Idiopathic Granulomatous Mastitis: Manifestations at Multimodality Imaging and Pitfalls.

Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast entity characterized by lobulocentric granulomas. IGM has a persistent or recurrent disease course and affects parous premenopausal women with a history of lactation. It has also been associated with hyperprolactinemia. The most common clinical sign is a palpable tender mass. However, the nonspecific manifestations and varied demographic features of this condition, as well as the other similar-appearing and superimposed breast entities, pose substantial diagnostic challenges. Entities with similar manifestations include inflammatory breast cancer (IBC), infective mastitis, foreign body injection granulomas, mammary duct ectasia, diabetic fibrous mastopathy, and systemic granulomatous processes. The strategy for imaging IGM depends on patient age, clinical manifestations, and risk factors. Targeted ultrasonography, mammography, and less commonly, magnetic resonance imaging have proven to be useful for imaging evaluation. Core-needle biopsy, with or without fine-needle aspiration for cytopathologic examination, and culture analysis are usually required to exclude IBC and other benign inflammatory breast processes. Patients with IGM have an excellent prognosis when they are appropriately treated with oral steroids or second-line immunosuppressive and prolactin-lowering medications. However, surgical excision may be an option for patients in whom medication therapy is unsuccessful. Imaging surveillance can be offered to patients with incidentally encountered IGM or mild symptoms. Clinical suspicion for this rare disease and the breast imager's prompt diagnosis can lead to an improved patient outcome. The purpose of this article is to review the imaging manifestations of IGM in a multimodality case-based format and to describe relevant clinical and imaging-based differential diagnoses. The associated pitfalls, epidemiologic and histopathologic factors, clinical manifestations, natural course, and management of IGM also are discussed. ©RSNA, 2018.

TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo.

Anticancer topoisomerase "poisons" exploit the break-and-rejoining mechanism of topoisomerase II (TOP2) to generate TOP2-linked DNA double-strand breaks (DSBs). This characteristic underlies the clinical efficacy of TOP2 poisons, but is also implicated in chromosomal translocations and genome instability associated with secondary, treatment-related, haematological malignancy. Despite this relevance for cancer therapy, the mechanistic aspects governing repair of TOP2-induced DSBs and the physiological consequences that absent or aberrant repair can have are still poorly understood. To address these deficits, we employed cells and mice lacking tyrosyl DNA phosphodiesterase 2 (TDP2), an enzyme that hydrolyses 5'-phosphotyrosyl bonds at TOP2-associated DSBs, and studied their response to TOP2 poisons. Our results demonstrate that TDP2 functions in non-homologous end-joining (NHEJ) and liberates DSB termini that are competent for ligation. Moreover, we show that the absence of TDP2 in cells impairs not only the capacity to repair TOP2-induced DSBs but also the accuracy of the process, thus compromising genome integrity. Most importantly, we find this TDP2-dependent NHEJ mechanism to be physiologically relevant, as Tdp2-deleted mice are sensitive to TOP2-induced damage, displaying marked lymphoid toxicity, severe intestinal damage, and increased genome instability in the bone marrow. Collectively, our data reveal TDP2-mediated error-free NHEJ as an efficient and accurate mechanism to repair TOP2-induced DSBs. Given the widespread use of TOP2 poisons in cancer chemotherapy, this raises the possibility of TDP2 being an important etiological factor in the response of tumours to this type of agent and in the development of treatment-related malignancy.

Halo nevi in Turner syndrome.

Turner syndrome is a genetic disorder characterized by an abnormal or missing X-chromosome. Rarely reported cutaneous manifestations in Turner syndrome include hemangiomas, angiokeratomas, hirsutism, and halo nevi. A recent study demonstrated an increased prevalence of halo nevi in Turner syndrome when compared to vitiligo. We present a case of halo nevi with multiple melanocytic nevi in an 11-year-old patient with Turner syndrome on growth hormone.

Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency.

