Plasma miRNA expression profile in pediatric pineal pure germinomas.

Background: Pure germinomas account for 40% of pineal tumors and are characterized by the lack of appreciable tumor markers, thus requiring a tumor biopsy for diagnosis. MicroRNAs (miRNA) have emerged as potential non-invasive biomarkers for germ cell tumors and may facilitate the non-invasive diagnosis of pure pineal germinomas. Material and methods: A retrospective chart review was performed on all patients treated at the Children's Cancer Hospital Egypt diagnosed with a pineal region tumor between June 2013 and March 2021 for whom a research blood sample was available. Plasma samples were profiled for miRNA expression, and DESeq2 was used to compare between pure germinoma and other tumor types. Differentially expressed miRNAs were identified. The area under the curve of the receive;r operating characteristic curve was constructed to evaluate diagnostic performance. Results: Samples from 39 pediatric patients were available consisting of 12 pure germinomas and 27 pineal region tumors of other pathologies, including pineal origin tumors [n = 17; pineoblastoma (n = 13) and pineal parenchymal tumors of intermediate differentiation (n = 4)] and others [n = 10; low-grade glioma (n = 6) and atypical teratoid rhabdoid tumor (n = 4)]. Using an adjusted p-value <0.05, three miRNAs showed differential expression (miR-143-3p, miR-320c, miR-320d; adjusted p = 0.0058, p = 0.0478, and p = 0.0366, respectively) and good discriminatory power between the two groups (AUC 90.7%, p < 0.001) with a sensitivity of 25% and a specificity of 100%. Conclusion: Our results suggest that a three-plasma miRNA signature has the potential to non-invasively identify pineal body pure germinomas which may allow selected patients to avoid the potential surgical complications.

Nephrectomy for Pediatric Renal Tumors: A Modified Surgical Approach to Minimize Post-operative Intestinal Obstruction.

BACKGROUND: The authors present a modified surgical technique during tumor nephrectomy in children with a conservative approach towards small bowel manipulation and cutting of the peritoneal reflections. We aimed to evaluate this modified surgical approach regarding the incidence of post-operative small bowel obstruction (SBO), and its technical utility. METHODS: The study includes all children with unilateral renal tumors who underwent radical nephrectomy and lymph nodes sampling at our tertiary center from 2010 to 2022. The modified technique was performed via the usual transverse incision. We cut the peritoneal reflections short of the cecum or short of the sigmoid colon. The colon is reflected over SB packing it, proceeding to nephrectomy and lymph nodes sampling. Data included demographics, clinical characteristics, treatment strategy, operative details, post-operative SBO, and overall outcomes. RESULTS: The study included 890 patients with a median age of 3.2 years. The median tumor largest diameter was 13 cm (range: 9-18 cm). The modified surgical technique was adopted in 287 patients (32.3 %). Forty-three patients (43/890, 4.8 %) had post-operative SBO. Out of them, only 4 cases were operated on using the modified surgical technique (p-value<0.001). There were no significant differences between both techniques regarding timing of surgery, tumor rupture, lymph nodes sampling, and tumor size (p-value = 0.775, 0.328, 0.216, and 0.563, respectively). CONCLUSIONS: The modified surgical approach is significantly correlated with lower incidence of post-operative SBO with no increased risk of tumor rupture or incomplete lymph nodes sampling. The timing of surgery or tumor characteristics had no significant impact on the technical utility of the modified surgical approach. LEVEL OF EVIDENCE: Level IV.

Evaluating the baseline survival outcomes of the "six Global Initiative for Childhood Cancer index cancers" in Africa.

Limited survival data for the six Global Initiative for Childhood Cancer (GICC) priority cancers are available in Africa. Management of pediatric malignancies in Africa is challenging due to lack of resources, setting-specific comorbidities, high rates of late presentation and treatment abandonment. Reporting of outcome data is problematic due to the lack of registries. With the aim of evaluating the feasibility of baseline outcomes for the six index cancers, we present a descriptive analysis of respective survival rates in Africa. The survival rates were between 18% (lower middle-income countries) to 82.3% (upper middle-income countries) for acute lymphoblastic leukemia, between 26.9% (low-income countries) to 77.9% (upper middle-income countries) for nephroblastoma, between 23% (low-income countries) to 100% (upper middle-income countries), for retinoblastoma, 45% (low-income countries) to 95% (upper middle-income countries) for Hodgkin lymphoma and 28% (low-income countries) to 76% (upper middle-income countries) for Burkitt lymphoma. Solutions to improve survival rates and reported outcomes include establishing and funding sustainable registries, training and to actively include all countries in consortia from different African regions.HighlightsContinental differences in childhood cancer management such lack of resources, setting-specific comorbidities, high rates of late presentation and treatment abandonment, present challenges to the achievement of Global Initiative for Childhood Cancer goals.The available data registries do not adequately inform on the true incidences and outcomes of childhood cancers in Africa.The pathophysiology of some childhood cancers in Africa are associated with high-risk prognostic factors.Outcomes can be improved by greater regional collaboration to manage childhood cancer based on local resources and tumor characteristics.Some individual countries have reached the Global Initiative for Childhood Cancer goals for single cancers and it should be possible for more African countries to follow suit.

