15 research outputs found
Estimating brain volume loss after radiation therapy in children treated for posterior fossa tumors (Corpus callosum and whole brain volume changes following radiotherapy in children).
Background More than half of pediatric tumors of central nervous system (CNS) primarily originate in the posterior fossa and are conventionally treated with radiation therapy (RT).Objectives The objective of this study was to establish whether corpus callosum volumes (CCV) and whole brain volumes (WBV) are correlated and to determine the impact of whole-brain lowvs high-dose RT on brain parenchymal volume loss as assessed using each technique.Material and methods Of the 30 identified children (6-12 years) with newly diagnosed posterior fossa tumors treated with cranial RT, including focal and whole-brain RT, suitable imaging was obtained for 23. Radiotherapy regimens were the following: no whole-brain RT (Group 1, n = 7), low-dose whole-brain RT (30 Gy, Group 3, n = 7) in addition to focal boost. Magnetic resonance images (MRIs) were analyzed at baseline and follow-up (median 14 months). The CCVs were manually segmented on midline sagittal slice (n = 23), while WBVs were segmented semi-automatically using Freesurfer (n = 15). This was done twice (6-month interval) for all baseline CCV measurements and 5 randomly selected WBV measurements to establish measurement reproducibility. Correlations between CCV and WBV were investigated and percentage of children demonstrating reduction in CCV or WBV noted.Results Correlation between baseline CCV and WBV was not significant (p = 0.37). Measurement reproducibility was from 6% to -9% for CCV and from 4.8% to -1.2% for WBV. Among the children studied, 30.4% (7/23) had >9% reduction in CCV at follow-up, while 33.3% (5/15) had >1.2% reduction in WBV. Five of 7 patients with CCV loss were not picked up by WBV measurements. Similarly, 3 of 5 patients with WBV loss were not picked up by CCV measurements.Conclusions The CCV and the WBV are unrelated and may indicate different brain parenchymal losses following RT. Up to a third of posterior fossa tumors treated with RT have measurable CCV or WBV loss; incidence was equivalent in lowvs high-dose whole-brain RT
Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans
This is the final version. It first appeared at http://www.nature.com/ncomms/2015/150901/ncomms9086/full/ncomms9086.html.Human-imprinting disorders are congenital disorders of growth, development and metabolism, associated with disturbance of parent of origin-specific DNA methylation at imprinted loci across the genome. Some imprinting disorders have higher than expected prevalence of monozygotic twinning, of assisted reproductive technology among parents, and of disturbance of multiple imprinted loci, for which few causative trans-acting mutations have been found. Here we report mutations in NLRP5 in five mothers of individuals affected by multilocus imprinting disturbance. Maternal-effect mutations of other human NLRP genes, NLRP7 and NLRP2, cause familial biparental hydatidiform mole and multilocus imprinting disturbance, respectively. Offspring of mothers with NLRP5 mutations have heterogenous clinical and epigenetic features, but cases include a discordant monozygotic twin pair, individuals with idiopathic developmental delay and autism, and families affected by infertility and reproductive wastage. NLRP5 mutations suggest connections between maternal reproductive fitness, early zygotic development and genomic imprinting.L.E.D. and F.I.R. were supported by the Medical Research Council (MR/J000329/1). J.B.,
K.B., B.H., L.S. M.B. and T.E. were supported by Bundesministerium fu?r Bildung und
Forschung (grant number 01GM1513A and 01GM1513C) and C.T. was supported by an
Ipsen Fellowship Grant. The cohort ?Imprinting Disorders-Finding out Why? was
accrued through the support of the Newlife Foundation for Disabled Children and
through support from the Wessex NIHR clinical research network and NIHR Wellcome
Southampton clinical research facility. Funding for DNA collection and methylation
analysis of normal control samples was provided in part by the National Institutes of
Health R01 AI091905-01, R01 AI061471 and R01 HL082925. ERM thanks Action
Medical Research for support
Diagnosis and treatment of thyroid cancer in children in the multicenter analysis in Poland for PPGGL
Introduction: Differentiated thyroid carcinoma (DTC) in
children presents different biological behavior in comparison
to adults. Authors presents preliminary results of multicenter
analysis concerning incidence, diagnostics and treatment
of DTC in children.
Material and methods: The study is a retrospective analysis
of 107 pediatric patients from 14 academic centers based
on the data from 2000 to 2005 obtained by questionnaire in
hospitals involved in the treatment of DTC in children.
