Management of Neuroendocrine Breast Carcinoma (NEBC): Review of Literature.

Extra pulmonary high-grade poorly differentiated neuroendocrine carcinomas (EP-NECs) are rare tumors that usually arise in the gastrointestinal and genitourinary tracts. Primary neuroendocrine carcinoma of the breast (NEBC) is extremely rare, representing less than 0.1% of all breast cancers and less than 1% of neuroendocrine neoplasms. Consequently, they can be misdiagnosed as other types of breast cancer, however, proper immunohistochemical (IHC) studies can assist with making the correct diagnosis. Management of NEBC can be challenging given the paucity of evidence-based literature and should not routinely follow the therapeutic guidelines of other breast cancers. In this article, we review the current literature regarding the management of NEBC.

Insulinoma maligno: PET/TC con 18F-DOPA y 68Ga-DOTATATE y tratamiento con 177Lu-DOTATATE / Malignant insulinoma: 18F-DOPA and 68Ga-DOTATATE PET/CT and treatment with 177Lu-DOTATATE

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Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength.

In light of the limited treatment options of diabetic polyneuropathy (DPN) available, suitable animal models are essential to investigate pathophysiological mechanisms and to identify potential therapeutic targets. In vivo evaluation with current techniques, however, often provides only restricted information about disease evolution. In the study of patients with DPN, magnetic resonance neurography (MRN) has been introduced as an innovative diagnostic tool detecting characteristic lesions within peripheral nerves. We developed a novel multicontrast ultra high field MRN strategy to examine major peripheral nerve segments in diabetic mice non-invasively. It was first validated in a cross-platform approach on human nerve tissue and then applied to the popular streptozotocin(STZ)-induced mouse model of DPN. In the absence of gross morphologic alterations, a distinct MR-signature within the sciatic nerve was observed mirroring subtle changes of the nerves' fibre composition and ultrastructure, potentially indicating early re-arrangements of DPN. Interestingly, these signal alterations differed from previously reported typical nerve lesions of patients with DPN. The capacity of our approach to non-invasively assess sciatic nerve tissue structure and function within a given mouse model provides a powerful tool for direct translational comparison to human disease hallmarks not only in diabetes but also in other peripheral neuropathic conditions.

Diagnosis and pathologic characteristics of medullary thyroid carcinoma-review of current guidelines.

Background: Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of this malignancy is therefore important. Methods: We reviewed the current clinical practice guidelines and recent literature on mtc, and here, we summarize the recommendations for its diagnosis and workup. We also provide an overview of the pathology of mtc. Results: A neuroendocrine tumour, mtc arises from parafollicular cells ("C cells"), which secrete calcitonin. As part of the multiple endocrine neoplasia (men) type 2 syndromes, mtc can occur sporadically or in a hereditary form. This usually poorly delineated and infiltrative tumour is composed of solid nests of discohesive cells within a fibrous stroma that might also contain amyloid. Suspicious nodules on thyroid ultrasonography should be assessed with fine-needle aspiration (fna). If a diagnosis of mtc is made on fna, patients require baseline measurements of serum calcitonin and carcinoembryonic antigen. Calcitonin levels greater than 500 pg/mL or clinical suspicion for metastatic disease dictate the need for further imaging studies. All patients should undergo dna analysis for RET mutations to diagnose men type 2 syndromes, and if positive, they should be assessed for possible pheochromocytoma and hyperparathyroidism. Summary: Although the initial diagnosis of a suspicious thyroid nodule is the same for differentiated thyroid carcinoma and mtc, the remainder of the workup and diagnosis for mtc is distinct.

Detection of infectious laryngotracheitis virus (Gallid herpesvirus-1) from clinically infected chickens in Egypt by different diagnostic methods.

Infectious laryngotracheitis (ILT) disease is an acute highly contagious viral disease leading to massive economic losses to the national poultry industry. This study aimed to identify the most accurate and rapid diagnostic methods to rescue layer poultry farms from intense outbreaks in Egypt. Fifty pathological specimens were collected and subjected to virus isolation (VI), histopathology, direct fluorescent antibody technique (FAT) and polymerase chain reaction (PCR). Egg inoculation revealed stunted growth and white pock lesions on chorioallantoic membranes (CAM) in 23 samples. Isolation and propagation of infectious laryngotracheitis virus (ILTV) in cell culture showed syncytia formation 5 days post infection in 20 inoculated samples. PCR resulted in successful amplification of a 647 bp fragment of the thymidine kinase (TK) gene in 25 field samples. Histopathological examination of inoculated CAM showed intranuclear inclusion bodies with infiltration of inflammatory cells. Direct FAT showed intra-cytoplasmic apple green reactions in 18 examined tracheal tissues. PCR has been shown to be more sensitive, accurate and rapid than VI, FAT and histopathological examination.

