Perioperative Management of Pheochromocytomas and Sympathetic Paragangliomas

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia, respectively. PPGLs have the highest degree of heritability among endocrine tumors. Currently, ~40% of PPGL individuals have a genetic germline and there exist at least 12 different genetic syndromes related to these tumors. Metastatic PPGLs are defined by the presence of distant metastases at sites where chromaffin cells are physiologically absent. Approximately 10% of pheochromocytomas and ~40% of sympathetic paragangliomas are linked to metastases explaining why complete surgical resection is the first-choice treatment for all PPGL patients. The surgical approach is a high-risk procedure requiring perioperative management by a specialized multidisciplinary team in centers with broad expertise. In this review, we summarize and discuss the most relevant aspects of perioperative management in patients with pheochromocytomas and sympathetic paragangliomas.

Social behavior in RASopathies and idiopathic autism

Background RASopathies are genetic syndromes that result from pathogenic variants in the RAS-MAPK cellular signaling pathway. These syndromes, which include neurofibromatosis type 1, Noonan syndrome, cardiofaciocutaneous syndrome, and Costello syndrome, are associated with a complex array of medical and behavioral health complications. Despite a heightened risk for social challenges and autism spectrum disorder (ASD), few studies have compared different aspects of social behavior across these conditions. It is also unknown whether the underlying neuropsychological characteristics that contribute to social competence and socially empathetic (“prosocial”) behaviors differ in children with RASopathies as compared to children with nonsyndromic (i.e., idiopathic) ASD. Methods In this cross-sectional, survey-based investigation, caregivers of preschool and school-aged children with RASopathies (n = 202) or with idiopathic ASD (n = 109) provided demographic, medical, and developmental information about their child, including psychiatric comorbidities. For children who were able to communicate verbally, caregivers also completed standardized rating scales to assess social competence and empathetic behavior as well as symptoms of hyperactivity/inattention and emotional problems. Results As compared to children with idiopathic ASD, children with RASopathies were rated as demonstrating more resilience in the domain of empathy relative to their overall social competence. Similarities and differences emerged in the psychological factors that predicted social behavior in these two groups. Stronger communication skills and fewer hyperactive-impulsive behaviors were associated with increased empathy and social competence for both groups. Greater emotional challenges were associated with lower social competence for children with RASopathies and stronger empathy for children with idiopathic ASD. Among children with RASopathy and a co-occurring ASD diagnosis, socially empathetic behaviors were observed more often as compared to children with idiopathic ASD. Conclusions Findings suggest that the development of social behavior among children with RASopathies involves a distinct pattern of strengths and weaknesses as compared to a behaviorally defined disorder (idiopathic ASD). Identification of areas of resilience as well as behavioral and social challenges will support more targeted intervention.

Reappraisal of the Subtropical Guidelines on Palivizumab Prophylaxis in Congenital Heart Disease

Objective: To define the impact of associated abnormalities on the efficacy of the novel subtropical guidelines for palivizumab prophylaxis on respiratory syncytial virus (RSV)-related hospitalizations in patients with hemodynamically significant congenital heart disease (hsCHD).Method: This prospective study enrolled every patient seen at a tertiary care center for hsCHD, who was born between 2014 and 2018 and received at least 1 dose of palivizumab, according to the subtropical guidelines. The patients were followed until the age of 2 years.Results: A total of 772 patients (49% male) were enrolled. Cyanotic CHD was seen in 46% of patients, of whom 23% had associated abnormalities. Lung/airway abnormalities (14%) were the most common followed by the genetic syndromes associated with CHD (7.3%). Among the 772 patients, RSV-related hospitalizations occurred in 3.2 and 2.2% children aged ≤ 12 and 13–24 months, respectively. Most of the RSV infections occurred in patients no longer satisfying the criteria for palivizumab prophylaxis. The patients with associated abnormalities but not the type of CHD, patient age, and patient sex were risk factors for RSV-related hospitalizations. The rates of RSV-related hospitalizations, admission to the intensive care unit, and endotracheal intubation were higher for patients with associated anomalies than for other patients before 24 months of age (10.2 vs. 4.0%, 67 vs. 33%, and 39 vs. 4.2%, p = 0.004, 0.06, 0.013, respectively).Conclusion: Children with abnormalities, especially genetic syndromes and lung/airway problems associated with CHD, are at high risk for RSV-related hospitalization. Our current subtropical guidelines for palivizumab prophylaxis in patients with hsCHD, should be revised to include the results of this study.

