Multifunctional nanoparticles for the treatment and diagnosis of osteosarcoma.

Osteosarcoma (OS) is a common primary malignant bone tumor in adolescents. Currently, the commonly used treatment strategies for OS include surgery, chemotherapy and radiotherapy. However, these methods have some problems that cannot be ignored, such as postoperative sequelae and severe side effects. Therefore, in recent years, researchers have been looking for other means to improve the treatment or diagnosis effect of OS and increase the overall survival rate of patients. With the development of nanotechnology, nanoparticles (NPs) have presented excellent properties in improving the therapeutic efficacy of drugs for OS. Nanotechnology makes it possible for NPs to combine various functional molecules and drugs to achieve multiple therapeutic effects. This review presents the important properties of multifunctional NPs for the treatment and diagnosis of OS and focuses on the research progress of common NPs applied for drug or gene delivery, phototherapy and diagnosis of OS, such as carbon-based quantum dots, metal, chitosan and liposome NPs. Finally, the promising prospects and challenges of developing multifunctional NPs with enhanced efficacy are discussed, which lays the foundation and direction for improving the future therapeutic and diagnostic methods of OS.

Nanomaterial-assisted determination of osteosarcoma by antibody-osteopontin-aptamer sandwich ELISA.

Immobilization and detection of small molecules is one of the challenging tasks in any given sensing system as the dissociation equilibrium constant is higher. Generating a right immobilization system with small molecules is mandatory for developing the drug-discovery process and disease identification. Immobilizing smaller probes on the ELISA plate is challenging because of its less adsorption on the polystyrene (PS) substrate. This research work developed an iron nanomaterial-based linker to attach osteopontin-specific aptamer on PS substrate. Iron oxide nanoparticle was attached on PS plate through amine modification and then antibody was attached by COOH reaction. On the osteopontin-modified plate, osteosarcoma biomarker of osteopontin was identified by its specific antibody and aptamer sandwich with the detection limit of 1 nM. Further, biofouling experiments with other molecules, such as lysozyme, and complementary aptamer failed to show the ELISA adsorption signal, indicating the iron oxide nanoparticle-modified PS plate specifically recognizes osteopontin. This research work effectively identifies the lesser abundance of osteopontin and helps to diagnose the osteosarcoma-related problems.

Significant interaction between high-dose methotrexate and high-dose piperacillin-tazobactam causing reversible neurotoxicity and renal failure in an osteosarcoma patient.

INTRODUCTION: Pharmacokinetic interaction of high-dose methotrexate (MTX) and other concomitantly administered renally secreted medicinal products may lead to insufficient methotrexate serum level decrease and significant MTX toxicity. CASE REPORT: We report the case of an 18-year-old male patient treated with high-dose MTX for an osteosarcoma and with high-dose piperacillin-tazobactam at the same time. MTX serum levels were severely elevated 24 hours after the MTX infusion and did not decrease in accordance with the specific calcium folinate rescue protocol. The patient experienced renal failure accompanied by neurological symptoms, most consistent with MTX-related renal and CNS toxicity.Management and outcome: After discontinuation of piperacillin-tazobactam, intensified calcium folinate rescue therapy, and IV hydration, the MTX serum levels decreased appropriately, and toxicity symptoms resolved. DISCUSSION: Severe MTX-related toxicity, caused by drug-drug interaction, suggests that the concomitant use of high-dose MTX and high-dose piperacillin-tazobactam should be avoided generally.

Local dissemination of osteosarcoma observed after massage therapy: a case report.