Assessment of Contraceptive Use by Marriage Type Among Sexually Active Men in Nigeria.

Marital status, from the perspective of men (and especially sexually active men), as a potential factor that influences contraceptive use for the purposes of fertility control, has received little consideration in the scientific literature. This study thus assesses contraceptive use among sexually active men occupying different marital statuses. The study employed the 2013 Nigeria Demographic and Health Survey dataset. Using a total sample of 11,476 weighted sexually active men, the study revealed that 30% of the sampled population were currently using contraceptives, with condom as the dominant method (65.9%). The unadjusted odds of contraceptive use was significantly higher (9.4; confidence interval [8.1, 10.9]) among single men than married. Other factors include wealth, educational attainment, ethnicity, region, religion, and age. The study concludes that there are significant differences in contraceptive use between the single and married men and, therefore, recommends that policy and programs be put in place to promote consistent use of contraceptives among married men in Nigeria.

Anticoccidial and hepatoprotective effects of artemisinin liquid extract, cinnamon essential oil and clove essential oil against Eimeria stiedae infection in rabbits.

Coccidiosis is one of the most dangerous diseases that affect poultry, resulting in worldwide economic losses. Plant extracts and essential oils have been used as potential alternatives for chemotherapeutics, because they don't have the negative consequence of creating tissue residue and drug resistance. Therefore, this study had been conducted to determine the efficacy of artemisinin liquid extract, cinnamon essential oil and clove essential oil against Eimeria stiedae in rabbits. Sixty New Zealand white rabbits were divided into six equal groups, where group 1 and group 2 represented the negative and the positive controls, respectively, and groups 3-6 were infected with Eimeria stiedae and received 15 ppm toltrazuril, 200 ppm artemisinin, 100 mg/kg cinnamon oil, and 100 mg/kg clove oil, respectively. The results showed that artemisinin had a significant beneficial role in protection against hepatic coccidiosis: it mitigated the clinical symptoms, reduced the mortality rates, improved body weight and feed conversion, decreased the oocyst output, prevented oxidative stress, improved biochemical parameters, and decreased the lesion formation. Moreover, it has been found that cinnamon and clove essential oils induced partial protection against hepatic coccidiosis. Our findings suggested that artemisinin liquid extract and cinnamon and clove essential oils could be used for protection against hepatic coccidiosis. However, further investigations are needed in order to elucidate the active components, optimal doses, and mode of action of these extracts and essential oils before their clinical applications.

Anticoccidial and hepatoprotective effects of artemisinin liquid extract, cinnamon essential oil and clove essential oil against Eimeria stiedae infection in rabbits

@#Coccidiosis is one of the most dangerous diseases that affect poultry, resulting in worldwide economic losses. Plant extracts and essential oils have been used as potential alternatives for chemotherapeutics, because they don’t have the negative consequence of creating tissue residue and drug resistance. Therefore, this study had been conducted to determine the efficacy of artemisinin liquid extract, cinnamon essential oil and clove essential oil against Eimeria stiedae in rabbits. Sixty New Zealand white rabbits were divided into six equal groups, where group 1 and group 2 represented the negative and the positive controls, respectively, and groups 3–6 were infected with Eimeria stiedae and received 15 ppm toltrazuril, 200 ppm artemisinin, 100 mg/kg cinnamon oil, and 100 mg/kg clove oil, respectively. The results showed that artemisinin had a significant beneficial role in protection against hepatic coccidiosis: it mitigated the clinical symptoms, reduced the mortality rates, improved body weight and feed conversion, decreased the oocyst output, prevented oxidative stress, improved biochemical parameters, and decreased the lesion formation. Moreover, it has been found that cinnamon and clove essential oils induced partial protection against hepatic coccidiosis. Our findings suggested that artemisinin liquid extract and cinnamon and clove essential oils could be used for protection against hepatic coccidiosis. However, further investigations are needed in order to elucidate the active components, optimal doses, and mode of action of these extracts and essential oils before their clinical applications.

Analysis of Immune Cells in Single Sciatic Nerves and Dorsal Root Ganglion from a Single Mouse Using Flow Cytometry.

