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Background: Over the course of terminal cancer towards the end-of-life, children may experience symptoms that lead to distressing critical situations (CS) for the child and caregivers., Methods: We analysed the records of 133 children cared for by our paediatric palliative care team (PPCT) from 01/98-12/09. A CS was defined as deterioration of a condition caused by a symptom, which was life-threatening or acutely scaring the patient (pt) or caregivers., Results: The majority of pts who died sustained no CS. In 38 (28.6%) pts 45 CS occurred. These accumulated towards the end-of-life (62.2% within the last week). About two-thirds were anticipated. There was no clustering of CS during the night/weekend. Leading symptoms were neurological. In 4 CS a pre-hospital emergency physician was alerted. 5 pts were readmitted to hospital. Most CS (88.9%) could be controlled in the home setting., Discussion: Despite anticipation, a relevant number of pts developed CS, which needed either additional medical intervention or other support by the PPCT. Considering the distressing and suffering character of status epilepticus and dyspnoea, it is important to thoroughly address these conditions in palliative care., Conclusion: Advanced planning, close contact, good communication, detailed parental information, and a 24-h on-call service can reduce CS in children with terminal cancer. CS are mainly manageable within the home setting. Treatment of CS should focus on the child's symptoms and wishes, and the needs of the whole family., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: In Germany, 500 children die of malignancies per year. Many families wish to be cared for in a home setting at the end-of-life., Methods: Families of children who were cared for by the paediatric palliative care team (PPCT) in a home setting between 01.02.2003 to 30.09.2009 were included in the survey. The questionnaire consisted of 87 items with nominal scaled variables and numeric rating scales (NRS; 1-4, lowest to highest satisfaction) as response options., Results: 84 relatives of 49 children participated (response rate 53.2%). Duration of care varied between 3-246 days. All 49 patients died at home. 98.8% of the respondents were satisfied with their decision for home care. The symptoms pain (86.9%) and fatigue (85.7%) were reported most frequently. Satisfaction with symptom control was high (NRS 3.55±0.49). The respondents were satisfied with communication (NRS 3.73±0.57) and end-of-life care (NRS 3.85±0.90). Satisfaction with psychosocial care (NRS 3.24±0.87) was significantly lower (p<0.05). Parents who stayed in contact with the PPCT by phone and in person were more satisfied with aftercare., Discussion: From parental view satisfying home-care of children with cancer is feasible. Symptom control succeeds in a home setting., (© Georg Thieme Verlag KG Stuttgart · New York.)

Despite the implementation of new antifungal drugs, invasive aspergillosis (IA) still remains a considerable challenge in pediatric oncology with a severe mortality. Prophylactic and therapeutic measurement have to be evaluated in these rare but poor prognostic patients. Therefore the entire group of patients at risk of developing IA has to be defined before cooperative prospective trials. In a retrospective analysis including all our patients with malignancies we looked for patients with proven/probable IA. Cases of the period from 2003 to 2008 were analyzed in detail.In the period between 2003 to 2008 24 of 755 patients were affected by proven/ probable IA. Compared to former studies incidence increased from 1.3%in 1980 to 3.4% in 2008. AML patients with or without allogeneic/haploidentical stem cell transplantation were at highest risk (24% and 25% respectively, in comparison to 1% in ALL-patients). Survival after 2 years was 50% for patients with AML and IA. In patients with high risk to develop IA the effect of intensified, intravenous antimycotic prophylaxis has to be proven prospectively in a cooperative and randomized setting., (© Georg Thieme Verlag KG Stuttgart · New York.)

In Germany and Central Europe, congenital disorders leading to secondary hemochromatosis are rare. The majority of these patients are treated in peripheral medical institutions. As a consequence, the experience of each institution in the treatment of secondary hemochromatosis in patients with congenital anemia is limited. Recent developments concerning new chelating agents, their combination for intensified chelation and new possibilities to diagnose and monitor iron overload have important consequences for the management of patients with secondary hemochromatosis and increase its complexity enormously. Therefore, the development of a guideline for rational and efficient diagnostics and treatment was necessary. The new guideline was developed within a formal consensus process and finally approved by a consensus conference with participants from both the pediatric and adult German hematology societies (GPOH and DGHO). Apart from general information and recommendations, the guideline contains 9 consensus statements on diagnostics (iron status, siderotic complications, chelator side-effects), the start of chelation, indications for intensified chelation, iron elimination in specific disorders, and iron elimination after stem cell transplantation. Here, these consensus statements are presented and discussed in detail. For the complete text of the guideline, please visit the AWMF homepage at http://www.leitlinien.net ., (© Georg Thieme Verlag KG Stuttgart · New York.)