The ATM kinase is a master regulator of the DNA damage response to double-strand breaks (DSBs) and a well-established tumour suppressor whose loss is the cause of the neurodegenerative and cancer-prone syndrome Ataxia-Telangiectasia (A-T). A-T patients and Atm-/- mouse models are particularly predisposed to develop lymphoid cancers derived from deficient repair of RAG-induced DSBs during V(D)J recombination. Here, we unexpectedly find that specifically disturbing the repair of DSBs produced by DNA topoisomerase II (TOP2) by genetically removing the highly specialised repair enzyme TDP2 increases the incidence of thymic tumours in Atm-/- mice. Furthermore, we find that TOP2 strongly colocalizes with RAG, both genome-wide and at V(D)J recombination sites, resulting in an increased endogenous chromosomal fragility of these regions. Thus, our findings demonstrate a strong causal relationship between endogenous TOP2-induced DSBs and cancer development, confirming these lesions as major drivers of ATM-deficient lymphoid malignancies, and potentially other conditions and cancer types.

Frequency of simvastatin prescriptions with potentially interacting medications in a Veterans Affairs health care system.

OBJECTIVE: The primary objective of this review is to quantify the proportion of patients on simvastatin, an HMG-CoA reductase inhibitor (commonly known as statin), who received concurrent prescriptions for potentially interacting chronicuse medications. The secondary objective is to determine the frequency with which simvastatin was prescribed above its recommended dose when administered concomitantly with known interacting medications. METHODS: A retrospective review of computerized outpatient pharmacy records from a Veterans Affairs Medical Center and its associated ambulatory clinics was performed in September 2002. RESULTS: A total of 12,240 patients had an active prescription for a statin. The majority of patients (95%, N = 11,677) were on simvastatin therapy, and 1,231 (10.5%) of the patients on simvastatin were prescribed at least 1 potentially interacting medication. More than one half (57.8%) of simvastatin doses were above the maximum recommended daily dose when prescribed with potentially interacting medications. CONCLUSION: This analysis supports the need for vigilance in reviewing the dose of simvastatin in patients receiving interacting medications. Health care systems should consider strategies to educate health care professionals on prevention of drug interactions and adverse patient outcomes.

ATM specifically mediates repair of double-strand breaks with blocked DNA ends.

Ataxia telangiectasia is caused by mutations in ATM and represents a paradigm for cancer predisposition and neurodegenerative syndromes linked to deficiencies in the DNA-damage response. The role of ATM as a key regulator of signalling following DNA double-strand breaks (DSBs) has been dissected in extraordinary detail, but the impact of this process on DSB repair still remains controversial. Here we develop novel genetic and molecular tools to modify the structure of DSB ends and demonstrate that ATM is indeed required for efficient and accurate DSB repair, preventing cell death and genome instability, but exclusively when the ends are irreversibly blocked. We therefore identify the nature of ATM involvement in DSB repair, presenting blocked DNA ends as a possible pathogenic trigger of ataxia telangiectasia and related disorders.

Problemas a largo plazo de un programa hospitalario de cirugía sin ingreso / Long term problems with an outpatient surgery hospital program

En la presente revisión, y apoyándonos en nuestra experiencia en el Hospital Comarcal de Jaca, intentaremos poner de relieve y discutir los beneficios y los problemas que generan las unidades de cirugía sin ingreso. Analizaremos los distintos tipos de programas ambulatorios y los modelos de unidad quirúrgica, mostrando sus ventajas e inconvenientes. Por último, intentaremos proponer diversas líneas para mejorar la calidad ofertada, la satisfacción del usuario y la relación coste / efectividad de los procesos quirúrgicos.

In this paper we will try to stand out and discuss the benefits and difficulties generated by outpatient units according to our experience. We will analyse the different types of surgical programs, showing advantages and drawbacks. Finally, we will propose several ways in order to improve quality assurance, user’s satisfaction and cost / effectiveness relation of surgical processes.