Did salvage ICE chemotherapy improve the outcome in primary resistant/relapsing stage III/IV neuroblastoma?

AbstractBackground and purposeNeuroblastoma is the most common extracranial and deadly solid tumor in children. It accounts for 15% of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at “high risk” of treatment failure.The aim of this study is to evaluate the response rate of salvage chemotherapy by the ICE (Ifosfamide, Carboplatin, and Etoposide) regimen when administered to previously treated primary refractory or progressive high risk neuroblastoma patients.Patients and methodsSixty-six patients from the National Cancer Institute (NCI), Cairo University and the Children Cancer Hospital Egypt (CCHE) received salvage chemotherapy (ICE) either due to primary resistance in 51/66 (77.2%) or due to disease progression on primary chemotherapy in 15/66 (22.8%).ResultsThey were 40 males (60.6%) and 26 females (39.4%). Patients’ age ranged between 3months and 12.5years. The most common tumor site was suprarenal, followed by retroperitoneal mass. Two patients (3%) died from chemotherapy toxicity during ICE administration. Evaluation of tumor response in the remaining 64 patients showed the following: CR/PR in 24 patients (36.5%), SD in 11 patients (16.6%), and PD in 29 patients (43.9%).Fourteen patients (21.2%) were considered eligible for auto BMT, while 50/64 patients (78.8%) failed this second line (salvage) chemotherapy and had palliative lines of therapy.By the end of the study (May 2010), 47/66 (71.2%) of the patients were still alive, while 19/66 (28.8%) were dead. Two out of 14 patients (14.2%) who underwent HSCT died from post transplantation disease progression, while 12/14 (85.8%) were in CCR.ConclusionChemotherapy by ICE for primary resistant or progressive stage III/IV NB seems well tolerated. With a 36.6% response rate, 18% CCR, and 3% treatment mortality rate, it could be considered a good salvage therapy in the category of patients who are condemned for palliation

IgY antibodies: The promising potential to overcome antibiotic resistance

Antibiotic resistant bacteria are a growing threat to global health security. Whilst the emergence of antimicrobial resistance (AMR) is a natural phenomenon, it is also driven by antibiotic exposure in health care, agriculture, and the environment. Antibiotic pressure and inappropriate use of antibiotics are important factors which drive resistance. Apart from their use to treat bacterial infections in humans, antibiotics also play an important role in animal husbandry. With limited antibiotic options, alternate strategies are required to overcome AMR. Passive immunization through oral, nasal and topical administration of egg yolk-derived IgY antibodies from immunized chickens were recently shown to be effective for treating bacterial infections in animals and humans. Immunization of chickens with specific antigens offers the possibility of creating specific antibodies targeting a wide range of antibiotic-resistant bacteria. In this review, we describe the growing global problem of antimicrobial resistance and highlight the promising potential of the use of egg yolk IgY antibodies for the treatment of bacterial infections, particularly those listed in the World Health Organization priority list

Environmental, maternal, and reproductive risk factors for childhood acute lymphoblastic leukemia in Egypt : a case-control study

BACKGROUND\ud Acute lymphocytic leukemia (ALL) is the most common pediatric cancer. The exact cause is not known in most cases, but past epidemiological research has suggested a number of potential risk factors. This study evaluated associations between environmental and parental factors and the risk for ALL in Egyptian children to gain insight into risk factors in this developing country.\ud METHODS\ud We conducted a case-control design from May 2009 to February 2012. Cases were recruited from Children's Cancer Hospital, Egypt (CCHE). Healthy controls were randomly selected from the general population to frequency-match the cumulative group of cases by sex, age groups (<1; 1 - 5; >5 - 10; >10 years) and region of residence (Cairo metropolitan region, Nile Delta region (North), and Upper Egypt (South)). Mothers provided answers to an administered questionnaire about their environmental exposures and health history including those of the father. Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated using logistic regression with adjustment for covariates.\ud RESULTS\ud Two hundred ninety-nine ALL cases and 351 population-based controls frequency-matched for age group, gender and location were recruited. The risk of ALL was increased with the mother's use of medications for ovulation induction (ORadj = 2.5, 95 % CI =1.2 -5.1) and to a lesser extend with her age (ORadj = 1.8, 95 % CI = 1.1 - 2.8, for mothers ≥ 30 years old). Delivering the child by Cesarean section, was also associated with increased risk (ORadj = 2.01, 95 % CI =1.24-2.81).\ud CONCLUSIONS\ud In Egypt, the risk for childhood ALL appears to be associated with older maternal age, and certain maternal reproductive factors

