Unilateral synchronous breast tumors. Rare association of myofibroblastoma and osteosarcoma

The authors describe the case of a patient with two particularly rare contiguous tumors, myofibroblastoma and osteosarcoma, in the same breast. Rare does not mean untreatable, and the chance of recovery is no less than with more common tumors. However, rare tumors do present a significant problem for pathologists due to diagnostic difficulties, and so an exact prognosis is not always possible.

Twenty years experience in oncologic surgery for primary cardiac tumors

Introduction. Primary cardiac tumors are uncommon in cardiac surgery. To investigate the clinical presentation, surgical results and long-term follow-up we retrospectively analyzed our experience in the treatment of primary cardiac tumors. Patients and methods. Ninety-one patients with primary cardiac tumors underwent surgery in our department in the last 20 years. Fifthy-one patients were female, the mean age was 62,2 years. Sixty-three had myxomas, 22 had papillary fibroelastoma, 4 had malignant neoformations and 2 had other benign tumors. Results. All myxomas, fibroelastomas and angiomyolipoma were radically removed. Only a palliative treatment was possible in malignant disease. In-hospital mortality was 1.2%. The mean follow-up time was 78.5 months. Three patients had recurrence of myxoma, all patients with malignant disease dead during the follow-up. Discussion. Primary benign cardiac tumors can be treated with low morbidity and mortality. The follow-up demonstrates that radical surgery is curative in case of benign tumors. The prognosis of malignant tumors is still poor. Palliative procedures have small impact on survival in these patients.

Successful management of evisceration occurred after exploratory laparotomy for bilateral ovarian micropapillary serous borderline tumors

Micropapillary serous borderline tumor of the ovary is characterized by a more frequent association with extraovarian, especially invasive, implants. The aim of this study was to report the clinicopathological findings of a rare case of micropapillary serous borderline tumor of the ovary since there are less than 100 similar cases in the published literature. Additionally, the successful management of evisceration that complicated the postoperative stay of the patient is analyzed. The incidence of this severe complication is estimated between 0.29-2.3%. There are four main causes: suture tearing through the fascia, knot failure, suture failure, and extrusion of abdominal contents between sutures placed too far apart. At least 50% of the cases are due to technical error with a potentially lethal result.

Analysis of the role of the transcription factor C/EBPβ in controlling uterine functions during early pregnancy

Embryo implantation into the endometrium is a complex biological process involving the integration of steroid hormone signaling, endometrial tissue remodeling and maternal- fetal communications. A successful pregnancy is the outcome of the timely integration of these events during the early stages of implantation. The involvement of ovarian steroid hormones, estrogen (E) and progesterone (P), acting through their cognate receptors, is essential for uterine functions during pregnancy. The molecular mechanisms that control the process of implantation are undergoing active exploration. Through our recent efforts, we identified the transcription factor, CCAAT Enhancer Binding Protein Beta (C/EBPb) as a prominent target of estrogen and progesterone signaling in the uterus. The development of a C/EBPb-null mouse model, which is infertile, presented us with an opportunity to analyze the role of this molecule in uterine function. We discovered that C/EBPb functions in two distinct manners: (i) by acting as a mediator of E-induced proliferation of the uterine epithelium and (ii) by controlling uterine stromal cell differentiation, a process known as decidualization, during pregnancy. My studies have delineated important mechanisms by which E regulates C/EBPb expression to induce DNA replication and prevent apoptosis of uterine epithelial cells during E-induced epithelial growth. In subsequent studies, I analyzed the role of C/EBPb in decidualization and uncovered a unique mechanism by which C/EBPb regulates the synthesis of a unique laminin-containing extracellular matrix (ECM) that supports stromal cell differentiation and embryo invasion. In order to better define the role of laminin in implantation, we developed a laminin gamma 1-conditional knockout mouse model. This is currently an area of ongoing investigation. The information gained from our analysis of C/EBPb function in the uterus provides new insights into the mechanisms of steroid hormone action during early pregnancy. Ultimately, our findings may aid in the understanding of dysregulation of hormone-controlled pathways that underlie early pregnancy loss and infertility in women.

