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Humanized immunotoxins: a new generation of immunotoxins for targeted cancer therapy. Favorable outcome of allogeneic hematopoietic stem cell transplantation for relapsed or refractory acute promyelocytic leukemia in childhood. Agreement among and within groups of pathologists in the classification of rhabdomyosarcoma and related childhood sarcomas: report of an international study of four pathology classifications. In vivo potentiation of radiation response by topotecan in human rhabdomyosarcoma xenografted into nude mice. Although frequently omitted, details of the design should be included in reports of phase 1 trials. Bar-coding technology was first introduced into medical settings about 20 years ago. In a study of more than 9,000 2-year survivors of childhood cancer, a 14-fold excess of leukemia was observed, primarily attributable to prior therapy with alkylating agents. The introduction of antibiotics and chemotherapy led to the near abandonment of arsenic-based treatments by the mid 20th century. Cause-specific mortality and second cancer incidence after non-Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Treatment Surgery the surgical approach to a pineoblastoma can be either endoscopic or open. The chart review method is readily available and commonly used but is often inaccurate due to the lack of precise documentation and hindsight bias. Thiopurine methyltransferase deficiency in childhood lymphoblastic leukaemia: 6-mercaptopurine dosage strategies. The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition. The trisomy 21 is the first event that may predispose the cells to a proliferative advantage or further mutations. The most common metastatic sites are the lungs, bones, bone marrow, or combinations thereof. Biology of childhood osteogenic sarcoma and potential targets for therapeutic development: meeting summary. Leukemic involvement of the spleen characteristically is diffusely infiltrative and causes splenomegaly rather than a discrete splenic mass. Rarely, an unusual condition such as myositis ossificans, pyogenic myositis, or inflammatory myofibrohistiocytic proliferation (also known as pseudosarcomatous myofibroblastic tumor or inflammatory pseudotumor of the bladder) may be discovered. In multivoxel methods, more time is required to acquire the spectra, but the voxel size is smaller and representative of more homogeneous tissue. Association of delivered drug dose and outcome for children with acute lymphoblastic leukemia and unfavorable presenting features. Current protocols call for 4 to 5 courses of neoadjuvant chemotherapy, followed by surgery and then radiotherapy to treat any residual disease. Benign lesions are likely to remain unchanged in size, while lesions that increase or decrease in size are more likely to be metastases. End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System. These tumors occur throughout the body and tumors isolated to the liver appear as scattered case reports in both children and adults. Comparative renal tubular toxicity of chemotherapy regimens including ifosfamide in patients with newly diagnosed sarcomas. In single-voxel methods, the spectra are obtained during a short period of time, but the volume of interest is usually large and contains heterogeneous tissue. Examples would include an interhemispheric, transcallosal, interforniceal approach (superior) and the occipital transtentorial route (posterior). Such tumors may have a predilection for leptomeningeal dissemination at diagnosis. Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. The main reconstructive options include autologous bone grafts, structural bone allografts (intercalary or osteoarticular), and metallic endoprosthetics.

