[Show abstract][Hide abstract] ABSTRACT: Use of PET/MR in children has not previously been reported, to the best of our knowledge. Children with systemic malignancies may benefit from the reduced radiation exposure offered by PET/MR. We report our initial experience with PET/MR hybrid imaging and our current established sequence protocol after 21 PET/MR studies in 15 children with multifocal malignant diseases. The effective dose of a PET/MR scan was only about 20% that of the equivalent PET/CT examination. Simultaneous acquisition of PET and MR data combines the advantages of the two previously separate modalities. Furthermore, the technique also enables whole-body diffusion-weighted imaging (DWI) and statements to be made about the biological cellularity and nuclear/cytoplasmic ratio of tumours. Combined PET/MR saves time and resources. One disadvantage of PET/MR is that in order to have an effect, a significantly longer examination time is needed than with PET/CT. In our initial experience, PET/MR has turned out to be an unexpectedly stable and reliable hybrid imaging modality, which generates a complementary diagnostic study of great additional value.
[Show abstract][Hide abstract] ABSTRACT: Purely intracranial soft tissue sarcomas (ISTS) are very rare among children. A retrospective database analysis of the Cooperative Weichteilsarkom Studiengruppe (CWS) and brain tumor (HIT) registries was conducted to describe treatment and long-term outcome of children and adolescents with ISTS. Nineteen patients from Germany, Austria and Switzerland were reported between 1988 and 2009. Median age at diagnosis was 9.7 years (range, 0.5-17.8). Central pathological review was performed in 17 patients. Eleven patients underwent a total and five a subtotal tumor resection. A biopsy was done in one patient. In two patients no data concerning extent of initial resection was available. Radiotherapy was performed in 15 patients (first-line, n = 11; following progression, n = 4). All but one patient received chemotherapy (first-line, n = 7, following progression, n = 5; first-line and following progression, n = 6). With a median follow-up of 5.8 years (range, 0.6-19.8) ten patients were alive in either first or second complete remission. Seven patients died due to relapse or progression and two were alive with progressive disease. Estimated progression-free and overall survival at 5 years were 47 % (±12 %) and 74 % (±10 %), respectively. About 50 % of patients with ISTS remain relapse-free after 5 years. Multimodality treatment including complete tumor resection and radio-/chemotherapy is required to achieve sustained tumor control in patients with ISTS. Early initiation of postoperative non-surgical treatment seems to be important to prevent recurrence. Due to the intracranial localization local therapy should follow the recommendations used in brain tumors rather than in soft tissue sarcomas, whereas chemotherapy should be guided by histological subtype.
Journal of Neuro-Oncology 12/2012; 111(3). DOI:10.1007/s11060-012-1020-3 · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and its prognosis has considerably improved over the past 2 decades due to new therapeutic approaches. In some cases, however, it can develop very rapidly and cause possibly fatal complications. We report on the case of an 11-year-old boy with ALL, who rapidly developed severe lactic acidosis and abdominal compartment syndrome. He died of multiorgan failure only 5 days after diagnosis of ALL had been established. Autopsy revealed systemic leukemic infiltrations. We suppose that the mass of tumor cells induced a cascade of metabolic and endocrine reactions, which not only triggered the rapid progression of the disease but were also accountable for the lack of response to treatment. The pathophysiology of abdominal compartment syndrome as a rare and in our case ultimately fatal complication of ALL is described.
[Show abstract][Hide abstract] ABSTRACT: The standard treatment protocol for acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) in childhood includes intravenous therapy with asparaginase (Asp), which may cause hyperammonemia. In this study, all patients receiving asparaginase therapy at the Hospital for Children and Adolescents of the University of Leipzig between January 2002 and December 2007 were reviewed for the occurrence of hyperammonemia. Fifty-four patients were identified (22 girls, 32 boys; mean age 5.8 years). Blood ammonia concentrations were determined in 4 patients due to suspicious clinical signs. All showed hyperammonemia with NH(3) concentrations between 260 and 700 μmol/L. They received specific acute detoxification therapy consisting in protein restriction, administration of benzoic acid, glucose/insulin. All 4 recovered completely. All patients receiving therapeutic regimes that include asparaginase (Asp) should be monitored for the development of transient hyperammonemia.
