. However, the emergence of personalized medicine in ovulation induction and embryology has shifted the focus to assessing the individual status of the endometrium. The endometrium is considered receptive during an individually defined period, the window of implantation (WOI), when the mother permits a blastocyst to attach and implant. This individual receptivity status can now be objectively diagnosed using the endometrial receptivity array (ERA) developed in 2011. The ERA, together with a computational algorithm, detects the unique transcriptomic signature of endometrial receptivity by analyzing 238 differentially expressed genes and reliably predicting the WOI. We and others have illustrated the utility of this personalized diagnostic approach to discriminate between individual physiological variation in endometrial receptivity and unknown endometrial pathology, deemed as causal in recurrent implantation failure (RIF). An international randomized controlled trial ("The ERA as a diagnostic guide for personalized embryo transfer." ClinicalTrials.gov Identifier: NCT01954758) is underway to determine the clinical value of this endometrial diagnostic intervention in the work-up for reproductive care. In this review, we analyse the current clinical practice in the diagnosis of the endometrial factor together with new avenues of research.
Carneiro, Andrea Lucia Bastos; de Cassia de Maio Dardes, Rita; Haidar, Mauro Abi
The aim of this study was to summarize the evidence of endometrial safety and quality of life assessment in postmenopausal women taking raloxifene (RLX) + estrogens (E). Clinical studies reporting RLX + E were identified using Medline and LILACS and through reviewing reference lists of highly significant publications. Articles published in Portuguese, Spanish, and English from the past 10 years were considered. Six corresponding clinical trials were identified. Different estrogen formulations, doses, and routes were used. The primary outcome of the selected studies also differed. Most of the studies found a benefit profile on RLX + E on women's quality of life, satisfaction with the treatment, and vaginal dryness. Some studies showed an increased endometrial thickness after 3 months of treatment. Most biopsies revealed benign endometrial proliferation; only two women experienced endometrial hyperplasia, both of them after 24 weeks of treatment. There are only a few clinical trials that evaluated endometrial safety and quality of life with RLX + E in postmenopausal women. The benefits shown on quality of life and endometrial safety are not certified. Larger studies are deemed necessary to define the better estrogen form and to evaluate the safety and efficacy of long-term use of RLX + E.
Rauch, Gaiane M.; Kaur, Harmeet; Choi, Haesun; Ernst, Randy D.; Klopp, Ann H.; Boonsirikamchai, Piyaporn; Westin, Shannon N.; Marcal, Leonardo P.
Endometrial and cervical cancer are the most common gynecologic malignancies in the world. Accurate staging of cervical and endometrial cancer is essential for determining the correct treatment approach. The current FIGO (International Federation of Gynecology and Obstetrics) staging system does not include modern imaging modalities. However, magnetic resonance imaging (MRI) has proven to be the most accurate noninvasive imaging modality for staging of endometrial and cervical carcinomas and often assists in patients risk stratification and treatment decisions. Multiparametric MR imaging is increasingly being used in the evaluation of the female pelvis. This approach combines anatomic T2-weighted imaging with functional imaging, i.e. dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI). In endometrial and cervical cancer MR imaging is used to guide treatment decisions through an assessment of the depth of myometrial invasion and cervical stromal involvement in endometrial cancer, and of tumor size and parametrial invasion in cervical cancer. However, the efficacy of MRI in achieving accurate local staging is dependent on technique and image quality. In this article we discuss optimization of the MR imaging protocol for endometrial and cervical cancer. The use of thin section high resolution (HR) multi-planar T2 weighted images with simple modifications such as double oblique T2 weighted images supplemented by diffusion weighted imaging and contrast enhanced MRI are reviewed. PMID:25019443
Savidan, Julie; Kaeser, Mélanie; Belhaj-Saïf, Abderraouf; Schmidlin, Eric; Rouiller, Eric M
From a case study, we describe the impact of unilateral lesion of the hand area in the primary motor cortex (M1) on manual dexterity and the role of the intact contralesional M1 in long-term functional recovery. An adult macaque monkey performed two manual dexterity tasks: (i) "modified Brinkman board" task, assessed simple precision grip versus complex precision grip, the latter involved a hand postural adjustment; (ii) "modified Klüver board" task, assessed movements ranging from power grip to precision grip, pre-shaping and grasping. Two consecutive unilateral M1 lesions targeted the hand area of each hemisphere, the second lesion was performed after stable, though incomplete, functional recovery from the primary lesion. Following each lesion, the manual dexterity of the contralesional hand was affected in a comparable manner, effects being progressively more deleterious from power grip to simple and then complex precision grips. Both tasks yielded consistent data, namely that the secondary M1 lesion did not have a significant impact on the recovered performance from the primary M1 lesion, which took place 5months earlier. In conclusion, the intact contralesional M1 did not play a major role in the long-term functional recovery from a primary M1 lesion targeted to the hand area. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Thissen, Monique; Udrea, Andreea; Hacking, Michelle; von Braunmuehl, Tanja; Ruzicka, Thomas
With the advent of smartphone devices, an increasing number of mHealth applications that target melanoma identification have been developed, but none addresses the general context of melanoma and nonmelanoma skin cancer identification. In this study a smartphone application using fractal and classical image analysis for the risk assessment of skin lesions is systematically evaluated to determine its sensitivity and specificity in the diagnosis of melanoma and nonmelanoma skin cancer along with actinic keratosis and Bowen's disease. In the Department of Dermatology, Catharina Hospital Eindhoven, The Netherlands, 341 melanocytic and nonmelanocytic lesions were imaged using SkinVision app; 239 underwent histopathological examination, while the rest of 102 lesions were clinically diagnosed as clearly benign and not removed. The algorithm has been calibrated using the images of the first 233 lesions. The calibrated version of the algorithm was used in a subset of 108 lesions, and the obtained results were compared with the medical findings. On the 108 cases used for evaluation the algorithm scored 80% sensitivity and 78% specificity in detecting (pre)malignant conditions. Although less accurate than the dermatologist's clinical eye, the app may offer support to other professionals who are less familiar with differentiating between benign and malignant lesions. An mHealth application for the risk assessment of skin lesions was evaluated. It adds value to diagnosis tools of its type by taking into consideration pigmented and nonpigmented lesions all together and detecting signs of malignancy with high sensitivity.
Braun, Michael M; Overbeek-Wager, Erika A; Grumbo, Robert J
Endometrial cancer is the most common gynecologic malignancy. It is the fourth most common cancer in women in the United States after breast, lung, and colorectal cancers. Risk factors are related to excessive unopposed exposure of the endometrium to estrogen, including unopposed estrogen therapy, early menarche, late menopause, tamoxifen therapy, nulliparity, infertility or failure to ovulate, and polycystic ovary syndrome. Additional risk factors are increasing age, obesity, hypertension, diabetes mellitus, and hereditary nonpolyposis colorectal cancer. The most common presentation for endometrial cancer is postmenopausal bleeding. The American Cancer Society recommends that all women older than 65 years be informed of the risks and symptoms of endometrial cancer and advised to seek evaluation if symptoms occur. There is no evidence to support endometrial cancer screening in asymptomatic women. Evaluation of a patient with suspected disease should include a pregnancy test in women of childbearing age, complete blood count, and prothrombin time and partial thromboplastin time if bleeding is heavy. Most guidelines recommend either transvaginal ultrasonography or endometrial biopsy as the initial study. The mainstay of treatment for endometrial cancer is total hysterectomy with bilateral salpingo-oophorectomy. Radiation and chemotherapy can also play a role in treatment. Low- to medium-risk endometrial hyperplasia can be treated with nonsurgical options. Survival is generally defined by the stage of the disease and histology, with most patients at stage I and II having a favorable prognosis. Controlling risk factors such as obesity, diabetes, and hypertension could play a role in the prevention of endometrial cancer.
Endometrial Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma; Uterine Corpus Carcinosarcoma
Koopaeei, Mahshid Majlessi; Inglehart, Marita R; McDonald, Neville; Fontana, Margherita
There is a large variation among clinicians when managing deep carious lesions (DCLs). The purpose of this study was to assess general dentists' (GDs), pediatric dentists' (PDs), and endodontists' (EDs) diagnostic methods, clinical decision-making considerations, treatment strategies, and knowledge, behavior, and attitudes related to the diagnosis and treatment of DCLs. A total of 175 GDs, 511 PDs, and 377 EDs responded to a nationwide Web-based survey. Most EDs (68%) and GDs (47%) practiced complete caries removal. PDs (31%) were more likely than GDs (12%) and EDs (4%) to remove carious tissues partially. Dentin hardness was the most important diagnostic criterion used during caries excavation (GDs, 90%; PDs, 72%; EDs, 88%). Only 30% of GDs, 17% of PDs, and 90% of EDs used diagnostic tests (for example, a cold test) when assessing pupal health. A substantial percentage of respondents considered endodontic treatment as a choice for treating DCLs in asymptomatic teeth in young patients (GDs, 40%; PDs, 30%; EDs, 40%). GDs rarely used a rubber dam when treating these lesions. Most respondents practiced complete caries removal until hard dentin was felt, using hardness as the primary excavation criterion, and did not use pulp diagnostic tests routinely before making decisions about treatment of teeth with DCLs. Efforts should be made to translate the growing body of evidence supporting the use of conservative caries removal criteria to preserve pulpal health and tooth structure integrity when managing DCLs. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.
Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul
Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly
Vaitkuviene, Aurelija; Auksorius, E.; Fuchs, D.; Gavriushin, V.
An effort has been made to detect neopterin spectrum in fluorescence of premalignant endometrial tissue and to estimate the number of fluorophores naturally existing in the tissue with fluorescence present above the noise level. Endometrial Tissue fluorescence was measured in vitro by excitation with the third harmonic of Nd YAG laser. Multivariate curve resolution was used for testing neopterin presence in endometrial tissue. Fluorescence spectra ofneopterin was measured and used as a target spectrum for testing. Seven factors -fluorescence ofnatural fluorophores ofendometrial tissue were found to be present above the noise level in the overall autofluorescence. Neopterin concentration may be too low in endometrial tissue to make its fluorescence above the noise level because neopterin spectrum was not found to be among the spectra resolved by multivariate curve resolution. An intensity increase in the neopterin spectrum spectral region in hyperplastic endometrial samples might be associated with neopterin concentration increase.
Bohîlțea, R E; Furtunescu, F; Dosius, M; Cîrstoiu, M; Radoi, V; Baroș, A; Bohîlțea, L C
Endometrial cancer represents the most frequent gynecological malignant affection in the developed countries, in which the incidence of cervical cancer has significantly decreased due to the rigorous application of screening methods and prophylaxis. According to its frequency, endometrial cancer is situated on the fourth place in the category of women's genital-mammary malignant diseases, after breast, cervical and ovarian cancer in Romania. The incidence and mortality rates due to endometrial cancer have registered an increasing trend worldwide and also in Romania, a significant decrease of the age of appearance for the entire endometrial pathology sphere being noticed. At the national level, the maximum incidence is situated between 60 and 64 years old, the mortality rate of the women under 65 years old being high in Romania. The study evaluates endometrial cancer, from an epidemiologic point of view, at the national level compared to the international statistic data.
