Solitary infantile choriocarcinoma of the liver: MRI findings

Infantile hepatic choriocarcinoma is a rare, highly malignant germ-cell tumour believed to result from a choriocarcinoma of the placenta that spreads to the child. Most infants present with a characteristic clinical picture of anaemia, hepatomegaly and precocious puberty. Imaging findings, including conventional MRI, may be non-specific. To improve the accuracy of diagnosis, we present the imaging findings of contrast-enhanced dynamic MRI in a 4.5-month-old boy with infantile hepatic choriocarcinom

Real-time broad-range PCR versus blood culture. A prospective pilot study in pediatric cancer patients with fever and neutropenia

Materials and methods: In a pilot study, results of real-time broad-range (16S rRNA) polymerase chain reaction (PCR) performed on 45 blood samples of pediatric cancer patients with fever and neutropenia were compared with blood culture results. Results: The PCR assay used, having proven a high sensitivity in artificially spiked blood samples, was positive in only three of ten blood culture-positive samples, and it was positive in 10 of 35 (29%) culture-negative samples. Conclusion: This broad-range PCR assay, which may identify not-grown bacteria potentially contributing to fever, needs improvement in sensitivity, and different reasons for positive PCR in negative blood culture samples need to be assessed before clinical applicatio

Protonentherapie mit "Spot-Scanning" bei Rhabdomyosarkomen im frühen Kindesalter: Erste Erfahrungen am PSI

Ziel:: Die Durchführbarkeit und Verträglichkeit der Spot-Scanning-Protonentherapie in tiefer Sedierung bei Kindern mit Rhabdomyosarkomen (RMS) sollten geprüft werden. Patienten und Methodik:: Seit 2004 werden junge Kinder am Paul Scherrer Institut (PSI), Villigen, Schweiz, auch in tiefer Sedierung mit Protonen bestrahlt. Ausgewertet wurden Kinder unter 5 Jahren mit RMS im Bereich des Kopfes und Körperstamms. Alle Kinder waren in eine Therapieoptimierungsstudie eingeschlossen und wurden prospektiv hinsichtlich der Verträglichkeit der Bestrahlung untersucht. Ergebnisse:: Neun Kinder im medianen Alter von 1,9 Jahren wurden untersucht (sechs embryonale RMS und je ein alveoläres, undifferenziertes und nicht klassifizierbares RMS). Die Lokalisationen waren parameningeal (n = 4), orbital (n = 3), Kopf-Hals-Bereich (n = 1) und Prostata (n = 1). Bei allen Kindern lag ein IRS-Stadium III vor. Die Bestrahlung erfolgte ausschließlich mit Protonen (Gesamtdosen 46-54 CGE [Cobalt-Gray-Äquivalent]). Akuttoxizitäten Grad 3 oder 4 nach RTOG/EORTC traten ausschließlich im Bereich des Knochenmarks auf. Schlussfolgerung:: Die Protonentherapie bei RMS im frühen Kindesalter war problemlos durchführbar und hervorragend verträglich. Prospektive, standardisierte Erhebungen von Spättoxizität und Lebensqualität sind essentiel

Burkitt's lymphoma with bilateral cavernous sinus and mediastinal involvement in a child

We report a 12-year-old boy who presented with incomplete right ophthalmoplegia, exophthalmos and headache. Initial CT and MRI revealed a mass in the right cavernous sinus. During tumour work-up, CT identified additional tumour within the mediastinum. Biopsy of the mediastinal lesion identified Burkitt's lymphoma. We report on this case because radiologists and clinicians should be alerted to identify sites of primary Burkitt's lymphoma outside of the central nervous system if clinical symptoms indicate, or imaging shows, CNS lesions. Primary CNS involvement in Burkitt's lymphoma is rar

Family Characteristics as Risk Factors for Childhood Acute Lymphoblastic Leukemia: A Population-Based Case-Control Study

