Promising response to vemurafenib and cobimetinib treatment for BRAF V600E mutated craniopharyngioma: a case report and literature review.

Craniopharyngiomas are tumors that arise from the remnants of Rathke's pouch along the nasopharynx to the diencephalon. Current standard of care includes maximal surgical resection versus adjuvant radiation if a maximal resection is unfeasible. Pharmacological therapy with MAPK targeted agents is an emerging therapeutic option for tumors with BRAF V600E mutations. We report a 45-year-old male with a strictly third ventricle papillary craniopharyngioma with a BRAF V600E mutation. After initial surgery with subtotal resection, the patient demonstrated durable response to targeted BRAF and MEK inhibitor therapy with vemurafenib and cobimetinib. Our report suggests that targeted therapy may reduce the need for radiation and impact surgical interventions in select cases.

Surgical approaches, anaesthetic management and outcome in pediatric superior mediastinal tumors.

BACKGROUND: Pediatric superior mediastinal tumors are a heterogeneous group of tumors with marked variation in pathology and extension. We reviewed our experience with different surgical approaches to tumors originating from or extending to superior mediastinum in pediatrics. PATIENTS AND METHODS: The medical records of all patients who had undergone resection for superior mediastinal tumors in Children's Cancer Hospital - Egypt, between January 2008 to December 2015, were reviewed for demographic data, clinico-pathological features, radiologic findings, operative techniques and outcome. RESULTS: The study included 20 patients. Diagnosis included: germ cell tumors (n=8), neuroblastoma (n=4), soft tissue sarcoma (n=3), thymolipoma (n=2), infantile fibromatosis (n=1), calcifying fibrous tumor (n=1), and thymic carcinoma (n=1). Tumor extension was divided into tumors extending unilaterally to one hemithorax (n=9), tumors extending bilaterally to both hemithoraces (n=4), and cervico thoracic junction tumors (n=7). Extended lateral thoracotomy was used in 8 patients. Other approaches included trapdoor (n=5), clamshell (n=4), cervical approach (n=2) and double level lateral thoracotomy (n=1). There was no perioperative mortality, and postoperative morbidity was 20%. At the end of December 2016, 15 patients were alive free of disease, 5 patients developed local and/ or distant relapse. CONCLUSION: Pediatric superior mediastinal tumors could be divided into 3 groups according to tumor extension. Each group has an optimum surgical approach that achieves the best exposure for adequate resection. However, further research is needed to confirm the conclusion as this was a descriptive study and the sample size was too small for valid statistical analysis.

Role of FDG-PET scan in the management of pediatric mature B cell non-Hodgkin's lymphoma. CCHE experience.

AIM OF WORK: To evaluate the sensitivity (Se), specificity (Sp), and predictive values (PV) of PET scan during management of pediatric mature B cell non-Hodgkin's lymphoma (NHL) in comparison with conventional computed tomography (CT) scan. PATIENTS AND METHODS: A retrospective study enrolled on pediatric NHL patients at Children Cancer Hospital Egypt (CCHE) during the period from July 2007 to the end of June 2013. RESULTS: For 115 pediatric patients diagnosed with mature B cell NHL, 152 PET and 152 CT scans were done simultaneously. Median age was 5.7years. They were 85 males (74%) and 30 females (26%). One hundred twenty six scans (82.9%) were done for 100 (87%) Burkitt lymphoma (BL) patients, while 26 scans (17.1%) were done for 15 (13.0%) patients with diffuse large B cell NHL (DLBC). Nineteen examination (12.5%) were done before starting chemotherapy (group 1), 107 (70.3%) at time of evaluation (group 2), and 26 (17.1%) during follow up (group C). Overall sensitivity was 91.6% for PET and 70.0% for conventional CT (p=0.02). Specificity was 84.1% for PET and 58.9% for CT (p<0.001). Positive predictive value (PPV) for PET was 50%, while was 22% for CT scan (p<0.001). Negative predictive value (NPV) for PET was 98%, and 92% for CT (p=0.01). CONCLUSION: PET scan is significantly more sensitive than conventional CT in the management of aggressive pediatric mature B cell NHL. PET negativity is an excellent indicator of tumor response.

Vitamin D receptor gene polymorphism in Egyptian pediatric acute lymphoblastic leukemia correlation with BMD.

INTRODUCTION: We studied the frequencies of the 3' and 5'-end vitamin D receptor (VDR) gene polymorphisms and their correlation with bone mineral density (BMD) in Egyptian pediatric acute lymphoblastic leukemia (ALL) patients receiving calcium and vitamin D supplements. The purpose of this study is to find out the relation between VDR polymorphism and the response to vitamin D intake in pediatric ALL cases who receive corticosteroid therapy which predispose to osteoporosis. This study might shed the light on some genetic variants that are effect the response of individuals to vitamin D therapy. METHODS: Forty newly diagnosed pediatrics ALL cases were studied. Three SNPs at the 3'-end of the VDR gene (BsmI rs1544410, ApaI rs739837and TaqI rs731236) and two SNPs at the 5'-end (Cdx-2 rs11568820 and GATA rs4516035) were analyzed by Allelic discrimination assay. Of those twenty-six cases with initial BMD data available were further analyzed with regards to the effect of various VDR genotypes/haplotypes on BMD. RESULTS: The genotype frequencies at 3'-end of VDR gene were, TaqI TT 23%, Tt 54% and tt 23%, BsmI bb 19.2%, Bb 65.4% and BB 15.4% and ApaI AA 12%, Aa 27% and aa 61%. The frequencies at the 5'-end were Cdx-2 GG 34.5%, GA 54% and AA 11.5% and GATA AA 8%, AG 50% and GG 42%. Eight and four possible haplotypes were observed at the 3' and 5'-ends of the VDR gene respectively. The Tt genotype was significantly correlated with high BMD as compared to other TaqI genotypes (P = 0.0420). There was a trend towards higher BMD with the genotype Bb as compared to other BsmI genotypes. No statistical significance was found between the other VDR genotypes or haplotypes studied and BMD. CONCLUSIONS: This is the first report on VDR gene polymorphisms in Egyptian pediatric ALL patients. The Tt genotype was associated with increased BMD. Our study showed marked genetic heterogeneity in VDR gene in Egyptian pediatric ALL patients.

Langerhans Cell Histiocytosis (LCH) in Egyptian Children: Does Reactivation Affect the Outcome?

OBJECTIVE: To report a single centre outcome of management of Langerhans cell histiocytosis (LCH), a clonal disease with involvement of various body systems. METHODS: Retrospective analysis of 80 pediatric LCH patients at Children Cancer Hospital-Egypt between July 2007 and December 2011 was performed. Patients were stratified and treated according to LCH III protocol. The median follow up period was 42 mo (range: 1.18 to 71 mo). RESULTS: At wk 6 and 12, 'better' response was obtained in 61 (76 %) and 74 (93 %) patients respectively. Afterwards, reactivation occurred in 25 patients (38 %), of them multiple episodes occurred in 5 patients (6.25 %), managed by repetition of 1st line treatment for once or more. The 5 y overall survival (OS) and event free survival (EFS) was 96.3 and 55 % respectively. At last follow up, better status was reached in 70 patients, 3 in each 'intermediate' and 'worse' status. Three high risk patients died and one patient was lost to follow up. CONCLUSIONS: In a single Egyptian pediatric LCH experience, the response to treatment is satisfactory and survival remains the rule except in high risk organs disease that still needs a new molecule for salvage. However in multiple reactivations, patients do well with repetition of the 1st line of treatment with or without methotrexate.

Risk of postpartum uterine synechiae following uterine compression suturing during postpartum haemorrhage.

BACKGROUND: Uterine compression suturing is considered a successful, safe, inexpensive and simple method for the conservative treatment of atonic postpartum haemorrhage (PPH). However, insufficient data are available about the potential risk of subsequent intrauterine synechiae (IUS). AIM: To determine the risk of postpartum uterine synechiae in women who received isolated uterine compression suturing for the management of major uncontrolled PPH. MATERIALS & METHODS: All women with major PPH from May 2005 to June 2011 were reviewed retrospectively. Diagnostic hysteroscopy was performed to assess the uterine cavity in the 27 women who successfully underwent isolated uterine compression suturing for major atonic PPH and fulfilled the study inclusion and exclusion criteria. RESULTS: Among the 27 women who underwent isolated uterine compression suturing, 5 (18.5%) were found to have IUS on hysteroscopic examination. The mode of delivery for all women who developed IUS was caesarean section. Among these five women, three had mild IUS, one had moderate IUS and one had severe IUS. All adhesions were later successfully resected by hysteroscopy, except for one case with dense IUS. CONCLUSIONS: Uterine compression suturing was found to be associated with a risk of postpartum uterine synechiae formation, which may subsequently affect future fertility.