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An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Microarray analysis reveals differential gene expression patterns and regulation of single target genes contributing to the opposing phenotype of TrkA- and TrkB-expressing neuroblastomas. After division of the precentral cerebellar vein and surrounding arachnoid, the lesion is subjected to biopsy and then debulked using the ultrasonic aspirator. Chemotherapy is associated with improved survival in adult patients with primary extremity synovial sarcoma. Prognosis of children with soft tissue sarcoma who relapse after achieving a complete response. Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: potential mechanism of action. Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia group B study 8541. The granulocytopenia that occurs as a consequence of therapy-induced marrow hypoplasia, or with disease progression, places patients at risk for potentially life-threatening infections, but the value of granulocyte transfusions is limited and not well defined. Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic syndrome: a single-center experience. An extra-adrenal location and symptoms of catecholamine excess are more common in children than in adults. In a review of these studies, 30% of children with primary tumor resection had macro or microscopic residual tumor. Some genetic syndromes are associated with cancer at an early age, such as Down syndrome with leukemia and familial adenomatous polyposis with infantile hepatoblastoma. All aspects of therapy should be set forth, including surgical procedures to be used and supportive care guidelines. The lesions are usually rounded, sometimes slightly lobulated; their margins are clear, without infiltration of adjacent structures. Often, the diagnosis of intrathymic neoplasm is simplified when a prominent thymus is seen in conjunction with lymphadenopathy in other areas of the mediastinum or hila. In: Proceedings of the 100th Annual Meeting of the American Association for Cancer Research. The concept of combining two molecules, which act at different phases of T-cell activation, has also being evaluated in pediatric and adult patients with high-risk acute lymphoblastic and myelogenous leukemias. Half-lives listed for drugs in this chapter are the postdistributive (terminal, elimination) half-lives, unless otherwise noted. Results that fall between the dashed and solid lines (closed circles) will result in study continuation. Outcome and staging evaluation in malignant germ cell tumors of the ovary in children and adolescents: an Intergroup study. Low frequency of clonotypic Ig and T-cell receptor gene rearrangements in t(4;11) infant acute lymphoblastic leukaemia and its implication for the detection of minimal residual disease. Because there is growing suspicion that a malnourished state impairs ability of the host to tolerate anticancer therapy, possibly decreasing response to treatment, the early use of parenteral alimentation is warranted if less invasive approaches are precluded by gastrointestinal dysfunction. In pediatric trials, late adverse affects include second malignancies, sterility, and cognitive dysfunction. The nadir of blood counts occurs 4 to 5 weeks after administration, and the platelet count tends to be the most affected. Other recurrent genetic abnormalities have also been noted,234 but none are capable of distinguishing between high-grade and low-grade lesions. Future work will define the remaining susceptibility loci, as well as how they interact with each other and with environmental exposures. The prospect of gene therapy for human diseases was initially welcomed with great enthusiasm fueled by unrealistic expectations from investigators, clinicians, and the general public alike.

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The most common adverse events reported in children were nausea, vomiting, fatigue, diarrhea, and transaminitis. Variability in response assessment in solid tumors: effect of number of lesions chosen for measurement. Vascular endothelial growth factor expression in human neuroblastoma: up-regulation by hypoxia. The purpose of stratification is to ensure that patients with different prognoses are evenly distributed over treatments. Adverse Drug Event Reporting Not all adverse events are due to errors or mistakes. All of the currently known syndromes associated with a predisposition for developing brain tumors have an autosomal dominant pattern of inheritance, and somatic mutations have been demonstrated in specific genes for each Table 26A. Even with aggressive attempts at surgical resection, tumor relapse is common and tumor-free survival rates of not more than 25% to 30% can be achieved. The role of each modality is determined by the anticipated clinical behavior of the tumor in individual cases, considering both clinical and tumor genomic features. In addition to providing a broader range of coverage against naturally resistant tumor cells, combination chemotherapy also may prevent or delay the development of acquired resistance in initially responsive tumors and provide additive or synergistic cytotoxic effects if agents with different mechanisms of action are selected. Using these methods, investigators can detect one cell with a leukemic immunophenotype in 1,000 to 10,000 normal cells. Aplastic presentation of acute lymphoblastic leukemia: evidence for cellular inhibition of normal hematopoietic progenitors. Pharmacokinetics of high-dose cyclophosphamide in patients with metastatic bronchogenic carcinoma. Phase I clinical trial of recombinant human endostatin administered as a short intravenous infusion repeated daily. High-dose cytosine arabinoside and etoposide: an effective regimen without anthracyclines for refractory childhood acute non-lymphocytic leukemia. It is important to recognize that gross total resection in high-risk patients is generally attempted during or at the end of induction chemotherapy, and so long postoperative recovery will just delay the institution of cytotoxic therapy. However, for most intraparenchymal tumors, a well-defined tumor capsule