A 15-year-old boy with AML develops a fulminant candida krusei sepsis complicated by acute blindness due to enophthalmitis and subsequent bleeding during prolonged pancytopenia after induction therapy. Despite a low dose prophylaxis with oral nystatine and i. v. amphotericin B (ampho B) three times a week (0.8 mg/kg). Under an early intensified therapy with ampho B (1.5 mg/kg/d) combined with 5-flucytosin (160 mg/kg/d)the sepsis could be controlled and visual acuity slowly improved. A vitrectomy is due to the bleeding unavoidable. Despite a therapy delay of 4 weeks and omission of two cycles of the intensification treatment the patient is in continuous complete remission for longer than 10 years after diagnosis. If it is within the treatment protocols manageable to detect patients with increased sensitivity against cytostatic drugs and correspondingly highly sensitive leukemic cells, such complications could be avoided due to primary treatment adaptation., (Georg Thieme Verlag KG Stuttgart.New York.)

Background: The aim of this study is to identify clinical "red flags" that may assist the general pediatrician in detecting patients with an acute lymphoblastic leukemia (ALL)., Patients and Methods: Medical history and clinical findings of 189 children and adolescents, diagnosed with ALL between 1/1995 and 7/2004, were analyzed retrospectively., Results: Only 50% of patients presented with symptoms known in children with leukemia (fever, fatigue, paleness, hemorrhage); 5% were diagnosed accidentally in the absence of any clinical symptoms. The majority of patients had a medical history up to few weeks; in 11% of patients up to several months without impairing curability. 95% of the patients presented at diagnosis with enlargement of lymphnodes, liver and/or spleen. The characteristic laboratory constellation included mono-, respectively bi- or trilinear pathology of the blood count and with blasts in the blood smear., Conclusion: The clinical diagnosis of ALL relies on physical examination and the blood count including microscopic examination. Therefore, the alertness of the treating paediatrician with regard to clinical findings and a pathologic blood count is more important than elaborate laboratory investigations. In uncertain cases, a close follow-up examination may help to unmask ALL, which will most likely be stratified in the low-risk-group., (Georg Thieme Verlag KG Stuttgart.New York.)

In Germany annually 1,500-3,000 children die from life-limiting diseases. Symptoms and course of disease differ considerably depending on the character of the underlying disease. Due to the desire of the children and their families to spend the end of life at home a paediatric palliative home care service was founded at the university children's hospital of Duesseldorf. In the last 20 years a specialised paediatric palliative team evolved from an unstructured voluntary activity. Prospective aims are an area-wide professional supply of all paediatric palliative patients and the improvement of the cooperation with the resident paediatrician and paediatric palliative nursing services. Furthermore the establishment of networks as well as a proper communication among the professionals is inalienable.

Anthracyclines are very potent drugs in the therapy of malignancies in childhood. The major dose limiting adverse effect of these drugs is the risk of dilated cardiomyopathy. We performed a retrospective study on 168 patients who were treated with anthracyclines for a malignant disease with or without chest radiation at the department of Pediatric Hematology and Oncology at the University of Duesseldorf between 2000 and 2004. During and after chemotherapy the patients were screened by echocardiography and ECG examinations prior to each administration of anthracyclines. Only four patients presented with adverse cardiac events, one of whom developed acute cardiac failure. This patient was additionally treated with chest radiation. Three of the four patients showed intermittent arrhythmias, mainly supraventricular tachycardia. One of them presented with atrial ectopic tachycardia and left ventricular dysfunction. We conclude that the frequency of cardiac sequelae after chemotherapy with anthracyclines is low under present guidelines. Detection of early cardiac sequelae may be more difficult than in the past. Only one patient with cardiac sequelae in our study group was diagnosed by regular performed examinations for cardiac sequelae of chemotherapy. We therefore need to modify our screening methods to increase the effectiveness of detection of cardiac dysfunction prior to clinical manifestation.

