N. Graf

In order to find out whether sialic acid (SA) is suitable as a tumor marker this compound was determined in the sera of 48 healthy and of 168 sick children. In healthy children under six months of age lower concentrations of SA were found (x = 41 +/- 5 mg/dl) than in subjects aged six months to 18 years (x = 68 +/- 8 mg/dl). Inflammatory diseases of various etiologies lead to a significant increase in both age groups (x = 93 +/- 28 mg/dl), the same could be observed in subjects up to 14 days after surgery. In children with malignant disorders the concentration of SA was significantly higher (x = 83 +/- 27 mg/dl) than in the healthy subjects, but not higher than in patients with inflammatory diseases. We conclude that SA might play a role in the follow up protocol of patients with malignant tumors.

The European project p-medicine creates an information technology infrastructure that facilitates the development from current medical practice to personalised medicine. The main access point to this infrastructure is the p-medicine portal that provides clinicians, patients, and researchers a platform to collaborate, share data and expertise, and use tools and services to improve personalised treatments of patients. In this document, we describe the community-based structure of the p-medicine portal and provide information about the p-medicine security framework implemented in the portal. Finally, we show the user interface and describe the p-medicine tools and services integrated in the portal.

Chemotherapy planning in pediatric oncology is complex and time-consuming. The correctness of the calculation according to state-of-the-art research is crucial for curing the child. Computer-assistance can be of great value. The objective of our research was to work out a meta-model of chemotherapy planning based on the Unified Modeling Language (UML). The meta-model is used for the development of an application system which serves as a knowledge-acquisition tool for chemotherapy protocols in pediatric oncology as well as for providing protocol-based care. We applied evolutionary prototyping, software reengineering techniques and grounded theory, a qualitative method in social research. We repeated the following steps several times over the years: Based on a requirements analysis (i) a meta-model was developed or adapted, respectively (ii). The meta-model served as a basis for implementing evolutionary prototypes (iii). Further requirements were identified (i) from clinical use of t...

Midazolam/ketamine sedation has been used successfully in children undergoing painful invasive procedures. The authors prospectively assessed inter- and intra-individual variability in ketamine dosage for sedation in repetitive invasive procedures in children with malignancies. A total of 92 invasive procedures (58 lumbar punctures, 34 bone marrow biopsies; range: 2-9 procedures/patient) were performed on 25 children (median age: 12 years). Intravenous sedation consisted of 0.1 mg midazolam/kg and 0.5-1.0 mg ketamine/kg. Incremental dosages of ketamine (0.33 mg/kg) were given if necessary to achieve or maintain deep sedation. Primary outcome measure was the inter- and intraindividual ketamine dosage required to achieve adequate sedation; secondary outcome measures were the number of procedures with adequate sedation (Ramsay score of > 4), the number of adverse side effects, and the need for therapeutic interventions. All 92 invasive procedures were completed with satisfactory sedation levels in 88 procedures (95.7%). There was a great inter- and intraindividual variability in ketamine dosage required to achieve or maintain adequate sedation. In 12% of procedures side effects were seen, which required no or only minor interventions. Due to great inter- and intraindividual differences, ketamine dosage should be titrated toward the desired level of sedation. Thus, ketamine can be adjusted to the individual's need while achieving adequate sedation.

