Uta Bierbach

Ethanol-lock technique in the treatment of bloodstream infections in pediatric oncology patients with broviac catheter.

Purpose: To assess the ethanol‐lock technique as a means of treating central venous line infections. Bloodstream infections in patients with tunneled central venous catheters can lead to removal of the lines. Methods: Twenty‐eight children and adolescents aged 2 to 18 years, with different types of cancer, had Broviac catheters and presented with positive blood culture and clinical signs of infection between January 2000 and December 2001. The ethanol‐lock technique was performed 24 times in 18 patients in addition to empiric (initially) and specific (after antibiogram) intravenous antibiotic treatment. In another 15 cases, 13 children were treated with systemic antibiotics alone. Results: Sixty‐seven percent of the patients treated with ethanol locks had no infectious relapse of any kind within 4 weeks of treatment or during subsequent aplasia, compared with 47% treated with systemic antibiotics alone. In one boy the catheter infection could not be cleared with systemic antibiotics alone, but after one course of ethanol locks no more blood culture‐positive infectious episodes were observed. No severe clinical side effects of ethanol flush were observed. Mild symptoms that occurred were tiredness, headaches, dizziness, nausea, and light‐headedness. Conclusions: The ethanol‐lock technique appears to be a safe, well tolerated, and effective way to treat central venous line infections, even in small children. A prospective randomized study should be designed to compare antibiotic‐lock, ethanol‐lock technique, and systemic antibiotics alone in the treatment of device‐associated bloodstream infection.

PET/MR in children. Initial clinical experience in paediatric oncology using an integrated PET/MR scanner

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.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

PurposeThe objective of this study was to evaluate positron emission tomography (PET) using 18F-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.MethodsFDG 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.ResultsFDG 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.ConclusionFDG 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.

Transient Hyperammonemia Due to L -Asparaginase Therapy in Children with Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

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 NH3 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.

Does the Expression of c-kit (CD117) in Neuroendocrine Tumors Represent a Target for Therapy?

Abstract:  Neuroendocrine tumors are very heterogeneous, develop from a variety of tissues, and can be difficult to diagnose. Without the clinical manifestation of metastases, it is often difficult to characterize them as malignant. Even so‐called completely (R0) resected tumors can spread clinically visible metastases within a few months after initial surgery. Treatment options for neuroendocrine tumors including pheochromocytoma are limited. Molecular targeted therapies using tyrosine kinase inhibitors might prove to be helpful in patients with these tumors. In an immunohistochemical study, we examined KIT in 26 pheochromocytomas, 8 of which were malignant (3 adrenal pheochromocytomas, 5 paragangliomas). KIT expression was found in one of these 8 malignant tumors. This 2.5‐cm‐large adrenal pheochromocytoma originated from a woman with neurofibromatosis type 1 and spread into spine, skull, and lung. KIT expression could be demonstrated in 5% of tumor cells. On the basis of KIT expression immunohistochemically, we treated patients with neuroendocrine (i.e., medullary thyroid cancer) and other tumors with imatinib 400 mg per day, but without efficacy after 2 months of therapy. Similar results were shown by other investigators. Therefore, monotherapy with imatinib may not be efficacious in patients with neuroendocrine tumors that express KIT. Tyrosine kinase inhibitors such as sorafenib that targets several receptors in addition to KIT may be more efficacious in treating patients with neuroendocrine tumors.

Mixed hepatoblastoma and teratoma of the liver in a 3-year-old child: a unique combination and clinical challenge

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.

Central lactic acidosis, hyperventilation, and respiratory alkalosis: leading clinical features in a 3-year-old boy with malignant meningeal melanoma

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.

Recurrent polytopic chromaffin paragangliomas in a 9-year-old boy resulting from a novel germline mutation in the von Hippel-Lindau gene.

Pheochromocytomas are frequently associated with inherited cancer syndromes such as von Hippel-Lindau disease (VHL). Retinal angioma and hemangioblastomas of the central nervous system are hallmarks of VHL, but its clinical variety is remarkably broad. Pheochromocytomas as the sole or first manifestation of VHL are rare but have been observed. In this case report, the authors describe an unusual case of initial collapse, seizures, and hypertensive crisis in a child who later was found to have multiple extraadrenal pheochromocytomas. Molecular diagnostics revealed a novel point mutation in the VHL gene (VHL nt. 406 T-->G). Only 7 months after the first lesions had been removed, a new paraganglioma developed in the contralateral periadrenal region. When encountering pheochromocytomas in children, the clinician should be aware that an associated tumor syndrome might be present, and appropriate molecular screening should be initiated. Molecular genetics aid in the clinical decision-making and clinical management of individual patients with pheochromocytoma.

Fulminant and fatal course of acute lymphoblastic leukemia due to lactic acidosis and suspected abdominal compartment syndrome.

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.

Scapula as an uncommon site of Langerhans cell histiocytosis in an infant

least 13 complementation groups have been distinguished: A, B, C, D1, D2, E, F, G, I, J, L, M and N. Complementation groups in 13 reported FA patients with VACTERL phenotype were also analyzed and all patients were assigned to complementation groups A, C, D1, E, F, and G. The small number of VACTERL patients makes determination of the specific complementation groups of FA difficult. Although the etiology and pathogenesis of VACTERL association are not known, an adriamycin rat model has been used as a reliable model for the VACTERL association. Adriamycin intercalates with DNA, resulting in inhibition of DNA and RNA syntheses, DNA fragmentation, and altered DNA repair. Recent evidence suggests that FA proteins function as signal transducers and DNA-processing molecules in a DNA damage response network. The mechanism by which an FA gene mutation leads to a multitude of congenital anomalies observed in FA is, however, unknown. We speculated that defects in DNA damage responses play a part in both embryogenesis and hematopoiesis. In conclusion, the curative treatment for FA is allogeneic stem cell transplantation, which is more successful in younger patients with a smaller cumulative volume of transfused blood prior to transplantation. In patients with congenital malformations a timely diagnosis of FA can lead to appropriate genetic counseling and therapy. References