BACKGROUND: Limited evidence is available regarding the dissemination of tumor tissues due to compression during massage therapy, a routine procedure in patients with various symptoms in Asian countries. CASE PRESENTATION: A 12-year-old male presented at a massage clinic with pain and swelling of his left knee, which worsened the same night. Consistent with conventional osteosarcoma, radiography revealed cortical bone destruction, osteoblastic changes, and periosteal reactions. Magnetic resonance imaging revealed a tumor in the distal femur, an extraskeletal mass, and an infiltrative lesion in the intramuscular and neurovascular areas surrounding the distal femur; this was considered as hemorrhage and dissemination of the tumor tissue. 18Fluorine-labelled fluorodeoxyglucose-positron emission tomography and computed tomography revealed multiple metastases in the spine, liver, and lung. Consistent with osteosarcoma, histopathological examination revealed tumor cell proliferation with extensive pleomorphism and mitoses. Despite undergoing chemotherapy, radiation therapy, and hip disarticulation, the patient died due to multiple metastases 13 months after the initial diagnosis. CONCLUSIONS: The present case suggests association of massage therapy with the local dissemination of tumor tissues, although influence of massage therapy on metastatic lesions remains unclear. Massage therapists should be aware of the possibility for dissemination of hidden malignancies due to the procedure.

The Effect of Clown Intervention on Self-Report and Biomarker Measures of Stress and Fatigue in Pediatric Osteosarcoma Inpatients: A Pilot Study.

BACKGROUND: Pediatric cancer patients experience different psychological processes during hospitalization that may regulate the immune response and affect recovery and response to cancer treatment. In this study, we aimed to examine the feasibility of longitudinal testing of psychophysiological parameters of stress and fatigue in pediatric osteosarcoma patients hospitalized for chemotherapy submitted to clown intervention; and to investigate whether changes in the levels of biomarkers are associated with psychological stress and fatigue levels in these patients after the clown intervention. METHODS: A pretest-posttest quasi-experimental pilot study was conducted at the pediatric oncology inpatient unit in a comprehensive cancer care center in Brazil including children and adolescents with osteosarcoma hospitalized for chemotherapy. Eight saliva samples were collected, comprising 4 at baseline (pre-intervention) and 4 after the clown intervention (+1, +4, +9, and +13 hours post-awakening). Salivary cortisol, α-amylase (sAA), cytokines, and matrix metalloproteinase-9 (MMP-9) levels were determined using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Stress and fatigue were measured by Child Stress Scale-ESI and PedsQL Multidimensional Fatigue Scale respectively. Bivariate association analysis between stress and fatigue scores and biomarker levels were investigated using nonparametric statistics. Effect sizes were calculated for each outcome variable. RESULTS: Six pediatric osteosarcoma patients were enrolled with no missing data. No significant effects sizes were observed for psychophysiological outcomes. Effect sizes ranged from 0.54 (cortisol) to 0 (interleukin-1ß [IL-1ß]). Decreasing overall trends were observed for cortisol levels for all 6 pediatric osteosarcoma patients over time. In addition, a similar pattern of tumor necrosis factor-α (TNF-α) levels over time was found for all 6 patients. Patients with metastatic osteosarcoma showed a linear trend for a decrease in MMP-9 levels between 1 and 9 hours after the clown intervention and restoration to basal levels after 13 hours. CONCLUSIONS: The results of this pilot study suggest that it is feasible longitudinally measure psychophysiological outcomes in the pediatric osteosarcoma inpatients for chemotherapy. Clown intervention merits further study as a way to reduce stress as well as fatigue, since that the stress and cytokines measurements are feasible based on our work.

ECCO Essential Requirements for Quality Cancer Care: Soft Tissue Sarcoma in Adults and Bone Sarcoma. A critical review.

BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Sarcoma: essential requirements for quality care • Sarcomas - which can be classified into soft tissue and bone sarcomas - are rare, but all rare cancers make up more than 20% of cancers in Europe, and there are substantial inequalities in access to high-quality care. Sarcomas, of which there are many subtypes, comprise a particularly complex and demanding challenge for healthcare systems and providers. This paper presents essential requirements for quality cancer care of soft tissue sarcomas in adults and bone sarcomas. • High-quality care must only be carried out in specialised sarcoma centres (including paediatric cancer centres) which have both a core multidisciplinary team and an extended team of allied professionals, and which are subject to quality and audit procedures. Access to such units is far from universal in all European countries. • It is essential that, to meet European aspirations for high-quality comprehensive cancer control, healthcare organisations implement the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis and follow-up, to treatment, to improve survival and quality of life for patients. CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality service for soft tissue sarcomas in adults and bone sarcomas. The ECCO expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary teams is guaranteed to all patients with sarcoma.