A major problem for children receiving Wilms tumor (WT) chemotherapy is hepatotoxicity, which may even be life-threatening. Dactinomycin (AMD) has been shown to be an important factor, as has abdominal irradiation. In the nephroblastoma trial and study SIOP-9 (SIOP-9) two different regimens for the application of AMD were used (standard dose over 3-5 days vs. double dose on a single day). In children at increased risk for local relapse, postoperative abdominal irradiation was given. We analyzed the influence of AMD and radiotherapy on the development of hepatotoxicity in 481 children treated in centers of the German Paediatric Oncology and Haematology Society (GPOH). A special questionaire was sent out for all patients with reduced treatment or delay of more than 1 week because of hepatotoxicity. Because SIOP and the National Wilms Tumor Study (NWTS) used different criteria to asses hepatotoxicity,we applied both definitions. All 72 cases of mild or severe hepatotoxicity occurred during treatment with AMD over 3-5 days with the standard dose (9.4-22.5 microgram/kg/week) compared to none in the group receiving a double dose on 1 day (3.75-8 microgram/kg/week; P < 0.001). Irradiation of the right abdomen, including parts of the liver, enhanced liver toxicity significantly, with a relative risk (RR) of 2.6 (P < 0.003). Preoperative liver toxicity was more frequent in smaller children (P = 0.02) and especially if no dose reduction was done in children with body weight of less than 12 kg (RR 5.3, P = 0.01). If severe liver toxicity was defined according to NWTS criteria, 10% of all treated patients were affected compared to 4.8% if McDonald's criteria for hepatic veno-occlusive disease (VOD) were applied. To diminish the hepatotoxicity of WT treatment, AMD dose intensity should be reduced (below 10 microgram/kg per week), especially in smaller children or when the liver is irradiated.

The authors prospectively assessed intraindividual variability in propofol dosage for induction of sedation in repetitive procedures in children with malignancies. A total of 80 procedures were performed in 24 children. Primary outcome measure was the intraindividual propofol dose required to achieve adequate sedation. Intraindividual variability in propofol dosage required to achieve adequate sedation was 0.0-2.2 mg.kg-1. Twenty-five percent of the patients had a dose range of 0.0-0.5 mg x kg-1; 37.5%, >0.5-1.0 mg x kg-1; and 37.5% >1.0-2.2 mg x kg-1. Due to remarkable intraindividual differences, propofol dosage should be titrated toward the desired level of sedation.

Idarubicin (IDR) is one of the most effective, but also toxic drugs in the treatment of AML. The standard dose used in children and adults is 8-12 mg/m2 during induction. To improve outcome, we increased the IDR dose from 12 mg/m2 (standard dose in study AML-BFM 93), applied over three days during induction therapy (AIE = Ara-C, Idarubicin, Etoposide) to 14 mg/m2 in a pilot study including 17 patients (16 with de novo AML, one with secondary AML). Outcome and toxicities were compared with the other patients of study AML-BFM 93, treated with 3 x 12 mg/m2 IDR or 6 x 30 mg/m2 daunorubicin (DNR). Patients of the pilot study achieved a good blast cell reduction in the bone marrow on day 15, a high CR rate of 94% and a low relapse rate (3/17 pts.), however, not significantly different to the IDR (12 mg/m2) group. Hematological toxicity was high, median duration until neutrophil recovery > 500/microliter was 25.0 (12-66) days, and similar to the IDR (12 mg/m2) and DNR groups. Duration of thrombocytopenia (time to > 20,000/microliter) was 21 (10-66) days in the pilot study compared to 19 (7-26) days in DNR patients (p = 0.08). Four of 17 pilot patients presented with severe WHO grades 3/4 of mucositis during induction. One patient died in long-lasting aplasia after the 3rd treatment block. Results of this pilot study show that the IDR 14 mg/m2 regimen was effective but also toxic. According to our results which, however, are based on small patient numbers, an improved outcome compared to the IDR 12 mg/m2 regimen seems to be unlikely, therefore the possibly increased toxicity might not be acceptable.

In the context of more than 20 therapy optimizing clinical trials in pediatric oncology an extensive documentation with a big number of case report forms was developed in the last 20 to 25 years. Across these trials same information is partially captured in different terminological ways, by which documentation about patients in the clinics is made more difficult. Terminology of therapy optimizing clinical trials of German Society for Pediatric Oncology and Hematology (GPOH) is standardized by a central "standards committee". As a first result the basic data set of GPOH could be revised and made available in internet via http://www.dospo.uni-hd.de. A basis of a unique documentation language in pediatric oncology is available for German speaking regions.

