Tyrosine kinase inhibitors in sarcoma treatment

Sarcomas are a group of rare mesenchymal malignant tumors that arise from transformed cells of the mesenchymal connective tissue, which are challenging to treat. The majority of sarcomas are soft tissue sarcomas (STSs; 75%) and this heterogeneous group of tumors is further comprised of gastrointestinal stromal tumors (~15%) and bone sarcomas (10%). Although surgery remains the current primary therapeutic approach for localized disease, recurrent, metastatic and refractory sarcomas require cytotoxic chemotherapy, which usually yields poor results. Therefore the efficiency of sarcoma treatment imposes a difficult problem. Furthermore, even though progress has been made towards understanding the underlying molecular signaling pathways of sarcoma, there are limited treatment options. The aim of the present study was therefore to perform a systematic literature review of the available clinical evidence regarding the role of tyrosine kinase inhibitors (TKIs) in patients with recurrent or refractory STSs and bone sarcomas over the last two decades. Tyrosine kinases are principal elements of several intracellular molecular signaling pathways. Deregulation of these proteins has been implicated in driving oncogenesis via the crosstalk of pivotal cellular signaling pathways and cascades, including cell proliferation, migration, angiogenesis and apoptosis. Subsequently, small molecule TKIs that target these proteins provide a novel potential therapeutic approach for several types of tumor by offering significant clinical benefits. Among the eligible articles, there were 45 prospective clinical trials, primarily multicentric, single arm, phase II and non-randomized. Numerous studies have reported promising results regarding the use of TKIs, mainly resulting in disease control in patients with STSs. The lack of randomized clinical trials demonstrates the ambiguous efficiency of various studied treatment options, which therefore currently limits the approved drugs used in clinical practice. Research both in clinical and preclinical settings is needed to shed light on the underlying molecular drivers of sarcomagenesis and will identify novel therapeutic approaches for pretreated patients.     

THE INFLUENCE OF FAMILY TYPE ON CHILDREN''S BEHAVIOUR AND DEVELOPMENT AT FIVE YEARS

Development and behaviour at five years were assessed in children from a national cohort; comparisons were drawn between those living in one-parent families, in step-parent families and with both natural parents. On average, children from one-parent families scored worst and children from two-parent families best on tests of behaviour, vocabulary and visuomotor co-ordination. The differences remained significant after allowing for associated influences. The behaviour of children from one-parent families and step-parent families was perceived on average as more 'anti-social' than that of children from two-parent families. Children in one-parent families were seen on average as marginally more 'neurotic' than children in two-parent families.     

Comparison of skeletal and dental morphology in asymptomatic volunteers and symptomatic patients with unilateral disk displacement without reduction

The purpose of this study was to evaluate the effect of unilateral disk displacement without reduction (UDDN) on the skeletal and dental pattern of affected individuals. There were 12 symptomatic female patients and 46 asymptomatic normal female volunteers. All study participants had bilateral high-resolution magnetic resonance scans in the sagittal (closed and open) and coronal (closed) planes to evaluate the temporomandibular joints. Linear and angular cephalometric measurements were taken to evaluate the skeletal, denture base, and dental characteristics of the two groups. ANOVA was used to compare the symptomatic subjects with the control subjects. A few skeletal differences were found. There was an overall reduction in length of the anterior (S-Na) and total (S-Ba) cranial base measurements in the UDDN group. The mandibular plane angle was steeper and the posterior ramal height (Ar-Go) was shorter in the symptomatic group. The only dental difference found was a relative infraeruption of the lower first molar. This study suggests that subjects with UDDN may manifest altered craniofacial morphology. Although the cephalometric measurements used did not account for any asymmetry, previous studies have shown that UDD may cause mandibular asymmetry. Presence of asymmetry and altered craniofacial morphology should alert the clinician especially while orthodontically treating children and surgical patients.     