Itinerário terapêutico de adolescentes com osteossarcoma: implicações para o diagnóstico precoce / Therapeutic study of teens with osteosarcoma: implications for early diagnosis / Itinerario terapéutico de adolescentes con osteosarcoma: implicaciones para el diagnóstico temprano

Vários fatores interferem na demora do diagnóstico e tratamento de adolescentes portadores de osteossarcoma. O objetivo deste artigo foi descrever o itinerário terapêutico de adolescentes portadores de osteossarcoma. Trata-se de estudo descritivo, do tipo relato de caso, realizado numa instituição pública especializada em Oncologia no estado do Rio de Janeiro. Foram realizados três estudos de casos de adolescentes portadores de osteossarcoma amputados com a descrição do itinerário terapêutico. Foram identificadas questões relacionadas a dificuldades do diagnóstico precoce, como a relação familiar com o adolescente, a fragilidade de uma rede de saúde adequada ao adolescente e a dificuldade de um diagnóstico de câncer infantil. O diagnóstico precoce deve ser divulgado por meio de um sistema de saúde integrado da atenção básica com o atendimento especializado. É fundamental, para que ocorra a detecção precoce do osteossarcoma nos adolescentes, um sistema de saúde integrado, da atenção básica com o atendimento especializado, a fim de evitar a descoberta de novos casos mais tardiamente.

Several factors interfere with the delay of diagnosis and treatment of adolescents suffering from osteosarcoma. The purpose of this article wasto describe the therapeutic itinerary of adolescents suffering from osteosarcoma. This is a descriptive study of type case report, carried out in apublic institution specialized in Oncology in the State of Rio de Janeiro. Three case studies of adolescents suffering from osteosarcoma amputees with the description of the itinerary were conducted. Related issues have identified the difficulties of early diagnosis, as the family relationship with the teenager; the fragility of a health network suitable for the teenager and the difficulty of a diagnosis of childhood cancer. Early diagnosis shouldbe disclosed through a system of integrated health basic attention with the specialized care. It is essential for early detection of osteosarcoma in adolescents, an integrated health system, basic care with specialized care, in order to prevent the discovery of new cases later.

Son varios los factores que interfieren en la demora del diagnóstico y tratamiento de adolescentes con osteosarcoma. El propósito de este artículoera describir el itinerario terapéutico de adolescentes con osteosarcoma. Se trata de un estudio descriptivo de caso llevado a cabo en una institución pública especializada en oncología en el estado de Río de Janeiro. Se realizaron tres estudios de caso de adolescentes con osteosarcoma amputados con la descripción del itinerario terapéutico. Se identificaron problemas relacionados con las dificultades del diagnóstico temprano, tales como larelación familiar con el adolescente; la fragilidad de la red de salud adecuada para el adolescente y la dificultad del diagnóstico de cáncer infantil.El diagnóstico temprano debe ser revelado a través de un sistema de atención básica de la salud integrado con atención especializada. Para la detección temprana del osteosarcoma en adolescentes es fundamental que el sistema de salud sea integrado, de atención básica con atención especializada, para evitar el descubrimiento de nuevos casos más tarde.

[Histopathological diagnostic concordance in bone and soft tissue sarcomas between two comprehensive cancer centers from eastern and western Europe: a collaborative experience]. / La concordance du diagnostic histopathologique des sarcomes osseux et des tissus mous entre deux centres anticancéreux de l'Europe de l'Est et de l'Ouest : une expérience de collaboration.