is not present, and the resection must proceed via gradual internal debulking until the boundary between tumor and normal brain is reached. Clinical development of O6-benzylguanine, an agent that robustly potentiated the in vitro activity of nitrosoureas against glioblastoma cell lines,66 illustrates this problem. Carmustine, an inhibitor of glutathione reductase, potentiates the hepatotoxicity of high doses of acetaminophen in animals. In an overlapping group of patients, the gene expression profile of 46 snap-frozen medulloblastoma specimens were analyzed and validated with reverse transcriptase polymerase chain reaction and in situ hybridization. Most pediatric experience has been in recurrent tumors, particularly ependymomas and glial neoplasms; as a part of primary therapy, radiosurgical "boost" has been added when standard radiation management and chemotherapy have not achieved early "complete response," particularly in ependymoma, malignant germ cell histiotypes, and high-grade gliomas. The challenge is how to subtype a tumor as either embryonal or alveolar when the histology is alveolar but the fusion gene is absent. Nontoxicity endpoints in phase I trial designs for targeted, non-cytotoxic agents. Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia. Diagnostic ultrasound is relatively quick and inexpensive, uses no ionizing radiation, has no known adverse effects, and usually does not require sedation or anesthesia. Daily portal imaging data can be used to correct any offsets of the isocenter, balancing added accuracy with the additional exposure. Is maintenance chemotherapy in acute lymphoblastic leukemia being optimally delivered Phenytoin alters the disposition of topotecan and Ndesmethyl topotecan in a patient with medulloblastoma. Molecular epidemiology of deletions and mutations of the latent membrane protein 1 oncogene of the Epstein-Barr virus in posttransplant lymphoproliferative disorders. The number for each indicates the number of patients for whom information about that variable was available. The bioexpandable prosthesis: a new perspective after resection of malignant bone tumors in children. These data also confirmed the utility of neoadjuvant chemotherapy in facilitating the resection of these lesions, especially in regards to reducing tumor spillage or rupture. The extent of the growth deficit depends on the age of the patient at the time of treatment and the contribution of a specific epiphysis in the radiation field to the total growth of the body or the limb.

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Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. Both tumors show sheets of sometimes poorly differentiated and atypical cells with high proliferative activity and intermixed pseudofollicular structures. If the affected identical twin developed leukemia as an infant, the concordance rate is almost 100%. Resection of the residual mass demonstrated viable tumor mapping to this area of radiographic abnormality. Although these tumors are classified as nonmyogenic spindle cell sarcomas, they are quite distinct in their treatment, prognosis, and survival. If extravasation occurs, sodium thiosulfate should be injected into the area as rapidly as possible to neutralize the drug. Most consistently, a reciprocal chromosomal translocation between chromosomes 11 and 22, the t(11;22) (q24;q12), is present in about 85% of these tumors12,13 and is therefore considered pathognomonic for the disease. Like other benign liver tumors, small lesions may be asymptomatic incidental findings. Some yolk sac tumor may present after removal of neonatal sacrococcygeal teratoma, and retrospectively, yolk sac tumor microfoci can be detected immunohistochemically in these tumors. Analyses of sporadic osteosarcomas also showed preferential mutation of the paternal allele. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. When present, bone pain usually resolves quickly after initiation of antileukemic therapy. It is also used in the treatment of chronic myelogenous leukemia, histiocytosis, and inflammatory bowel disease. The establishment of clear treatment recommendations for pediatric germ cell tumors is difficult due to the inability to define widely accepted risk groups. Laboratory Profile Hematologic and chemical blood parameters show nonspecific changes that may correlate with disease extent. Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Most data have been derived from radiation effects following conventional fractionation. Gonadoblastoma Gonadoblastoma is a benign tumor found in dysgenetic gonads of phenotypic female subjects who have at least a portion of the Y chromosome. This is important if the new treatment is clearly more desirable than the standard in some other way. More than 90% of disease presents with localized lymphadenopathy (usually clinical stage I). A common surgical pitfall is not to attempt upfront resection of the abdominal tumor just because lung metastases are visualized. Outcome of children with cystic partially differentiated nephroblastoma treated with or without chemotherapy. B: Gross photograph of an eye with a retinoblastoma showing an exophytic growth pattern. Bloody peritoneal fluid is considered a sign of soilage, whether or not gross or microscopic tumor is identified in the fluid. The role for limited surgical resection to decompress cystic components or remove peripheral tumor resulting in more limited radiation target volumes is yet under study. Problematic situations for lymph node sampling include patients with cervical, high thoracic, or large abdominal primary tumors that are unresectable. Cytomorphology of childhood lymphoblastic leukaemia: a prospective study of 2000 patients. These tumors tend to entirely fill the cavity and produce floating tumor spheres called vitreous seeds. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Carbogen breathing with nicotinamide improves the oxygen status of tumours in patients. Pneumocystis pneumonia presents with fever, dyspnea, and cough usually associated with interstitial infltrates. A case of malignant rhabdoid tumor arising from soft parts in the prepubic region.