Assessment of patient effective radiation dose and associated radiogenic risk from extracorporeal shock-wave lithotripsy

The aim of the present study was to calculate patient effective dose and associated radiogenic risk from fluoroscopy guided extracorporeal shock-wave lithotripsy procedures. Fluoroscopy required during extracorporeal shock-wave lithotripsy was classified in two types identified by beam orientation: antero-posterior and 30 degrees anterior-oblique projected exposures. Duration of each exposure was monitored in 124 patients undergoing extracorporeal shock-wave lithotripsy treatment for ureteral stones. The dose from a kidney-ureter-bladder radiograph and the dose per min of fluoroscopy along antero-posterior and anterior-oblique projections were measured at 13 organs/tissues using an anthropomorphic phantom and thermoluminescence dosimetry. A radio-opaque object was placed in the phantom to simulate an ureteral stone at the proximal and distal ureter. The total effective dose in male and female patients with proximal ureteral stones was 1.71 mSv and 1.82 mSv, respectively. The corresponding values for male and female patients with distal ureteral stones was 0.76 mSv and 1.62 mSv, respectively. In the United States, the theoretical sex-averaged radiogenic excess of fatal cancers was estimated to be 140 per million and 85 per million of patients treated for proximal and distal ureteral stone, respectively. The average radiogenic risk for genetic defect associated to treatments of proximal and distal ureteral stones was found to be 2.5 and 24.4 per million of births, respectively. The radiation risk from a typical fluoroscopy guided extracorporeal shock-wave lithotripsy treatment of ureteral stones is low. Presented data may be used to determine patient effective dose from extracorporeal shock-wave lithotripsy procedures performed in any laboratory.     

Tumor progression and serum anti-HuD antibody concentration in patients with paraneoplastic neurological syndromes

The aim of this study was to investigate whether there are clues for a correlation between tumor progression and serum anti-Hu antibody concentration in patients with anti-Hu-associated paraneoplastic neurological syndromes (PNS). 19 patients with anti-Hu-associated PNS were assigned to three groups according to the course of tumor progression. Group 1 corresponds to patients with rapid tumor progression [n = 5; mean survival in months/standard deviation (SD); 24/10]; in group 2 patients with a favorable tumor prognosis were included (n = 7; mean/SD 79/25, 6 patients still alive); group 3 consisted of patients in whom tumor progression could not be assessed (n = 7; mean/SD 23/20). The anti-Hu antibody concentrations in sera were measured in a recombinant HuD-ELISA. In sera from patients of group 1 the anti-Hu antibody concentration was modest (mean OD 0.56, SD 0.08) whereas a significantly higher anti-Hu antibody concentration was detected in sera from patients with a favorable tumor prognosis (group 2, mean OD 1.86, SD 0.34). These results hint at a negative correlation between tumor progression and the anti-Hu antibody concentration in sera from patients with PNS. These findings confirm and extend previous reports of more indolent tumor growth in patients with an anti-Hu immune response.     

False allegations of child physical abuse: a case of Münchausen by proxy-like syndrome?

The diagnosis of factitious disorder by proxy is still under investigation. Few studies have researched the psychological status and potential underlying psychopathology of the perpetrator, as well as the impact on the child's development and the pathological reactions of rearing a child within the context of a distorted reality. In this article, we present the case of a 12-year-old boy where this diagnosis was suspected. Both he and his parents brought forth false allegations of repeated physical abuse induced by his schoolteacher. The parents presented with shared psychosis and the child presented with conduct disorder, factitious disorder, and emotional problems. We suggest that this case represents a Münchausen by proxy-like syndrome involving both the legal and medical systems. Hypotheses regarding the pathogenesis of symptoms in the child are noted, underscoring the differences between Münchausen by proxy syndrome appearing in infancy with that appearing in older children.     

Management of childhood diseases during the Byzantine period: V − Hydrocephalus

Hydrocephalus was a recognizable medical problem during the Byzantine period. In the medical texts of the time it was attributed to the pressure that was applied on the newborn's head during labour. The suggested treatments focused on the relief of the symptoms only and surgical methods were believed to be helpful in very rare cases.     

Management of childhood diseases during the Byzantine period: VI − Ocular diseases

Ocular manifestations were recognizable and are reported in the Byzantine medical treatises from the 4th to the 15th century AD. Herbal, mineral and chemical substances in the form of collyria were used by the Byzantine physicians for the treatment of ocular abnormalities and ophthalmic diseases of the childhood. Surgical intervention was not recommended at this age.