INTRODUCTION: This study aims to assess the degree of concordance of histological diagnosis of bone and soft tissue sarcomas between a Comprehensive Cancer Center (CCC) of Eastern Europe - not specialized in this area of pathology - and an important CCC of Western Europe, which is one of the coordinators of a clinical reference network in sarcoma pathology. The goal is to have an overview of the sarcomatous pathology in a region of Eastern Europe and to discover diagnostic discrepancies between the two centers, while determining their cause. MATERIALS AND METHODS: The initial diagnosis was compared with the revised diagnosis on 110 specimens from 88 patients with bone or soft tissue sarcomas from East-European CCC, in a one-year period of time. RESULTS: Complete diagnostic agreement was observed in 55 cases (62.5%), a partial agreement in 23 cases (26.1%) and a major disagreement in 10 cases (11.4%). Major discrepancies of the histological type was observed in only 3 cases (3.4%): one case of discordance benign/malignant and 2 cases of discordance mesenchymal/non mesenchymal. Minor histological discrepancies - not affecting the management of the patient - were observed in 18 cases (20.4%). A major discordance in grading - potentially changing the management of the patient - was noted in 7 cases (7.9%), and a minor discrepancy in 5 cases (5.7%). DISCUSSIONS: Some histological types were clearly overdiagnosed, like "adult fibrosarcomas" and "malignant peripheral nerve sheet tumors" (MPNST), mostly converted after the audit into "undifferentiated spindle cell sarcomas" or other types of sarcomas. Some "unclassified" sarcomas and "undifferentiated pleomorphic sarcomas" could be re-classified with the aid of an extensive panel of antibodies. Overall, immunohistochemistry was responsible, but not in exclusivity, for half of the minor discrepancies, and for 2 out of 3 cases of major histological discrepancies. Otherwise, the main cause of discrepancies was the difficulties in the interpretation of the morphology. Molecular biology was decisive in one case. Most grading discrepancies resulted from the appreciation of the mitotic index. CONCLUSIONS: The profile of the sarcomatous pathology in the northwest region of Romania does not appear to differ significantly from other parts of Europe or the world, but a prospective epidemiological study would be necessary to confirm this assessment. The expansion of immunohistochemical antibody panel, the over-specialization of pathologists and, in the future, the establishment of a national network of referral centers in sarcoma pathology, are required for a high level of histological diagnosis in Eastern Europe. A periodic external audit, continuing this trans-European collaboration between the two centers, would be beneficial for monitoring progress.

Intraoperative microwave inactivation in-situ of malignant tumors in the scapula.

OBJECTIVE: To explore the feasibility and effect of microwave in situ inactivation of malignant primary or metastatic tumors in the scapula. METHODS: Seventeen patients (12 men, 5 women, mean age 48 years [range, 13-59 years]) with malignant primary or metastatic tumors involving the scapula were treated by microwave inactivation between June 1998 and February 2008. There were 12 malignant primary bone and 5 metastatic tumors. In 14 cases Area Sl was involved and in 3 cases both Areas S1 and S2. All 17 cases were by making a dorsal arc- or "∩-" shaped incision to expose the tumor, protecting the surrounding soft tissues with a copper grid, and then heated the tumors locally with 2450 MHz microwave to 50°C for 20 min, after which all or some of the necrotic tumor tissue was removed, preserving the support role of the scapula. RESULTS: The operation time was 60-180 min (mean 120 min) and blood loss was 300-1000 mL (mean 460 mL). No serious intraoperative or postoperative complications occurred in any patient. The patients were followed up for 3 months to 10 years (mean 4.2 years). Three patients with Ewing's sarcoma in the scapula had pulmonary, cerebral and systemic multiple metastases and died 8~24 months after surgery. Three patients with malignant fibrous histiocytoma died of pulmonary and systemic multiple metastases 10~22 months after surgery; one patient had recurrence 6 months after surgery and survived with tumor. Five patients with metastatic tumor in the scapula died of non-scapular metastatic tumor 6~14 months after surgery. The other five patients with primary malignant bone tumors had no recurrence or metastasis during follow-up. Three cases had restricted extension of the shoulder joint with unrestricted protraction and retroflexion after surgery. CONCLUSION: In situ microwave inactivation features simple surgery, reliable effects and patient acceptability, making it an ideal surgical method for malignant tumors in the scapula.