Nerve-resident immune cells in the peripheral nervous system (PNS) are essential to maintaining neuronal integrity in a healthy nerve. The immune cells of the PNS are affected by injury and disease, affecting the nerve function and the capacity for regeneration. Neuronal immune cells are commonly analyzed by immunofluorescence (IF). While IF is essential for determining the location of the immune cells in the nerve, IF is only semi-quantitative and the method is limited to the number of markers that can be analyzed simultaneously and the degree of surface expression. In this study, flow cytometry was used for quantitative analysis of leukocyte infiltration into sciatic nerves or dorsal root ganglions (DRGs) of individual mice. Single cell analysis was performed using DAPI and several proteins were analyzed simultaneously for either surface or intracellular expression. Both sciatic nerves from one mouse that were treated according to this protocol generated ≥ 30,000 single nucleated events. The proportion of leukocytes in the sciatic nerves, determined by expression of CD45, was approximately 5% of total cell content in the sciatic nerve and approximately 5-10% in the DRG. Although this protocol focuses primarily on the immune cell population within the PNS, the flexibility of flow cytometry to measure a number of markers simultaneously means that the other cells populations present within the nerve, such as Schwann cells, pericytes, fibroblasts, and endothelial cells, can also be analyzed using this method. This method therefore provides a new means for studying systemic effects on the PNS, such as neurotoxicology and genetic models of neuropathy or in chronic diseases, such as diabetes.

Distribution of serum concentrations reported for macroenzyme aspartate aminotransferase (macro-AST).

BACKGROUND: The presence of macroenzyme (M) is often the explanation of an isolated elevation of aspartate aminotransferase (AST). Where M is identified, it is reasonable for the clinician to ask where an individual patient's result fits in with known concentrations of M. In this context, we conducted a survey of literature to examine the distribution of reported serum concentrations of macro-AST. We also analyzed the distribution data to examine whether elevations were consistent with simple alteration of circulatory half-life (t1/2) of M relative to normal AST. METHODS: Distributions of M were compiled from the literature. These distributions were compared to predictions based on fixed changes in t1/2 applied to the reference interval for AST. RESULTS: There was a bimodal distribution of literature values for M (n =51), comprised roughly of populations A (M <200 U/L; 60% of total) and B (M >200 U/L; 40% of total). The two distributions were reasonably well characterized by a simple projection to the right of the reference interval for AST according to increased t1/2 (A: t1/2 =3.3 days; B: t1/2 =19.8 days) relative to AST (t1/2 =0.7 days). CONCLUSIONS: Knowledge of distributions for M may be useful in discussion with clinicians regarding significance of M for individual patients. Distributions for M were consistent with the simplest explanation for elevated AST due strictly to an extended circulatory lifetime for M. Caveats to analysis, however, include selection within literature data mainly for patients with various co-morbidities.

Immunohistochemical Expression of MCAM/CD146 in Canine Melanoma.

MCAM/CD146 (melanoma cell adhesion molecule/CD146) is a transmembrane immunoglobulin superfamily cell adhesion molecule involved in transendothelial migration and signal transduction. It is expressed in melanoma, squamous cell carcinoma, prostatic, ovarian, cervical and endometrial cancers and promotes tumour growth, angiogenesis and metastasis. Melanoma is the most common malignant oral tumour of dogs and also arises in the skin, nail bed and footpad. The aim of this study was to investigate the immunohistochemical expression of MCAM/CD146 in 51 canine melanomas, including oral, cutaneous and ocular tumours. Seventeen of the 51 (33.3%) cases were negative, eight (15.7%) were weakly positive, seven (13.7%) were moderately positive and 19 (37.3%) were strongly positive. MCAM/CD146 was expressed by both oral and cutaneous melanomas; however, the intensity and the extent of the immunoreactivity was higher in oral (P = 0.009) than in cutaneous tumours (P = 0.058). Most ocular melanomas did not express MCAM/CD146 (P = 0.256). Expression of MCAM/CD146 by canine melanomas may suggest the molecule as a target for treatment, especially in oral melanomas.

STZ causes depletion of immune cells in sciatic nerve and dorsal root ganglion in experimental diabetes.

Streptozotocin (STZ) treatment, a common model for inducing diabetes in rodent models, induces thermal hyperalgesia and neuronal toxicity independently of hyperglycemia by oxidizing and activating TRPA1 and TRPV1. Following treatment with STZ, CD45+ immune cells were found to be depleted in sciatic nerve (SN) and DRG in mice, prior to hyperglycemia. Macrophages were also lost in DRG and NFκB-p65-activation was increased in SN macrophages. Immune cells were significantly reduced in both SN and DRG up to three weeks, post-treatment. Loss of PNS-resident macrophages in response to STZ-mediated toxicity may affect the regenerative capacity of the nerve in response to further injury caused by diabetes.

