Investigational Paradigms in Downscoring and Upscoring DCIS: Surgical Management Review

Counseling patients with DCIS in a rational manner can be extremely difficult when the range of treatment criteria results in diverse and confusing clinical recommendations. Surgeons need tools that quantify measurable prognostic factors to be used in conjunction with clinical experience for the complex decision-making process. Combination of statistically significant tumor recurrence predictors and lesion parameters obtained after initial excision suggests that patients with DCIS can be stratified into specific subsets allowing a scientifically based discussion. The goal is to choose the treatment regimen that will significantly benefit each patient group without subjecting the patients to unnecessary risks. Exploring the effectiveness of complete excision may offer a starting place in a new way of reasoning and conceiving surgical modalities in terms of “downscoring” or “upscoring” patient risk, perhaps changing clinical approach. Reexcison may lower the specific subsets' score and improve local recurrence-free survival also by revealing a larger tumor size, a higher nuclear grade, or an involved margin and so suggesting the best management. It seems, that the key could be identifying significant relapse predictive factors, according to validated risk investigation models, whose value is modifiable by the surgical approach which avails of different diagnostic and therapeutic potentials to be optimal. Certainly DCIS clinical question cannot have a single curative mode due to heterogeneity of pathological lesions and histologic classification

Baryogenesis through gradual collapse of vortons

We evaluate the matter-antimatter asymmetry produced by emission of fermionic carriers from vortons which are assumed to be destabilized at the electroweak phase transition.The velocity of contraction of the vorton, calculated through the decrease of its magnetic energy, originates a chemical potential which allows a baryogenesis of the order of the observed value. This asymmetry is not diluted by reheating if the collapse of vortons is distributed along an interval of ~ 10^-9 sec.Comment: 14 pages, Latex, no figure

Atypical polypoid adenomyoma follow-up and management: Systematic review of case reports and series and meta-analysis

BACKGROUND: Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative treatment is proposed despite the high recurrence rate and the association with endometrial cancer.Our aim was to assess the risk of recurrence with different conservative treatments in fertile ages and the prevalence of malignant or pre-malignant associated lesions to better address an adequate patient counselling when treatment modalities are discussed. METHODS: This study is a systematic review and meta-analysis of case reports and case series about APA management and follow-up. A literature search was carried from Medline and Scopus for studies published from January 1, 1980 to December 31, 2018. RESULTS: We included 46 observational studies and 296 cases in fertile women. The prevalence of APA relapse was 44% (CI.95 33-57%) and was lower in cases treated with operative hysteroscopy (22%; CI.95 11-39%) than in cases treated with blind curettage and polypectomy (38%; CI.95 15-67%). The prevalence of the concomitant or during the follow-up diagnosis of endometrial carcinoma was 16% (CI.95 9-29%). The risk of cancer development during follow-up was significantly less in cases treated with histeroscopy (10.56% new cumulative diagnosis at 5 years follow up; CI.95 0-23.7%) than blind curettage and polypectomy (35.5% new cumulative diagnosis at 5 years; CI.95 11.65-52.92%; P\u200a<\u200a.05). Medical treatment with medroxyprogesterone acetate after surgery does not reduce APA recurrence. Pregnancy was observed in 79% cases in which the desire was expressed. CONCLUSION: This review suggests that conservative treatment performed by operative hysteroscopy is the optimal choice because it lowers the risk of recurrence, improves the accuracy of concomitant carcinoma or hyperplasia diagnosis, and leaves the possibility of future pregnancies

Quantification of Women Who Could Benefit from Hormone Therapy after Endometrial Cancer Treatment: An Analysis of SEER Data

Our primary aim was to estimate the magnitude of stage I endometrial cancer (EC) survivors that could benefit from hormonal therapy (HT). Our secondary aims were to assess EC incidence in women below 50 and below 60 over the years, and analyze the overall survival and any influencing factors. We analyzed the endometrioid EC data from the Surveillance, Epidemiology, and End Results (SEER) program according to women’s age, tumor stage, and grade. We analyzed the proportions of EC survivors below 50 and below 60 years of age and stratified those age groups by race. For age distribution and survival analysis SEER, 18 registries’ research data (2000–2018) were analyzed. We analyzed the SEER 12 registries’ research data (1992–2019) for incidence time trends. Our investigation found a 14% and 40% cumulative prevalence of stage I EC that occurs in women below 50 or 60 years, respectively. EC’s prevalence has progressively risen in recent decades, but cancer-specific mortality remains low. The increasing number of women affected by EC in premenopause or early postmenopause face an 18 years-survival rate of 96.86% and 95.73%, respectively. A significant proportion of low-grade EC survivors can potentially benefit from HT treatment, and this requires awareness of other aspects of their health or quality of life, in addition to cancer treatments