Brooke-Spiegler Syndrome - an underrecognized cause of multiple familial scalp tumors: report of a new germline mutation

BACKGROUND: Brooke-Spiegler syndrome (BSS) is probably an underdiagnosed genodermatosis that predisposes for the development of cylindromas, spiradenomas and trichoepitheliomas mainly of the head and neck. Wide phenotypic variability regarding the number and type of lesions can be observed within a family. Mutations of the CYLD gene are identified in the vast majority of cases and play a key role in BSS pathogenesis. MAIN OBSERVATIONS: Two first degree relatives with numerous erythematous telangiectatic nodules of the scalp present for decades, with recurring tendency regardless the multiple previous excisions. Histopathological review of the lesions revealed predominantly "spiradenocylindromas" in the proband and cylindromas in her sister. The suspicion of BSS was confirmed after detection of a new nonsense germline mutation of CYLD (c.1783C>T pGln 595*) in the proband. CONCLUSIONS: BSS diagnosis can be challenging and is based on clinical-pathological correlation, positive familial association and identification of CYLD mutations. CYLD exerts antineoplastic effects by downregulating intracellular NF-κB signalling pathways. The reported mutation affecting the ubiquitin-specific protease domain leads to a truncated and catalytically inactive enzyme. Despite the expanding list of CYLD mutations no firm genotype-phenotype correlation is known so far. Early recognition and treatment of BSS avoid disfiguring changes like "turban tumor".

Metabolic tug-of-war in tumors results in diminished T cell antitumor immunity.

NlmCategory="UNASSIGNED">Glycolytic activity in T cells governs T cell responses by controlling various cellular processes, including proliferation, survival, and effector functions. We recently showed that the tumor microenvironment diminishes T cell antitumor responses by depriving glucose to infiltrating T cells. Moreover, metabolic rewiring tumor-reactive T cells sustain T cell metabolic fitness and antitumor responses.

Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors

Adoptive immunotherapy and oncolytic virotherapy are two promising strategies for treating primary and metastatic malignant brain tumors. We demonstrate the ability of adoptively transferred tumor-specific T cells to rapidly mediate the clearance of established brain tumors in several mouse models. Similar to the clinical situation, tumor recurrences are frequent and result from immune editing of tumors. T cells can eliminate antigen-expressing tumor cells but are not effective against antigen loss variant (ALV) cancer cells that multiply and repopulate a tumor. We show that the level of tumor antigen present affects the success of adoptive T cell therapy. When high levels of antigen are present, tumor stromal cells such as microglia and macrophages present tumor peptide on their surface. As a result, T cells directly eliminate cancer cells and cross-presenting stromal cells and indirectly eliminate ALV cells. We were able to show the first direct evidence of tumor antigen cross-presentation by CD11b+ stromal cells in the brain using soluble, high-affinity T cell receptor monomers. Strategies that target brain tumor stroma or increase antigen shedding from tumor cells leading to increased crosspresentation by stromal cells may improve the clinical success of T cell adoptive therapies. We evaluated one potential strategy to complement adoptive T cell therapy by characterizing the oncolytic effects of myxoma virus (MYXV) in a syngeneic mouse brain tumor model of metastatic melanoma. MYXV is a rabbit poxvirus with strict species tropism for European rabbits. MYXV can also infect mouse and human cancer cell lines due to signaling defects in innate antiviral mechanisms and hyperphosphorylation of Akt. MYXV kills B16.SIY melanoma cells in vitro, and intratumoral injection of virus leads to robust, selective and transient infection of the tumor. We observed that virus treatment recruits innate immune cells iii to the tumor, induces TNFα and IFNβ production in the brain, and results in limited oncolytic effects in vivo. To overcome this, we evaluated the safety and efficacy of co-administering 2C T cells, MYXV, and neutralizing antibodies against IFNβ. Mice that received the triple combination therapy survived significantly longer with no apparent side effects, but eventually relapsed. Based on these findings, methods to enhance viral replication in the tumor and limit immune clearance of the virus will be pursued. We conclude that myxoma virus should be further explored as a vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses.

Uterine artery impedance during the first eight postpartum weeks

The aim of this study was to construct reference ranges for the uterine artery (UtA) mean pulsatility (PI) and resistance (RI) indices from 1-8 weeks postpartum. A prospective, cross-sectional, and observational study was performed with 320 healthy women from week 1 through week 8 postpartum. UtAs were examined transvaginally using colour and pulsed Doppler imaging, and the means of the right and left values of the PI and RI, as well as the presence or absence of a bilateral protodiastolic notch, were recorded. The 5(th), 50(th) and 95(th) reference percentile curves for the UtA-PI and UtA-RI were derived using regression models. The adjusted reference intervals uncovered a convergence trend at the week 8 time-point, although impedance was lower at the week 1 time-point in multiparous women compared with primiparous women. The notching prevalence was 22.5% (9/40) at week 1 and 95.0% (38/40) at week 8. The study revealed consistent evidence of a progressive increase of postpartum uterine impedance and provided new average UtA-PI and UtA-RI reference charts for weeks 1 through 8. Multiparity does not change the trend but does impart a lower rate of increase, likely as a consequence of previous vascular structural and functional differences.