BACKGROUND: To date, few risk factors for childhood acute lymphoblastic leukemia (ALL) have been confirmed and the scientific literature is full of controversial "evidence." We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL). METHODOLOGY/PRINCIPAL FINDINGS: In this population-based nationwide matched case-control study, patients 0-14 years of age with ALL diagnosed 1991-2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05-1.31; p = 0.004), remaining stable (trend OR 1.14, 95% CI 0.99-1.31; p = 0.060) after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01-1.28, p = 0.032) and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0-14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0-4 years (OR per sibling 0.85, 95% CI 0.68-1.06; p = 0.141) and a positive trend for ALL diagnosed at age 5-9 (OR 1.34, 95% CI 1.05-1.72; p = 0.019), with some evidence for an effect modification (p-value for interaction  = 0.040). CONCLUSIONS: As in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence

Quantitative profiling of housekeeping and Epstein-Barr virus gene transcription in Burkitt lymphoma cell lines using an oligonucleotide microarray

BACKGROUND: The Epstein-Barr virus (EBV) is associated with lymphoid malignancies, including Burkitt's lymphoma (BL), and can transform human B cells in vitro. EBV-harboring cell lines are widely used to investigate lymphocyte transformation and oncogenesis. Qualitative EBV gene expression has been extensively described, but knowledge of quantitative transcription is lacking. We hypothesized that transcription levels of EBNA1, the gene essential for EBV persistence within an infected cell, are similar in BL cell lines. RESULTS: To compare quantitative gene transcription in the BL cell lines Namalwa, Raji, Akata, Jijoye, and P3HR1, we developed an oligonucleotide microarray chip, including 17 housekeeping genes, six latent EBV genes (EBNA1, EBNA2, EBNA3A, EBNA3C, LMP1, LMP2), and four lytic EBV genes (BZLF1, BXLF2, BKRF2, BZLF2), and used the cell line B95.8 as a reference for EBV gene transcription. Quantitative polymerase chain reaction assays were used to validate microarray results. We found that transcription levels of housekeeping genes differed considerably among BL cell lines. Using a selection of housekeeping genes with similar quantitative transcription in the tested cell lines to normalize EBV gene transcription data, we showed that transcription levels of EBNA1 were quite similar in very different BL cell lines, in contrast to transcription levels of other EBV genes. As demonstrated with Akata cells, the chip allowed us to accurately measure EBV gene transcription changes triggered by treatment interventions. CONCLUSION: Our results suggest uniform EBNA1 transcription levels in BL and that microarray profiling can reveal novel insights on quantitative EBV gene transcription and its impact on lymphocyte biology

CRISPR activation screen identifies TGFβ-associated PEG10 as a crucial tumor suppressor in Ewing sarcoma

As the second most common pediatric bone and soft tissue tumor, Ewing sarcoma (ES) is an aggressive disease with a pathognomonic chromosomal translocation t(11;22) resulting in expression of EWS-FLI1, an "undruggable" fusion protein acting as transcriptional modulator. EWS-FLI1 rewires the protein expression in cancer cells by activating and repressing a multitude of genes. The role and contribution of most repressed genes remains unknown to date. To address this, we established a CRISPR activation system in clonal SKNMC cell lines and interrogated a custom focused library covering 871 genes repressed by EWS-FLI1. Among the hits several members of the TGFβ pathway were identified, where PEG10 emerged as prime candidate due to its strong antiproliferative effect. Mechanistic investigations revealed that PEG10 overexpression caused cellular dropout via induction of cell death. Furthermore, non-canonical TGFβ pathways such as RAF/MEK/ERK, MKK/JNK, MKK/P38, known to lead to apoptosis or autophagy, were highly activated upon PEG10 overexpression. Our study sheds new light onto the contribution of TGFβ signalling pathway repression to ES tumorigenesis and suggest that its re-activation might constitute a novel therapeutic strategy