Bohîlțea, RE; Ancăr, V; Cirstoiu, MM; Rădoi, V; Bohîlțea, LC; Furtunescu, F
Rationale: Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania, reaching in 2013 the average value of 8.06/ 100,000 women, and 15.97/ 100,000 women within the highest risk age range, having in recent years an increasing trend, being higher in urban than in rural population. Annually, approximately 800 new cases are registered in our country. The estimated lifetime risk of a woman to develop endometrial cancer is of about 1,03%. Based on an abnormal uterine bleeding, 35% of the endometrial cancers are diagnosed in an advanced stage of the disease, with significantly diminished lifetime expectancy. Objective: Drafting a national program for the early diagnosis of endometrial cancer. Methods and Results: We proposed a standardization of the diagnostic steps and focused on 4 key elements for the early diagnosis of endometrial cancer: investigation of abnormal uterine bleeding occurring in pre/ post-menopausal women, investigating features/ anomalies of cervical cytology examination, diagnosis, treatment and proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Discussion: Improving medical practice based on diagnostic algorithms addresses the four risk groups, by improving information system reporting and record keeping. Improving addressability cases by increasing the health education of the population will increase the rate of diagnosis of endometrial cancer in the early stages of the disease. Abbreviations: ACOG = American Society of Obstetricians and Gynecologists, ASCCP = American Society for Colposcopy and Cervical Pathology, PATT = Partial Activated Thromboplastin Time, BRCA = Breast Cancer Gene, CT = Computerized Tomography, IFGO = International Federation of Gynecology and Obstetrics, HLG = Hemoleucogram, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, BMI = Body Mass Index, INR
Chatzikokkinou, Paraskevi; Thorfinn, Johan; Angelidis, Ioannis K; Papa, Giovanni; Trevisan, Giusto
Cutaneous endometriosis of the umbilicus is an unusual condition with unclear pathogenetic mechanisms that might be mistaken for a malignant condition. A 46-year-old woman presented with a cutaneous black mass in the umbilicus. The lesion was removed surgically and histological analyses revealed that it consisted of endometrial tissue. There was no recurrence at 18-month follow-up. Endometriosis of the umbilicus is a rare condition and the pathogenesis is not completely elucidated. According to one theory, intraperitoneal endometrial tissue is translocated during endoscopic surgery or other surgical procedures that involve the umbilicus. However, in this case there was no history of abdominal wall surgery. We conclude that endometriosis is important to consider in cases of unclear skin lesions of the umbilicus, even in cases with no previous abdominal surgery. Moreover, umbilical endometriosis of the skin can have different appearances that resemble malignant tumors, and radical surgery with histology is therefore indicated.
Stubert, J.; Gerber, B.
Endometrial carcinoma is the most common carcinoma of the female genital tract. Its most important clinical sign is postmenopausal bleeding. An endometrial biopsy is essential for diagnosis. Treatment decisions are governed by tumour risk assessment and patient comorbidity, which is often present. Pelvic and paraaortic lymph node dissection is unnecessary in low risk cases (definition: pT1 a, G1/2) and adjuvant radiotherapy and systemic treatments are usually avoidable. Treatment of high-risk patients (G3 and/or pT1b) and palliative cases is difficult and not well standardised. New molecular-based subtype classification may help treatment decision making in future. PMID:26941450
Wang, Lianlian; Li, Jingxi; Shi, Zhan
Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR): 0.77, 95% CI: 0.62–0.96, I2: 63.0%), especially in North America (summary RR: 0.87, 95% CI: 0.79–0.95). A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97–0.99). Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk. PMID:26184301
Li, Fei; Zhang, Ming; Zhang, Yuanzhen; Liu, Teng; Qu, Xinlan
The present study aimed to investigate whether gonadotropin-releasing hormone analogues (GnRH-as), including GnRH agonists and antagonists, affect endometrial homeobox (Hox) a10 DNA methylation during the implantation window in mice. GnRH analogue mouse models were used and were treated with either human menopausal gonadotropin (HMG) and a GnRH agonist or HMG and a GnRH antagonist. Uterus samples were collected 48 h after GnRH analogue treatment or ovulation. Bisulfite sequencing polymerase chain reaction (PCR), quantitative-PCR and western blot analysis were performed to assess Hoxa10 and integrin β3 expression. Scanning electron microscope analyses were conducted to analyze pinopode development. Compared with the natural cycle control mice, mice in the GnRH analogue groups were found to exhibit increased levels of methylation at the Hoxa10 promoter, decreased Hoxa10 mRNA and protein expression and disrupted pinopode development. These findings suggest that GnRH-as may be associated with altered Hoxa10 DNA methylation, thus GnRH-as may affect uterine Hoxa10 expression and endometrial receptivity.
Boruban, Melih C; Altundag, Kadri; Kilic, Gokhan S; Blankstein, Josef
Controversies are still seen in the histological differential diagnosis of hyperplasia and well-differentiated endometrial carcinoma. Prediction of endometrial cancer in patients with hyperplasia with atypia, with the available markers has not been reliable yet. Hence these patients require more attention in the clinical management. Endometrial hyperplasia is proliferation of endometrial glands resulting in a higher gland : stroma ratio. Cytological atypia, which may progress to or co-exist with endometrial cancer and other pathological changes, result from estrogen stimulation unopposed by progesterone. Biomarkers whose expression is altered in cases of endometrial hyperplasia or cancer such as progesterone receptor, insulin-like growth factor I, retinaldehyde dehydrogenase type II, and secreted frizzled-related protein 4, seem to be promising to use as early-stage tumor markers. Mutation of PTEN is present in 83% of endometrial adenocarcinoma cases, making it the most frequent early molecular genetic alteration in type 1 endometrial tumors, which are generally associated with hyperplasia. p53 gene mutation is not found in endometrial hyperplasia, but researchers have detected this mutation in 20% of cases of endometrial carcinoma and 90% of cases of serous endometrial tumors. Cyclooxygenase-2 is important in tumorogenic transformation of hyperplasia. Expression of cyclooxygenase-2 decreases apoptosis, increases angiogenesis, and is related to invasiveness. Cyclooxygenase-2 expression increases significantly in cases of well-differentiated endometrial adenocarcinoma. Prostaglandin E2 is known to regulate aromatase gene expression and is the product of cyclooxygenase-2. The data about aromatase inhibitors are promising; in breast cancer patients, treatment with tamoxifen induces uterine abnormalities as early as 3 months after the initiation of therapy. In contrast, these abnormalities are not seen in patients who receive aromatase inhibitors and switched therapy
McGuane, Jonathan T; Watson, Katherine M; Zhang, Jamie; Johan, M Zahied; Wang, Zhao; Kuo, Gabriel; Sharkey, David J; Robertson, Sarah A; Hull, M Louise
The factors that predispose one-tenth of reproductive-aged women to endometriosis are poorly understood. We determined that genetic deficiency in transforming growth factor β1 impairs endometriosis-like lesion growth in mice. Given that seminal plasma is an abundant source of transforming growth factor β, we evaluated the effect of exposure to seminal plasma on the growth of endometrial lesions. Human endometrial explants were exposed to seminal plasma or to control medium before transfer to Prkdc(scid)-mutant (severe combined immunodeficient) mice. Xenografts exposed to seminal plasma showed an eightfold increase in volume and a 4.3-fold increase in weight after 14 days. These increases were associated with increased proliferation of endometrial epithelial cells and enhanced survival and proliferation of human stromal cells compared with those in control lesions, in which human stromal cell persistence was negligible. Although the distribution of macrophages was altered, their number and activation status did not change in response to seminal plasma. Seminal plasma stimulated the production of a variety of cytokines in endometrial tissue, including growth-regulated oncogene, granulocyte macrophage colony-stimulating factor, and IL-1β. These data suggest that seminal plasma enhances the formation of endometriosis-like lesion via a direct effect on endometrial cell survival and proliferation, rather than via macrophage-mediated mechanisms. These findings raise the possibility that endometrial exposure to seminal plasma could contribute to endometriotic disease progression in women.
Alafuzoff, Irina; Pikkarainen, Maria; Al-Sarraj, Safa; Arzberger, Thomas; Bell, Jeanne; Bodi, Istvan; Bogdanovic, Nenad; Budka, Herbert; Bugiani, Orso; Ferrer, Isidro; Gelpi, Ellen; Giaccone, Giorgio; Graeber, Manuel B; Hauw, Jean-Jacques; Kamphorst, Wouter; King, Andrew; Kopp, Nicolas; Korkolopoulou, Penelope; Kovács, Gábor G; Meyronet, David; Parchi, Piero; Patsouris, Efstratios; Preusser, Matthias; Ravid, Rivka; Roggendorf, Wolfgang; Seilhean, Danielle; Streichenberger, Nathalie; Thal, Dietmar R; Kretzschmar, Hans
This interlaboratory study evaluated the reproducibility of the assessments of neuritic plaques and neurofibrillary tangles (NFTs)--the hallmark lesions of Alzheimer disease--and compared the staining between the BrainNet Europe centers. To reduce the topography-related inconsistencies in assessments, we used a 2-mm tissue microarray (TMA) technique. The TMA block included 42 core samples taken from 21 paraffin blocks. The assessments were done on Bielschowsky and Gallyas silver stains using an immunohistochemical (IHC) method with antibodies directed to beta-amyloid (IHC/Abeta) and hyperphosphorylated tau (IHC/HPtau). The staining quality and the assessments differed between the participants, being most diverse with Bielschowsky (good/acceptable stain in 53% of centers) followed by Gallyas (good/acceptable stain in 57%) and IHC/Abeta (good/acceptable stain in 71%). The most uniform staining quality and assessment was obtained with the IHC/HPtau method (good/acceptable stain in 94% of centers). The neuropathologic diagnostic protocol (Consortium to Establish a Registry for Alzheimer Disease, Braak and Braak, and the National Institute of Aging and Reagan [NIA-Reagan] Institute) that was used significantly influenced the agreement, being highest with NIA-Reagan (54%) recommendations. This agreement was improved by visualization of NFTs using the IHC/HPtau method. Therefore, the IHC/HPtau methodology to visualize NFTs and neuropil threads should be considered as a method of choice in a future diagnostic protocol for Alzheimer disease.
Miller, A M; Figueiredo, J E F; Chaves, C L; Ruas, E A; Balbi-Peña, M I; Colauto, N B; Paccola-Meirelles, L D
Measures to control maize white spot (MWS) caused by Pantoea ananatis are preferentially based on resistant cultivars. A lack of knowledge on the genetic variability of pathogens could interfere with the development and utilization of controlling strategies in this pathosystem. The main goals of this study were to investigate the genetic variability of 90 P. ananatis isolates from three different eco-geographical regions of Brazil by amplified fragment length polymorphism (AFLP), and to determine the presence of a universal P. ananatis plasmid in isolates from tropical Brazil. Analysis of genetic similarity by AFLP allowed us to categorize the 90 isolates into two groups. However, no correlation between the collecting sites and genetic groupings was observed. The polymorphism percentage found in P. ananatis ranged between 24.64 and 92.46%, and genetic diversity was calculated to be 0.07-0.09. The analysis of molecular variance showed that 99.18% of genetic variability was within the populations, providing evidence that evolutionary forces were acting on these populations. All P. ananatis isolates showed the P. ananatis universal plasmid (280 or 352 kb). This is the first report on the presence of a universal P. ananatis plasmid from MWS lesions in the tropical area.