Assistive Technology to Promote Adaptive Skills in Children and Adolescents With Rett Syndrome

Rett syndrome is classified within the rare genetic syndromes, characterised by intellectual delays, extensive motor impairments, lack of speech and communication difficulties, sensorial deficits, and problems in adaptive responding. That clinical conditions may be deleterious on their social image, status, and quality of life. A practice for addressing this problem is technology-based interventions. The use of assistive technologies, in particular microswitches, with children with RTT has been shown to effectively change the impact on their quality of life, facilitating access to recreational activities and improving their performance. Through the use of technology-aided programs, a child with RTT and multiple disabilities will be ensured with an independent access to positive stimulation. In this chapter, a selective literature review was carried out considering Rett Syndrome, assistive technologies, quality of life, and rare genetic syndromes. Empirical data demonstrated the effectiveness and suitability of interventions with AT, allowing participants to increase their level of independence.

Thyroid Cancer In Children: A Multicenter International Study Highlighting Clinical Features And Surgical Outcomes Of Primary And Secondary Tumors

Background: Thyroid gland malignancy is rare in pediatrics (0.7% of tumors); only 1.8% are observed in patients < 20 yrs with a higher prevalence recorded in females and adolescents. Risk factors include genetic syndromes - MEN disorders, autoimmune disease and ionizing radiation exposure. Radiotherapy is also linked with increased risk of secondary thyroid cancers. The present study describes the clinical features and surgical outcomes of primary and secondary thyroid tumors. Methods: Institutional data was collected on pediatric patients with thyroid cancer during 2000 - 2020 from 8 International Surgical Oncology centers. Statistical analysis was performed using GraphPad Prism. Results: Of 255 cases of thyroid cancer, only 13 (5.1%) were secondary tumors. Primary thyroid malignancies were more likely to be multifocal in origin (odds ratio [OR] 1.993, 95% confidence interval [CI] 0.7466-5.132, p 0.2323), had bilateral glandular location (OR 2.847, 95% CI 0.6835-12.68, p 0.2648) and proved metastatic at 1st diagnosis (OR 1.259, 95% CI 0.3267-5.696 p>0.999). Secondary tumors showed a higher incidence of disease relapse (OR 1.556, 95% CI 0.4579-5.57, p 0.4525) and surgical morbidity (OR 2.042, 95% CI 0.7917-5.221, p 0.1614) including hypoparathyroidism and recurrent laryngeal nerve injury. Overall survival (OS) was 99% at 1 year and 97% after 10 years. No EFS differences were evident with primary vs. secondary tumors (Chi square 0.7307, p 0.39026). Conclusions: This multicenter study demonstrates excellent survival for pediatric thyroid malignancy. Secondary tumors exhibit greater disease relapse (15.8% vs 10.5%) and a higher incidence of surgical related complications (36.8% vs 22.2%).

Rare Genetic Syndromes and Oral Anomalies: A Review of the Literature and Case Series with a New Classification Proposal

Rare genetic syndromes, conditions with a global average prevalence of 40 cases/100,000 people, are associated with anatomical, physiological, and neurological anomalies that may affect different body districts, including the oral district. So far, no classification of oral abnormalities in rare genetic syndromes is present in the literature. The aim of this narrative review is to analyze literature on rare genetic syndromes affecting dento-oro-maxillofacial structures (teeth, maxillary bones, oral soft tissues, or mixed) and to propose a classification according to the detected oral abnormalities. In addition, five significant cases of rare genetic syndromes are presented. The Scale for the Assessment of Narrative Review Articles (SANRA) was followed for this review. From 674 papers obtained through PubMed search, 351 were selected. Sixty-two rare genetic syndromes involving oral manifestations were found and classified. The proposed classification aims to help the clinician to easily understand which dento-oro-maxillofacial findings might be expected in the presence of each rare genetic syndrome. This immediate framework may both help in the diagnosis of dento-oro-maxillofacial anomalies related to the underlying pathology as well as facilitate the drafting of treatment plans with the involvement of a multidisciplinary team.