Nonchromosomal birth defects and risk of childhood acute leukemia : An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations

Risk stratification and pattern of cardiotoxicity in pediatric Ewing sarcoma

Introduction: Anthracycline chemotherapy contributes to improved outcomes in Ewing sarcoma; however, the most feared complication is cardiotoxicity. Echocardiograms were routinely used to monitor cardiac function after anthracycline treatment. Nevertheless, indices chosen to assess cardiac toxicity vary significantly among different centers, and no uniform protocol has been accepted as ideal. Methods: This retrospective study included children with Ewing sarcoma treated at Children’s Cancer Hospital Egypt over 4 years. All echocardiograms and related clinical assessments were reviewed. Results: In total, 149 patients (median age 11 years; range 1–18 years) were included. Although all patients had a reduced ejection fraction compared with their baseline echocardiogram, only 39 patients developed cardiotoxicity (26%): 43% acute-onset, 36% chronic early-onset, and 21% chronic late-onset. There were no statistically significant association between the frequency of myocardial dysfunction and risk factors, including age, sex, follow-up duration, cumulative doxorubicin dose, and mediastinal irradiation. Over one-third (39%) of the patients with cardiac toxicity regained normal cardiac parameters, whereas seven patients died of acute cardiac toxicity. Conclusion: The routine use of echocardiography to screen for anthracycline-induced cardiac toxicity before and during chemotherapy identified myocardial dysfunction. Early medical intervention can improve cardiac parameters. Improved screening techniques with better sensitivity and predictability are needed

Association of serum levels of epidermal growth factor with disease severity in patients with unresectable hepatocellular carcinoma

Aim: Epidermal growth factor (EGF) is a mitogen for hepatocyte grown in vitro, and its expression is up-regulated during liver regeneration. EGF also plays an important role in tumor initiation and progression. The goal of this study is to assess whether EGF is associated with advanced hepatocellular carcinoma (HCC) and also whether it is a predictive factor of shortened survival.Methods: Serum EGF levels were evaluated in a total of 151 subjects: 51 patients with unresectable HCC, (21 of them were eligible for transarterial chemoembolization (TACE) and serum EGF levels were measured before and 1 week after TACE), 40 patients with chronic hepatitis without cirrhosis, 40 patients with cirrhosis, and 20 healthy controls. Patient demographic and laboratory variables were evaluated as predictive factors of survival in a Cox regression multivariate analysis using SPSS software.Results: The mean serum level of EGF in patients with HCC was 784.49 pg/mL, which was significantly higher (P &lt; 0.05) than all other groups. Mean EGF level in cirrhotic patients was 144.69 pg/mL; in those with chronic hepatitis C without cirrhosis, it was 338.64 pg/mL; and in healthy controls, it was 297.15 pg/mL. In group Ia patients who underwent TACE, the mean serum level of EGF was 759.76 ± 287.88 pg/mL before TACE, and 801.14 ± 276.12 pg/mL 1 week after treatment (P = 0.34). On multivariate Cox regression analysis only age (P = 0.03) and higher serum EGF level (P = 0.005), were inversely correlated with overall survival.Conclusion: EGF levels were found to be significantly higher in HCC patients and together with age were the only predictors of poor survival in these patients. There was an increase in EGF levels 1 week after TACE in response to hypoxia; however, this increase was not statistically significant