Anidjar, Maurice; Cussenot, Oliver; Avrillier, Sigrid; Ettori, Dominique; Teillac, Pierre; Le Duc, Alain
We have designed a program using laser induced autofluorescence spectroscopy as a possible way to characterize urothelial tumors of the bladder. The autofluorescence spectra were compared between normal, suspicious and tumor areas of human bladder. Three different pulsed laser wavelengths were used for excitation: 308 nm (excimer), 337 nm (nitrogen) and 480 nm (dye laser). Excitation light was delivered by a specially devised multifiber catheter introduced through the working channel of a regular cystoscope under saline irrigation. The fluorescence light was focused into an optical multichannel analyzer detection system. The data was evaluated in 25 patients immediately before resection of a bladder tumor. Spectroscopic results were compared with histopathology. Upon 337 nm and 480 nm excitations, the overall intensity of the fluorescence spectra from bladder tumors was clearly reduced in comparison with normal urothelium, regardless of the stage and the grade of the tumor. upon 308 nm excitation, the shape of tumor fluorescence spectra, including carcinoma in situ, differed drastically from that of normal tissue. In this case, no absolute intensity measurements are needed and clear diagnosis can be achieved from fluorescence intensity ratio (360/440 nm). This spectroscopic study could be particularly useful for the design of a simplified autofluorescence imaging device for real-time routine detection of occult urothelial neoplastic lesions.
Membrillo-Romero, Alejandro; Gonzalez-Lanzagorta, Rubén; Rascón-Martínez, Dulce María
Puncture biopsy and fine needle aspiration guided by endoscopic ultrasound has been used as an effective technique and is quickly becoming the procedure of choice for diagnosis and staging in patients suspected of having pancreatic cancer. This procedure has replaced retrograde cholangiopancreatography and brush cytology due to its higher sensitivity for diagnosis, and lower risk of complications. To assess the levels of pancreatic enzymes amylase and lipase, after the puncture biopsy and fine needle aspiration guided by endoscopic ultrasound in pancreatic lesions and the frequency of post-puncture acute pancreatitis. A longitudinal and descriptive study of consecutive cases was performed on outpatients submitted to puncture biopsy and fine needle aspiration guided by endoscopic ultrasound in pancreatic lesions. Levels of pancreatic enzymes such as amylase and lipase were measured before and after the pancreatic puncture. Finally we documented post-puncture pancreatitis cases. A total of 100 patients who had been diagnosed with solid and cystic lesions were included in the study. Significant elevation was found at twice the reference value for lipase in 5 cases (5%) and for amylase in 2 cases (2%), none had clinical symptoms of acute pancreatitis. Eight (8%) of patients presented with mild nonspecific pain with no enzyme elevation compatible with pancreatitis. Pancreatic biopsy needle aspiration guided by endoscopic ultrasound was associated with a low rate of elevated pancreatic enzymes and there were no cases of post-puncture pancreatitis. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.
Shentsov, A A; Markina, L D
The adaptation of teenagers to an educational process in a computer class with the optimum hygienic parameters was studied. The modified procedure "Examinees' emotional assessment of musical tracks" was established to efficiently prevent autonomic dysfunctions and emotional disorders.
Hastings, Jeffrey W; Alston, Meredith J; Mazzoni, Sara E; Stickrath, Elaine
The aim of the study was to determine the frequency that endometrial biopsies (EMBs) performed on postmenopausal (PMP) women with benign endometrial cells (BECs) on Pap test are adequate for assessing malignancy or hyperplasia. This is a case series including all PMP women older than 55 years at a single academic institution between January 2008 and September 2015 with a Pap test result including BEC. Patients were identified via an internal cytology database. Patient data, the ability to obtain an EMB, and the result of the EMB were collected. An adequate EMB was defined as the presence of glands and stroma sufficient to assess for endometrial hyperplasia and/or malignancy. Descriptive statistics were performed, and then univariable and logistic regression analyses were used to evaluate associations of patient factors and adequacy of EMB. One hundred sixteen women met inclusion criteria. One hundred seven had an EMB scheduled (92%) and of those 91 EMBs were obtained (85%). Of the obtained biopsies, 63 were inadequate to rule out the diagnosis of hyperplasia and/or malignancy (69%). Of these, 19 patients underwent pelvic ultrasound (30%), 12 followed up with repeat Pap test (19%), and 4 underwent dilation and curettage (6%). Of the adequate biopsies, 5 had a diagnosis of hyperplasia (18%) and 5 with malignancy (18%). In PMP women with BEC on Pap test, adequate EMB was only obtained in 31% of patients. Most patients without an adequate biopsy had no further workup of their abnormal Pap test.
Marino, G; Barna, A; Rizzo, S; Zanghì, A; Catone, G
Endometrial polyps (EPs) are tumour-like lesions reported frequently in domestic carnivores. The present report describes the clinical and pathological features of EPs in 21 bitches. Most affected bitches had a regular reproductive history. Five bitches had no clinical signs and eleven showed clinical signs of pyometra. Four bitches had a large EP which resulted in compression of the abdominal viscera. One bitch had an acute uterine torsion. A clinical diagnosis of EPs was only made when the lesions were large and identified by abdominal palpation or ultrasound. Grossly, the EPs were 5-25 cm in diameter and were single, sessile or pedunculated. They were often associated with cystic endometrial hyperplasia. Microscopically, the EPs were fibroglandular with the stroma sometimes being haemorrhagic and infiltrated by inflammatory cells. In one case, there were areas of stromal smooth muscle and epithelial squamous metaplasia, which may have been consistent with preneoplastic change.
McCampbell, A S; Mittelstadt, M L; Dere, R; Kim, S; Zhou, L; Djordjevic, B; Soliman, P T; Zhang, Q; Wei, C; Hursting, S D; Lu, K H; Broaddus, R R; Walker, C L
Endometrial carcinoma (EC) exhibits the strongest association with obesity of all cancers. Growth of these tumors is driven by PI3K/AKT activation, and opposed by tumor suppressors, including the tuberous sclerosis complex 2 (TSC-2) and p27, with inactivation of TSC2 and loss or cytoplasmic mislocalization of p27 both being linked to PI3K/AKT activation. However, little is known about the involvement of p27 in the development of EC arising in the setting of obesity, especially its role early in disease progression. Using a panel of EC cell lines, in vitro studies using PI3K inhibitors provided evidence that p27 rescue contributes to the efficacy of interventions that inhibit endometrial cell growth. In "at risk" obese patients, and in an animal model of obesity-associated EC (Tsc2-deficient Eker rats), p27 was moderately-to-severely reduced in both "normal" endometrial glands as well as in endometrial complex atypical hyperplasia (obese women), and endometrial hyperplasia (obese rats). In obese Eker rats, an energy balance intervention; caloric restriction from 2-4 months of age, reduced weight, increased adiponectin and lowered leptin to produce a favorable leptin:adiponectin ratio, and reduced circulating insulin levels. Caloric restriction also increased p27 levels, relocalized this tumor suppressor to the nucleus, and significantly decreased hyperplasia incidence. Thus, dietary and pharmacologic interventions that inhibit growth and decrease risk for development of endometrial lesions are associated with increased expression and nuclear (re)localization of p27. These data suggest that p27 levels and localization may be useful as a biomarker, and possible determinant, of risk for EC arising in the setting of obesity.
TORRES, Marianna Guanaes Gomes; SANTOS, Aline da Silva; NEVES, Frederico Sampaio; ARRIAGA, Marcel Lautenschlager; CAMPOS, Paulo Sérgio Flores; CRUSOÉ-REBELLO, Iêda
Objectives The aim of this study was to evaluate the detection of enamel-dentin occlusal caries using photostimulable phosphor plates. Material and Methods The ability to detect enamel-dentin occlusal caries in 607 premolars and molars from 47 patients between 10 and 18 years old, referred to the School of Dentistry of the Federal University of Bahia, Brazil, was evaluated based on clinical and radiographic examinations, using the criteria proposed in a previous study. A total of 156 bitewing digital images were obtained using Digora® (Soredex Medical Systems, Helsinki, Finland) phosphor plates. The plates were scanned and the images were captured and displayed on a computer screen. Image evaluation was done using Digora® for Windows 2.1 software, Soredex®. The radiologists were allowed to use enhancement tools to obtain better visibility during scoring of the teeth based on the radiographic criteria proposed in a previous study. Descriptive analysis and chi-squared proportion tests were done at 5% significance level. Results The results of clinical examination showed a higher prevalence of teeth with a straight dark line or demineralization of the occlusal fissure (score 1) and a lower prevalence of sealed teeth (score 5). In the bitewing digital images, 47 teeth presented visible radiolucency, circumscribed, in dentin under occlusal enamel (enamel-dentin caries lesions). Conclusions Correlating the clinical and radiographic findings, it was found that in the majority of teeth diagnosed by radiographic images as having enamel-dentin caries, no caries could be detected by clinical examination. PMID:21986650
Piecuch, Adam; Dziewit, Bartosz; Segiet, Oliwia; Kurek, Józef; Kowalczyk-Ziomek, Grażyna; Wojnicz, Romuald; Helewski, Krzysztof
Introduction It is generally accepted that mitochondria are a primary source of intracellular reactive oxygen species (ROS). Under physiological circumstances they are permanently formed as by-products of aerobic metabolism in the mitochondria. To counter the harmful effect of ROS, cells possess an antioxidant defence system to detoxify ROS and avert them from accumulation at high concentrations. Mitochondria-located manganese superoxide dismutase (MnSOD, SOD2) successfully converts superoxide to the less reactive hydrogen peroxide (H2O2). To the best of our knowledge, there are no available data regarding immunohistochemical expression of MnSOD in colorectal neoplastic tissues. Aim To investigate the immunohistochemical expression status of MnSOD in colorectal premalignant and malignant lesions. Material and methods This study was performed on resected specimens obtained from 126 patients who had undergone surgical resection for primary sporadic colorectal cancer, and from 114 patients who had undergone colonoscopy at the Municipal Hospital in Jaworzno (Poland). Paraffin-embedded, 4-µm-thick tissue sections were stained for rabbit polyclonal anti SOD2 antibody obtained from GeneTex (clone TF9-10-H10 from America Diagnostica). Results Results of our study demonstrated that the development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. Samples of adenocarcinoma with G2 and G3 grade showed significantly higher levels of immunohistochemical expression of this antioxidant enzyme. Moreover, patients with the presence of lymphovascular invasion and higher degree of regional lymph node status have been also characterised by higher levels of MnSOD expression. The samples of adenoma have been characterised by higher levels of MnSOD expression in comparison to normal mucosa as well. Interestingly, there was no significant correlation between expression and histological type of adenoma. Conclusions Development
Zheng, Bin; Pu, Jiantao; Park, Sang Cheol; Zuley, Margarita; Gur, David
In this study we randomly select 250 malignant and 250 benign mass regions as a training dataset. The boundary contours of these regions were manually identified and marked. Twelve image features were computed for each region. An artificial neural network (ANN) was trained as a classifier. To select a specific testing dataset, we applied a topographic multi-layer region growth algorithm to detect boundary contours of 1,903 mass regions in an initial pool of testing regions. All processed regions are sorted based on a size difference ratio between manual and automated segmentation. We selected a testing dataset involving 250 malignant and 250 benign mass regions with larger size difference ratios. Using the area under ROC curve (A Z value) as performance index we investigated the relationship between the accuracy of mass segmentation and the performance of a computer-aided diagnosis (CAD) scheme. CAD performance degrades as the size difference ratio increases. Then, we developed and tested a hybrid region growth algorithm that combined the topographic region growth with an active contour approach. In this hybrid algorithm, the boundary contour detected by the topographic region growth is used as the initial contour of the active contour algorithm. The algorithm iteratively searches for the optimal region boundaries. A CAD likelihood score of the growth region being a true-positive mass is computed in each iteration. The region growth is automatically terminated once the first maximum CAD score is reached. This hybrid region growth algorithm reduces the size difference ratios between two areas segmented automatically and manually to less than +/-15% for all testing regions and the testing A Z value increases to from 0.63 to 0.90. The results indicate that CAD performance heavily depends on the accuracy of mass segmentation. In order to achieve robust CAD performance, reducing lesion segmentation error is important.