ABSTRACT Solid-pseudopapillary tumor of the pancreas constitutes a very rare benign or low-grade malignant lesion occurring most commonly in young women and girls. It was first described by Frantz. Local infiltration, distant metastasis and recurrence are very rare. Until today, the histogenetic origin of the tumor cell remains to be elucidated. In 1996, solid-pseudopapillary tumor of the pancreas was introduced in the World Health Organization (WHO) classification of tumors of the exocrine pancreas. Our case report--like a recently published work by Lange et al.--intends to underline the significance of solid-pseudopapillary tumor in the differential diagnosis of a pancreatic mass.

The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients. Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remission (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory. Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P < .001) and had larger tumor volumes compared with nonmetastatic patients (P < .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P < .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P < .001). Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome.

Blasts isolated from bone marrow aspirates or blood samples of patients with acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) were compared for uptake of methotrexate (MTX) and formation of MTX polyglutamates (MTX-Glu(n)). Red blood cells (RBC) from the same patient samples were also analyzed. Blasts were isolated by standard density centrifugation. RBC were prepared from the pellet of the same centrifugation. MTX-Glu(n) were analyzed by means of HPLC and radiochemical quantification. In lymphoblasts isolated from blood, the distribution patterns of MTX-Glu(n) were the same as in bone marrow lymphoblasts, but the total amount of MTX-Glu(n) accumulated in blood lymphoblasts was reduced by 41% 51% when compared to the same number of bone marrow lymphoblasts of the same patient. RBC accumulated MTX but no formation of MTX-Glu(n) occurred. The determination of MTX and MTX-Glu(n) in lymphoblasts isolated from blood samples of patients with common ALL provides qualitative information on the capacity of the blasts to form MTX-Glu(n) since distribution patterns of MTX and MTX-Glu(n) parallel that of bone marrow lymphoblasts. The amounts of MTX-Glu(n) accumulated, however, were much lower in blood lymphoblasts. Blood lymphoblasts are therefore not useful for a quantitative analysis of MTX-Glu(n). The contribution of RBC to MTX and MTX-Glu(n) in vitro is only marginal and residual RBC in lymphoblast preparations from bone marrow can therefore be ignored.

To determine the prognosis of children with stage II and III of low or intermediate risk histology (SIOP classification) in unilateral localised Wilms tumour (WT) after neoadjuvant chemotherapy according to the trial and study of the International Society of Paediatric Oncology, SIOP 93-01. Patients with unilateral localised WT and stage II or III with low (LR) or intermediate risk (IR) histology between 6 months and 18 years of age, were selected from the total sample of patients registered in the SIOP 93-01 study between June 1993 and December 2001. All patients received 4 weeks of actinomycin-D/vincristine before surgery. Postoperative chemotherapy consisted of actinomycin-D, vincristine and epirubicin/doxorubicin for 27 weeks. Flank or whole abdomen irradiation was given for stage III. Event-free survival (EFS) and overall survival (OS) were analysed for various subgroups. Of 1476 registered patients 594 (40%) met the inclusion criteria for this analysis. Four hundred and two (67%) had stage II disease and 563 (95%) had intermediate risk histology. Median tumour volume was 439 ml at diagnosis and 163 ml after preoperative chemotherapy. With a median follow-up of 8 years, 5-year EFS was 90% (95% confidence interval [95% CI]: 87-92%) and OS 95% (95% CI: 93-97%). Patients with stage III, blastemal type histology and a large volume at surgery had a worse outcome. Treatment for stage II and III LR or IR WT is successful in a neoadjuvant setting as advised by the SIOP. Stage, tumour volume and blastemal type histology are the most important prognostic factors.

During a period of 9 years we used the pediatric BFM-NHL protocol for treatment of 14 adult patients with Burkitt's lymphoma or L3 acute lymphoblastic leukemia. Ten of 14 patients obtained a complete remission including 5/8 with stage-IV disease or B-ALL. After a median follow-up of 55 months none of these ten patients relapsed. The projected survival after 8 years is 71%. Toxicity was moderate, with one early death; a tumor lysis syndrome occurred in four patients. From our experience we conclude that the BFM-NHL protocol is very effective in adult patients, with a high cure rate and acceptable toxicity, even in advanced stages of disease.