Clinicopathological significance of SOX9 and ß-catenin expression in pre-neoadjuvant chemotherapy cases of osteosarcoma: molecular and immunohistochemical study.

The molecular pathogenesis of osteosarcoma (OS), the most frequent primary malignant bone tumor of all age groups, is still obscure. Since multidrug chemotherapeutic regimens were introduced in the 1970s, survival rates have been stationary. The Wnt-ß-catenin signaling cascade and SOX9 have a significant contribution to skeletal growth, development, and tumorigenesis. In the present work, an attempt was made to examine the role and clinicopathological significance of ß-catenin and SOX9 in 46 cases of pre-neoadjuvant chemotherapy OS tissues compared to 10 cases of non-neoplastic bone. The mRNA levels of both markers were assessed by qRT-PCR, and protein levels of ß-catenin were analyzed by immunohistochemistry. The results were correlated with different clinicopathological parameters. SOX9 mRNA levels were significantly elevated in OS compared to non-neoplastic bone, and higher levels were significantly associated with the occurrence of fluid-fluid levels (indicating blood-containing cystic spaces) and osteolytic radiological pattern. Although ß-catenin mRNA and protein levels were higher in OS compared to non-neoplastic bone, only the protein levels reached statistical significance. Higher ß-catenin mRNA levels were significantly associated with tumor size, while higher protein levels were significantly associated with the histologic subtype, mitotic count, and radiological pattern. No significant association was noted with any of the other evaluated parameters. OS showing higher SOX9 mRNA expression and lower ß-catenin mRNA and protein expression exhibited longer estimated overall survival times approaching statistical significance. To conclude, while high expression of ß-catenin and SOX9 suggests their possible involvement in OS development, their prognostic role may need further research.

Prognostic value of microRNA-125a expression status in molecular groups of pediatric medulloblastoma.

PURPOSE: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Current treatment allows decent survival rates but often with life-long morbidity. Molecular classification provides a base for novel therapeutic approaches. However, these groups are heterogeneous. MicroRNA-125a has a tumor suppressor function. It is downregulated in several tumors. The expression of microRNA-125a in MB patients remains unclear. Therefore, this study was designed to evaluate the expression of microRNA-125a in molecular groups of pediatric MB patients in Egyptian population and its clinical significance. METHODS: Formalin-fixed, paraffin-embedded tissue blocks from 50 pediatric MB patients were retrospectively collected. Immunohistochemistry for ß-catenin, GAB1, YAP1, and p53 was done for molecular classification. MicroRNA-125a expression analysis was done using qRT-PCR. Follow-up data were obtained from patients' records. RESULTS: MicroRNA-125a expression was significantly lower in MB patients showing large cell/anaplastic (LC/A) histology and in the non-WNT/non-SHH group. Lower levels of microRNA-125a showed a tendency toward poor survival rates; however, difference was not significant. Infants and larger preoperative tumor size were significantly associated with lower survival rates. On a multivariate analysis, preoperative tumor size was an independent prognostic factor. CONCLUSION: MicroRNA-125a expression was significantly lower in categories of pediatric MB patients with worse prognosis namely LC/A histology and the non-WNT/non-SHH group suggesting a pathogenetic role. MicroRNA-125a expression could represent a promising prognostic factor and a potential therapeutic target in the non-WNT/non-SHH group which represents the most common and the most heterogeneous group of pediatric MBs coupled with the highest rates of disseminated disease. Preoperative tumor size represents an independent prognostic factor.

Effects of COVID-19 on Pediatric Cancer Care: A Multicenter Study of 11 Middle Eastern Countries.

During the COVID-19 pandemic, major challenges are facing pediatric cancer centers regarding access to cancer centers, continuity of the anti-cancer therapy, hospital admission, and infection protection precautions. Pediatric oncologists actively treating children with cancer from 29 cancer centers at 11 countries were asked to answer a survey from May 2020 to August 2020 either directly or through the internet. COVID-19 pandemic affected the access to pediatric cancer care in the form of difficulty in reaching the center in 22 (75.9%) centers and affection of patients' flow in 21 (72.4%) centers. Health care professionals (HCP) were infected with COVID-19 in 20 (69%) surveyed centers. Eighteen centers (62%) modified the treatment guidelines. Care of follow-up patients was provided in-hospital in 8(27.6%) centers, through telemedicine in 10 (34.5%) centers, and just delayed in 11 (38%) centers. Pediatric oncologists had different expectations about the future effects of COVID-19 on pediatric cancer care. Seventy-six percent of pediatric oncologists think the COVID-19 pandemic will increase the use of telemedicine. Fifty-five percent of pediatric oncologists think if the COVID-19 pandemic persists, we will need to change chemotherapy protocols to less myelosuppressive ones. Collaborative studies are required to prioritize pediatric cancer management during COVID-19 era.