Since 1962, desferrioxamine (deferoxamine, DFO) has been utilized for the treatment of secondary hemosiderosis. For about 30 years, DFO therapy has been performed as nightly continuous subcutaneous infusion. About 20 years ago, the first oral iron chelator (deferiprone, DFP) was presented. Concerns about potential side effects were responsible for the late acceptance and license of this drug which is limited to the use as second-line therapy for patients with thalassemia major. During recent years, chelation therapy and its evaluation started to progress rapidly. Clinical research and drug development as well as the introduction of new methods for the assessment of iron overload contributed to these advances. By using cardiac T2 (*) MRI it was possible to examine the specific effect of a chelator on myocardial siderosis. Clinical studies using this method indicated superiority of DFP compared to DFO with respect to the treatment of myocardial siderosis. Several retrospective and first prospective clinical trials seem to confirm this observation. In parallel, treatment strategies based on the combination of DFO and DFP have been developed. Using both drugs simultaneously or sequentially, additive and synergistic effects contribute to the fast elimination of iron from different organs at risk for siderotic damage. Deferasirox (DSX) is a recently developed oral chelator which shows good efficacy and tolerability in patients with transfusional hemosiderosis due to various underlying disorders. Long-term studies will define the future importance of DSX for iron chelation treatment. For the first time, there is a choice between three commercially available chelating agents for patients with transfusional iron overload. This will allow a highly effective, individually tailored treatment hopefully leading to a fundamental improvement of patients' life expectancy and quality.

With the introduction of "hypertransfusion" regimens the extent of disease- and therapy-related hemosiderosis has become the survival limiting factor for patients with beta-thalassemia major as iron transferred with transfusions cannot be excreted by physiological means. Subsequent introduction of deferoxamine therapy for iron elimination and prophylaxis of hemosiderosis has improved prognosis and life quality of these patients considerably. We report our experience with seven adolescent patients with beta-thalassemia and ineffective subcutaneous therapy and severe hemosiderosis-related organ complications. For that reason they received i. v. intensified chelate therapy. The patients were given 70 to 120 mg/kg DFO 7 days a week continuously via a Port-a-cath or Hickman central venous line. Under high-dose i. v. DFO therapy, serum ferritin levels significantly decreased in all patients. Target serum ferritin levels of 3 000 ng/ml were reached after 12 to 20 months of treatment. In 3 of the 5 patients that were treated for longer than 43 months serum ferritin levels even dropped below 2 000 ng/ml. Serum ferritin levels also correlated well with SQUID examinations. Therefore, monitoring of serum ferritin may be useful to monitor patient's compliance and control intensified DFO therapy. Continuous administration of the intensified DFO therapy induced normalization of liver function and left ventricular cardiac function in all patients who are still alive. Two patients died due to cardiac decompensation. In five patients 19 episodes of central catheter-related infections were observed (1.5 infections per 1 000 catheter days). No DFO-associated allergic reactions nor irreversible organ dysfunction were observed. Our results indicate that intensified i. v. DFO therapy is an effective and safe method for treatment of severe organ dysfunction in patients with thalassemia major. The most severe problems are catheter-related infections and inconsistent long-term compliance.

Background: There is a striking need for additional therapies of bone marrow oedema (BME) and aseptic osteonecrosis (AON) in paediatric oncology patients. Hyperbaric oxygenation (HBO) therapy used in the treatment of osteoradionecrosis is demonstrated effectiveness. Aim of this retrospective analysis was to investigate whether HBO-therapy might lead to subjective as well as objective effects in the treatment of BME and/or AON in paediatric oncology patients with acute lymphoblastic leukaemia (ALL) or Non-Hodgkin lymphoma (NHL)., Patients and Methods: Between 11/1988 and 01/2001 27/291 (9.3 %) patients with ALL or NHL were diagnosed with a BME and/or AON in the Clinic for Paediatric Oncology, Haematology, and Immunology at University of Dusseldorf. 19/27 patients were submitted to HBO-therapy. Patients received average 45 HBO-treatments per patient (min. 13, max. 80 treatments). The affected regions were re-evaluated with MRI for radiological extent of lesions every 3 months. Pain in its intensity and localisation was serially recorded during HBO-therapy as key symptom in 11 of 19 patients., Results: 27 patients (15 females, 12 males; mean age at diagnosis of malignancy 8.2 +/- 4.7 (SD) years, range 7 months to 16 years) presented with 138 lesions. 133/138 lesions were localised in the lower extremities. At diagnosis of BME and/or AON, 78/133 lesions were shown in females and 55/133 lesions in male. Girls < 10 years predominantly presented BME (33 BME vs. 6 AON), girls aged > 10 years predominantly offered AON (28 AON vs. 11 BME). BME was more often exhibited in boys < 10 years (34 BME vs. 10 AON) and rarely in boys > 10 years (4 BME vs. 6 AON). 11 patients treated with HBO-therapy were serially evaluated for pain intensity throughout their HBO-therapy courses by visual analogue scale (VAS) assessment. During the first 15 treatment courses the HBO-therapy a clear-cut reduction of pain was observed. The mean pain score before the first HBO-treatment unit was 2.4 +/- 2.7 (X +/- SD), decreased before the fifth to 1.6 +/- 1.7 and prior to the 35 (th) and 40 (th) HBO treatment to 0. Girls < 10 years treated with HBO showed an increase of BME (31 --> 46) and declining AON numbers (6 --> 2). Girls > 10 years with and without HBO-therapy showed decrease of BME lesions (7 --> 4 vs. 4 --> 0), whereas AON increased in the HBO-treated group (28 --> 29) as well as the non-treated group (0 --> 4). Males < 10 years showed an increase in BME lesion numbers despite HBO intervention (24 --> 26). The AON lesion numbers dropped in parallel (6 --> 3). Male patients not treated with HBO showed constant numbers of BME (11-->11) and a decreased numbers of AON (4 --> 2). All differences are statistically not significant., Conclusions: Children and adolescents diagnosed with ALL or NHL have a risk for accruement of BME and/or AON irrespective of the age, with an almost exclusive involvement of the lower extremities. Lesions of pedal bones and ankle joints predominantly affect children < 10 years. Lesions of knee and hip joints predominantly affect children > 10 years. In children < 10 years of age we demonstrate declining AON numbers and conversion of AON to BME thereby implicating possible beneficial effect of HBO in such patients. HBO failed to show beneficial effect on BME whether by preventing new lesions or by improving existent lesions in children > 10 years.