From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

Gonadotrope Tumors.

Gonadotrope tumors arise from the gonadotropes of the adenohypophysis. These cells rarely give rise to hyperplasia, usually only in the setting of long-standing premature gonadal failure. In contrast, gonadotrope tumors represent one of the most frequent types of pituitary tumors. Despite their relatively common occurrence, the pathogenesis of gonadotrope tumors remains unknown. Effective nonsurgical therapies remain out of reach. We review the pituitary gonadotrope from the morphologic and functional perspectives to better understand its involvement as the cell of origin of a frequent type of pituitary tumor.

Infected concha bullosa mimicking a malignant lesion on 18F-FDG PET/CT / Concha bullosa infectada imitando una lesión maligna en 18F-FDG PET/TC

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Accuracy of FDG-PET/CT and paraneoplastic antibodies in diagnosing cancer in paraneoplastic neurological syndromes / Utilidad de la PET/TC con FDG y los anticuerpos paraneoplásicos para el diagnóstico de neoplasia en el síndrome neurológico paraneoplásico

Objective. There is still no consensus about whether to perform PET/CT to detect carcinoma in paraneoplastic neurological syndromes (PNS) in patients with or without antibodies. The aim of this study is to determine the diagnostic accuracy of PET/CT and antibodies in patients with PNS. Material and Methods. A retrospective study was conducted on patients with clinically suspected PNS between 2008 and 2013. The association between histopathological findings, paraneoplastic antibodies, and PET/CT findings were evaluated. Sensitivity and specificity for the detection of underlying malignancy were calculated for PET/CT and paraneoplastic antibodies. Results. A total of 42 patients were analyzed. Of these 42 patients, 32 (75%) had a classical PNS, 6 (14%) had positive PET/CT findings, and 34 were tested for the presence of antibodies (anti-Hu Ab, anti-Yo Ab, and anti-Ri Ab). Twenty one of 34 patients had positive antibodies. Of the 6 patients with positive PET/CT findings, 6 had positive histopathological results. Among 21 patients with positive biomarkers, carcinoma was confirmed only in 5 patients. One patient with negative antibodies, but positive PET/CT findings, was diagnosed with a tumor. Gastric carcinoma was detected in 1 patient with negative PET/CT findings and antibodies during follow-up. Based on the results, PET/CT was found to have 85.71% sensitivity, 100% specificity, 100% positive and 97.22% negative predictive values in the detection of tumors. Conclusion. PET/CT has a certain diagnostic accuracy for detecting underlying malignancy in patients with PNS, regardless of the presence of paraneoplastic antibodies (AU)

Objetivo. No hay un criterio unánime para realizar PET/TC en la detección de carcinoma en pacientes de síndrome neurológico paraneoplásico (PNS), con o sin anticuerpos. Nuestro objetivo es buscar la utilidad diagnóstica de la PET/TC y los anticuerpos en pacientes con PNS. Material y métodos. Se examinaron retrospectivamente los pacientes con sospecha clínica de PNS estudiados entre 2008 y 2013. Se evaluó la asociación entre los resultados histopatológicos, los anticuerpos y los resultados de la PET/TC. Se calcularon la sensibilidad y la especificidad de la PET/TC y de los anticuerpos paraneoplásicos para la detección de malignidad. Resultados. Se analizaron un total de 42 pacientes. De ellos 32 pacientes (el 75%) tenían un PNS clásico. A todos se les había realizado PET/TC y 6 (el 14%) tuvieron resultados positivos. Se determinó la presencia de anticuerpos en 34 pacientes (anticuerpos anti-Hu, anticuerpos anti-Yo y anticuerpos anti-Ri). Veintiuno de los cuales dieron positivo. Los 6 pacientes con resultados PET/TC positivos tuvieron resultados histopatológicos positivos. Entre los 21 pacientes con biomarcadores positivos, el carcinoma se confirmó solo en 5 pacientes. A un paciente con resultado negativo para anticuerpos, pero positivo en la PET/TC, se le diagnosticó un tumor. Se detectó carcinoma gástrico en un paciente con resultados negativos en la PET/TC y anticuerpos en el periodo de seguimiento. Según los resultados, se comprobó que la PET/TC tiene un 85,71% de sensibilidad, un 100% de especificidad, con valor predictivo positivo de 100% y valor predictivo negativo de 97,22% en la detección de tumores. Conclusión. La PET/TC tiene un cierto grado de exactitud diagnóstica para detectar malignidad subyacente en pacientes con PNS, sin importar la presencia de anticuerpos paraneoplásicos (AU)