MISO Broadcast Channel under Unequal Link Coherence Times and Channel State Information.

The broadcast channel may experience unequal link coherence times due to a number of factors including variation in node mobility or local scattering conditions. This means the block fading model for different links may have nonidentical block length, and the channel state information for the links may also not be identical. The faster the fading and the shorter the fading block length, the more often the link needs to be trained and estimated at the receiver, and the more likely that channel state information (CSI) is stale or unavailable at the transmitter. This paper investigates a MISO broadcast channel where some receivers experience longer coherence intervals and other receivers experience shorter coherence intervals and must estimate their receive-side CSI (CSIR) frequently. We consider a variety of transmit-side CSI (CSIT) conditions for the abovementioned model, including no CSIT, delayed CSIT, or hybrid CSIT. To investigate the degrees of freedom region, we employ interference alignment and beamforming along with a product superposition that allows simultaneous but noncontaminating transmission of pilots and data to different receivers. Outer bounds employ the extremal entropy inequality as well as a bounding of the performance of a discrete, memoryless, multiuser, multilevel broadcast channel. For several cases, inner and outer bounds are established that either partially meet, or the gap diminishes with increasing coherence times.

Avoiding liver transplantation in post-treatment extent of disease III and IV hepatoblastoma.

BACKGROUND: Primary liver transplantation is recommended for central post-treatment extent of disease (POST-TEXT) III and IV hepatoblastoma. The aim of this study was to prospectively assess the safety and oncological efficacy of aggressive non-transplant extended hepatic resection in these patients. METHODS: A prospective study involved 18 children with central pretreatment extent of disease (PRETEXT) III and IV: three had primary liver transplantation whereas 15 underwent hepatic resection after neoadjuvant chemotherapy. RESULTS: Median tumor volume was 317 mL (range, 135-546 mL). After four cycles of chemotherapy, POST-TEXT stage was III in 12 patients and IV in three patients. There was no perioperative mortality. Postoperative complications consisted of two bile leaks, one temporary decompensation and one sub-phrenic collection requiring drainage. One and 3 year disease-free survival was 93.3% and 73.3% respectively. The 3 year overall survival was 86.6%. Four patients developed recurrence, of whom two died. Early recurrence in 1 year occurred in one patient. All recurrences were distant metastases. CONCLUSIONS: Extended major hepatic resection for selected cases of POST-TEXT III and IV hepatoblastoma is a technically challenging but feasible approach with acceptable morbidity and mortality rates. Oncological outcomes are similar to liver transplantation without the long-term commitment of immunosuppression or donor risk and morbidity, but a potential donor should always be organized on standby.

Effect of Nigella sativa seed administration on prevention of febrile neutropenia during chemotherapy among children with brain tumors.

PURPOSE: Seeds of Nigella sativa (NS) are used to combat various disease conditions through their antibacterial effects. To evaluate the seeds' potential, we studied their effect on the prevention of febrile neutropenia (FN) in children with brain tumors. METHODS: A randomized pretest-post-test control group study including 80 children (2-18 years) with brain tumors undergoing chemotherapy were equally allocated into two groups. Intervention group received 5 g of NS seeds daily throughout treatment while controls received nothing. CBC with differentials, incidence of FN, and LOS were noted on each follow-up. RESULTS: The majority of children 38/40 (95%), of the intervention group, took the seeds for 3-9 consecutive months. Eight out of 372 (2.2%) FN episodes were experienced by children of intervention group compared to controls 63/327 (19.3%) (p = 0.001) and a shorter LOS (median = 2.5 days) vs 5 days in the control group (p = 0.006). Children in both groups belonged to almost same geographical area with similar socio-economic background. Weights of children were almost equal at diagnosis. CONCLUSION: NS seeds showed a decrease in incidence of FN in children with brain tumors with shortening of subsequent LOS which may improve their outcome and thereby quality of life. Larger scale studies are needed to further evaluate the seeds' potential.

Diffusion-weighted MRI and in-phase/opposed-phase sequences in the assessment of bone tumors.

