Routine surveillance imaging after end of therapy for pediatric extracranial tumors: A retrospective analysis

Frequent surveillance imaging is routine practice for pediatric patients after cancer therapy. This retrospective study evaluated the follow‐up of 301 children with extracranial tumors diagnosed between 2002 and 2012, at a tertiary pediatric cancer center in Beirut, Lebanon. Recurrence occurred in 15% of patients, at a median of 12 months after end of primary therapy. Outcome was not different comparing patients with recurrence detected via imaging surveillance versus clinically. False positive findings in 55 patients led to further interventions. These results raise important questions regarding benefit of current surveillance practices as standard care, especially in countries with limited resources.     

Central nervous system germinoma: retrospective study of six cases]

PURPOSE: Retrospective analysis of six patients with intracranial germinoma treated in INO and a literature review. MATERIALS AND METHODS: Six patients were treated from 1993 to 1998, for histologically verified primary intracranial germinoma. Median age was 18 years (range: 14-26 years). All patients received chemo-radiotherapy (4FP + radiotherapy from 30 to 50 Gy). RESULTS: 4 tumours were in complete remission. Two patients have kept non-evolutive residual cyst. Five patients are alive with non-evolutive disease after 15-40 months of follow-up (average: 27 months). One patient was lost to follow-up, 14 months after treatment, without disease. CONCLUSION: The treatment of intracranial germinoma is currently first line chemotherapy followed by low-dose and limited irradiation.     

Intracranial Hodgkin disease: case report]

Hodgkin disease intracranial lesions are uncommon. We report the case of a 24-year-old man who presented with an intracranial relapse without other evidence of disease 24 months after multiple drug therapy and extended field radiation therapy for stage III Bb type 3 Hodgkin disease. The patient was treated by whole brain irradiation (40 Gy/20 fractions/4 weeks). Six months after completion of therapy, the patient had a second relapse, with bilateral inguinal metastatic nodes, which were treated by a second line polychemotherapy. The patient was free of disease 9 months later.     

Effect of thrombopoietin receptor agonists on markers of coagulation and P-selectin in patients with immune thrombocytopenia

Thrombopoietin-receptor-agonists (TPO-RA) are effective treatments of immune thrombocytopenia (ITP). Previous long-term TPO-RA clinical trials have shown that thrombotic events occurred in 6% of TPO-RA-treated ITP patients. To explore the increased risk of thrombosis, the effects of TPO-RA on markers of coagulation and P-selectin were studied.

The study comprised two ITP cohorts and controls. Cohort 1 included 26 patients with sequential samples acquired before and during treatment with TPO-RA. Cohort 2 included a single sample in 18 patients on TPO-RA for more than one year. Thrombin generation (endogenous thrombin potential (ETP)) prothrombin fragments 1 + 2 (F₁₊₂), D-dimer, and plasminogen-activator-inhibitor-1 (PAI-1) were measured as well as soluble P-selectin (sP-selectin). Sequential expression of encoding genes for P-selectin (SELP) and PAI-1 (SERPINE1) was determined in four patients in cohort 1.

Significantly higher levels of F₁₊₂, D-dimer, and PAI-1 were found in ITP patients before TPO-RA treatment and in patients on long-term TPO-RA treatment than in controls. Pre-treatment levels of sP-selectin did not differ from controls. Analysis of longitudinal trends showed an increase in platelet count, sP-selectin, and PAI-1 after initiation of TPO-RA, followed by gradual decline. Platelet count and sP-selectin remained at higher levels throughout the study, whereas PAI-1 did not. Levels of other studied parameters did not show significant changes after initiation of treatment. Expression of SELP was up-regulated after initiation of TPO-RA, while the expression of SERPINE1 showed no significant changes.

In conclusion, elevated pre-treatment levels of F₁₊₂, D-dimer and PAI-1 are compatible with ITP being an intrinsically pro-thrombotic condition. After TPO-RA treatment, there were no significant changes in markers of coagulation activation or fibrinolysis, except for an initial increase in PAI-1 and a significant increase in sP-selectin both of which may contribute to increased thrombotic risk associated with TPO-RA treatment in ITP.     

AAV4-mediated Expression of IGF-1 and VEGF Within Cellular Components of the Ventricular System Improves Survival Outcome in Familial ALS Mice

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron cell death in the cortex, brainstem, and spinal cord. Extensive efforts have been made to develop trophic factor-based therapies to enhance motor neuron survival; however, achievement of adequate therapeutic delivery to all regions of the corticospinal tract has remained a significant challenge. Here, we show that adeno-associated virus serotype 4 (AAV4)-mediated expression of insulin-like growth factor-1 (IGF-1) or vascular endothelial growth factor (VEGF)-165 in the cellular components of the ventricular system including the ependymal cell layer, choroid plexus [the primary cerebrospinal fluid (CSF)-producing cells of the central nervous system (CNS)] and spinal cord central canal leads to trophic factor delivery throughout the CNS, delayed motor decline and a significant extension of survival in SOD1^G93A transgenic mice. Interestingly, when IGF-1- and VEGF-165-expressing AAV4 vectors were given in combination, no additional benefit in efficacy was observed suggesting that these trophic factors are acting on similar signaling pathways to modestly slow disease progression. Consistent with these findings, experiments conducted in a recently described in vitro cell culture model of ALS led to a similar result, with both IGF-1 and VEGF-165 providing significant motor neuron protection but in a nonadditive fashion. These findings support the continued investigation of trophic factor-based therapies that target the CNS as a potential treatment of ALS.     