The prognosis for patients with osteosarcoma who have received prior manipulative therapy.

We evaluated the long-term outcome of patients with an osteosarcoma who had undergone prior manipulative therapy, a popular treatment in Asia, and investigated its effects on several prognostic factors. Of the 134 patients in this study, 70 (52%) patients had manipulative therapy and 64 (48%) did not. The age, location, and size of tumour were not significantly different between the groups. The five-year overall survival rate was 58% and 92% in the groups with and without manipulative therapy (p = 0.004). Both the primary and overall rates of lung metastasis were significantly higher in the manipulative group (primary: 32% vs 3%, p = 0.003; overall lung metastasis rate: 51.4% vs 18.8%, p < 0.001). Patients who had manipulative therapy had higher local recurrence rates in comparison to patients who did not (29% vs 6%, p = 0.011). The prognosis for patients with osteosarcoma who had manipulative therapy was significantly poorer than those who had not. Manipulative therapy was an independent factor for survival. This form of therapy may serve as a mechanism to accelerate the spread of tumour cells, and therefore must be avoided in order to improve the outcome for patients with an osteosarcoma.

Initial presentation and management of osteosarcoma, and its impact on disease outcome.

OBJECTIVE: To evaluate the initial presenting symptoms and management of osteosarcoma in Hong Kong Chinese children, in relation to any possible impact on disease outcomes. DESIGN: Retrospective study. SETTING: A tertiary referral centre of bone cancer in a university teaching hospital in Hong Kong. PATIENTS: All children aged younger than 18 years with a diagnosis of osteosarcoma who received treatment from March 1994 to October 2005. RESULTS: A total of 51 children were studied. The median age of onset was 13 (range, 3-20) years; 61% were males. The tumours were located in the distal femur and proximal tibia, which accounted for 45% and 22% of the cases, respectively; 24% of patients had metastatic disease at presentation. Swelling (76%) and pain (90%) were the most common presenting complaints. Approximately one third of the patients had a preceding history of trauma. The median duration of initial symptoms to first medical consultation of any sort was 30 (range, 0-360) days. The median time from the first consultation to a definitive diagnosis was 21 (range, 0-350) days; 25% were diagnosed more than 52 days after presentation. Bonesetters were initially consulted by 37% of these patients. From presentation to diagnosis, the median duration was 61 (range, 4-361) days. Analysis of the duration of pre-diagnosis symptoms did not correlate significantly with the development of metastatic disease, response to chemotherapy, feasibility of limb salvage surgery, relapse rates, or survival rates. CONCLUSIONS: In Hong Kong, initial consultation to bonesetters was common. A relatively long delay in between symptom onset and diagnosis of osteosarcoma was encountered. The public and medical practitioners should be made aware of this disease, especially in adolescents.

[Changes of 3-tesla 31P-MR spectroscopy of bone and soft tissue tumors].