Class I Antigens down Regulation as Markers of Increased Risk for Development and Progression of Breast Cancer from Benign Breast Lesions...Based Assessment of MHC Class I Antigens down Regulation as Markers of Increased Risk for Development and Progression of Breast Cancer from 5b...subsequent development of breast cancer from precancerous lesions, and as prognostic markers for progression from primary to metastatic disease. The major
Torres, Anna; Kozak, Joanna; Korolczuk, Agnieszka; Rycak, Dominika; Wdowiak, Paulina; Maciejewski, Ryszard; Torres, Kamil
Pathogenesis of endometrial cancer has been connected with alterations of microRNA expression and in particular miR-205 up–regulation was consistently reported in this carcinoma. Presented study aimed to investigate if inhibition of miR-205 expression using LNA-modified-nucleotide would attenuate endometrial cancer cells proliferation in vitro and in vivo. In the course of the study we found that the proliferation of endometrial cancer cells (HEC-1-B, RL-95, KLE, Ishikawa) transfected with LNA-miR-205-inhibitor and evaluated using real time cell monitoring as well as standard cell proliferation assay, was significantly decreased. Next, LNA-miR-205-inhibitor was used to assess the in vivo effects of miR-205 inhibition of endometrial cancer growth. Cby.Cg-Foxn1
Torres, Anna; Kozak, Joanna; Korolczuk, Agnieszka; Rycak, Dominika; Wdowiak, Paulina; Maciejewski, Ryszard; Torres, Kamil
Pathogenesis of endometrial cancer has been connected with alterations of microRNA expression and in particular miR-205 up-regulation was consistently reported in this carcinoma. Presented study aimed to investigate if inhibition of miR-205 expression using LNA-modified-nucleotide would attenuate endometrial cancer cells proliferation in vitro and in vivo.In the course of the study we found that the proliferation of endometrial cancer cells (HEC-1-B, RL-95, KLE, Ishikawa) transfected with LNA-miR-205-inhibitor and evaluated using real time cell monitoring as well as standard cell proliferation assay, was significantly decreased. Next, LNA-miR-205-inhibitor was used to assess the in vivo effects of miR-205 inhibition of endometrial cancer growth. Cby.Cg-Foxn1/cmdb mice bearing endometrial cancer xenografts were intraperitoneally injected with nine dosages of 25mg/kg of miR-205-LNA-inhibitor or scramble control or phosphatase buffered saline and were observed for 32 days. We found that systemic administration of miR-205-LNA-inhibitor was technically possible, and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals.In conclusion our results suggest that systemic delivery of miR-205-LNA-inhibitor is feasible, devoid of significant toxicity, and could be a promising treatment strategy for endometrial cancer. Therefore it warrants further studies in other animal models.
Le Gallo, Matthieu; Bell, Daphne W.
BACKGROUND Endometrial cancer is responsible for ~74,000 deaths amongst women worldwide each year. It is a heterogeneous disease that consists of multiple different histological subtypes. In the United States, the majority of deaths from endometrial carcinoma are attributed to the serous and endometrioid subtypes. An understanding of the fundamental genomic alterations that drive serous and endometrioid endometrial carcinomas lays the foundation for the identification of molecular markers that could improve the clinical management of patients presenting with these tumors. CONTENT Herein we review the current state of knowledge of the somatic genomic alterations that are present in serous and endometrioid endometrial tumors. We present this knowledge in a historical context – reviewing the genomic alterations that have been identified over the past two decades or more, from studies of individual genes and proteins, followed by a review of very recent studies that have conducted comprehensive, systematic surveys of genomic, exomic, transcriptomic, epigenomic, and proteomic alterations in serous and endometrioid endometrial carcinomas. SUMMARY The recent mapping of the genomic landscape of serous and endometrioid endometrial carcinomas has resulted in the first comprehensive molecular classification of these tumors and has distinguished four molecular subgroups: a POLE ultramutated subgroup, a hypermutated/microsatellite unstable subgroup, a copy number low/microsatellite stable subgroup, and a copy number high subgroup. This molecular classification may ultimately serve to refine the diagnosis and treatment of women with endometrioid and serous endometrial tumors. PMID:24170611
Zanghì, A; Catone, G; Marino, G; Quartuccio, M; Nicòtina, P A
Endometrial polypoid adenomyomatosis in an 8-year-old German shepherd bitch is described. The lesion was associated with ovarian granulosa cell tumour and pyometra; grossly, it consisted of sessile or pedunculated processes with both epithelial and non-epithelial components, in which smooth muscle cells were predominant. The endometrium was diffusely atrophic and showed multifocal squamous metaplasia. The findings are discussed as possible consequences of the functioning ovarian tumour and pyometra, but an involvement of growth factors is also proposed.
Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IV Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer
Horst, K; Von Harten, R; Weber, C; Andruszkow, H; Pfeifer, R; Dienstknecht, T; Pape, H C
Bankart and Hill-Sachs lesions are often associated with anterior shoulder dislocation. The MRI technique is sensitive in diagnosing both injuries. The aim of this study was to investigate Bankart and Hill-Sachs lesions with MRI to determine the correlation in occurrence and defect sizes of these lesions. Between 2006 and 2013, 446 patients were diagnosed with an anterior shoulder dislocation and 105 of these patients were eligible for inclusion in the study. All patients were examined using MRI. Bankart lesions were classified as cartilaginous or bony lesions. Hill-Sachs lesions were graded I-III using a modified Calandra classification. The co-occurrence of injuries was high [odds ratio (OR) = 11.47; 95% confidence interval (CI) = 3.60-36.52; p < 0.001]. Patients older than 29 years more often presented with a bilateral injury (OR = 16.29; 95% CI = 2.71-97.73; p = 0.002). A correlation between a Bankart lesion and the grade of a Hill-Sachs lesion was found (ρ = 0.34; 95% CI = 0.16-0.49; p < 0.001). Bankart lesions co-occurred more often with large Hill-Sachs lesions (O = 1.24; 95% CI = 1.02-1.52; p = 0.033). If either lesion is diagnosed, the patient is 11 times more likely to have suffered the associated injury. The size of a Hill-Sachs lesion determines the co-occurrence of cartilaginous or bony Bankart lesions. Age plays a role in determining the type of Bankart lesion as well as the co-occurrence of Bankart and Hill-Sachs lesions. This study is the first to demonstrate the use of high-quality MRI in a reasonably large sample of patients, a positive correlation of Bankart and Hill-Sachs lesions in anterior shoulder dislocations and an association between the defect sizes.
Camargo-Díaz, Felipe; García, Valeria; Ocampo-Bárcenas, Azucena; González-Marquez, Humberto; López-Bayghen, Esther
Poor endometrial quality is associated with more than a third of embryo implantation failures. Current ultrasonography technology lacks the capacity to determine efficiently the endometrial receptivity during ongoing cycle transfers. We analyzed the relationship between the gene expression profile associated with implantation and clinical pregnancy from endometrial cells taken during embryo transfer. Seventy-six patients submitted to a standard ovarian stimulation protocol, in vitro fertilization, and good quality embryos were collected (morphological assessment). Endometrial samples were taken with ultrasonography guidance and cells were Hematoxylin and Eosin stained for morphological identification. Total RNA was extracted and the expression of Mucin 1 (MUC1), Homeobox A10 (HOXA-10), Leukemia Inhibitor Factor (LIF), Colony Stimulating Factor-1 (CSF-1), and ribosomal 18 s (endogenous control) were analyzed using RT-qPCR. Presence of a gestational sac, β-hGC (≥10 mIU/mL on Day 20), and a fetal heartbeat were used to determine a positive embryo implantation and pregnancy. Samples collected from same cycle embryo transfer showed clear morphological staining for endometrial cells (80-90% of the cells). Cells in the sample were molecularly identified as the endometrium (HOXA-10 positive and MUC-1 negative). CSF-1 expression was 4.55-fold and LIF expression was 12.25-fold higher in patients who became pregnant. Both increases were statistically significant (p < 0.05). Here, we provide evidence of a new method to assess endometrial receptivity. Furthermore, we demonstrate that the expression profile, based on LIF and CSF-1, showed a difference between a receptive and a non-receptive endometrium.
Arikan, G; Reich, O; Weiss, U; Hahn, T; Reinisch, S; Tamussino, K; Pickel, H; Desoye, G
The aim of this study was to evaluate the rate of transtubal dissemination of endometrial carcinoma cells by hysteroscopy and the functional viability of disseminated tumor cells by assessing cell adhesion in an in vitro model. We studied 24 uteri obtained at TAH+BSO in patients with endometrial carcinoma. Further inclusion criteria were negative peritoneal cytology, no involvement of the uterine serosa or extrauterine disease, and endometrial surface involvement >1 cm in diameter. In vitro fluid hysteroscopy was performed with a 5-mm single-flow rigid hysteroscope. A maximum of 150 ml saline was infused at a maximum pressure of 100 mm Hg for a maximum of 3 min. Fluid running off through the tubes was collected. The cell suspension was enriched by a density gradient centrifugation. The isolated cells had a mean viability of 90% as judged by trypan blue exclusion. Viable cells (5 x 10(4) per 2-cm(2) polyvinyl chloride well plate) were cultured with equal parts of Dulbecco's modified Eagle's minimal essential medium and Ham's F-12 for 24 h. The endpoint of the analysis was the adherence of tumor cells to the polyvinyl chloride well plate, which was taken as a proxy for functional cell viability. Cytological evaluation was performed separately by two cytologists blinded to the source and date of the smears. Transtubal fluid dissemination was seen in 20 of 24 (83%) uteri. Tumor cells were found in 17 specimens (71%). In 10 (42%) specimens the disseminated tumor cells were functionally viable. Our model suggests that hysteroscopy can cause dissemination of malignant cells into the abdominal cavity from uteri containing endometrial carcinoma and that these cells can be functionally viable and adhere to a matrix. Copyright 2001 Academic Press.
Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitro fertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER.
Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitro fertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER. PMID:26538853
Simões, Jorge; Gonçalves, Matilde; Matos, Isabel
A woman in her mid-60s presented with a bulky mass on the anterior abdominal wall. She had a previous incidental diagnosis of endometrial adenocarcinoma FIGO stage IB following a vaginal hysterectomy. Physical exam and imaging revealed a well circumscribed bulging tumour at the umbilical region, measuring 10 × 9 × 9 cm, with overlying intact skin and subcutaneous tissue. Surgical resection was undertaken, and histological examination showed features of endometrial carcinoma. She began chemotherapy and is alive with no signs of recurrent disease one year after surgery. This case brings up to light an atypical location of a solitary metastasis of endometrial carcinoma. PMID:25349753
Kadirogullari, Pinar; Atalay, Cemal Resat; Sari, Mustafa Erkan
Introduction Endometrial hyperplasia has been associated with the presence of concomitant endometrial carcinoma. In this study, patients who were diagnosed with endometrial hyperplasia and had hysterectomy, determination of the incidence of endometrial cancer accompanying postoperatively and clinical parameters associated with cancer are aimed. Materials and Methods Endometrial biopsies were taken from patients for various reasons and among them 158 patients diagnosed with endometrial hyperplasia from pathologic examination results were retrospectively evaluated. All of the patient’s age, parity, weight, transvaginal ultrasound measured by endometrial thickness, concomitant systemic disease (diabetes, hypertension, hypothyroidism), tamoxifen use, hormone use and whether in reproductive age or menopause were all questioned. Patients who applied with endometrial cancer, their cervical stromal involvement, lymph node involvement, cytology positivity and omental metastases were examined. Patients were classified according to their stage and grade. Patients who had intraoperative frozen were re-evaluated. Results Fifteen cases with preoperative endometrial hyperplasia diagnosed with endometrial cancer postoperatively, 2 cases had complex hyperplasia without atypia and 13 cases had complex atypical hyperplasia. The rate of preoperative hyperplasia with postoperative endometrial cancer was found to be 10.8% where by 15 cases of patients diagnosed with endometrial cancer postoperatively 11 cases were in postmenopausal period. In patients diagnosed with endometrial cancer according to their histologic types 14 cases had endometrioid adenocarcinoma while one patient with preoperative complex hyperplasia without atypia was diagnosed with serous papillary carcinoma postoperatively. Evaluation of stages in patients diagnosed with cancer, 7 cases of patients had stage IA, 7 cases of patients had stage IB, and 7 cases cases of patients with serous papillary carcinoma were
Healey, Catherine S; Ahmed, Shahana; O'Mara, Tracy A; Ferguson, Kaltin; Lambrechts, Diether; Garcia-Dios, Diego A; Vergote, Ignace; Amant, Frederic; Howarth, Kimberley; Gorman, Maggie; Hodgson, Shirley; Tomlinson, Ian; Yang, Hannah P; Lissowska, Jolanta; Brinton, Louise A; Chanock, Stephen; Garcia-Closas, Montserrat; Hall, Per; Liu, Jianjun; Shah, Mitul; Pharoah, Paul D P; Thompson, Deborah J; Rebbeck, Timothy R; Strom, Brian L; Dunning, Alison M; Easton, Douglas F; Spurdle, Amanda B
Recent large--scale association studies, both of genome-wide and candidate gene design, have revealed several single-nucleotide polymorphisms (SNPs) which are significantly associated with risk of developing breast cancer. As both breast and endometrial cancers are considered to be hormonally driven and share multiple risk factors, we investigated whether breast cancer risk alleles are also associated with endometrial cancer risk. We genotyped nine breast cancer risk SNPs in up to 4188 endometrial cases and 11,928 controls, from between three and seven Caucasian populations. None of the tested SNPs showed significant evidence of association with risk of endometrial cancer.
Ahmed, Shahana; O’Mara, Tracy A.; Ferguson, Kaltin; Lambrechts, Diether; Garcia-Dios, Diego A.; Vergote, Ignace; Amant, Frederic; Howarth, Kimberley; Gorman, Maggie; Hodgson, Shirley; Tomlinson, Ian; Yang, Hannah P.; Lissowska, Jolanta; Brinton, Louise A.; Chanock, Stephen; Garcia-Closas, Montserrat; Hall, Per; Liu, Jianjun; Shah, Mitul; Pharoah, Paul D.P.; Thompson, Deborah J.; Rebbeck, Timothy R.; Strom, Brian L.; Dunning, Alison M.; Easton, Douglas F.; Spurdle, Amanda B.
Recent large--scale association studies, both of genome-wide and candidate gene design, have revealed several single-nucleotide polymorphisms (SNPs) which are significantly associated with risk of developing breast cancer. As both breast and endometrial cancers are considered to be hormonally driven and share multiple risk factors, we investigated whether breast cancer risk alleles are also associated with endometrial cancer risk. We genotyped nine breast cancer risk SNPs in up to 4188 endometrial cases and 11 928 controls, from between three and seven Caucasian populations. None of the tested SNPs showed significant evidence of association with risk of endometrial cancer. PMID:21965274
Park, Kyung-Jin; Haak, Rainer; Ziebolz, Dirk; Krause, Felix; Schneider, Hartmut
This study evaluated (1) the detection and assessment of non-cavitated occlusal carious lesions by spectral domain optical coherence tomography (SD-OCT) and (2) the impact of varying angle of incidence (AI) of probe light and refractive index matching (RIM). Nine extracted human molars with 18 occlusal lesions (ICDAS code 2) were visually selected. 18 regions of interest (ROI) were imaged with SD-OCT under varying AI (0°, ±5°, ±10°, ±15°) and with/without application of glycerine at 0°. X-ray micro computed tomography (μCT) was used as a validation standard. μCT and OCT signals were categorized according to the lesion extent: 1-sound, 2-lesion limited to half of enamel, 3-lesion limited to enamel, 4-lesion into dentin. Agreement between both methods was assessed. Intra- and inter-examiner reproducibility analyses were conducted. Cohen's kappa coefficient (κ), Spearman's rho correlation (rs) and Wilcoxon test (α=0.05). Slight to moderate agreement (κ=0.153) between μCT and OCT was obtained at an AI of 0° (Wilcoxon: p=0.02). With variation of Al a substantial agreement (κ=0.607) was observed (p=0.74). Spearman's correlation between both methods was 0.428 at 0°, 0.75 with varying AI and 0.573 with glycerine. Kappa values for intra-and inter-examiner analysis ranged between 0.81 and 0.88 and between 0.25 and 0.73, respectively. Variation of AI improves the detectability of non-cavitated occlusal carious lesions. RIM can enhance signal-to-noise ratio. OCT could provide additional diagnostic information in single and longitudinal assessments of occlusal carious lesions. Copyright © 2017 Elsevier Ltd. All rights reserved.
Fernández-Murga, L; Hermenegildo, C; Tarín, J J; García-Pérez, M-Á; Cano, A
ABSTRACT Objective To describe the effect of the intermittent administration of vaginal progesterone and a low-dose estradiol patch on endometrial stability, as assessed by the rate of amenorrhea and endometrial stimulation. Methods This was an open study in which 64 moderately symptomatic, postmenopausal women were treated in the outpatient clinic of our University Hospital for different intervals up to 1 year. The treatment consisted of a combination of patches delivering 25 µg/day estradiol and intravaginal pills containing 100 mg of micronized progesterone. Patches and pills were administered concomitantly in a twice-a-week protocol. The endometrial response was assessed by endovaginal ultrasound completed with suction biopsy when required. Results Both cumulative amenorrhea and no-bleeding rates increased progressively and reached 88.9% and 100.0%, respectively, by the 12th month. Isolated or repetitive episodes of bleeding, bleeding and spotting, or only spotting were reported by three, four, and 12 women, respectively. Endometrial thickness remained unaltered. Endometrium was atrophic in the seven women in whom a biopsy was performed. Conclusion The substantially reduced progestogen load determined by this combination achieved an acceptable incidence of spotting or bleeding when associated with a low estrogenic dose. There was no apparent endometrial stimulation. Additional studies are required to confirm this observation.
Anastasiadis, Panagiotis; Koutlaki, Nikoleta; Liberis, Vasilios; Tsikouras, Panagiotis; Dimitraki, Marina; Liberis, Anastasios; Galazios, George
Peritoneal washing cytology and imprint cytology of pelvic lymph nodes samples were used to evaluate the rapid cytologic detection of peritoneal and retroperitoneal spread of endometrial cancer. We undertook a study on 194 endometrial cancer patients who underwent primary treatment in the Gynecologic Clinic, Democritus University of Thrace. All patients were subjected to peritoneal washing (PW) cytology and imprint cytology performed on lymph node sampling. The cytologic specimens were stained by May-Grünwald Giemsa (MGG) and Haematoxylin eosin (HE) techniques. Cell-blocks prepared from peritoneal washings (PWs) and the lymph node samples were sent for histologic examination. The cytologic fi ndings were correlated to histologic results. Rapid intraoperative cytology provides a useful diagnostic technique for the assessment of endometrial cancer spread. HE and MGG stain presented different values of sensitivity and specifi city in the detection of peritoneal and retroperitoneal spread of endometrial cancer. Cytologic assessment of intraperitoneal and retroperitoneal spread of endometrial cancer is a rapid, intraoperative procedure, which provides the surgeon with useful information regarding the stage of the disease and the subsequent therapeutic approach.
Brusseau, Elisabeth; Detti, Valérie; Coulon, Agnès; Maissiat, Emmanuèle; Boublay, Nawèle; Berthezène, Yves; Fromageau, Jérémie; Bush, Nigel; Bamber, Jeffrey
We previously developed a 2D locally regularized strain estimation technique that was already validated with ex vivo tissues. In this study, our technique is assessed with in vivo data, by examining breast abnormalities in clinical conditions. Method reliability is analyzed as well as tissue strain fields according to the benign or malignant character of the lesion. Ultrasound RF data were acquired in two centers on ten lesions, five being classified as fibroadenomas, the other five being classified as malignant tumors, mainly ductal carcinomas from grades I to III. The estimation procedure we developed involves maximizing a similarity criterion (the normalized correlation coefficient or NCC) between pre- and post-compression images, the deformation effects being considered. The probability of correct strain estimation is higher if this coefficient is closer to 1. Results demonstrated the ability of our technique to provide good-quality strain images with clinical data. For all lesions, movies of tissue strain during compression were obtained, with strains that can reach 15%. The NCC averaged over each movie was computed, leading for the ten cases to a mean value of 0.93, a minimum value of 0.87 and a maximum value of 0.98. These high NCC values confirm the reliability of the strain estimation. Moreover, lesions were clearly identified for the ten cases investigated. Finally, we have observed with malignant lesions that compared to ultrasound data, strain images can put in relief a more important lesion size, and can help in evaluating the lesion invasive character.
