Hala Taha

High levels of oxidative DNA damage in lymphocyte DNA of premenopausal breast cancer patients from Egypt

Egypt shows a parallel increase in premenopausal breast cancer and environmental pollution. The purpose of this study is to explore a possible relationship between oxidative DNA damage, urinary estrogen metabolites and breast cancer in Egyptian premenopausal women. We conducted a pilot study of Egyptian breast cancer involving 29 cases and 32 controls and analysed lymphocyte DNA levels of 7,8-dihydro-8-oxo-2′-deoxyguanine (8-oxo-dG), a measure of oxidative DNA damage using high performance liquid chromatography with electro-chemical detection (HPLC-ECD) method. We analysed levels of urinary estrogen metabolites, 2-hydroxyestrone (2-OHE) and 16α-hydroxyestrone (16α-OHE) by an enzyme immuno assay. We also collected residential, occupational, and reproductive histories of all study subjects. We detected, in all subjects, exceptionally high levels of 8-oxo-dG and thus oxidative DNA damage, the levels (mean 8-oxo-dG/105 dG ± SD) were significantly (P < 0.01) higher in breast cancer cases (139.4 ± 78.4) than in controls (60.9 ± 51.5). Urinary 2-OHE and 16α-OHE or their ratio was not significantly different between cases and controls. However, 8-oxo-dG levels were positively correlated (P < 0.05) with 2-OHE and 16α-OHE from cases while controls showed a negative correlation (P < 0.05). Urban residence (Odds Ratio [OR] 3.1; Confidence interval [CI], 1.1 – 9.3), infertility (OR [9.8]; CI [1.1 – 89.7]), age (OR [2.6]; CI [1.4 – 4.6]) and 8-oxo-dG (OR 5.8; CI 1.9 – 17.5) levels were found to be significant predictors of breast cancer. Our finding of exceptionally high levels of 8-oxo-dG, a common result of oxidative DNA damage, warrant future studies on a larger population of premenopausal women in Egypt with consideration of other susceptibility markers and dietary characteristics.

Endoscopic third ventriculostomy before tumor surgery in children with posterior fossa tumors, CCHE experience

ObjectiveThis is a retrospective study to evaluate the effectiveness of endoscopic third ventriculostomy (ETV) performed in children with posterior fossa tumors and hydrocephalus in an attempt to classify the selected cases who could benefit from ETV as a permanent CSF diversion procedure.MethodsDuring the period between January 2008 and December 2008, 40 patients with posterior fossa tumors and associated hydrocephalus were treated inside the Children’s Cancer Hospital, Egypt (CCHE)—with ETV in order to relieve the increased intracranial pressure while awaiting their definite tumor surgery.ResultsETV was successful in relieving hydrocephalus clinically and radiologically in 26 patients with different posterior fossa pathologies, with the highest success rate in glioma (100%), followed by 50% in ependymoma and 47.6% in medulloblatoma. In the other 14 cases, preoperative ETV failed in permanently resolving hydrocephalus and patients required the insertion of a ventriculoperitoneal (VP) shunt after their posterior fossa surgery and during their follow-up period.ConclusionETV should be considered as an alternative procedure to VP shunt in controlling severe hydrocephalus related to posterior fossa tumors, to relieve symptoms quickly during the preoperative period while patients await their definite tumor excision. Patients with ependymomas and gliomas, with totally excised tumors, are better candidates for ETV than those with medulloblastomas. However, ETV cannot always prevent postoperative hydrocephalus in all cases of posterior fossa tumor, the thing that makes using postoperative VP shunt an alternative.