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Noninvasive detection of multidrug resistance in patients with hematological malignancies: are we there yet Spectra can be acquired using a single- or multivoxel techniques, with short (10 to 30 ms) or long (135 to 280 ms) echo times. Sometimes, a large rapidly growing infantile hepatic hemangioma can be life-threatening with intractable highoutput cardiac failure from intralesional arteriovenous shunting, intraperitoneal hemorrhage, respiratory distress as a result of pulmonary congestion, and massive hepatomegaly compressing abdominal vasculature and producing abdominal compartment syndrome. Is retroperitoneal lymph node dissection necessary for adult paratesticular rhabdomyosarcoma Extrahepatic growth and macrovascular involvement is indicated by adding one or more of the following: V, vena cava or all three hepatic veins involved; P, main portal or both portal branches involved; C, involvement of the caudate lobe; E, extrahepatic contiguous growth. Here, the intent is to offer a specific example, using soft tissue tumors, that can be generalized to the diagnosis and management of childhood cancer in general, particularly the issues of morphology, genetic defects, malignancy (or lack thereof), prognosis, and appropriate treatment. Mitoxantrone differs from the anthracyclines by virtue of its 3-ring nucleus, its symmetrical aminoalkyl side chains, and its lack of a glycosidic substituent, which is important for water solubility of the anthracyclines. Now internal hemipelvectomy (removal of the bony pelvis leaving a neurovascularly intact limb in place) can frequently be performed. Multiple clinical trials have addressed the additive value of involved-field radiation to multiagent chemotherapy, P. The advantages of small specimen biopsies are that they can often be performed with minimal or no anesthesia and are less invasive than an open procedure. False-positive results using these cell surface proteins can occur when platelets adhere to the surface of blasts. Recurrent 1;17 translocations in human neuroblastoma reveal nonhomologous mitotic recombination during the S/G2 phase as a novel mechanism for loss of heterozygosity. Animal Models the development of innovative modalities for the treatment of retinoblastoma has been hampered by the lack of suitable animal models of this uniquely human disease. Four histologic subtypes are further included in this category based on tissue architecture, the presence of fibrosis, and the features of the associated inflammatory infiltrate. This presentation of retinoblastoma is seen in children with an average age of 6 years. Although most tumor vaccine strategies are directed at one or two phases of immune activation, improving one phase usually improves the other phases as well. Novel therapies for high-risk disease include pupil thermotherapy,137 high-dose chemotherapy with stem cell rescue,138 ophthalmic artery chemoinfusion,139 and gene therapy. Claims of no benefit should be accompanied by a confidence interval around the observed difference; a calculated probability. Biological background of pediatric medulloblastoma and ependymoma: a review from a translational research perspective. Longer term improvements in cure rates are likely only to come from a more precise understanding of the biological basis of neuroblastoma. Immunotherapy for osteosarcoma: genetic modification of T cells overcomes low levels of tumor antigen expression. Is chest x-ray or high-resolution computed tomography scan of the chest sufficient investigation to detect pulmonary metastasis in pediatric differentiated thyroid cancer High-resolution array-based comparative genomic hybridization of medulloblastomas and supratentorial primitive neuroectodermal tumors. All fluid, bone marrow, and tissue biopsy specimens should be adequate in quantity and appropriately prepared for special studies including karyotyping, molecular genetic studies, and immunophenotyping. Although chemotherapy effectively delays the initiation of chemotherapy in children with hypothalamic/chiasmatic gliomas, many will progress after chemotherapy and ultimately require radiation therapy. A complete physical examination should be performed, with particular attention to regional lymphatic structures and to the surrounding tissues. Value of S-100 protein in the diagnosis of soft tissue tumors with particular reference to benign and malignant Schwann cell tumors. Excluding nonmelanoma skin cancer, transplant recipients younger than 25 years carry as high as a 50-fold increased risk of cancer compared with the general population in the same age group. Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma. Around 50% of prepubertal girls will maintain sufficient ovarian function to enter puberty and menstruate regularly, and the remainder will require ovarian hormone replacement to avoid the side effects of low estrogen production. National and international consensus regarding prognostic factors used for risk categorization will facilitate comparison of treatment regimens and evaluation of new agents and modalities. Elevated dihydrofolate reductase and impaired methotrexate transport as elements in methotrexate resistance in childhood acute lymphoblastic leukemia.

