Cardiac tumours in children

Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT) and Magnetic Resonance Imaging (MRI) of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor

Aneuploidy and chromosomal instability in cancer: a jackpot to chaos

Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. Patients with constitutive aneuploidies are more susceptible to certain types of cancers, suggesting that changes in chromosome copy number could positively contribute to cancer evolution. On the other hand, chromosomal imbalances have been observed to have detrimental effects on cellular fitness and might trigger cell cycle arrest or apoptosis. Furthermore, mouse models for CIN have led to conflicting results. Taken together these findings suggest that the relationship between CIN, aneuploidy and cancer is more complex than what was previously anticipated. Here we review what is known about this complex ménage à trois, discuss recent evidence suggesting that aneuploidy, CIN and GIN together promote a vicious cycle of genome chaos. Lastly, we propose a working hypothesis to reconcile the conflicting observations regarding the role of aneuploidy and CIN in tumorigenesis

The epidemiology of neonatal tumours: Report of an international working group

Neonatal tumours occur every 12,500-27,500 live births and comprise 2% of childhood malignancies, but there is little clarity as to their real prevalence, sites of origin and pathological nature as reported series vary. As an entity, neonatal tumours provide a unique window of opportunity to study tumours in which minimal environmental interference has occurred. The majority of tumours present with a mass at birth (e.g., teratomas, neuroblastomas, mesoblastic nephroma, fibromatosis), which are not infrequently identified on antenatal ultrasound. Histologically, teratoma and neuroblastoma remain the two main tumour types encountered with soft tissue sarcoma, renal tumours, CNS tumours and leukaemia being the next most common tumour types identified. Malignant tumours are uncommon in the neonatal period per se and benign tumours may have malignant potential. A particular problem exists in clinical classification, as histological features of malignancy do not always correlate with clinical behaviour. Benign tumours may also be life threatening because of their size and location. Other tumours may demonstrate local invasiveness, but no metastatic potential, and tumours that are clearly malignant may demonstrate unpredictable or uncertain behaviour. Screening programmes have brought more tumours to light, but do not appear to affect the overall prognosis. They may provide clues to the stage at which tumours develop in foetu. The aetiology of cancer in children is multifactorial and includes both genetic and environmental factors. The association between congenital abnormalities and tumours is well established (15% of neonatal tumours). Genetic defects are highly likely in neonatal tumours and include those with a high risk of malignancy (e.g., retinoblastoma), but also genetically determined syndromes with an increased risk of malignancy and complex genetic rearrangements. Tumours are mostly genetically related at a cellular level and factors influencing cellular maturation or apoptosis within the developing foetus may continue to operate in the neonatal period. Cytogenetics of neonatal neoplasms appear to differ from neoplasms in older children, thus possibly explaining some of the observed differences in clinical behaviour. Certain constitutional chromosome anomalies, however, specifically favour tumuors occurring in the foetal and neonatal period. In support of this hypothesis, certain cytogenetic anomalies appear to be specific to neonates, and a number of examples are explored. Other environmental associations include ionizing radiation, drugs taken during pregnancy, infections, tumours in the mother and environmental exposure.Revie

Unsaturated Germanium and Phosphorus-compounds - Reactions of Germaphosphenes With Alpha-ethylene Aldehydes and Ketones

Germaphosphenes MeS2Ge=PR (R: 2,4,6-triisopropylphenyl (Is), 1; 2,4,6-tri-tert-butylphenyl (Ar), 2) react with a-ethylene aldehydes and ketones to give [2 + 2] and [2 + 4] cycloadditions (for aldehydes) and [2 + 4] cycloadditions and 1,2-additions (for ketones). Four- and six-membered ring derivatives can be easily differentiated by P-31 NMR chemical shifts which are, respectively, +36 to +89 ppm and -33 to -77 ppm. 5a', obtained from 2 and crotonaldehyde, has been structurally characterized by X-ray diffraction: the six-membered ring (germaoxaphosphorinene) conformation is a sofa form, with large folding along the Ge-C axis. A NMR study at various temperatures for 3a, 3a', and 5a' displays dynamic phenomenon including phosphorus and ring inversion. The low DELTAG* values (respectively 18.2,13.7, and 13.2 kcal/mol) seem mainly due to substitution of phosphorus by the electropositive germanium and particularly to large steric effects; the 2,4,6-tri-tert-butylphenyl group lowers the inversion barrier by 5 kcal/mol when compared with the 2,4,6-triisopropylphenyl group