PURPOSE: To evaluate the role of diffusion-weighted apparent diffusion coefficient (ADC) and in-phase/opposed-phase sequences in the differentiation of benign and malignant osseous tumors. MATERIALS AND METHODS: At 1.5T, routine sequences were compared to diffusion-weighted and in-phase/opposed-phase in 63 patients. Routine sequence magnetic resonance imaging (MRI) scoring, mean ADC value, and in-phase/opposed-phase signal intensity ratio (SIR) was obtained. Statistical analysis included significance, receiver operating characteristic (ROC), and linear correlation between the three parameters. RESULTS: In all, 38 patients had malignant tumors and 25 patients had benign tumors. Benign and malignant tumors showed different routine sequence scores (P < 0.001). Mean ADC of the benign lesions ranged 0.9-3.2 × 10(-3) mm(2) /sec of mean ± SD (1.9 ± 0.6). In malignant tumors, the mean ADC ranged 0.6-1.9 × 10(-3) mm(2) /sec of mean ± SD (1.1 ± 0.4) (P < 0.0001). There was a possible differentiation between malignant and benign tumors at a threshold of 1.1 × 10(-3) mm(2) /sec of sensitivity and specificity of 94.1% and 70.3%, respectively. SIR for benign tumors ranged 0.2-1.0 of mean ± SD (0.6 ± 0.3). For malignant lesions SIR ranged 0.4-1.2 of mean ± SD (0.8 ± 0.3). Benign and malignant tumors show statistically significant SIR at P < 0.022 with possible differentiation at a threshold of 0.75 of sensitivity and specificity of 70.3% and 76.5%, respectively. Simple linear correlation between both ADC and SIR was significant at P < 0.01 with correlation coefficient (r) = 0.45. CONCLUSION: Diffusion-weighted and in-phase/opposed-phase imaging might be used in addition to conventional MRI as a routine tool for differentiation of benign and malignant tumors. J. Magn. Reson. Imaging 2016;44:565-572.

Lymphadenopathy in a series of Egyptian pediatric patients and the role of pathology in the diagnostic workup.

Assessment of lymphadenopathy in children represents a diagnostic challenge because of the extensive differential diagnoses, including reactive and malignant conditions. Knowledge of the etiologic pattern of lymphadenopathy in a given geographical region is essential for making a confident diagnosis or for suspecting a disease. Hence, the present study was carried out to identify different etiologies of lymphadenopathy in children in our region and to assess parameters commonly associated with malignancy, with an emphasis on the role of pathology. One hundred and twenty patients aged 1 month to 18 years were included in the study. They were sorted into neoplastic and nonneoplastic (infectious and noninfectious) groups. In 56 patients, biopsy (fine needle aspiration cytology [FNAC], core needle, or excision biopsy) was essential to reach the final diagnosis. Sensitivity of FNAC in the differentiation between neoplastic and nonneoplastic lymphadenopathy was 92.3%, and specificity was 90.0%, with a diagnostic accuracy of 91.3%. We concluded that malignancy should be suspected in the following conditions: presence of abdominal or multiple symptoms; symptom duration of 1-6 months; generalized lymphadenopathy; multiple groups of lymph node (LN) involved; LN size > 2 cm; amalgamated, hard, fixed, and nontender LNs; certain abnormal complete blood count findings; blast cells in blood film; and elevated lactate dehydrogenase level. In such cases, LN biopsy is highly recommended. A final diagnosis was achieved after integrating information from history and clinical findings with the laboratory, radiological, pathological, and microbiological findings. Accordingly, an algorithm for primary diagnostic evaluation of children with lymphadenopathy is suggested.

Lymphadenopathy in a Series of Egyptian Pediatric Patients and the Role of Pathology in the Diagnostic Workup.

Assessment of lymphadenopathy in children represents a diagnostic challenge because of the extensive differential diagnoses including reactive and malignant conditions. Knowledge of the etiologic pattern of lymphadenopathy in a given geographical region is essential for making a confident diagnosis or suspecting a disease. Hence, the present study was carried out to identify different etiologies of lymphadenopathy in children in our region, and assess parameters commonly associated with malignancy, with an emphasis on the role of pathology in the diagnostic workup. One hundred and twenty patients aged one month to 18 years were included in the study. They were sorted into neoplastic and non-neoplastic (Infectious and non-infectious). In only 56 patients, biopsy, whether fine needle aspiration cytology (FNAC), core needle or excision biopsy, was essential to reach the final diagnosis. Sensitivity of FNAC in the differentiation between neoplastic and non-neoplastic lymphadenopathy was 92.3%, specificity 90.0%, with a diagnostic accuracy of 91.3%. We concluded that malignancy should be suspected in the following conditions: presence of abdominal or multiple symptoms, symptoms duration of 1-6 months, generalized lymphadenopathy, multiple groups of lymph node (LN) involved, LN size > 2 cm, amalgamated, hard, fixed and non-tender LNs, certain abnormal CBC findings, blast cells in blood film and elevated LDH level. In such cases, LN biopsy is highly recommended. A final diagnosis was achieved after integrating information from history and clinical findings with those of the laboratory, radiological, pathological and microbiological findings. Accordingly, an algorithm for primary diagnostic evaluation of children with lymphadenopathy is suggested.