Freiman, Moti; Nickisch, Hannes; Prevrhal, Sven; Schmitt, Holger; Vembar, Mani; Maurovich-Horvat, Pál; Donnelly, Patrick; Goshen, Liran
The goal of this study was to assess the potential added benefit of accounting for partial volume effects (PVE) in an automatic coronary lumen segmentation algorithm that is used to determine the hemodynamic significance of a coronary artery stenosis from coronary computed tomography angiography (CCTA). Two sets of data were used in our work: (a) multivendor CCTA datasets of 18 subjects from the MICCAI 2012 challenge with automatically generated centerlines and 3 reference segmentations of 78 coronary segments and (b) additional CCTA datasets of 97 subjects with 132 coronary lesions that had invasive reference standard FFR measurements. We extracted the coronary artery centerlines for the 97 datasets by an automated software program followed by manual correction if required. An automatic machine-learning-based algorithm segmented the coronary tree with and without accounting for the PVE. We obtained CCTA-based FFR measurements using a flow simulation in the coronary trees that were generated by the automatic algorithm with and without accounting for PVE. We assessed the potential added value of PVE integration as a part of the automatic coronary lumen segmentation algorithm by means of segmentation accuracy using the MICCAI 2012 challenge framework and by means of flow simulation overall accuracy, sensitivity, specificity, negative and positive predictive values, and the receiver operated characteristic (ROC) area under the curve. We also evaluated the potential benefit of accounting for PVE in automatic segmentation for flow simulation for lesions that were diagnosed as obstructive based on CCTA which could have indicated a need for an invasive exam and revascularization. Our segmentation algorithm improves the maximal surface distance error by ~39% compared to previously published method on the 18 datasets from the MICCAI 2012 challenge with comparable Dice and mean surface distance. Results with and without accounting for PVE were comparable. In contrast
Dominick, Sally; Hickey, Martha; Chin, Jason; Su, H Irene
Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015. Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology. Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or
Objective The SNP309 polymorphism (T-G) in the promoter of MDM2 gene has been reported to be associated with enhanced MDM2 expression and tumor development. Studies investigating the association between MDM2 SNP309 polymorphism and endometrial cancer risk reported conflicting results. We performed a meta-analysis of all available studies to explore this association. Methods All studies published up to August 2013 on the association between MDM2 SNP309 polymorphism and endometrial cancer risk were identified by searching electronic databases PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database (CBM). The association between the MDM2 SNP309 polymorphism and endometrial cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results Eight case–control studies with 2069 endometrial cancer cases and 4546 controls were identified. Overall, significant increase of endometrial cancer risk was found when all studies were pooled in the meta-analysis (GG vs. TT: OR = 1.464, 95% CI 1.246–1.721, P < 0.001; GG vs. TG + TT: OR = 1.726, 95% CI 1.251–2.380, P = 0.001; GG + TG vs. TT: OR = 1.169, 95% CI 1.048–1.304, P = 0.005). In subgroup analysis by ethnicity and HWE in controls, significant increase of endometrial cancer risks were observed in Caucasians and studies consistent with HWE. In subgroup analysis according to study quality, significant associations were observed in both high quality studies and low quality studies. Conclusions This meta-analysis suggests that MDM2 SNP309 polymorphism contributes to endometrial cancer susceptibility, especially in Caucasian populations. Further large and well-designed studies are needed to confirm this association. PMID:24423195
Simcock, Bryony; Narayan, Kailash; Drummond, Elizabeth; Bernshaw, David; Wells, Elizabeth; Hicks, Rodney J
The optimal method of assessing disease distribution in endometrial cancer is widely debated. Knowledge of disease distribution assists in planning adjuvant radiotherapy; in this study we used positron emission tomography/computed tomography (PET/CT) to assess disease distribution before radiotherapy. Seventy-three consecutive patients referred to the Peter MacCallum Cancer Centre for adjuvant radiotherapy for endometrial cancer, with either high-risk disease after a hysterectomy or recurrent disease, had a PET/CT before treatment. The findings on PET/CT and clinical course were recorded. PET/CT found additional disease in 35% of postoperative patients, changing planned treatment in 31%. In the group with known recurrence, additional disease was found in 72%, changing management in 36%. PET/CT is a valuable tool for planning radiotherapy in endometrial cancer.
Caruso, Damiano; De Cecco, Carlo N; Schoepf, U Joseph; Schaefer, Amanda R; Leland, Parker W; Johnson, Dustin; Laghi, Andrea; Hardie, Andrew D
The purpose was to assess image quality of portal-venous phase dual-energy computed tomography (DECT) for liver lesions. We performed 120-kVp-equivalent linear-blended (LB) and monoenergetic reconstructions from 40 to 190 keV by standard (VMI) and advanced virtual monoenergetic (VMI+) methods. Diagnostic performance, and quantitative and qualitative image analyses were assessed and compared. Liver contrast to noise ratio peaked at 40 keV_VMI+, while image quality and reader preference peaked at 50 keV_VMI+. 50 keV_VMI+ scored overall higher diagnostic performance: lesion sensitivity 95.4% vs. 83.3% for both 75 keV_VMI and LB. DECT improves assessment of hypoenhancing liver lesions on portal venous phase. 50 keV_VMI+ demonstrated the highest image quality and diagnostic performance over VMI and LB. Copyright © 2016 Elsevier Inc. All rights reserved.
Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer
Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma
Masuda, Hirotaka; Maruyama, Tetsuo; Hiratsu, Emi; Yamane, Junichi; Iwanami, Akio; Nagashima, Takashi; Ono, Masanori; Miyoshi, Hiroyuki; Okano, Hirotaka James; Ito, Mamoru; Tamaoki, Norikazu; Nomura, Tatsuji; Okano, Hideyuki; Matsuzaki, Yumi; Yoshimura, Yasunori
Human uterine endometrium exhibits unique properties of cyclical regeneration and remodeling throughout reproductive life and also is subject to endometriosis through ectopic implantation of retrogradely shed endometrial fragments during menstruation. Here we show that functional endometrium can be regenerated from singly dispersed human endometrial cells transplanted beneath the kidney capsule of NOD/SCID/gamma(c)(null) immunodeficient mice. In addition to the endometrium-like structure, hormone-dependent changes, including proliferation, differentiation, and tissue breakdown and shedding (menstruation), can be reproduced in the reconstructed endometrium, the blood to which is supplied predominantly by human vessels invading into the mouse kidney parenchyma. Furthermore, the hormone-dependent behavior of the endometrium regenerated from lentivirally engineered endometrial cells expressing a variant luciferase can be assessed noninvasively and quantitatively by in vivo bioluminescence imaging. These results indicate that singly dispersed endometrial cells have potential applications for tissue reconstitution, angiogenesis, and human-mouse chimeric vessel formation, providing implications for mechanisms underlying the physiological endometrial regeneration during the menstrual cycle and the establishment of endometriotic lesions. This animal system can be applied as the unique model of endometriosis or for other various types of neoplastic diseases with the capacity of noninvasive and real-time evaluation of the effect of therapeutic agents and gene targeting when the relevant cells are transplanted beneath the kidney capsule.
Painter, Jodie N; O'Mara, Tracy A; Marquart, Louise; Webb, Penelope M; Attia, John; Medland, Sarah E; Cheng, Timothy; Dennis, Joe; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley V; Beckmann, Matthias W; Ekici, Arif B; Fasching, Peter A; Hein, Alexander; Rübner, Matthias; Czene, Kamila; Darabi, Hatef; Hall, Per; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Amant, Frederic; Annibali, Daniela; Depreeuw, Jeroen; Lambrechts, Diether; Neven, Patrick; Cunningham, Julie M; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica M J; Ashton, Katie A; Otton, Geoffrey; Proietto, Anthony; Mints, Miriam; Tham, Emma; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Tomlinson, Ian; Dunning, Alison M; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B
The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls. Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 × 10(-17)). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m(2) of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89-2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44-1.68, per 5 kg/m(2)). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10-1.39; P = 5.3 × 10(-4)). There was evidence of directional pleiotropy (P = 1.5 × 10(-4)). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 × 10(-4)), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS. BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503-10. ©2016 AACR. ©2016 American Association for Cancer Research.
Chiang, Sarah; Lee, Cheng-Han; Stewart, Colin J R; Oliva, Esther; Hoang, Lien N; Ali, Rola H; Hensley, Martee L; Arias-Stella, Javier A; Frosina, Denise; Jungbluth, Achim A; Benayed, Ryma; Ladanyi, Marc; Hameed, Meera; Wang, Lu; Kao, Yu-Chien; Antonescu, Cristina R; Soslow, Robert A
Recognition of high-grade endometrial stromal sarcoma is important because of its aggressive clinical behavior. Morphologic features of YWHAE-NUTM2 high-grade endometrial stromal sarcoma may overlap with other uterine sarcoma types. BCOR immunoexpression was studied in these tumors and their morphologic mimics to assess its diagnostic utility. BCOR immunohistochemical staining was performed on archival tissue from 28 high-grade endometrial stromal sarcomas with classic morphology (20 YWHAE-NUTM2, 5 ZC3H7B-BCOR, 3 BCOR-ZC3H7B), 3 high-grade endometrial stromal sarcomas with unusual morphology and unknown gene rearrangement status, 66 low-grade endometrial stromal sarcomas, 21 endometrial stromal nodules, 38 uterine leiomyosarcomas, and 19 uterine leiomyomas. Intensity of nuclear staining and percentage of positive tumor cells were recorded. Strong diffuse nuclear BCOR staining (defined as >95% of tumor cells) was seen in the round cell component of all 20 (100%) classic YWHAE-NUTM2 high-grade endometrial stromal sarcomas and the 3 unusual high-grade endometrial stromal sarcomas which prompted FISH studies confirming YWHAE rearrangement in 2 tumors. Genomic PCR confirmed the presence of BCOR exon 16 internal tandem duplication in the third case. Diffuse BCOR staining was strong in three and weak in one BCOR-rearranged high-grade endometrial stromal sarcoma while absent in the remaining four BCOR-rearranged tumors. BCOR staining was weakly positive in <5% of tumor cells in 4 of 66 (6%) low-grade endometrial stromal sarcomas and 1 of 18 (6%) endometrial stromal nodules and weakly to moderately positive in <5-40% of tumor cells in 6 of 31 (19%) leiomyosarcomas. No BCOR staining was seen in the remaining low-grade endometrial stromal sarcomas, endometrial stromal nodules, leiomyosarcomas, or any of the leiomyomas. BCOR immunohistochemical staining is a highly sensitive marker for YWHAE-NUTM2 high-grade endometrial stromal sarcoma with both classic and unusual morphology
... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and...
... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and...
... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and...
Jick, H; Walker, A M; Rothman, K J
Vital statistics show that a rise in incidence of endometrial cancer began in the mid-1960s on the West Coast of the United States. This rise was continuous and reached a peak in 1975. Elsewhere, incidence rates for endometrial cancer rose during the 1970s. It now seems evident that much of the rise in all areas of the country was due to replacement estrogen treatment. We estimated from data obtained from the Commission on Professional and Hospital Activities-Professional Activity Study of Ann Arbor, Michigan, that over 15,000 cases of endometrial cancer were caused by replacement estrogens during the five-year period 1971--1975 alone. This represents one of the largest epidemics of serious iatrogenic disease that has ever occurred in this country. With the substantial fall in estrogen sales starting in January 1976, there has been an associated decline in the incidence rates of endometrial cancer nationwide. PMID:7356090
... endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA...) Indication: Only to evaluate the endometrium, and (ii) Contraindications: Pregnancy, history of uterine...
... endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA...) Indication: Only to evaluate the endometrium, and (ii) Contraindications: Pregnancy, history of uterine...
... endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA...) Indication: Only to evaluate the endometrium, and (ii) Contraindications: Pregnancy, history of uterine...
... and pipette, or catheter. This device is used to study endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA's: (i) “Use of International...
... and pipette, or catheter. This device is used to study endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA's: (i) “Use of International...
Lee, Chulsung; Lee, Dustin; Darling, Cynthia L.; Fried, Daniel
The high transparency of dental enamel in the near-infrared (NIR) at 1310 nm can be exploited for imaging dental caries without the use of ionizing radiation. The objective of this study is to determine whether the lesion contrast derived from NIR imaging in both transmission and reflectance can be used to estimate lesion severity. Two NIR imaging detector technologies are investigated: a new Ge-enhanced complementary metal-oxide-semiconductor (CMOS)-based NIR imaging camera, and an InGaAs focal plane array (FPA). Natural occlusal caries lesions are imaged with both cameras at 1310 nm, and the image contrast between sound and carious regions is calculated. After NIR imaging, teeth are sectioned and examined using polarized light microscopy (PLM) and transverse microradiography (TMR) to determine lesion severity. Lesions are then classified into four categories according to lesion severity. Lesion contrast increases significantly with lesion severity for both cameras (p<0.05). The Ge-enhanced CMOS camera equipped with the larger array and smaller pixels yields higher contrast values compared with the smaller InGaAs FPA (p<0.01). Results demonstrate that NIR lesion contrast can be used to estimate lesion severity.