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Extravasation of this drug can result in severe local tissue damage and ulceration. This will represent the first therapy for neuroblastoma specifically developed for a mutated oncogenic driver. The hazards of biopsy in patients with malignant primary bone and softtissue tumors. Enucleative surgery for stage I nephroblastoma with a normal contralateral kidney. Stage 4S has been retained as a distinct stage, based on the favorable outcome generally experienced with these patients,213,254,255,256 and because of recent biological evidence distinguishing these patients from infants with conventional stage 4 disease. In select cases, a combination of vascularized auto- and allografting techniques may be optimal. Gemtuzumab ozogamicin for relapsed and refractory acute myeloid leukemia and myeloid sarcomas. Anteroposterior radiograph (A) of the left femur shows a mixed sclerotic and lytic process of the distal left femoral metadiaphysis with "sunburst" periosteal reaction medially, a classic appearance of osteosarcoma. By direct infiltration either through the optic nerve into the brain, or through the choroid into the orbit soft tissues and bones. The cells are larger and obviously more mature than those forming pineoblastoma, although there may be a mixture of both types in some tumors. Association of radical surgery and cyclic polychemotherapy (with vincristine, methotrexate and adriamycin) in the treatment of some forms of osteosarcoma. B: Histologic photograph showing poorly differentiated retinoblastoma cells with high nuclear: cytoplasmic ratio, increased mitotic activity (solid arrow), and increased apoptosis (hollow arrow). In addition, molecularly targeted agents may specifically interfere with critical developmental pathways and block the progression from immature to mature adult tissues. Only a few randomized pediatric trials have compared treatment outcome after chemotherapy alone with combined-modality therapy. Lesions that grow medially and encroach on or expand within the lateral ventricle can be approached transcallosally or transfrontally, through the middle frontal gyrus, whereas tumors that extend laterally in the nondominant hemisphere may be approached through the insula after the sylvian fissure has been opened. Laboratory Workup Laboratory evaluations that should be performed preoperatively include a complete blood count with differential, liver function tests, renal function including urinalysis, electrolytes, and serum calcium. This technique has been successfully applied to the chemotherapy administration process in children with cancer and can lead to the more rapid adaptation of safety interventions, such as the use of preprinted order sets. Selection of patients for radiation avoidance, integration of modern radiotherapeutic approaches for improved conformal delivery of dose, and further reduction in the volume of treatment remain important questions for study in the context of the excellent disease control rates already achieved with traditional radiation techniques. Less than 10% of the administered dose of cyclophosphamide is metabolized via this pathway, but up to 50% of the ifosfamide is dechloroethylated, resulting in a greater rate of production of the potentially toxic byproduct chloroacetaldehyde compared with cyclophosphamide. Multidrug adjuvant chemotherapy for osteosarcoma: interim report of the Southwest Oncology Group Studies. Sagittal T1 images of the entire spine with gadolinium are obtained with axial T1 images obtained as needed. Retrospective analyses have shown an association of chemotherapy dose intensity with response and survival rates. Although statistical concerns play an important role in aiding committee deliberations, interim monitoring decisions are multifaceted. In children younger than 3 years, more than 85% of tumors may occur in the posterior fossa. Using this technique, the volume of the bowel exposed to radiation doses exceeding 30 Gy can be limited. Cardiac dysfunction induced by novel targeted anticancer therapy: an emerging issue. Even a simple order has multiple elements requiring prescriber vigilance to write correctly. Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism. Intravenous contrast is useful for optimal assessment of the parenchyma of the liver, spleen, and kidneys; evaluation of intratumoral necrosis; and differentiation of blood vessels from other structures such as lymph nodes, particularly in the mediastinum and retroperitoneum.