Prevalence and determinants of distress among oncology patients at a tertiary care medical city in Riyadh,Saudi Arabia

Objectives:To estimate the prevalence of distress in patients with cancer in Saudi Arabia and to identify common psychosocial stressors in these patients. We also looked for associations between distress and psychological, sociodemographic, and medical factors.Methods:This cross-sectional study was performed in the oncology outpatient clinic at King Saud University Medical City, Riyadh, Saudi Arabia, from January 2018 to December 2019. It included 280 patients with breast cancer, colorectal cancer, or lymphoma. Sociodemographic information was collected using questionnaire, along with information on medical history and any psychiatric history. Distress was assessed using the Distress Thermometer and Problem List. Satisfaction with social support was rated using the visual analog scale. All patients were screened for depression using the Patient Health Questionnaire 9-item depression scale and anxiety using the Generalized Anxiety Disorder 7-item scale.Results:The prevalence of distress in our study population was found to be 46%. Distress was associated with several practical, family, emotional, and physical stressors in the problem list. Logistic regression identified predictors of distress to be anxiety (odds ratio [OR] 8.7, confidence interval [CI] 1.98-38.24, p=0.002) and receiving radiotherapy (OR 3.6, CI 1.33-9.99, p=0.009), while Saudi nationality (OR 0.22, CI 0.05-0.95, p=0.037) and stage I cancer (OR 0.18, CI 0.05-1.40, p=0.002) were associated with low distress.Conclusion:Approximately half of cancer patients were found to have distress. Anxiety, advanced cancer stage, and radiotherapy were independently associated with distress.     

Chronic lead exposure may be associated with erectile dysfunction

IntroductionHeavy metals constitute significant potential threats to human health in both occupational and environmental settings. Research examining the etiology of lead toxicity-induced hypertension reveals that the free radical production and lowering of inherent antioxidant reserves resulting from lead toxicity are directly related to vasoconstriction underlying lead-induced hypertension. A similar mechanism would affect smooth muscle relaxation in the cavernous tissue leading to erectile dysfunction (ED).AimIs to study the possible hazardous effect of chronic lead exposure on the erectile function, and to document the deposition of lead in the cavernous tissue.MethodsThe study group consisted of 34 men with ED, consecutively scheduled for penile implant insertion at Cairo University Hospital, as well as 15 controls. We determined the blood lead level for the two groups by the use of atomic absorption spectrophotometry. Sixteen of the 34 patients, and none of the 15 controls, had elevated lead serum levels (above 25 [g/dL]).Main Outcome MeasuresWe estimated the levels of two reactive oxygen species (ROS) and four antioxidants in peripheral blood for the two groups. At the time of penile implant insertion, we prepared cavernous tissue paraffin sections stained with Mallory–Parker stain to study lead deposition. We also prepared ultrathin sections for electron microscopy. We estimated cavernous tissue lead level.ResultsThe ED group had significantly higher blood lead level when compared with the control group. A significant positive correlation was found between the blood lead level and cavernous tissue lead level of the ED group. Individuals with high blood lead had significantly higher levels of serum ROS and significantly lower levels of serum antioxidants, compared with those having low blood lead. Histological sections from patients with high blood lead showed deposition of grayish lead granules in the cavernous tissue.ConclusionsChronic lead exposure may be associated with ED. Anis TH, ElKaraksy A, Mostafa T, Gadalla A, Imam H, Hamdy L, and Abu el-Alla O. Chronic lead exposure may be associated with erectile dysfunction.     

Review and audit of the post‐surgical MRI breast: Pictorial essay

Audit of contrast‐enhanced breast MRI performed over a 3‐year period in a single institution to describe and summarise the changes seen after surgery and radiation therapy for primary breast cancer, breast augmentation and oncoplastic surgery. Seventy women were identified and reviewed (100 breast MRIs in total). The most common change seen was haemosiderin deposition. The early changes of skin thickening, oedema, seroma and background parenchymal enhancement decreased with time leaving residual breast shrinkage, haemosiderin/calcification and architectural distortion due to fibrosis and scarring.     

Neural Stem Cell Transplantation as a Therapeutic Approach for Treating Lysosomal Storage Diseases

Treating the central nervous system manifestations of subjects with neuropathic lysosomal storage diseases remains a major technical challenge. This is because of the low efficiency by which lysosomal enzymes in systemic circulation are able to traverse the blood brain barrier into the central nervous system. Intracranial transplantation of neural stems cells genetically modified to overexpress the respective deficient enzymes represents a potential approach to addressing this group of diseases. The unique properties of neural stem cells and progenitor cells, such as their ability to migrate to distal sites, differentiate into various cell types and integrate within the host brain without disrupting normal function, making them particularly attractive therapeutic agents. In addition, neural stem cells are amenable to ex vivo propagation and modification by gene transfer vectors. In this regard, transplanted cells can serve not only as a source of lysosomal enzymes but also as a means to potentially repair the injured brain by replenishing the organ with healthy cells and effecting the release of neuroprotective factors. This review discusses some of the well-characterized neural stem cell types and their possible use in treating neuropathic lysosomal storage diseases such as the Niemann Pick A disease.