Mismatch repair system in endometriotic tissue and eutopic endometrium of unaffected women

9Objective: To test the immunohistochemical staining pattern of some mismatch repair (MMR) system proteins in endometriotic tissue (ET) and eutopic endometrium. Methods: This was a retrospective study conducted at the Pathology and Obstetrics and Gynecology Departments of the Udine University Hospital. We analyzed 528 samples obtained from 246 patients affected by endometriosis and 71 samples from 71 patients with normal endometrium. A tissue microarray model was used to analyze the immunohistochemical expression of MMR system proteins. Results: Significant loss of MMR proteins was found in the stromal component of ETs. We found MSH2 to be expressed at a higher level than any other MMR system proteins in eutopic endometrium and ETs, to be significantly correlated to Ki-67 expression in both stromal and glandular components of ETs, and to be expressed at a significantly higher level in ETs than in eutopic endometrium. When considering the subgroup of endometriosis with high recurrence rate and glandular cytoplasmic staining for aurora A kinase, we found MMR proteins expressed at a significantly higher level in these ETs than in other ETs and eutopic endometrium of unaffected women. Conclusions: We found significant loss of MMR proteins (known to be associated with microsatellite instability) in the stromal component of ETs. The group of ETs with glandular cytoplasmic staining for aurora A kinase had higher MMR protein expression, suggesting an increased activity of this system. Our result suggests a novel role of increased MSH2 expression in cellular proliferation of endometriosis.openopenGrassi, T.; Calcagno, A.; Marzinotto, S.; Londero, A.P.; Orsaria, M.; Canciani, G.N.; Beltrami, C.A.; Marchesoni, D.; Mariuzzi, L.Grassi, T.; Calcagno, A.; Marzinotto, S.; Londero, Ambrogio P.; Orsaria, M.; Canciani, G. N.; Beltrami, Carlo Alberto; Marchesoni, Diego; Mariuzzi, Laur

Incidence and Risk Factors for Venous Thromboembolism in Female Patients Undergoing Breast Surgery

Albeit it does not have the highest venous thromboembolism (VTE) incidence compared to other neoplasms, breast cancer contributes to many VTE events because it is the most diagnosed tumor in women. We aim to analyze the occurrence and timing of VTE during the follow-up of patients who underwent breast surgery, the possible correlated factors, and the overall survival. This retrospective study included all female patients diagnosed with mammary pathology and surgically treated in our clinic between January 2002 and January 2012. Of 5039 women who underwent breast surgery, 1056 were found to have no evidence of malignancy, whereas 3983 were diagnosed with breast cancer. VTE rate resulted significantly higher in patients with invasive breast cancer than in women with benign breast disease or carcinoma in situ. Invasive cancers other than lobular or ductal were associated with a higher VTE rate. In addition, chronic hypertension, high BMI, cancer type, and evidence of metastasis turned out to be the most significant risk factors for VTE in women who underwent breast surgery. Moreover, VTE occurrence significantly impacted survival in invasive breast cancer patients. Compared to women with benign mammary pathology, VTE prevalence in women with breast cancer is significantly higher. The knowledge about the risk factors of VTE could be helpful as prognostic information, but also to eventually target preventive treatment strategies for VTE, as far as the co-existence of invasive breast cancer and VTE has a significantly negative impact on survival