Pediatric palliative care is still in its beginning. Most children with life-threatening disorders succumb with incomplete symptom control under in-patient conditions. Due to the limited number of patients and large hospital-home distances the realization of out-patient concepts of palliative care especially for children and adolescents with cancer is purposeful and beneficial. In a pilot project such an a aforementioned concept of pediatric palliative care proved successfully working despite insufficient conditions. Guidelines of pediatric palliative care are to be defined at short notice in order to ascertain autonomy and mobility of patients aiming at highest possible quality of life. The recently initiated program of integrating ambulatory and in-patient care within the regulations set forth in Germany's last health care system reform offers the chance of palliative home care of children in their terminal phase of life.

19 children and adolescents with intracranial tumors received a palliative therapy with H 15 at a maximum dose of 126 mg/kg BW/day. All patients had previously been treated with conventional therapy. No side effects were observed during a median 9 months application. The recently reported antiedematous effect of H 15 was documented by MRI in one patient with a peritumoral edema, thus sparing steroid therapy with its typical side effects. Five/19 children reported an improvement of their general health status; this might be a psychological effect of hope for tumor response during palliative care. Three/17 patients with malignant tumors showed a mainly transient improvement of neurological symptoms such as pareses and ataxia. Three further patients showed an increased muscular strength and one cachectic patient achieved a weight gain. These improvements might be attributed to the antiedematous effect of H 15. Because of the palliative situation of these patients, H 15 application was performed without prior rebiopsy for histological evaluation. Overlapping effects with a previous radiotherapy or chemotherapy may have occurred. An antiproliferative effect cannot be stated. To prevent an uncritical use of H 15, further studies with prospective central documentation have to be initiated to evaluate the clinical indications for H 15 in palliative therapy, optimal dosage and duration of application.

The prognosis and therewith the quality of life of patients with beta-thalassaemia major is decisively influenced by the compliance with the therapy of the patients and their families, who are massively burdened with this lifelong and much time requiring treatment. To improve the compliance with therapy a group of 10 afflicted adolescents and young adults aged between 15 and 27 years was founded in 1992. The aims are to get to know the reasons for the unsatisfactory compliance with therapy, to promote the exchange of experience how to deal with the disease and its treatment, to give comprehensive medical informations and to improve in this way the own responsibility and the compliance with therapy. At the monthly meetings aspects of interaction between parents and the child with a hereditary disease are discussed. Also the themes of self-image and body image of these adolescents are set who are stigmatized by thalassaemia and grow up in uncertainty about the development of their disease and often suffer from mortal fear. Possibilities and limits of integration of these chronically ill patients within school and profession, and not at last within the clinique are debated. Although two members of this group have died, our patients show more interest in their disease, their therapy and their prospects since the beginning of this psychosocial care. The compliance with therapy has become better in the majority of patients.

Since 1980, a growing number of pediatric patients with mutism following posterior fossa surgery have been recognized. This syndrome typically affects children and in rare cases young adults who become mute one or two days after tumor operation but do not show disturbances of consciousness or language comprehension. The disorder persists for 1 to 4 months. The pathogenesis is still unknown. Of 21 children who underwent surgery for large posterior fossa tumors between 1991 and 1995, 6 developed cerebellar mutism. Histologically the tumors were classified as astrocytoma WHO grade I, astrocytoma WHO grade II and ependymoma WHO grade III in one case and medulloblastoma WHO grade IV in three cases. Besides the clinical course, intraoperative findings and CT or MRI data are evaluated and discussed considering possible etiological hypotheses. Our own experience and also literature reviews suggest that the lesion of the cerebellar hemispheres might be the most important one of multiple factors causing cerebellar mutism. Generally the syndrome is transient. The diagnosis should not delay adjuvant therapy in patients with a malignancy.

Nowadays, endocrine problems like retarded sexual maturation and growth deficiency, lead to substantial suffering in patients with beta-thalassemia major. The aim of the present study is the differentiation between a possible insufficiency of the pituitary gland and dependent target organs, respectively. 12 patients (age 1.9-18.10 years) were examined by means of a combined pituitary function test. The corticotropic axis turned out to be normal as shown by a regular stimulation of cortisol in all patients tested. The thyrotropic function was unaffected in all children: elevated levels of TSH pointed to primary hypothyroidism. Pubertal values of LH and FSH were found in only 3 out of 7 patients at pubertal age. In 10 out of 12 children, stimulation led to a rise in STH levels above 10 ng/ml. On the whole, there was no evidence for pituitary insufficiency in beta-thalassemia major.

Between Nov. 83 and Oct. 84 15 children under chemotherapy for malignant diseases, 2 relatives and 2 nurses developed hepatitis-B antigen seropositivity. Epidemiological studies gave evidence for non-parenteral spread of the infection. The course of the disease was usually asymptomatic or mild. Amongst the patients who developed hepatitis-B there was a considerable number of children who had presented with a recurrence of their malignant disease. Two characteristic cases of hepatitis B are presented showing the wide range of clinical manifestations of this disease in immunocompromised children with ALL.

A new method of measuring the distal torsion of the femoral bone is introduced. The term "torsion" is defined, and the etiology of femoral torsion is scrutinized. The sources of error are discussed after a description of the process of measurement and of the calculation of the angle of torsion. The aim and value of this method are, firstly, to supply evidence for the existence of a prearthrosis factor of the patellofemoral joint, and, secondly, to be of practical importance for the consequences of surgery. These consequences will be discussed elsewhere.

The position of the supracondylar correction osteotomie during the treatment of the senile gonarthrosis is examined by controls of 17 patients with 21 performed osteotomies. The indication, the technique as well as the clinical and radiological results of the operation are critically dealt with. In case of a correct indication and when considering the contra-indication-like and existing strong osteoporosis, a distinct deficit of expansion and a most serious arthrosis-good results can be expected.

Using a new method for measuring the distal femoral torsion (Janssen a. Prüssner 1977) it is possible to determine the encreased medial torsion of the distal femur in most of the patients with dislocation of the patella. A group of patients with dislocated knee-cap was studied for this purpose. The characteristic clinical and x-ray features are listed and weighted according to their value. They throw a new light on the pathogenesis and pathomechanics of patellar luxation, and point to the need to reclassify the different types of luxations according to etiological aspects.

The efficiency and toxicity of Carboplatin, a derivate of cisplatin in clinical use since 1981, was investigated in combination with VP16 in 11 children with recurrent or refractory tumors. 10 patients received therapy as outpatients without hydration. 160 mg/m2/day of Carboplatin were administered days 1 to 3, or days 1 to 5 as one hour infusion, combined with VP16 100 mg/m2/day, days 1 to 3, or days 1 to 5 as one hour infusion. One patient received Carboplatin, 600 mg/m2, as 24 hrs. continuous infusion in combination with VM26, 150 mg/m2/day as one hour infusion, 8 hours after Carboplatin. 9 of the treated children had measurable disease. 3 of 9 patients achieved a tumor response of more than 50% (partial remission). 5 of 9 children showed tumor response of less than 50% (stable disease). 1 out of 9 patients had progressive disease. 8 of 9 patients reported improvement or disappearance of clinical symptoms after the first course. All patients had severe myelosuppression with different times to recover. The WBC nadir was 14 days after Carboplatin/VP16. The nadir platelet counts occurred 21 days after therapy with fast recovery. Non-hematological side effects were minimal.