Lee, Chulsung; Lee, Dustin; Darling, Cynthia L.; Fried, Daniel
The high transparency of dental enamel in the near-infrared (NIR) at 1310 nm can be exploited for imaging dental caries without the use of ionizing radiation. The objective of this study is to determine whether the lesion contrast derived from NIR imaging in both transmission and reflectance can be used to estimate lesion severity. Two NIR imaging detector technologies are investigated: a new Ge-enhanced complementary metal-oxide-semiconductor (CMOS)-based NIR imaging camera, and an InGaAs focal plane array (FPA). Natural occlusal caries lesions are imaged with both cameras at 1310 nm, and the image contrast between sound and carious regions is calculated. After NIR imaging, teeth are sectioned and examined using polarized light microscopy (PLM) and transverse microradiography (TMR) to determine lesion severity. Lesions are then classified into four categories according to lesion severity. Lesion contrast increases significantly with lesion severity for both cameras (p<0.05). The Ge-enhanced CMOS camera equipped with the larger array and smaller pixels yields higher contrast values compared with the smaller InGaAs FPA (p<0.01). Results demonstrate that NIR lesion contrast can be used to estimate lesion severity. PMID:20799842
Velasco, Ana; Pallares, Judit; Santacana, Maria; Yeramian, Andre; Dolcet, Xavier; Eritja, Nuria; Puente, Soraya; Sorolla, Anabel; Llecha, Nuria; Matias-Guiu, Xavier
Inactivation of a tumor suppressor gene typically occurs in two steps, thus fulfilling Knudson hypothesis. One "hit" is frequently a point mutation or a small deletion. The other alteration is usually a large genomic loss of part of a gene, or even part of a chromosome, or the whole chromosome. However, it is not clear which of these two events occurs first. Loss of heterozygosity (LOH) analysis allows the identification of one of the 2 hits. Although microsatellite polymerase chain reaction is the technique most frequently used to assess LOH, other different approaches can also be used. The LOH can also be assessed by restriction fragment length polymorphism analysis, single strand conformation polymorphism analysis, oligonucleotide microarrays capable to simultaneously determine the genotype of thousands of single-nucleotide polymorphism (single-nucleotide polymorphism arrays), comparative genomic hybridization, multiplex amplification and probe hybridization, and multiplex ligation-dependent probe amplification. In this article, the authors review the results obtained with molecular analysis of LOH in the understanding of development and progression of endometrial carcinoma. Particular attention is given to: (1) the presence of widespread LOH in nonendometrioid carcinoma, probably reflecting the existence of chromosomal instability; and (2) specific LOH patterns associated with some clinicopathologic features.
Lewin, Sharyn N
In 1988 the International Federation of Gynecologists and Obstetricians (FIGO) developed a surgical staging system for endometrial cancer. The FIGO staging system was recently revised in 2009 to reflect our growing understanding of the natural history of endometrial cancer. In this review, we describe the revised 2009 FIGO staging system for tumors of the uterine corpus and examine the effect of the new changes in the staging criteria.
Kirichenko, A K; Khorzhevskiĭ, V A
To study the endometrial vasculature in women with hydrosalpinx and to determine a possible correlation between its state and the morphometric parameters of other structural components of the uterine mucosa. The endometrium was studied in 20 patients with primary tubal infertility in hydrosalpinx. A control group included 20 women with established fertility and a regular menstrual cycle with a good obstetric and gynecological history. The spectrum of morphometric parameters included the relative volumes occupied by the endometrial glands and glandular epithelium; the height of the integumentary epithelium; and the number of stromal cells per mm2. Stereometric (glandular-stromal, epithelial-stromal) indices and epithelium/glandular lumen ratio were calculated. The endometrial vasculature was estimated by immunohistochemical assay of CD31- and CD34-expressing cells. There was a decrease in the specific volume occupied by positively stained vascular endotheliocytes and a predominance of the stromal component of the endometrium over its epithelial one. Correlations were found between the degree of development of the endometrial vasculature and endometrial glands, which reflects their normal relationships in the proliferation phase. In the study group, the correlation between the height of the integumentary epithelium and the development of the endometrial vasculature was moderately positive, which was absent in the control group where this correlation was strong and positive. The findings are evidence in favor of the negative impact of hydrosalpinx on the uterine mucosa. The found changes in the main endometrial structural components (vessels, glands, and stromal cells) reflect impaired mucosal maturation processes during the proliferation phase. The substantial negative impact of hydrosalpinx has an effect on the height of the integumentary epithelium of the endometrium. The given data suggest that there are significant and complex endometrial changes in hydrosalpinx
Simonetti, C; Lupoi, D; Di Giambattista, G; Sessa, V; Rosati, M; Orlacchio, A
Spinal injuries account for 5-15% of sport-related traumas. Equestrian sports are considered, together with rugby, motor sport and diving, the riskiest sport for severe spinal injuries. We investigated the biomechanical changes and repeated microtraumas in equitation. We examined with MR the lumbar spines of 12 professional horsewomen and horsemen, 18-51 years old (mean: 33.4 years), belonging to F.I.S.E. (the Italian Federation for Equestrian Sports) and classified as Olympic riders, Senior and Young European riders. An 0.3-T resistive and an 0.2-T permanent magnets with dedicated surface coils were used. We also examined a control group of non-professional healthy volunteers homogeneous by age. MR findings were classified as follows: 1) changes in normal bending and angles of the lumbar spine; 2) injuries and changes in lumbar disks; 3) changes in spinal ligaments; 4) vertebral body injuries. MR was very sensitive in the assessment of all lumbosacral components in all the athletes; besides yielding useful findings to integrate with clinical results, MR also has a predictive value relative to both the continuation of sports activity and the possible damage at the end of it.
González-Fernández, Maria L; Pérez-Castrillo, Saúl; Sánchez-Lázaro, Jaime A; Prieto-Fernández, Julio G; López-González, Maria E; Lobato-Pérez, Sandra; Colaço, Bruno J; Olivera, Elías R; Villar-Suárez, Vega
OBJECTIVE To assess the ability to regenerate an equine meniscus by use of a collagen repair patch (scaffold) seeded with mesenchymal stem cells (MSCs) derived from bone marrow (BM) or adipose tissue (AT). SAMPLE 6 female Hispano-Breton horses between 4 and 7 years of age; MSCs from BM and AT were obtained for the in vitro experiment, and the horses were subsequently used for the in vivo experiment. PROCEDURES Similarities and differences between MSCs derived from BM or AT were investigated in vitro by use of cell culture. In vivo assessment involved use of a meniscus defect and implantation on a scaffold. Horses were allocated into 2 groups. In one group, defects in the medial meniscus were treated with MSCs derived from BM, whereas in the other group, defects were treated with MSCs derived from AT. Defects were created in the contralateral stifle joint but were not treated (control samples). RESULTS Both types of MSCs had universal stem cell characteristics. For in vivo testing, at 12 months after treatment, treated defects were regenerated with fibrocartilaginous tissue, whereas untreated defects were partially repaired or not repaired. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MSCs derived from AT could be a good alternative to MSCs derived from BM for use in regenerative treatments. Results also were promising for a stem cell-based implant for use in regeneration in meniscal lesions. IMPACT FOR HUMAN MEDICINE Because of similarities in joint disease between horses and humans, these results could have applications in humans.
Zheng, Qiaoli; Wu, Haijian; Cao, Jiang
Background Adiponectin is an insulin-sensitizing hormone produced by adipocytes. It has been suggested to be involved in endometrial tumorigenesis. Published data have shown inconsistent results for the association between circulating adiponectin levels and endometrial cancer. In this study, we conducted a meta-analysis to evaluate the predictive value of circulating adiponectin levels on the development of endometrial cancer. Methods PubMed, Embase, ISI web of knowledge, and Cochrane databases were searched for all eligible studies, and the summary relative risk (SRR) was calculated. Additionally, we performed dose-response analysis with eight eligible studies. Results A total of 1,955 cases and 3,458 controls from 12 studies were included. The SRR for the ‘highest’ vs ‘lowest’ adiponectin levels indicated high adiponectin level reduced the risk of endometrial cancer [SRR = 0.40, 95% confidence interval (CI), 0.33–0.66]. Results from the subgroup analyses were consistent with the overall analysis. The SRR for each 1 µg/ml increase of adiponectin indicated a 3% reduction in endometrial cancer risk (95% CI: 2%–4%), and a 14% reduction for each increase of 5 µg/ml (95% CI: 9%–19%). No evidence of publication bias was found. Conclusions This meta-analysis demonstrates that low level of circulating adiponectin is a risk factor for endometrial cancer. PMID:26030130
Pocobelli, Gaia; Doherty, Jennifer A; Voigt, Lynda F; Beresford, Shirley A; Hill, Deirdre A; Chen, Chu; Rossing, Mary Anne; Holmes, Rebecca S; Noor, Zorawar S; Weiss, Noel S
Epidemiologic studies are consistent in finding that women who have had at least one birth are less likely to develop endometrial cancer. Less clear is whether timing of pregnancies during reproductive life influences risk, and the degree to which incomplete pregnancies are associated with a reduced risk. We evaluated pregnancy history in relation to endometrial cancer risk using data from a series of 4 population-based endometrial cancer case-control studies of women 45-74 years of age (1712 cases and 2134 controls) during 1985-2005 in western Washington State. Pregnancy history and information on other potential risk factors were collected by in-person interviews. Older age at first birth was associated with a reduced risk of endometrial cancer after adjustment for number of births and age at last birth (test for trend P = 0.004). The odds ratio comparing women at least 35 years of age at their first birth with those younger than 20 years was 0.34 (95% confidence interval = 0.14-0.84). Age at last birth was not associated with risk after adjustment for number of births and age at first birth (test for trend P = 0.830). Overall, a history of incomplete pregnancies was not associated with endometrial cancer risk to any appreciable degree. In this study, older age at first birth was more strongly associated with endometrial cancer risk than was older age at last birth. To date, there remains some uncertainty in the literature on this issue.