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Prosthetic survival and clinical results with use of large-segment replacements in the treatment of high-grade bone sarcomas. Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors. When the difference to be detected is reduced by half, the required sample size more than triples. Whether such abnormalities precede the development of leukemia or are a consequence of the disease is unclear. Through the various staging systems used, the different approaches to treatment adopted by the dominant multicenter study groups are reflected. Surgical intervention has two goals: to establish an accurate diagnosis and to determine the local-regional extent of disease. Preoperative transcatheter selective arterial chemoembolization can be used to induce surgical resectability of previously unresectable hepatoblastoma, especially in patients without distant metastases. Nonspecific findings such as head tilt, stiff neck, and weight loss may also occur. Treatment of intermediate risk rhabdomyosarcoma and undifferentiated sarcoma with alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. During resection, regional lymph nodes should be sampled to adequately assess the stage of the patient. The only tumors resected primarily were those deemed to be confined to a single section. Prognostic significance of radiological bone involvement in childhood acute lymphoblastic leukaemia. While classic congenital mesoblastic nephroma histologically resembles infantile myofibromatosis, the cellular congenital mesoblastic nephroma resembles infantile fibrosarcoma. Children who have achieved a complete cytogenetic and molecular response to imatinib and who have a matched related donor present a particular dilemma. Current explorations focus primarily on medulloblastoma, providing a potential advantage in dose distribution when targeting the primary tumor bed (especially with regard to cochlear and temporal lobe sparing) and the neuraxis (sparing exit from the spinal field, especially for thyroid and breast tissues). Compared with single-agent therapy, the use of drug combinations significantly increased the percentage of patients achieving complete remission and prolonged the duration of their remissions. Some studies have found specific neurocognitive deficits in attention, memory, coordination, fine motor speed, visual motor processing, mathematics, and spatial relations. The protein binding of etoposide is highly variable in cancer patients (range, 76% to 97%), and the degree of binding is correlated with the serum albumin level. Analysis of the results of first salvage therapy with three different treatment approaches for 163 patients. In general, high rates of long-term survival are characteristic as well, despite low but steady rates of disease progression even 10 years from diagnosis. These sites include the proximal fibula, clavicle, scapular body, and most areas of the ileum, ischium, and pubis of the pelvis. Historically, an orbital implant was not usually placed after enucleation for retinoblastoma because of potential interference with palpation of the socket and clinical detection of orbital tumor recurrence. These will be especially crucial in children with disseminated medulloblastoma as, to date, studies have not demonstrated a significant improvement in long-term survival for children in this patient population. A: Buphthalmus and nodularity of the inferior eyelid produced by extraocular extension of tumor. Chemotherapy for induction of remission of childhood acute myeloid leukemia followed by marrow transplantation or multiagent chemotherapy: a report from the Childrens Cancer Group. A flank incision does not allow examination of the contralateral kidney or adequate lymph node biopsy, and a small incision in all too many cases results in rupture of the tumor and requires subsequent abdominal irradiation. Latent membrane protein expression in posttransplant lymphoproliferative diseases. Abnormal constitutional karyotypes in patients with neuroblastoma: a report of four new cases and review of 47 others in the literature. The clinical presentation primarily reflects the site of tumor origin, the age and developmental level of the affected child, and, occasionally, the tumor type. Integrins alpha(v)beta3 and alpha(v)beta5 are expressed by endothelium of high-risk neuroblastoma and their inhibition is associated with increased endogenous ceramide. To be effective in preventing relapse, postinduction therapy must suppress leukemic growth and provide continuing leukemic cytoreduction, without permitting the emergence of drug-resistant clones.