[Show abstract][Hide abstract] ABSTRACT: Primary immune thrombocytopenia (ITP) in children is usually self-limiting and harmless but can, rarely, result in life-threatening complications. The case of an 11-year-old girl with ITP is presented who developed recurrent intracranial hemorrhages followed by cerebral infarctions. The clinical course was complicated by a graft-versus-host disease involving several organs. Treatment was performed according to the current international consensus report of 2010 with glucocorticoids, immunoglobulin G, anti-D-immunoglobulin and additionally embolisation of the splenic artery. The girl survived. Reliable predictors, preventive measures for life-threatening complications in ITP and more information about the effectiveness and side-effects of the recommended treatment are urgently needed.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to evaluate positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients.
FDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik.
FDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS.
FDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.
European Journal of Nuclear Medicine 10/2010; 37(10):1842-53. DOI:10.1007/s00259-010-1484-3 · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Log-term prognosis of children suffering from high-risk neuroblastomas is characterized by a shortened event-free survival, especially if metastases remain after chemotherapy. We report the case of a 3-year-old boy afflicted with a stage 4 neuroblastoma and persistent residual lymph node metastases despite the administration of a various number of treatment modalities. The insertion of a MIBG (metaiodobenzylguanidine) single-photon emission computed tomography (SPECT)-CT and radio-guided surgery implementing a hand held gamma probe finally allowed the exact localization and resection of the suspected lymphatic tissue. As a consequence, the child has been under event-free remission for 20 months. Because study-based knowledge is missing due to the small number of affected patients, individual case reports are helpful to improve future treatment strategies.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the pharmacokinetics and safety of voriconazole after intravenous (i.v.) administration in immunocompromised children (2 to 11 years old) and adults (20 to 60 years old) who required treatment for the prevention or therapy of systemic fungal infections. Nine pediatric patients were treated with a dose of 7 mg/kg i.v. every 12 h for a period of 10 days. Three children and 12 adults received two loading doses of 6 mg/kg i.v. every 12 h, followed by a maintenance dose of 5 mg/kg (children) or 4 mg/kg (adults) twice a day during the entire study period. Trough voriconazole levels in blood over 10 days of therapy and regular voriconazole levels in blood for up to 12 h postdose on day 3 were examined. Wide intra- and interindividual variations in plasma voriconazole levels were noted in each dose group and were most pronounced in the children receiving the 7-mg/kg dose. Five (56%) of them frequently had trough voriconazole levels in plasma below 1 microg/ml or above 6 microg/ml. The recommended dose of 7 mg/kg i.v. in children provides exposure (area under the concentration-time curve) comparable to that observed in adults receiving 4 mg/kg i.v. The children had significantly higher C(max) values; other pharmacokinetic parameters were not significantly different from those of adults. Voriconazole exhibits nonlinear pharmacokinetics in the majority of children. Voriconazole therapy was safe and well tolerated in pediatric and adult patients. The European Medicines Agency-approved i.v. dose of 7 mg/kg can be recommended for children aged 2 to <12 years.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the reliability and practical use of saliva for therapeutic drug monitoring of the antifungal agent voriconazole in immunocompromised patients, a paired-sample study was conducted. Plasma and saliva trough levels were measured in seven children and nine adults who required treatment for the prevention or therapy of systemic fungal infections. The pediatric patients received a voriconazole dosage of 7 mg/kg intravenously twice a day. Adults were treated with two loading doses of 6 mg/kg intravenously followed by a maintenance dose of 4 mg/kg intravenously twice a day. Based on 104 paired plasma/saliva specimens, we found a significant correlation between the voriconazole concentrations in blood and saliva (r > 0.95). The median saliva/plasma voriconazole concentration ratio was 0.34 in children and 0.40 in adults. Intra- and interpatient variability in the saliva/plasma ratios were 22% and 23% in children and 16% and 24% in adults, respectively. Thirty-three percent of plasma trough levels were below 1.0 microg/mL or above 6.0 microg/mL and occurred in six pediatric and four adult patients. Monitoring of salivary concentrations proved to be a realistic alternative in patients when blood drawing is difficult. Especially in therapeutic drug monitoring, an easier sample collection being noninvasive and painless is more acceptable to patients, particularly children.