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Abstract To evaluate the expression of markers correlated with cellular senescence and DNA damage (8-hydroxy-2\u2032-deoxy-guanosine (8-OHdG), p53, p21, APE1/Ref-1 (APE1), interleukin (IL-6 and IL-8) in placentas from healthy and pathologic pregnancies. This retrospective study considered a placental tissue micro-array containing 92 controls from different gestational ages and 158 pathological cases including preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes,low platelet count), small for gestational age (SGA)fetuses, and intrauterine growth restriction (IUGR) occurringat different gestational ages. In this study, we demonstrated a significant influence of gestational age on the expression in the trophoblast of 8-OHdG, p53, p21, APE1, and IL-6. In placentas of cases affected by PE, HELLP, or IUGR, there was an increased expression of 8-OHdG, p53, APE1, and IL-6 compared to controls (only IL-8 was significantly decreased in cases). In both groups of pathology between 22- and 34-week gestation and after 34-week gestation, APE1 levels were higher in the trophoblast of women affected by hypertensive disorders of pregnancy than women carrying an IUGR fetus. The cytoplasmic expression of 8-OHdG was increased in placentas in IUGR cases compared to PE or HELLP pregnancies. In cases after 34-week gestation, p21 was higher in SGA and IUGR than in controls and late PE. Moreover, p53 was increased after 34-week gestation in IUGR pregnancies. Placentas from pathological pregnancies had an altered expression of 8-OHdG, p53, p21, APE1, IL-6, and IL-8. The alterations of intracellular pathways involving these elements may be the cause or the consequence of placental dysfunction, but in any case reflect an impaired placental function, possibly due to increased aging velocity in pathologic cases

L’inconsistenza della diagnosi di cancro duttale in situ

Background: Classifying ductal carcinoma in situ (DCIS) remains problematical for interpretation of specified histological features and field selection where morphology is heterogeneous. Emphasis is placed on the role of intraductal proliferative lesions as risk factors of variable magnitude in subsequent development of invasive breast carcinoma. The present study is designed to investigate the relative contribution of diagnostic and treatment paradigms on the lack of consistency in the analysis of these lesions. Materials and methods: A cohort of in situ lesions of the breast was reviewed according to ductal intraepithelial neoplasia (DIN) classification adopted by the World Health Organization (WHO). In this retrospective study 458 patients with DIN diagnosed by core needle biopsy had undergone conservative or radical surgical treatment and SLNB in cases of DIN1C-DIN3. Results: Breast conservative surgery was the definitive treatment in 80% of cases. All the SLNs sampled showed 1.2 % (4/336) positivity of metastatic or micrometastatic nodal involvement by H&E stain while the IHC assessment for cytokeratin showed 4.5% (15/336) positivity. Conclusions: The widely recognised variation in the growth pattern of DCIS makes difficult to identify uniform indications for clinical procedure. Although the incidence of metastases in patient with initial diagnosis of DIN is considered to be low, SLNB remains an attractive option to guarantee oncological safety. In patients at high risk occult invasion does occur and without lymphatic analysis, undertreatment is possible

Phase diagrams in nonlocal PNJL models constrained by Lattice QCD results

Based on lattice QCD-adjusted SU(2) nonlocal Polyakov--Nambu--Jona-Lasinio (PNJL) models, we investigate how the location of the critical endpoint in the QCD phase diagram depends on the strenght of the vector meson coupling, as well as the Polyakov-loop (PL) potential and the form factors of the covariant model. The latter are constrained by lattice QCD data for the quark propagator. The strength of the vector coupling is adjusted such as to reproduce the slope of the pseudocritical temperature for the chiral phase transition at low chemical potential extracted recently from lattice QCD simulations. Our study supports the existence of a critical endpoint in the QCD phase diagram albeit the constraint for the vector coupling shifts its location to lower temperatures and higher baryochemical potentials than in the case without it.Comment: 23 pages, 10 figures. Version accepted in Phys. Part. Nucl. Lett. (to appear), references adde

Hybrid Stars in a Strong Magnetic Field

We study the effects of high magnetic fields on the particle population and equation of state of hybrid stars using an extended hadronic and quark SU(3) non-linear realization of the sigma model. In this model the degrees of freedom change naturally from hadrons to quarks as the density and/or temperature increases. The effects of high magnetic fields and anomalous magnetic moment are visible in the macroscopic properties of the star, such as mass, adiabatic index, moment of inertia, and cooling curves. Moreover, at the same time that the magnetic fields become high enough to modify those properties, they make the star anisotropic.Comment: Revised version with updated reference