Clinical presentation of intraocular retinoblastoma; 5-year hospital-based registry in Egypt

PURPOSE To study the presenting signs of Retinoblastoma in Egypt at Egypts main pediatric oncology referral center. METHODS This is a prospective descriptive study (hospital-based registry) conducted at Childrens Cancer Hospital Egypt between July 2007 and December 2012. RESULTS Out of 262 patients diagnosed with retinoblastoma, 244 were suffering from intra-ocular disease at presentation. One hundred thirty-nine (57%) patients presented with unilateral disease, while 105 (43%) suffered bilateral disease. The mean age at presentation was 20.6 ± 17 months, averaging 18.87 ± 11.76 months for bilateral and 25.72 ± 18.78 months for unilateral disease. The most common clinical presentation was leukocoria in 180 (73.8%) patients, strabismus in 32 (13.1%) patients and decreased visual acuity in 12 (4.9%) patients. Group D and E disease represented 62% of all affected eyes. Patients with advanced disease (Group C-E) had longer duration of symptoms. CONCLUSION In Egypt, retinoblastoma patients present more frequently with advanced disease. There is an ever-increasing need to develop a national team dedicated to studying disease significance and formulating a national awareness program.

Investigation and Management of a Rhizomucor Outbreak in a Pediatric Cancer Hospital in Egypt

We describe an outbreak of mucormycosis in a pediatric oncology hospital during December 2010 and the measures taken to stop it. The outbreak began with two consecutive cases of laboratory‐documented mucormycosis infections within 1 week. Investigations to track the source were conducted immediately. Air plate cultures from machines and ducts supplying patients’ rooms revealed the growth of Rhizomucor. Of five affected patients, all had acute leukemia and three were histopathologically proven. All patients were treated with liposomal amphotericin B after mucormycosis was diagnosed. Posaconazole was used as a secondary prophylaxis in one case. Three patients died. Pediatr Blood Cancer

High Risk Retinoblastoma: Prevalence and Success of Treatment in Developing Countries

Pediatric Oncology Department, Pathology Department, Ophthalmology Unit, Research Department, and Radiation Therapy Department, Children’s Cancer Hospital Egypt, Cairo, Egypt, National Eye Research Institute, Giza, Egypt, Egyptian National Cancer Institute, Cairo, Egypt, School of Medicine, Cairo University, Cairo, Egypt, and Institute of Neural Processing, Ulm University, Ulm, Baden-Württemberg, Germany

Phthisis Bulbi: Clinical and Pathologic Findings in Retinoblastoma

Purpose: Phthisis bulbi represents an ocular end-stage disease characterized by shrinkage and disorganization of the eye. We aim at identifying the pathologic changes of phthisis bulbi associated with retinoblastoma. Design: Retrospective observational case series study. Methods: 16 enucleated eyes were enrolled retrospectively between 2007 and 2012. Pathologic gross and microscopic findings were assessed. Results: Cases showed grossly shrunken eyes with a mean volume of 4.3 cc. Sclera was markedly thickened in the majority of cases with mean of 2272.8 μ. Choroid showed an average thickness of 1029 μ. Necrosis, dystrophic calcification, ossification, gliosis, residual viable tumor was identified in many cases. Pathologic high risk factors were seen in three specimens. Conclusions: We conclude that retinoblastoma must be considered in the differential diagnosis of phthisis bulbi in the pediatric patients and active tumor was present in half of the patients.

A change roadmap towards research paradigm in low-resource countries: retinoblastoma model in Egypt.

Research on childhood diseases represents a great global challenge. This challenge is maximized in both childhood cancer disciplines and developing world. In this paper, we aim at describing our institution experience in starting a structured childhood cancer research program in one of the developing countries in a short time based on philanthropic efforts. We used retinoblastoma as an example for what was conducted in this program. Starting in 2008, this program included improving clinical practice and its related supporting services besides developing new research services that both complement the clinical activities and pave the way towards creating a research foundation in the country. Results included developing hospital standard treatment protocols, developing national clinical trials, joining international consortia for childhood cancers clinical trials, developing data collection tools and real-time analytics, establishing a biobanking facility, and developing highly qualified team for conducting clinical, epidemiologic, and translational research studies. Moreover, this effort resulted in improving both clinical practice and patients’ awareness nationally. This model can be used for other startup facilities that aim at finding answers for their national health problems in low-resource setting.