OBJECTIVE: To study the characteristic changes of 31P-MR spectroscopy of bone and soft tissue tumors. METHODS: 41 patients were examined by phosphorus surface coil of 3 tesla MR machine, including 18 benign tumor foci and 28 malignant foci, and adjacent normal muscles. The areas under the peaks of various metabolites in the spectra were measured, including phosphomonoester (PME), inorganic phosphours (Pi), phosphodiester (PDE), phosphocreatine (Pcr), adenosine triphosphate (ATP) gamma, alpha, beta. The ratios of the metabolites to beta-ATP, NTP and Pcr were calculated. Intracellular pH was calculated according to the chemical shift change of Pi relative to Pcr. RESULTS: The ratios of Pcr/PME and PME/NTP in benign and malignant tumor groups were significantly different from those of the normal group (P<0.05). Between benign and malignant tumor groups, the ratios of PME/beta-ATP and PME/NTP were significantly different (P<0.05). CONCLUSION: Pcr/PME and PME/NTP are potential diagnostic indexes of bone and soft tissue tumors. PME/beta-ATP and PME/NTP are potential indexes of differential diagnosis of bone and soft tissue tumors.

The multidisciplinary management of osteosarcoma.

OPINION STATEMENT: Patients with suspected or confirmed osteosarcoma should be evaluated and treated at a comprehensive cancer center within a multidisciplinary sarcoma program that includes pediatric, medical and radiation oncologists, orthopedic and surgical oncologists, musculoskeletal pathologists, and radiologists. Successful treatment involves proper diagnosis, neoadjuvant and adjuvant multi-agent chemotherapy, and aggressive surgery with an emphasis toward limb-preserving procedures. Treatment of osteosarcoma should be undertaken within the framework of large cooperative group clinical trials for children, adolescents, and adults. Patients treated with osteosarcoma should be followed closely both for recurrence of disease and for development of late effects of the treatment of their cancer. The treatment of metastatic, recurrent and/or refractory disease is more controversial. Despite advances in systemic treatment, surgical technique, and supportive care, the overall outcome is still poor.

Dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features.

A 35-year-old Japanese man was admitted to the National Cancer Center, Tokyo, Japan, in December 2000, with a 2-month history of pain around the left thigh. Radiographs showed a poorly demarcated osteolytic lesion with focal mineralisation and endosteal scalloping in the left proximal femur. Biopsy showed a proliferation of highly anaplastic cells without any cartilaginous component. A wide excision of the left proximal femur with a replacement by endoprosthesis was carried out in February 2001 after treatment with methotrexate and 20 Gy radiation therapy. Pathological examination of the surgical specimen showed a focus of low-grade chondrosarcoma and the coexistence of telangiectatic osteosarcoma-like features. The patient was diagnosed with dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features. Lung metastasis appeared in July 2001 despite an adjuvant chemotherapy including methotrexate, cis-platinum and doxorubicin. The latest follow-up study in June 2004 showed multiple lung metastases. Establishing a definitive diagnosis of dedifferentiated chondrosarcoma may be difficult with limited small biopsy specimens. Dedifferentiated chondrosarcoma should be included in the differential diagnosis of osteolytic tumours with focal calcification and endosteal scalloping even if an extraosseous tumour component is not identified.

Osteogenic sarcoma of the sacral spine: an interdisciplinary team challenge.

A child with osteogenic sarcoma of the sacral spine has complex nursing and interdisciplinary team needs. The course of one patient is discussed, both from the patient and family's perspective and that of her inter-disciplinary care team. The need for a coordinated, holistic approach to care that involves advance planning, continual reassessment of goals, and clear communication among the team members and consulting services is clearly demonstrated.

[Tumor-like bone lesions of the forearm after karate training]. / Tumorartige Knochenalterationen am Unterarm nach Karatetraining.

INTRODUCTION: Differentiation between malignant bone tumors and tumor-like lesions after repetitive microtrauma following sport activities can be difficult just using radiographic methods. METHODS: We present the case of a fifteen year old karate fighter, who was examined by imaging diagnostics because of a progressive swelling and pain in the distal right forearm. RESULTS: A tumor-like appearance with bone mass formation in the x-ray, an enhancement in the surrounding tissue shown in the MRI and an increased activity in the bone scintigraphy made the diagnosis of an osteosarcoma very likely. Blood tests were not helpful. Only the evaluation of a bone biopsy could demonstrate hypertrophic reparative bone formation after multiple osseous microtrauma. Cast immobilisation reduced the osseous alteration. With the start of the training the swelling reappeared again but then finally vanished after modifying the training technique. DISCUSSION: The case demonstrates that even modern imaging techniques cannot always distinguish between tumor and tumor-like lesions caused by sports. It also stresses the importance of a correct technique in sports like karate.