Anticancer and Gene Expression Analysis of Piper nigrum Extract on Colon Cancer Cell Lines

One of the most prevalent malignancies among geriatrics is colorectal cancer (CRC), which starts to develop in the forms of genetic syndromes in young adults. The Piper nigrum is one important common spice used in the household having anticancer activities. The current study aims to evaluate P. nigrum seed extracts potency as anticancer against CRC cell line (COLO205). The extract is used to elucidate the MTT assay, DNA damage studies (COMET assay), Acridine Orange/Ethidium Bromide dual staining, cell death, cell cycle arrest using Flow cytometry, and regulation of Bcl-2, Bax & P53 gene regulation. To check the cell cytotoxicity by MTT assay methanolic extract was used. To evaluate anticancer activity the sample was extracted in methanol. RT-PCR was used to elevate gene expression studies of Bcl-2, Bax, and P53. In the dose-dependent mode, the extract inhibited the growth of COLO205 cells and the IC50 value was calculated at 48.2 μg/ml. The DNA fragmentation induced by apoptosis was the primary reason for the cell toxicity as observed by DNA damage studies & AO/EB dual staining technique. The extract concentration ranging from 40 & 80 μg/ml remarkably increased the proportion of cells in the S & G2/M phase. Cells at the late-apoptotic stage were found to be in the range of 22% - 57%. The Bax and P53 were upregulated and Bcl-2 was downregulated when treated with the extract. From this investigation underlying the mechanism of CRC was found to be P. nigrum extract caused to induce apoptosis and upregulation of tumor suppressor gene downregulation of apoptosis-suppressing gene bcl-2.

No Evidence of Abnormal Expression of Beta-Catenin and Bcl-2 Proteins in Pilomatricoma as One Clinical Feature of Tetrasomy 9p Syndrome

Background. Little is currently known about the genetics of pilomatricoma. A number of studies have reported some evidence that this disease may have a genetic association with mutations of CTNNB1 gene or expression of the beta-catenin protein. In this study, we reviewed literatures involving 30 patients with various genetic syndromes that have been linked to pilomatricoma and found that somatic mutations of the CTNNB1 gene were reported in 67% of patients. Pilomatricoma has been reported in patients with chromosome 9 rearrangements, including 4 patients with tetrasomy 9p syndrome and one patient with partial trisomy 9. In addition to beta-catenin, the expression of bcl2 was observed in pilomatricoma. Objectives. To report an additional case of tetrasomy 9p syndrome with concurrent pilomatricoma and to examine whether abnormal protein expressions of the CTNNB1 and/or BCL2 genes were present. Methods. Cytogenetic analysis was carried out on peripheral blood, biopsied skin, and pilomatricoma tissue obtained from a patient with tetrasomy 9p syndrome. Immunohistochemical staining was performed on the pilomatricoma tissue, using beta-catenin and bcl2 monoclonal antibodies. Results. SNP microarray revealed nonmosaic gain of the short arm of chromosome 9. A nonmosaic isodicentric chromosome 9 was identified in the peripheral blood but this rearranged chromosome was detected in only 8.3% of the skin fibroblasts. Chromosomal abnormalities were not detected in the pilomatricoma nor expression of beta-catenin or bcl2 proteins in our patient. Conclusion. Pilomatricoma could be a new clinical feature associated with tetrasomy 9p syndrome; however, we found no evidence of tetrasomy 9p or abnormal beta-catenin or bcl2 proteins of the CTNNB1 and BCL2 genes in our pilomatricoma patient.