Aggresomes predict poor outcomes and implicate proteostasis in the pathogenesis of pediatric choroid plexus tumors.

PURPOSE: Protein misfolding and aggregation result in proteotoxic stress and underlie the pathogenesis of many diseases. To overcome proteotoxicity, cells compartmentalize misfolded and aggregated proteins in different inclusion bodies. The aggresome is a paranuclear inclusion body that functions as a storage compartment for misfolded proteins. Choroid plexus tumors (CPTs) are rare neoplasms comprised of three pathological subgroups. The underlying mechanisms of their pathogenesis remain unclear. This study aims to elucidate the prognostic role and the biological effects of aggresomes in pediatric CPTs. METHODS: We examined the presence of aggresomes in 42 patient-derived tumor tissues by immunohistochemistry and we identified their impact on patients' outcomes. We then investigated the proteogenomics signature associated with aggresomes using whole-genome DNA methylation and proteomic analysis to define their role in the pathogenesis of pediatric CPTs. RESULTS: Aggresomes were detected in 64.2% of samples and were distributed among different pathological and molecular subgroups. The presence of aggresomes with different percentages was correlated with patients' outcomes. The ≥ 25% cutoff had the most significant impact on overall and event-free survival (p-value < 0.001) compared to the pathological and the molecular stratifications. CONCLUSIONS: These results support the role of aggresome as a novel prognostic molecular marker for pediatric CPTs that was comparable to the molecular classification in segregating samples into two distinct subgroups, and to the pathological stratification in the prediction of patients' outcomes. Moreover, the proteogenomic signature of CPTs displayed altered protein homeostasis, manifested by enrichment in processes related to protein quality control.

Management and outcome of pediatric metastatic Wilms' tumor at the National Cancer Institute, Egypt.

BACKGROUND: Wilms' tumor (WT) is the most common renal malignant tumor of childhood. Metastatic WT has a worse prognosis than localized disease. This study aims to assess the clinical outcome and different prognostic factors that influence treatment outcome of pediatric metastatic WT cases treated at National Cancer Institute (NCI), Egypt, between January 2008 and December 2015. Medical records were retrospectively reviewed for clinical, radiological and histopathological data, treatment received, and survival outcome. RESULTS: In the specified study period, 24/103 (23.3%) patients with WT were metastatic at presentation. The mean age was 5.25 ± 2.87 years (range 2.0-12.7). Abdominal swelling/mass was the commonest presentation (70.8%). Only 3 patients (12.5%) had combined lung and liver metastases while 21 patients (87.5%) had pulmonary-only metastases. All patients had favorable histology tumors with no anaplasia. Nine patients (37.5%) underwent upfront nephrectomy. Majority of patients (91.7%) had local stage III disease. Surgical complications were reported in 4 patients; 3 of them had up-front nephrectomy. Only 7/21 patients achieved rapid complete response of pulmonary nodules after 6 weeks of chemotherapy (CTH), and they had a better survival outcome. Patients were followed up till December 2017. Thirteen patients (54.1%) experienced events during the study period including 5 relapses, 6 cases with disease progression, and 2 patients died out of sepsis. The 3-year event-free and overall survival rates were 48.2% and 54.2%, respectively. CONCLUSION: Neo-adjuvant CTH followed by delayed nephrectomy seems more suitable approach in our institute. Pulmonary response to neo-adjuvant CTH appears to be a strong predictor for outcome.

Management and outcome of pediatric Wilms tumor with malignant inferior Vena cava thrombus: largest cohort of single-center experience.

BACKGROUND: Wilms tumor (WT) with an inferior Vena cava (IVC) malignant thrombus comprises 4-10% of all WT cases. METHODS: This retrospective analysis included 51 pediatric patients presenting at Children Cancer Hospital Egypt-57357 from July 2007 to December 2016 with the diagnosis of WT with malignant IVC thrombus. RESULTS: Median age at presentation = 4.4 years and 28 cases (55%) were females. Twenty-five patients (49%) were metastatic and 4 patients (7.8%) had bilateral disease. Forty-seven cases (92.2%) had favorable histology with no evidence of anaplasia. Level of thrombus extension at presentation was classified as infra-hepatic, retro-hepatic, supra-hepatic and intra-cardiac in 33, 9, 6 and 3 patients, respectively. Fifty patients started neoadjuvant chemotherapy (CTH) with 16 patients showing complete resolution of thrombus after 6 weeks of CTH. None of the patients developed thrombus progression after neoadjuvant CTH; one patient had stationary intra-cardiac thrombus, while remaining patients showed partial regression of their thrombus and had nephrectomy with en-bloc thrombectomy. The mean cranio-caudal dimension of IVC thrombi at initial presentation was 6.5 cm, and 3.6 cm post 6th week of CTH. The 5-year OS and EFS were 75.9% and 71.1%, respectively. There was no significant correlation of initial levels of thrombus extension with survival. CONCLUSION: Neoadjuvant chemotherapy followed by radical nephrectomy with en-bloc thrombectomy and radiotherapy seems a successful approach for management of patients with WT and IVC tumor thrombus. Measurement of the cranio-caudal dimension of thrombus and its response to treatment should be considered in the surgical planning.