Therapeutic drug monitoring 03/2010; 32(2):194-9. DOI:10.1097/FTD.0b013e3181cff20d · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary liver tumors in children are rare with malignant hepatoblastoma being the most common neoplasm. In this report, we describe the diagnosis and clinical management of a large liver tumor in a 3-year-old child that displayed the features of both, conventional hepatoblastoma and malignant teratoma. Pathological assessment on a pre-operative bioptical specimen showed an immature teratoid tumor with no area of hepatoblastic differentiation present. Histological and immunhistological examination of the resected tumor specimen additionally showed tumor areas of very different differentiation pattern intermixed with each other, namely areas of hepatoblastoma-typical and neuroblastoma-like morphology as well as areas of rhadomyosarcomatous differentiation.
After chemotherapy the tumor size increased and an extended right hemihepatectomy was performed. Post-operatively, the general condition of the child improved and adjuvant chemotherapy was started two weeks later. 36 months after initial diagnosis the patient is healthy, in good general condition, and without any sign of residual tumor disease.
Overall, we describe the diagnosis and clinical management of a large liver tumor in a 3-year-old child that displayed the features of both, conventional hepatoblastoma and malignant teratoma and was designated as mixed hepatoblastoma and teratoma. Though mesenchymal tumor portions can occur within hepatoblastomas, most commonly osteoid or chondroid, our case is different as it presents a large spectrum of mesenchymal and epithelial differentiation pattern in most of the lesion.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to compare diagnostic accuracy of whole-body (WB) MRI to a combined reference standard of conventional cross-sectional imaging methods and FDG-PET in the detection of malignant disease spread in children.
24 children (age between 5 and 18 years) with malignant diseases (mainly Hodgkin's lymphoma and different types of sarcoma) initially examined with conventional cross-sectional imaging methods (ultrasound, computed tomography, or magnetic resonance imaging) were examined prospectively with whole-body MRI (1.5T) and FDG-PET. Studies were read by two nuclear medicine physicians (FDG-PET) and two radiologists (WB-MRI) independently in a blinded manner and each study type was evaluated in consensus. The reference standard was defined as pathological lesions detected in the same location both in FDG-PET and another conventional cross-sectional imaging method.
Overall 190 lesions were detected by WB-MRI and 155 lesion were found by FDG-PET. 106 lesions fulfilled the criteria of the reference standard (42 osseous and 64 extraosseous lesions) from which 102 were detected by WB-MRI (sensitivity of 96%). All bone lesions were detected and extra-skeletal lesions were identified with a sensitivity of 93.8%. Overall 88 lesions detected by WB-MRI were not part of the reference standard from which 33 were lesions of the peripheral skeleton not imaged by conventional cross-sectional imaging studies. 4 lesions of the reference standard were not identified by WB-MRI which were all lymph nodes.
WB-MRI is a radiation free imaging technique with high sensitivity for the detection of malignant disease spread in particular beneficial for children. In patients with suspected bone lesions it should be considered for initial disease evaluation prior to specific and regional imaging methods to reduce the overall number of imaging examinations and radiation exposure.
European journal of radiology 04/2009; 74(1):256-61. DOI:10.1016/j.ejrad.2009.01.037 · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Schlüsselwörter Appendixkarzinoid, neuroendokrine Tumo-ren, MEN 1, Appendektomie, Karzinoidsyn-drom, Chromogranin A (CgA), 5-Hydroxyin-dolessigsäure (5 HIAA), DOTATOC-PET Zusammenfassung Das Appendixkarzinoid (AC) ist der häufigste neuroendokrine Tumor und wird als Zufallsbe-fund bei 0,3 % aller Appendektomien gefun-den. Die Prognose ist sehr gut, die 5-Jahres-Überlebensrate beträgt 99 %. Das AC kann im Rahmen von MEN 1 (Wermer-Syndrom) auf-treten. Bei einer Größe des AC unter 2 cm tre-ten äußerst selten Metastasen auf. Der Thera-pieansatz ist in der Regel die kurative Ap-pendektomie bei einem Tumorsitz im Apex und einer Tumorgröße kleiner 2 cm. Bei einem Tumor größer 2 cm oder einem Tumorsitz an der Appendix-Basis ist eine Hemikolektomie mit Lymphknotenresektion erforderlich. Der beste diagnostische und therapeutische Mar-ker im Serum ist Chromogranin A (CgA) und im 24-Stunden-Urin 5 Hydroxyindolessigsäu-re (5-HIAA). Patienten sollten in die interdis-ziplinäre, multizentrische Studie GPOH-MET 97 (GPOH: Gesellschaft für Pädiatrische On-kologie und Hämatologie, MET: maligne endo-krine Tumoren im Kindes-und Jugendalter) eingeschlossen und entsprechend den aktuel-len Richtlinien nachbetreut werden. Hierbei findet insbesondere das DOTATOC-PET An-wendung. Korrespondenzadresse: Miriam Wilhelm Universitätsklinik und Poliklinik für Kinder und Jugend-liche Leipzig Abteilung für Kinder-Hämatologie, -Onkologie und -Hä-mostaseologie Liebigstr. 