Adequate nutrition during cancer plays a decisive role in several clinical outcome measures, such as treatment response, quality of life, and cost of care. However, the importance of nutrition in children and young adults with malignancies is still an underestimated topic within pediatric oncology. The importance of our work is to reinforce and indicate that malnutrition in children with cancer should not be accepted at any stage of the disease or tolerated as an inevitable process. Unique to our manuscript is the close collaboration, the exchange of knowledge and expertise between pediatric oncologists and a nutritional specialist, as well as the comprehension of the mechanisms during cancer cachexia and malnutrition. We provide a critical review of the current state of research and new knowledge related to nutritional management in childhood cancer.

Following diagnosis of acute lymphoblastic leukaemia (ALL) in a 10-year-old girl, routine coagulation screening including von Willebrand factor antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo) and factor VIIIC (FVIII:C) detected no pathological findings. After the first HR2′ element of the high-risk group of the ALL-BFM 2000 protocol, the patient demonstrated extensive bleeding symptoms and acquired von Willebrand syndrome was diagnosed. VWF:Ag (13%), VWF:RCo (13%) and FVIII:C (27%) were decreased. Multimer analysis showed a loss of large multimers and a loss in triplet structures. The observed pattern was thought to be typical for monoclonal IgG gammopathy; however, in this case, unexpectedly, biclonal IgM gammopathy (κ and λ) was detected. After treatment with intravenous immunoglobulin over 5 days, coagulation factors increased to normal levels. Although this effect was assumed to be at best only temporary, especially in a case of IgM gammopathy, no further bleeding symptoms have been observed.

Trial registration number:

M208

Background

Idiopathic portal hypertension (IPH) is a disorder of unknown etiology and is characterized clinically by portal hypertension, splenomegaly, and hypersplenism accompanied by pancytopenia. This study evaluates the pathogenic concept of the disease by a systematic review of the literature and illustrates novel pathologic and laboratory findings.

Case Presentation

We report the first case of uncontrolled splenic hyperperfusion and enlargement with subsequent hypersplenism leading to life-threatening complications of IPH in infancy and emergent splenectomy.

Conclusions

Our results suggest that splenic NO and VCAM-1, rather than ET-1, have a significant impact on the development of IPH, even at a very early stage of disease. The success of surgical interventions targeting the splenic hyperperfusion suggests that the primary defect in the regulation of splenic blood flow seems to be crucial for the development of IPH. Thus, beside other treatment options splenectomy needs to be considered as a prime therapeutic option for IPH.

Objective

Fever of unknown origin (FUO) in children presents a diagnostic challenge. Differential diagnosis includes Systemic Onset Juvenile Idiopathic Arthritis (SJIA), an auto-inflammatory syndrome associated with activation of phagocytic cells which at presentation is difficult to differentiate from severe systemic infections. In this study, we investigated whether serum concentrations of the phagocytic pro-inflammatory protein S100A12 may help in the decision between antibiotic or immunosuppressive therapy in patients with FUO.

Methods

Serum samples were obtained from 45 healthy controls and 240 patients: 60 had SJIA, 17 Familial Mediterranean Fever (FMF), 18 Neonatal-Onset Multisystem Inflammatory Disease (NOMID), 17 Muckle Wells Syndrome (MWS), 40 Acute Lymphoblastic Leukemia (ALL), 5 Acute Myeloblastic Leukemia (AML), and 83 systemic infections. All samples were collected at presentation before initiation of anytreatment, and were analyzed for S100A12 by ELISA.

Results

In SJIA patients the mean S100A12 serum level was 7,190 ng/ml (95% confidence interval ±2,690), in FMF 6,720 ng/ml (±4,960), in NOMID 720 ng/ml (±450), in MWS 150 ng/ml (±60), in infections 470 ng/ml (±160), in ALL 130 ng/ml (±80), and in AML 45 (±60) compared to 50 ng/ml (±10) in healthy controls. Sensitivity and specificity of S100A12 to distinguish SJIA from infections were 66% and 94% respectively.

Conclusions

S100A12, a marker of granulocyte activation, is highly overexpressed in SJIA and FMF, which may point to so far unknown common inflammatory mechanisms in these diseases. The measurement of S100A12 serum levels may provide a valuable diagnostic tool in the evaluation of FUO.

Abstract

Epigenetic changes, including DNA methylation, are a common finding in cancer. In lung cancers methylation of cytosine residues may affect tumor initiation and progression in several ways, including the silencing of tumor suppressor genes through promoter methylation and by providing the targets for adduct formation of polycyclic aromatic hydrocarbons present in combustion products of cigarette smoke. Although the importance of aberrant DNA methylation is well established, the extent of DNA methylation in lung cancers has never been determined. Restriction landmark genomic scanning (RLGS) is a highly reproducible two-dimensional gel electrophoresis that allows the determination of the methylation status of up to 2000 promoter sequences in a single gel. We selected 1184 CpG islands for RLGS analysis and determined their methylation status in 16 primary non-small cell lung cancers. Some tumors did not show methylation whereas others showed up to 5.3% methylation in all CpG islands of the profile. Cloning of 21 methylated loci identified 11 genes and 6 ESTs. We demonstrate that methylation is part of the silencing process of BMP3B in primary tumors and lung cancer cell lines.