Zhang, Ying; Wang, Jian
Endometrial carcinoma is the most common type of female genital tract malignancy. Although endometrial carcinoma is a low grade curable malignancy, the condition of the disease can range from excellent prognosis with high curability to aggressive disease with poor outcome. During the last 10 years many researches have provided some new valuable data of optimal treatments for endometrial carcinoma. Progression in diagnostic imaging, radiation delivery systems, and systemic therapies potentially can improve outcomes while minimizing morbidity. Firstly, total hysterectomy and bilateral salphingo-oophorectomy is the primary operative procedure. Pelvic lymhadenectomy is performed in most centers on therapeutic and prognostic grounds and to individualize adjuvant treatment. Women with endometrial carcinoma can be readily segregated intraoperatively into “low-risk” and “high-risk” groups to better identify those women who will most likely benefit from thorough lymphadenectomy. Secondly, adjuvant therapies have been proposed for women with endometrial carcinoma postoperatively. Postoperative irradiation is used to reduce pelvic and vaginal recurrences in high risk cases. Chemotherapy is emerging as an important treatment modality in advanced endometrial carcinoma. Meanwhile the availability of new hormonal and biological agents presents new opportunities for therapy. PMID:20613958
The traditional approach for the treatment of endometrial cancer by laparotomy is increasingly being replaced by laparoscopic surgery. The advantages of laparoscopy have been well-documented. Laparoscopy avoids the morbidity of a laparotomy, overcomes the limitations of vaginal hysterectomy, provides adequate pathological information for an accurate surgical staging and expedites the postoperative recovery of patients. This paper reports the outcome of a series of 50 consecutive cases of laparoscopic hysterectomy and pelvic lymphadenectomy for endometrial cancers that were performed by the author. The objective is to review the perioperative, postoperative experience and survival outcomes of patients with endometrial cancer managed by laparoscopic surgery performed by a single surgeon. The records of 50 consecutive patients with endometrial cancers from October 1995 to October 2007 treated by laparoscopic pelvic lymphadenectomy and laparoscopic hysterectomy (total and assisted) were retrospectively reviewed. Data on patients' attributes, endometrial cancers, surgical procedures, surgical complications and morbidity, perioperative experience, length of hospital stays and clinical outcome were analysed. Laparoscopic surgery was successful in all 50 patients and is clearly an option for the treatment of early endometrial cancer. Careful patient selection and surgical competency are instrumental in ensuring successful treatment.
Norimatsu, Y; Yamaguchi, T; Taira, T; Abe, H; Sakamoto, H; Takenaka, M; Yanoh, K; Yoshinobu, M; Irino, S; Hirai, Y; Kobayashi, T K
The purpose of the present study was to evaluate the reproducibility of the cytological diagnosis of endometrial lesions by the Osaki Study Group (OSG) method of new cytological diagnostic criteria using BD SurePath(™) (SP)-liquid-based cytology (LBC). This cytological classification using the OSG method consists of six categories: (i) normal endometrium (NE), (ii) endometrial glandular and stromal breakdown (EGBD), (iii) atypical endometrial cells, cannot exclude atypical endometrial hyperplasia or more (ATEC-A), (iv) adenocarcinoma including atypical endometrial hyperplasia or malignant tumour (Malignancy), (v) endometrial hyperplasia without atypia (EH) and (vi) atypical endometrial cells of undetermined significance (ATEC-US). For this study, a total 244 endometrial samplings were classified by two academic cytopathologists as follows: 147 NE cases , 36 EGBD cases , 47 Malignant cases, eight ATEC-A cases, two EH cases and four ATEC-US cases. To confirm the reproducibility of the diagnosis and to study the inter- and intra-observer agreement further, a second review round followed at 3-month intervals, which included three additional cytopathologists. The inter-observer agreement of NE classes improved progressively from 'good to fair' to 'excellent', with values increasing from 0.70 to 0.81. Both EGBD and Malignancy classes improved progressively from 'good to fair' to 'excellent', with values increasing from 0.62-0.63 to 0.84-0.95, respectively. The overall intra-observer agreement between the first and the second rounds was 'good to fair' to 'excellent', with values changing from 0.79 to 0.85. All kappa improvements were significant (P < 0.0001). In this study, it seemed that the use of the OSG method as the new diagnostic criteria for SP-LBC preparation, may be a valid method to improve the precision (reproducibility) of endometrial cytology. © 2016 John Wiley & Sons Ltd.
Baimukanova, Gyulnar; Miyazawa, Byron; Potter, Daniel R.; Muench, Marcus O.; Bruhn, Roberta; Gibb, Stuart L.; Spinella, Philip C.; Cap, Andrew P.; Cohen, Mitchell J.; Pati, Shibani
BACKGROUND In current blood banking practices, platelets (PLTs) are stored in plasma at 22°C, with gentle agitation for up to 5 days. To date, the effects of storage and donor variability on PLT regulation of vascular integrity are not known. STUDY DESIGN AND METHODS In this study, we examined the donor variability of leukoreduced fresh (Day 1) or stored (Day 5) PLTs on vascular endothelial barrier function in vitro and in vivo. In vitro, PLT effects on endothelial cell (EC) monolayer permeability were assessed by analyzing transendothelial electrical resistances (TEER). PLT aggregation, a measure of hemostatic potential, was analyzed by impedance aggregometry. In vivo, PLTs were investigated in a vascular endothelial growth factor A (VEGF-A)-induced vascular permeability model in NSG mice, and PLT circulation was measured by flow cytometry. RESULTS Treatment of endothelial monolayers with fresh Day 1 PLTs resulted in an increase in EC barrier resistance and decreased permeability in a dose-dependent manner. Subsequent treatment of EC monolayers with Day 5 PLTs demonstrated diminished vasculoprotective effects. Donor variability was noted in all measures of PLT function. Day 1 PLT donors were more variable in their effects on TEER than Day 5 PLTs. In mice, while all PLTs regardless of storage time demonstrated significant protection against VEGF-A–induced vascular leakage, Day 5 PLTs exhibited reduced protection when compared to Day 1 PLTs. Day 1 PLTs demonstrated significant donor variability against VEGF-A–challenged vascular leakage in vivo. Systemic circulating levels of Day 1 PLTs were higher than those of Day 5 PLTs CONCLUSIONS In vitro and in vivo, Day 1 PLTs are protective in measures of vascular endothelial permeability. Donor variability is most prominent in Day 1 PLTs. A decrease in the protective effects is found with storage of the PLT units between Day 1 and Day 5 at 22°C, thereby suggesting that Day 5 PLTs are diminished in their ability to
Koh, V Mue; Shi, Y X; Tang, Q H
To investigate the clinical significance of p16 expression, a product of the cyclin dependent kinase inhibitor CDKN2 (also known as MTS1, multiple tumor suppressor 1) and assess its relationship with retinoblastoma protein expression in the pathogenesis of endometrial cancer. p16 and pRb expression were histochemically evaluated, using p16 and RB polyclonal antibodies on paraffin sections of 27 primary endometrial adenocarcinomas with no therapy prior to surgery, through the streptavidin peroxydase conjugated method. Further analyses were carried out using the polymerase chain reaction for exon 1 gene amplification to investigate the mechanism of abnormal p16 expression. p16 expression was detected in 100% of normal endometriums and in 74.04% of endometrial carcinomas (p < 0.05). This was significantly associated with tumor cell grade (p < 0.05). PCR analysis of exon 1 in five cases with no detectable p16 expression revealed four homozygous deletions. Additionally, the inverse correlation between RB and p16 expression was confirmed in this study, with 71.42% of tumors demonstrating inverse expression of p16 and RB (p < .005). p16 expression decrease is a significant event in endometrial carcinoma pathogenesis, and it is inversely correlated to tumor cell grade. Exon 1 homozygous deletion might be one of the mechanisms of loss of p16 expression. The p16/pRb growth suppressor pathway is targeted in human endometrial carcinoma.
Garcia-Velasco, Juan A; Fassbender, Amelie; Ruiz-Alonso, Maria; Blesa, David; D'Hooghe, Thomas; Simon, Carlos
Endometrial receptivity is still questioned today in women with endometriosis. The aim of this study was to assess the endometrial receptivity gene signature in patients with different stages of endometriosis by investigating transcriptomic modifications of their endometrium using the endometrial receptivity array (ERA) test. A prospective, interventional multicentre pilot trial was designed and implemented in two university-affiliated infertility units from Belgium and Spain. Gene expression microarray was used to diagnose the receptivity status by quantifying the expression of 238 specific genes directly related to human endometrial receptivity. Unsupervised hierarchical clustering showed no clustering of samples based on endometriosis stages. Two subgroups of samples clustered together corresponding on the day of the cycle in which the biopsy was taken (day 18 versus days 19-20). None of the 238 genes present in the ERA array were significantly over- or under- expressed in any of different stages of the disease compared with controls. Minimal differences were found when looking at the functional profile, suggesting that the possible effect from a clinical point of view may be meaningless. Endometrial receptivity gene signature during the implantation window does not vary significantly among patients with endometriosis even considering different stages compared with healthy women.
Jerath, Maya R.; Hoopes, P. Jack; Manganiello, Paul D.
The use of PDT for endometrial ablation has been the focus of much recent research. However, the mechanism of action, optimal treatment parameters, and long-term clinical effect are still poorly understood. This study was undertaken to further the understanding of the endometrial response to this drug/light- induced damage. Postpartum rat (Charles River) uterine horns were used as the animal model for fluorescence and treatment studies. Aminolevulinic acid was administered topically (intrauterine), and following a 0.5- to 3-hour drug incubation time, the endometrium was either removed and processed for fluorescence microscopy to assess drug localization or exposed to 150-200 J/cm2 of 630-nm laser light via a 1-cm cylindrical diffusing tip. The light=treated uterine horns were removed and histologically examine 7 to 10 days following treatment. The extent and character of uterine and endometrial damage (gross and histological analysis) were recorded for the varying light doses and incubation times. With topical (intrauterine) application of photosensitizer, incubation time and penetration ability of drug were found to be crucial factors. The use of a drug penetration enhancing vehicle produced greater tissue effects (endometrial ablation). These preliminary studies also showed that tissue effect is drug and light dose related and that the most profound effects may be vascular mediated. The study provided preliminary information for the use of PDT in gynecological applications such as endometrial ablation and female sterilization through Fallopian tube occlusion.
Wojciechowski, Michał; Krawczyk, Tomasz; Śmigielski, Janusz; Malinowski, Andrzej
Adhesive molecules like CD44 are well defined key players in the metastatic cascade in many cancers, including endometrial cancer. They could play a role of markers of invasion, metastasis and prognostic factors. The aim of the study is to assess a possible role of the CD44 as a marker of invasion in endometrial cancer, both at the moment of preoperative workup and final staging. Available for analysis were archival specimens of 51 patients who had underwent curettage and surgery between 2002 and 2007. An immunohistochemical study for CD44 expression was performed in curettage and postoperative specimens. Normal endometrium of 20 randomly chosen patients was used as a control group. In endometrial cancer the expression of CD44 was significantly more intensive than in normal endometrium. In postoperative specimens, the CD44 expression was weaker in serous than in endometrioid cancer. There was no significant correlation between the adhesion molecule expression and clinicopathological features: grade,depth of invasion, cervical involvement, serosal and adnexal involvement, lymph-vascular space involvement, lymph node and distant metastases nor FIGO stage. An increased expression of CD44 in endometrial cancer suggests its possible role in pathogenesis of this disease, however, it doesn't seem to be crucial. Different expression of the CD44 in endometrioid and papillary-serous type may reflect different pathogenesis of these types of cancer. No statistically proved relation between the investigated molecule expression and clinicopathological parameters suggests scepticism about its use in diagnostic process of endometrial cancer.
Baxi, Seema N; Panchal, Nirav S
Cytology of the endometrium is an underused technique in diagnostic pathology. It has been used in the past for endometrial hyperplasia and carcinoma. Only few studies have used cytology in the diagnosis of dysfunctional uterine bleeding (DUB). Endometrial imprint cytology has been rarely used except for application of immunocytochemistry in diagnosis of endometrial carcinoma. The present study was conducted to evaluate whether it is possible to assign histopathology-like diagnosis by imprint cytology and also to evaluate its usefulness in the assessment of patients of dysfunctional uterine bleeding of low clinical suspicion. Imprint smears were made from 93 curettage materials duri