Results: Papillary thyroid cancer was diagnosed in 83 children,
follicular thyroid cancer in 10 children and medullary
thyroid cancer in 14 children. Incidence of DTC in children
was estimated between 18 and 23 cases per year. The biggest
group of patients consisted of children between 11 and
15 years of age, with girls to boys ratio 3.3 : 1. Clinically DTC
in children presented most often as solitary thyroid nodule.
Cervical lymphadenopathy was observed in 42% of patients.
Intraoperative verification indicated metastatic nodes
in 50% of children. Low stage DTC predominated (T1
in 36% and T2 in 26% of children). One step surgery was performed in 65% of children with DTC, two step surgery
in 25% of patients. I131 therapy was undertaken in 80% of
children. Lung metastases were indicated in post therapeutic
studies in 14% of children with DTC. Prophylactic thyroidectomies
were performed in 79% of children in the group
of patients with MTC and RET gene mutations.
Conclusions: The necessity of introduction of unified therapeutic
standard in children with DTC in Poland is underlined.Wstęp: Zróżnicowane raki tarczycy (DTC, differentiated thyroid
carcinoma) występują u dzieci rzadko. Większość przypadków
wykrywanych jest w wieku 11-17 lat. W odróżnieniu
od dorosłych DTC u dzieci prezentują odmienne zachowanie
biologiczne. Mała liczba przypadków DTC
w poszczególnych ośrodkach oraz względnie łagodny ich
przebieg utrudniają ocenę występowania i leczenia DTC
u dzieci w Polsce, uzależniając ją od wysiłków włożonych
w uzyskanie rzetelnych danych. Autorzy przedstawiają
wstępne wyniki analizy wieloośrodkowej dotyczące występowania,
diagnostyki i leczenia DTC u dzieci.
Materiał i metody: Podjęte badania są retrospektywną analizą
obejmującą lata 2000-2005, opartą na danych z historii
chorób uzyskanych z ankiet rozesłanych do ośrodków dla
dzieci i dorosłych podejmujących leczenie DTC. Do analizy
zgłoszono 107 pacjentów z 14 ośrodków akademickich
w Polsce. Analizie poddano wiek i płeć dzieci z DTC, wielkość
i lokalizację zmian w tarczycy, sposoby rozpoznawania
DTC, rodzaje i zakres wykonywanych zabiegów operacyjnych
oraz leczenie uzupełniające izotopem J131.
Wyniki: Raka brodawkowatego stwierdzono u 83 dzieci,
pęcherzykowego u 10 dzieci, a rdzeniastego u 14 dzieci. Częstość
występowania DTC u dzieci w Polsce wahała się między
18 a 23 przypadkami rocznie. W województwach: mazowieckim
i połączonych wielkopolskim i lubuskim wykazano
w okresie 2000-2005 wyższą (24 i 25) częstość występowania
DTC, w pozostałych województwach wykazywano
od 2 do 10 przypadków DTC. Największą grupę pacjentów
stanowiły dzieci w wieku 11-15 lat, a stosunek dziewcząt do chłopców wynosił 3,3 : 1. Klinicznie DTC prezentowały
się najczęściej jako pojedyncze guzki tarczycy. Limfadenopatię
szyjną w badaniu klinicznym stwierdzono
u 42% pacjentów, a śródoperacyjnie u 50% dzieci. U większości
pacjentów dominowały niższe stopnie zaawansowania
DTC (T1 u 36% i T2 u 26% dzieci). Operacje jednoetapowe
wykonano u 65% dzieci, operacje dwuetapowe u 25%
dzieci, a profilaktyczne tyreoidektomie u 79% dzieci z grupy
pacjentów z rakiem rdzeniastym tarczycy (MTC, medullary
thyroid cancinoma) i mutacją genu Ret. Leczenie izotopowe
J131 podjęto u 80% dzieci. Przerzuty do płuc w scyntygrafii
poterapeutycznej wykazano u 14% dzieci z DTC.
Wnioski: We wnioskach podkreśla się konieczność wdrożenia
na terenie całego kraju ujednoliconego i ocenianego
na podstawie obiektywnych przesłanek sposobu postępowania
z dziećmi z DTC
Exposure of children with neuroblastoma to ionizing radiation during computed tomography and nuclear medicine imaging – a single centre experience
Purpose: To calculate cumulative doses of ionizing radiation absorbed by children with neuroblastoma during diagnostic CT and NM scans. Method: Retrospective analysis of 267 CT and NM scans performed in 21 children treated in 2009–2015. Results: The cumulative effective dose absorbed per child ranged from 58 to 536 mSv and was highest in infants under 3 years. Conclusion: Children with suspected neuroblastoma may be exposed to significant doses of radiation during the whole period of diagnosis and monitoring the progress of treatment