Joint Practice Guidelines for Radionuclide Lymphoscintigraphy for Sentinel Node Localization in Oral/Oropharyngeal Squamous Cell Carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee

Altered responsiveness to pups in virgin female mice of the BTBR strain: Insights from pattern of c-Fos expression in brain regions involved in maternal behavior

BTBR is an inbred mouse strain that displays several behavioral alterations resembling the core symptoms of Autism Spectrum Disorder, including deficit in sociability. In the present study, we investigated whether the pup-induced maternal behavior in virgin female mice, a naturally rewarding behavior, is impaired in this strain similarly to social interaction with adult conspecifics. We firstly assessed the maternal responsiveness towards newly born pups expressed by either virgin female mice of the BTBR strain or of the normo-social B6 strain. Next, we examined in both strains the expression of c-Fos as a marker of neuronal activity in selected brain areas involved in the regulation of maternal behavior in rodents including the olfactory bulb, the medial preoptic area and the paraventricular nucleus (PVN). We also examined the effects of pup presentation on oxytocinergic neurons of the PVN, the major brain site of synthesis of oxytocin, which has a pivotal role in facilitation of maternal response and social responsiveness in general. As a final step, we assessed the c-Fos expression pattern comparing the effect of exposure to pups with that induced by exposure to another social stimulus, focusing on other areas implicated in maternal responsiveness as well as in the affective component of social behavior such as pyriform cortex and central and basolateral amygdala. Our data showed that BTBR virgin females are less responsive to presentation of pups in comparison to B6, in parallel with lower activation of brain areas implicated in the maternal and social responsiveness

Early Behavioral Alterations and Increased Expression of Endogenous Retroviruses Are Inherited Across Generations in Mice Prenatally Exposed to Valproic Acid

Prenatal treatment with the antiepileptic drug valproic acid (VPA) is associated with a significant risk of somatic anomalies, neurodevelopmental delays, and 7-10x increase in the incidence of autism spectrum disorders (ASD) in children. Rodents exposed to VPA in pregnancy show birth defects, deficits in neurodevelopment, and cognitive/social anomalies resembling those of ASD children. Mechanisms of VPA neurobehavioral toxicity are still unclear but as VPA is a non-selective inhibitor of histone deacetylases, epigenetic modifications are likely involved. This study was aimed to evaluate the transgenerational impact of prenatal VPA exposure on mouse early behavioral development, studying F-1, F-2, and F-3 generations after VPA challenge on gestational day (GD) 10.5. We also analyzed in brain and in peripheral blood mononuclear cells the expression levels of different endogenous retrovirus (ERV) families, potential biomarkers of derailed brain development, since human ERVs have been implicated in the pathogenesis of neurodevelopmental disorders (NDDs) such as ASD. Somatic effects of VPA were evident only in F-1 generation and more markedly in the female sex. Across F-1 and F-2 generations, VPA delayed righting reflex, increased motor activity, and reduced ultrasonic vocalizations. The behavioral changes in F-3 are milder though in the same direction. VPA increased expression of most ERVs across the three generations in brain and blood. In utero VPA induced neurodevelopmental alterations more marked in the maternal lineage that persisted also in F-3, suggesting ERVs as possible downstream effectors of the VPA epigenetic alterations

Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone deficient patients

INTRODUCTION: Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this paper is to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients. SUBJECTS AND METHODS: A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninty-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52.7%), 44 patients (47.3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy. RESULTS: Median age was significantly higher in fractured patients as compared to non-fractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0.37, 95% IC: 0.24-0.55, p<0.0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy. CONCLUSION: This study suggests that d3-GHR may protect AO-GHD particulary when treated with rhGH from the risk of VF

GROWTH HORMONE RECEPTOR ISOFORMS AND FRACTURE RISK IN ADULT-ONSET GROWTH HORMONE - DEFICIENT PATIENTS.

Introduction: Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients. Subjects and methods: A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52·7%), and 44 patients (47·3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy. Results: Median age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0·37, 95% IC: 0·24-0·55, P &lt; 0·0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy. Conclusion: This study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs