The chance of transition: strategies for multidisciplinary collaboration.

Many long-term childhood cancer survivors suffer from treatment-related late effects, which may occur in any organ and include a wide spectrum of conditions. Long-term follow-up (LTFU) is recommended to facilitate early diagnosis and to ensure better health outcomes. Due to the heterogeneity of these sequelae, different specialists work together in the diagnosis and treatment of these conditions. Experts from both pediatric and internal medicine are involved in age-appropriate care by providing a transition process. Hence, LTFU of childhood cancer survivors is a prototypic example of multidisciplinary care for patients with complex needs treated in a specialized setting. International collaborations of healthcare professionals and scientists involved in LTFU of childhood cancer survivors, such as the International Guideline Harmonization Group, compile surveillance recommendations that can be clinically adopted all over the world. These global networks of clinicians and researchers make a joint effort to address gaps in knowledge, increase visibility and awareness of cancer survivorship and provide an excellent example of how progress in clinical care and scientific research may be achieved by international and multidisciplinary collaboration.

Adolescents and young adults (AYA) with cancer: a position paper from the AYA Working Group of the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE).

It is well recognised that adolescents and young adults (AYA) with cancer have inequitable access to oncology services that provide expert cancer care and consider their unique needs. Subsequently, survival gains in this patient population have improved only modestly compared with older adults and children with cancer. In 2015, the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE) established the joint Cancer in AYA Working Group in order to increase awareness among adult and paediatric oncology communities, enhance knowledge on specific issues in AYA and ultimately improve the standard of care for AYA with cancer across Europe. This manuscript reflects the position of this working group regarding current AYA cancer care, the challenges to be addressed and possible solutions. Key challenges include the lack of specific biological understanding of AYA cancers, the lack of access to specialised centres with age-appropriate multidisciplinary care and the lack of available clinical trials with novel therapeutics. Key recommendations include diversifying interprofessional cooperation in AYA care and specific measures to improve trial accrual, including centralising care where that is the best means to achieve trial accrual. This defines a common vision that can lead to improved outcomes for AYA with cancer in Europe.

Teenagers and young adults with cancer in Europe: from national programmes to a European integrated coordinated project.

Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European Network for Cancer Research in Children and Adolescents programme (ENCCA), a specific European Network for Teenagers and Young Adults with Cancer has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high-quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and paediatric services to eliminate the gap in the management of TYA with cancer.

Development of curative therapies for Ewing sarcomas by interdisciplinary cooperative groups in Europe.

Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.

The state of research into children with cancer across Europe: new policies for a new decade.

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.

Health status at long-term follow-up in patients treated for extremity localized Ewing Sarcoma or osteosarcoma: a Scandinavian sarcoma group study.

BACKGROUND: The purpose of this study was to evaluate late effects and symptom complaints in long-term survivors (>5 years) of Extremity Bone Sarcoma (EBS survivors). The results were compared with findings in age- and gender-matched individuals from the general population (NORMs). PATIENTS AND METHODS: Among 155 EBS survivors approached, 133 (86%) were included, and 110 of them (83%) attended an outpatient examination. Health status was evaluated by a mailed questionnaire concerning demographic and current health issues, and physical examinations at the outpatient clinic. Age- and gender-adjusted normative controls were drawn from participants of the Health Study of Nord-Trøndelag County (HUNT 2). RESULTS: Median age at follow-up was 29 (15-57) years. Median follow-up was 12 (6-22) years. Of EBS survivors 42% had > or =1 somatic disease, 33% had ototoxicity and 13% had reduced renal function. EBS survivors were more likely to have heart disease (odds ratio [OR], 7.9; 95% confidence interval [95% CI], 2.5-25.3; P = 0.001), hypertension (OR, 3.4; 95% CI, 1.1-10.1; P = 0.03) and thyroid disease (OR, 3.0; 95% CI, 1.1-8.3; P = 0.04) compared to NORMs. EBS survivors reported more diarrhoea (29% vs. 19%, P = 0.02), palpitations (23% vs. 13%, P = 0.01) and shortness of breath (11% vs. 5%, P = 0.01) than NORMs. CONCLUSIONS: EBS survivors have poorer health status compared to age- and gender-matched controls. Long-term follow-up of these patients is therefore mandatory.

High-dose methotrexate: on the relationship of methotrexate elimination time vs renal function and serum methotrexate levels in 1164 courses in 264 Swedish children with acute lymphoblastic leukaemia (ALL).

PURPOSE: The objectives of the present study were to determine the relationship between methotrexate (MTX) elimination time and various aspects of renal function and to evaluate the prognostic value of elevated serum MTX and creatinine for delayed MTX elimination. PATIENTS AND METHODS: The majority of the 264 children were being treated for ALL. According to the NOPHO-92 protocol, 5 or 8 g MTX/m(2) was administered over 24 h. Serum creatinine was assessed daily. In 11 patients from one centre, renal function was studied in more detail using serum cystatin C, iohexol clearance, and urinary albumin, IgG and protein HC. RESULTS: Increased serum creatinine correlated significantly with the elimination time of MTX, whereas no indications were found of tubular or barrier function damage. Of the 1164 courses, 44 had delayed elimination of MTX (>/=120 h). Serum MTX >150 microM at the end of infusion had a sensitivity of 0.27 and a specificity of 0.94 to predict delayed MTX elimination, and >/=50% increase in serum creatinine during the first treatment day (creatinine ratio) had a sensitivity of 0.32 and a specificity of 0.99. The corresponding risk ratios were 5 and 19 for MTX >150 micro M and creatinine ratio, respectively. In courses with a normal elimination time (<72 h), 99% of the courses had a rise in serum creatinine of less than 50%. CONCLUSIONS: Elevation of serum creatinine by more than 50% is a better predictor of delayed elimination than the level of serum MTX at the end of MTX infusion, especially if information on previous creatinine measurements is used to reduce the impact of an occasionally low serum creatinine value before the start of the MTX infusion.

Trisomy 3 as the sole karyotypic change in a pediatric immature teratoma.

Cytogenetic analysis of short-term cultured cells from an immature ovarian teratoma of a 9-year-old girl disclosed an extra copy of chromosome 3 as the sole clonal abnormality. The fact that trisomy 3 was previously reported as the only karyotypic change in two ovarian germ-cell tumors--one teratoma NOS and one immature teratoma--suggests that gain of chromosome 3 constitutes an early and pathogenetically important change in a subset of female germ-cell tumors.

[Survey of clinical diagnoses and autopsy findings. Autopsy findings and sensitivity, specificity and predictive values for clinical diagnosis during the periods 1 July 1980-30 June 1081 and 1 July 1990-30 June 1993]. / Undersøgelse af kliniske diagnoser og obduktionsfund. Obduktionsfund og sensitivitet, specificitet og proediktive voerdier for klinisk diagnostik i perioderne 1.7.1980-30.6.1981 og 1.7.1990-30.6.1993.

The sensitivity, specificity and clinical accuracy of clinical diagnoses were determined and compared for two periods of time: 1.7.1980-30.6.1981 and 1.7.1990-30.6.1993 based on the analysis of 286 and 138 autopsies respectively. The autopsy rate decreased from 82.7% in the first period to 11.2% in the second. The first period shows a generally higher sensitivity and accuracy for positive diagnosis. Both periods reveal the lowest sensitivity for pulmonary embolism and the lowest accuracy for positive clinical diagnosis of pneumonia/bronchopneumonia. For malignancies and arteriosclerotic heart diseases significant discrepancy between the periods was demonstrated using the chi 2-test. The results are influenced by low autopsy rates causing fewer true-positive diagnoses and a declining sensitivity. This type of study is a useful tool for demonstrating changes in the diagnostic procedure. The present investigation demonstrates a need for further analysis of malignancies to explain the simultaneous decrease in sensitivity, specificity and accuracy in spite of an increasing number of malignancies in autopsy findings.

[Vaccination granuloma in the breast region--differential diagnosis]. / Vaccinationsgranulom i mammaregionen--en differentialdiagnose.

Vaccination granulomas (VG) caused by injection of aluminum adsorbed vaccines have not been described previously in the breast region. We therefore present eight cases, all in women. None of the small tumors were diagnosed as VG before the operation.

Primary malignant lymphoma of the salivary glands.

Five cases of primary malignant lymphomas of the salivary glands are reported. Four lymphomas arose in the parotid gland and one in the submandibular gland. All were non-Hodgkin lymphomas. In 4 cases the lymphomas were of low-grade malignancy, viz. 2 immunocytomas and 2 centroblastic/centrocytic malignant lymphomas, and 1 was a T-immunoblastic malignant lymphoma of high-grade malignancy. Four patients with localized disease were treated with radiotherapy and 1 patient with disseminated disease was treated with chemotherapy. One patient died from a disease unrelated to the malignant lymphoma, and 4 patients were alive at 66-136 months after treatment.

Chondrosarcoma of the larynx.

Chondrosarcoma of the larynx is a rare neoplasm. The characteristic features of this tumor are described, and a case in a 69-year-old woman is reported. This case demonstrates the difficulties of histological classification. On the first biopsy specimen a benign chondroma was diagnosed. However, the microscopical features of the excised tumor were those of a chondrosarcoma. It is generally accepted that radiotherapy is of no value; surgical treatment by laryngectomy is advised. Some authors recommend a conservative attitude towards these tumors, which are of low malignancy, the growth slow and the risk of local or distant metastases slight.

Adenolipoma of the thyroid gland.

A case of rare fat-cell-containing adenoma, an adenolipoma, in the thyroid gland is reported. Previously documented cases are reviewed. Diffuse lipomatosis of the thyroid, amyloid goitre with adipose tissue, and the relationship between lipomatosis and adenolipoma are discussed.

Myopathy in bone loss of ageing: improvement by treatment with 1 alpha-hydroxycholecalciferol and calcium.

1. Eleven patients with the bone loss of ageing were treated with the vitamin D analogue 1 alpha-hydroxycholecalciferol and calcium for 3--6 months. 2. Muscle biopsies were taken from the vastus lateralis before and after the treatment and the activity of several enzymes was measured. Succinate dehydrogenase and total phosphorylase activities, which are a measure of the oxidative capacity, were low and increased significantly with the treatment. The lactate dehydrogenase activity, which can be taken as a measure of the anaerobic metabolism, was normal and did not change with treatment. The phosphagen stores, ATP and creatine phosphate were low and increased to normal with treatment. 3. Histochemical classification of the fibre composition revealed that the treatment induced an increase in the relative number of fast-twitch a (FTa or type II A) fibres accompanied by a reduction of the fast-twitch b (FTb or type II B) fibres. The cross-sectional area of the FTa fibres also increased with the treatment. 4. The present findings indicate that treatment with the active vitamin D analogue, 1 alpha-hydroxycholecalciferol, and calcium improves the myopathy associated with the bone loss of ageing.

Treatment of senile osteoporosis with 1alpha-hydroxyvitamin D3.

About 30% of patients with clinical osteoporosis had histological signs of osteomalacia, in spite of normal serum 25-hydroxyvitamin D3 (25-OHD3). The excess osteoid disappeared during treatment with 1alpha-hydroxyvitamin D3 (1alpha-OHD3). These patients might have reduced ability to convert 25-OHD3 to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). The intestinal calcium absorption increased during treatment with 1alpha-OHD3, but this was accompanied by a rise in urinary calcium excretion. Photon absorptiometry of the forearm indicated increased bone mineral content during treatment with a daily dose of 2 microgram 1alpha-OHD3 and a supplement of 1 g of calcium. This therapeutic combination, however, caused frequent episodes of hypercalcaemia, so further studies are necessary to evaluate an appropriate dose of 1alpha-OHD3 with or without a calcium supplement.

Treatment of osteoporosis of ageing with 1alpha-hydroxycholecalciferol.

Seven patients with osteoporosis of ageing were treated with synthetic 1alpha-hydroxycholecalciferol (1alpha-H.C.C.) for 3-4 months. The compound was given at a daily oral dose of 2 mug together with an oral supplement of 1 g of calcium. Clinically there was a striking improvement in the patients' physical fitness. Increased bone formation and mineralisation were seen on iliac-crest bone biopsy, and this was supported by an increased osteoblastic activity demonstrated by histochemical measurement of alkaline-phosphatase activity. Bone histology furthermore showed a reduced bone resorption, which was supported by a reduced urinary excretion of total hydroxyproline. Photon absorptiometry of the forearm accorded with the histological findings, showing a significant increase in the bone mineral content. Serum-calcium rose in all patients, one developing a severe transitory hypercalcaemia. The urinary excretion of calcium and magnesium increased significantly. The serum concentrations of 25-hydroxycholecalciferol and parathyroid hormone were not significantly affected by the treatment. It is concluded that 1alpha-H.C.C. is an effective tool in the treatment of senile osteoporosis.