20a, 04103 Leipzig Tel.: 03 41/97 26–114, Fax: –099 Miriam.Wilhelm@medizin.uni-leipzig.de
[Show abstract][Hide abstract] ABSTRACT: Each year approximately 1,800 children are diagnosed with cancer in Germany. The orbit is a very rare manifestation site for malignancies in childhood. The most common primary malignant orbital tumour is the rhabdomyosarcoma. Secondary orbital tumours are generally metastases of neuroblastomas or haematological diseases. The five-year survival rate of children with rhabdomyosarcomas has increased to 90 % in the past 30 years due to innovations in radiation and chemotherapy.
A paediatric oncological interdisciplinary approach is taken in the diagnostics and therapy for these rare tumours and is based on therapy optimisation studies that include polychemotherapy, radiation therapy, and surgical treatment.
We discuss the current multimodal therapy strategies and results, as well as the role of the ophthalmologist, in the medical care of young patients with malignant orbital tumours, with examples of individual courses of rhabdomyosarcoma, non-Hodgkin's lymphoma, and metastases.
Orbital rhabdomyosarcoma is one of the few life-threatening diseases often first seen by an ophthalmologist. The ophthalmologist's prompt diagnosis and initiation of therapy therefore strongly influences the patient's chance of survival. The role of the ophthalmologist in the medical care of children with orbital malignancies includes a timely clinical diagnosis with histological confirmation, close monitoring of visual functions, the management of ocular complications, as well as long-term follow-up care to detect later therapeutic side effects and/or complications. The treatment of children with suspected tumours is best performed in paediatric oncological centres with access to all necessary specialties in order to ensure rapid diagnosis and therapy.
[Show abstract][Hide abstract] ABSTRACT: We report 4-year-old girl who was diagnosed with adrenocortical carcinoma when she was 2 years old. At the time of diagnosis there were no metastases, but 6 months later multiple liver metastases appeared. Following intensive chemotherapy the metastases resolved completely. Multifocal lesions were detected in the liver by US 16 months later. Their morphology on US and MRI differed from the previous metastases. Histopathological examination confirmed focal nodular hyperplasia. We discuss the origin and the uncommon appearance of multifocal nodular hyperplasia in hormone-active tumours such as adrenocortical carcinoma in children.
[Show abstract][Hide abstract] ABSTRACT: Meningeal tumors are extremely rare in children and are diagnostically as well as therapeutically challenging. Among the least common types of malignancies in childhood is malignant melanoma, counting for less than 1% of pediatric tumors. Due to the rarity and the wide spectrum of appearance, initial clinical features may be misleading. A 3-year-old boy was referred to our hospital with symptoms of hyperventilation, dyspnoea, tachycardia, respiratory alkalosis, inarticulate speech, and fatigue. Measurement of pH in cerebrospinal fluid (CSF) yielded central lactic acidosis despite alkalosis in peripheral blood. Diagnostic imaging procedures as well as histology and immunohistochemistry revealed the diagnosis of a malignant meningeal melanoma. We hypothesize that central lactate production of the tumor nests might have induced central acidification, thus inducing hyperventilation by stimulation of central chemoreceptors. This case is a model example of the key role of central pH as an inducer/suppressor of ventilation in humans and illustrates the critical importance of central pH for regulating both ventilation and acid-base homeostasis. Thus, pH of CSF should be measured whenever a malignant brain tumor is suspected.
European Journal of Pediatrics 05/2008; 167(4):483-5. DOI:10.1007/s00431-007-0507-y · 1.98 Impact Factor