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The risk of this complication is greatest immediately after initiation of treatment, when leukemic cell lysis releases P. Ferromagnetic materials, such as iron, cobalt, nickel, and certain types of stainless steel, strongly interact with magnetic fields. The prognosis in spindle-cell sarcoma depends on the expression of cyclin-dependent kinase inhibitor p27(Kip1) and cyclin E. Intracellular retention of cytosine arabinoside triphosphate in blast cells from children with acute myelogenous and lymphoblastic leukemia. Eastern Cooperative Oncology Group: a comparison of adjuvant doxorubicin and observation for patients with localized soft tissue sarcoma. Intensity-modulated radiation therapy with use of cone-down boost for pediatric head-and-neck rhabdomyosarcoma. The former requires cooperation of all the individual study investigators and is used relatively infrequently, though the overview analysis regularly conducted by the early breast cancer trialists169 and a recent analysis of transplant outcomes in pediatric leukemia are notable examples. Renal function should be measured in patients on metformin before considering the administration of intravascular contrast, and published guidelines for the safe administration of intravascular contrast agents for elective and emergent radiologic procedures in patients on metformin with normal or impaired renal function should be followed. Appropriate surveillance should be undertaken such as breast screening for girls with thoracic radiation, endocrine screening for thyroid cancer, cardiac and lung function for those with thoracic radiation, and ovarian function in those with abdominal radiation. Report of four cases of a hyalinizing, matrix-rich variant of rhabdomyosarcoma that may be confused with osteosarcoma, chondrosarcoma, or angiosarcoma. The designers must ensure that items are unambiguously presented, coding procedures are consistent and straightforward, the form is structured for efficiency in entering and keying the data, and the format of the data allows efficient analysis. Location of the retinoblastoma susceptibility gene(s) and the human esterase D locus. Ifosfamide has also been implicated as a cause of cardiomyopathy and arrhythmias at doses of 10 to 18 g/m2 in a transplant setting. Responder versus nonresponder comparisons: daunorubicin plus prednisone in treatment of acute nonlymphocytic leukemia [letter]. The prognostic value of testicular biopsy in childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group. Although investigators have suggested that complete tumor removal may be associated with longer survival and less frequent local recurrences, the degree of resection has not been associated with outcome in several studies. All reports are taken seriously and investigated (and rewarded) whether they come from pilots, mechanics, or maintenance personnel. These 143 patients were treated with moderately dose-intensive chemotherapy including cyclophosphamide, doxorubicin, cisplatin, and etoposide, as well as local radiation for any gross residual disease following delayed surgery. Further evidence of the increased risk for malignant peripheral nerve sheath tumour from a Scottish cohort of patients with neurofibromatosis type 1. Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics. Although our knowledge of the teratogenicity and mutagenicity of antileukemic therapy is incomplete, some data indicate that normal births occur in most cases in which women receive chemotherapy before gestation or after the first trimester. Hodgkin disease: prediction of outcome with 67Ga scintigraphy after one cycle of chemotherapy. It has been reported that the degree of differentiation decreases with age at enucleation. Patients with leukemia provide the greatest opportunities for sequential evaluations of agent effects on cancer cells, given the relative ease with which either peripheral blood or bone marrow can be sampled. Tissue microarrays are an effective quality assurance tool for diagnostic immunohistochemistry. Consensus has not been established among investigators regarding prognostic features that justify the risks of this aggressive approach. In addition, the process of registration can be used to verify that the patient meets the eligibility criteria. European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes. Acquired chromosome alterations such as aneuploidy, an additional Ph1 chromosome, trisomy 8, and loss of a p53 allele from aberrations in the short arm of chromosome 17 have been reported. Pain the evaluation and management of pain in pediatric oncology patients present a unique challenge. The informed consent of one parent is usually adequate if the child is being enrolled onto a study from which he or she may receive direct benefit from the research, such as in a therapeutic trial. High TrkA expression correlates with younger age at diagnosis, lower tumor stage, favorable biological features, and good outcome.