Incidence of kiaa1549-braf fusion gene in Egyptian pediatric low grade glioma

BackgroundLow grade gliomas are the most common brain tumor in children. Tandem duplication involving the KIAA1549 and the BRAF kinase genes results in a gene fusion that has been recently characterized in a subset of low grade glioma While there is no clear evidence that the KIAA1549-BRAF gene fusion has an effect on prognosis, it is an attractive target for therapy development and as a diagnostic tool.MethodsIn the current study we examine the prevalence of KIAA1549-BRAF gene fusion in pediatric patients diagnosed with low grade glioma in the Egyptian population and its relationship to clinical and histological subtypes. Sixty patients between the ages of 1 to 18 years were analyzed for the presence of KIAA1549-BRAF fusion gene products using reverse transcription-PCR and sequencing. The clinicopathologic tumor characteristics were then analyzed in relation to the different fusion genes.ResultsKIAA1549-BRAF fusion genes were detected in 56.6% of patients. They were primarily associated with pilocytic astrocytoma (74.2%) and pilomyxoid astrocytoma (60%). Translocation 15–9 was the most common, representing (55.8%) of all positive samples followed by 16–9 (26.4%) and 16–11 (8.8%). Pilocytic astrocytomas presented primarily with 15–9 (32.2%), 16–9 (25.8%) and 16–11 (6.4%) while pilomyxoid astrocytomas presented with 15–9 (46.6%), 16–9 (6.6%) and 16–11 (6.6%) translocations.ConclusionGene fusion is found to be significantly increased in cerebellar pilocytic astrocytoma tumors. Furthermore, 15–9 was found to have a higher incidence among our cohort compared to previous studies. While most of the gene fusion positive pilomyxoid astrocytomas were 15–9, we find the association none significant.

A multidisciplinary approach to improving the care and outcomes of patients with retinoblastoma at a pediatric cancer hospital in Egypt

ABSTRACT Background: Retinoblastoma poses a substantial burden in developing countries. We conducted this study to assess the effect of implementing a multidisciplinary approach and standardized protocols for treating pediatric patients with retinoblastoma at the Children’s Cancer Hospital Egypt (CCHE). Materials and Methods: In January 2011, the CCHE implemented standardized protocols for the diagnosis, treatment, and reporting of retinoblastoma cases. The hospital also introduced a new retinoblastoma management algorithm and data analysis system. In this study, we compared the pathologic features, tumor invasiveness, reporting, and survival of 276 pediatric patients who underwent enucleations of 290 eyes before or after the implementation of the retinoblastoma protocols. Results: Time to enucleation (indicating time needed for decision taking) decreased significantly within the neoadjuvant chemotherapy group for intraocular disease after January 2011 (68.7 ± 48 weeks vs. 47.3 ± 28.3 weeks; p < 0.05). Mean optic nerve stump length increased from 5.6 mm in the earlier period to 7.2 mm in the later period (p = 0.004). The overall quality of pathology reporting also improved during the later period. The probability of 3-year survival was significantly higher for patients during the later period (94.2% vs. 79.2%; p = 0.018). Conclusions: The implementation of standardized protocols and a multidisciplinary approach improved reporting; discrepancies in disease classification and the amount of missing data were reduced; and quality measures and prognostic capabilities of the team were substantially improved. Such established data-driven practice supports faster decision making to enucleate diseased eyes and save patients’ lives through providing measurable indicators.

Does primary tumor volume predict the outcome of pediatric nasopharyngeal carcinoma?: A prospective single-arm study using neoadjuvant chemotherapy and concomitant chemotherapy with intensity modulated radiotherapy.

Nasopharyngeal carcinoma is rare in children and adolescents; however, it has a better prognosis than in adults. Nevertheless, its prognostic factors are not clearly documented.