Soft tissue telangiectatic osteosarcoma in a young patient: imaging and immunostains.

Telangiectatic osteosarcoma of the soft tissue is rare and generally affects adults older than 50 years of age. We present the case of a 17-year-old male who developed a mass in the right thigh. The CT and MRI findings suggested a malignant hemorrhagic tumor without discernable osteoid matrix. Differential diagnosis included various hemorrhagic mesenchymal tumors. Histology revealed large multiple cysts lined with septae and filled with numerous giant cells, pleomorphic spindle cells, and occasionally an osteoid-like substance. Immunostaining for osteocalcin was positive in the cytoplasm of both stromal mononucleate and multinucleate giant cells. Surgery and adjuvant chemotherapy were applied and the patient survives to the time of writing after 30 months of follow-up without recurrence or metastasis.

Rm de los tumores musculoesqueléticos, estado actual y últimos avances / Magnetic resonance in musculoskeletal tumors: state of the art and recent advances

La Resonancia magnética (RM) se ha convertido en la técnica diagnóstica más importante para: 1) la estadificación local de las neoplasias primarias musculoesqueléticas, 2) para monitorizar la respuesta a la quimioterapia y 3) para detectar la recidiva tumoral. La RM es capaz de diagnosticar con exactitud la extensión local del tumor, ayudando a determinar los márgenes tumorales de seguridad durante la cirugía. La RM poscontraste es útil para valorar la presencia o ausencia de necrosis tumoral tras la quimioterapia. Si la RM demuestra ausencia de necrosis tumoral (típicamente menos de un 90 por ciento de necrosis en el tejido tumoral) se considera que la respuesta a la quimioterapia es pobre y que el tratamiento es ineficaz, siendo necesario cambiar el protocolo quimioterápico. Los estudios dinámicos de RM tras la administración de contraste paramagnético i.v. en bolo son particularmente útiles para valorar la respuesta a la quimioterapia. Hasta el momento actual el cálculo de los valores de la pendiente de las curvas de realce por contraste-tiempo se realizaba mediante análisis del ROI (región de interés). Sin embargo, los nuevos ordenadores son capaces de generar la 'imagen del primer paso de contraste' o 'imagen de la tasa de realce' y calcular la tasa de realce tisular midiendo cada uno de los puntos de la imagen y utilizando un algoritmo lineal, lo cual facilita la interpretación. Estas 'imágenes del primer paso de contraste' o 'imágenes de la tasa de realce' pueden también ser útiles para diferenciar el edema perineoplásico de la lesión tumoral y para detectar áreas de tumor residual o recidiva tumoral después de la cirugía y/o radioterapia. La RM de difusión es una nueva técnica que es potencialmente capaz de detectar y cuantificar la cantidad de necrosis tumoral tras la quimioterapia o radioterapia (AU)

Delayed methotrexate clearance in a patient with sickle cell anemia and osteosarcoma.

A 15-year-old girl with homozygous sickle cell anemia (HbSS) and osteosarcoma is described. Delayed clearance of methotrexate (MTX) after the second course of high-dose MTX (HDMTX) led to the development of renal and hepatic toxicities. Rescue was accomplished with high-dose leucovorin, intravenous carboxypeptidase G2, and thymidine. Although the renal and hepatic abnormalities resolved, focal tonic-clonic seizures developed, accompanied by abnormal brain imaging. Four weeks after this episode, all clinical and biochemical abnormalities resolved. Preexistent end-organ damage associated with HbSS may compromise the ability to deliver high-dose chemotherapy with curative intent in patients with malignant disease.