Reference ranges for uterine artery pulsatility index during the menstrual cycle: a cross-sectional study

Cyclic endometrial neoangiogenesis contributes to changes in local vascular patterns and is amenable to non-invasive assessment with Doppler sonography. We hypothesize that the uterine artery (UtA) impedance, measured by its pulsatility index (PI), exhibits a regular pattern during the normal menstrual cycle. Therefore, the main study objective was to derive normative new day-cycle-based reference ranges for the UtA-PI during the entire cycle from days 1 to 34 according to the isolated time effect and potential confounders such as age and parity.

Uterine artery Doppler in the management of early pregnancy loss: a prospective, longitudinal study

The pharmacological management of early pregnancy loss reduced substantially the need for dilation and curettage. However, prognostic markers of successful outcome were not established. Thus the major purpose of this study was to determine the sensitivity and specificity of the uterine artery pulsatility (PI) and resistance (RI) indices to detect early pregnancy loss patients requiring dilation and curettage after unsuccessful management.

Pregnancy after uterine artery embolization: a case report in a woman with leiomyomata

Background. Several pregnancies have been reported after embolization of uterine artery. This procedure is an accepted nonsurgical treatment for symptomatic uterine fibroids but its safety in women desiring future childbearing is not well established. Case Report. We present a 40-year-old woman with leiomyomata who became pregnant after previously undergone uterine artery embolization for three times. The placenta was previa and the fetus was in transverse position. She had a cesarean delivery of an appropriately grown fetus at 37 weeks, which was followed by uterine atony requiring hysterectomy. Conclusion. Although pregnancy-related outcomes remain understudied, the available reports evidence that pregnancies after uterine artery embolization may be at significantly increased risk for postpartum hemorrhage, cesarean delivery, abnormal placentation, and malpresentation. In patients who are undergoing this type of treatment and contemplating pregnancy, the possibility of adverse complications should be taken in consideration and women should be appropriately advised.

Superparamagnetic Liposomes for MRI Monitoring and External Magnetic Field-Induced Selective Targeting of Malignant Brain Tumors

International audience

Miomatosis uterina: frecuencia y características clínico-ecográficas en el Hospital Vicente Corral Moscoso, periodo 2010-2014

Antecedentes: La miomatosis es la neoplasia benigna más común en ginecología, presentándose en 20-30% en mujeres en edad fértil, es indicación frecuente de histerectomía entre los 35 y 54 años y puede producir infertilidad, coexistir con un embarazo y causar complicaciones en el mismo. Son tumores de fibras musculares lisas y tejido conectivo con manifestaciones clínicas variables dependiendo del tamaño, posición y número, aunque la mayoría son asintomáticos, es un diagnóstico común en ginecología y generan importantes gastos en salud. Objetivo: Determinar la frecuencia y las características clínico-ecográficas de la miomatosis uterina en las pacientes atendidas en el Hospital Vicente Corral Moscoso, periodo 2010- 2014 Metodología: Se realizó un estudio descriptivo, retrospectivo. El universo de estudio estuvo conformado por las historias clínicas de pacientes hospitalizadas en el departamento de ginecología del Hospital Vicente Corral Moscoso, periodo 2010-2014, los datos fueron analizados en la base de datos Excel 2010 y SPSS 20, los resultados fueron presentados en cuadros y gráficos, para las variables cualitativas se utilizó medidas de frecuencia absolutas y relativas; y para las variables cuantitativas medidas de tendencia central y dispersión. Resultados: Se obtuvieron 303 casos, se observó que el mayor número de casos (90.1%) se presentó en mujeres que tenían una edad mayor a 35 años con una media de 43.31 años y DS de 6.96. Los miomas más frecuentes fueron los intramurales (50.8 %); El síntoma de consulta más frecuente fue el sangrado transvaginal (74.6%)