The Second Pediatric Blood and Marrow Transplant Consortium International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation (HCT): Defining the Unique Late Effects of Children undergoing HCT for Immune Deficiencies, Inherited Marrow Failure Disorders, and Hemoglobinopathies

PubMed Central

Dietz, Andrew C.; Duncan, Christine N.; Alter, Blanche P.; Bresters, Dorine; Cowan, Morton J.; Notarangelo, Luigi; Rosenberg, Philip S.; Shenoy, Shalini; Skinner, Roderick; Walters, Mark C.; Wagner, John; Baker, K. Scott; Pulsipher, Michael A.

2016-01-01

An international consensus conference sponsored by the Pediatric Blood and Marrow Transplant consortium entitled, “Late Effects Screening and Recommendations Following Allogeneic Hematopoietic Cell Transplant for Immune Deficiency and Non-malignant Hematologic Disease was held in Minneapolis, Minnesota on May 10–11, 2016. The purpose of the conference was to address the unmet need for a greater understanding of and the screening for long-term complications in the growing population of survivors of transplantation for nonmalignant disorders. The conference focused on transplantation for hemoglobinopathy, immune deficiency, and inherited bone marrow syndromes. A multidisciplinary group of experts in the disease areas and transplant late effects presented the current state of understanding of how the underlying disease, pretransplant therapies, and transplant related factors uniquely interact to influence the development of late toxicities. Recommendations were put forth by the group for the late effects screening of survivors of transplantation for these non-malignant disorders. The findings and recommendations that came from this conference will be presented in a series of six additional manuscripts in the upcoming months. In this manuscript we explore the need for screening practices specific to the survivors of transplantation for non-malignant diseases and the metholodologic challenges associated with the study of these patients. PMID:27737772

National practice patterns and outcomes of pediatric nephrectomy: comparison between urology and general surgery.

PubMed

Suson, Kristina D; Wolfe-Christensen, Cortney; Elder, Jack S; Lakshmanan, Yegappan

2015-05-01

In adults nephrectomy is under the purview of urologists, but pediatric urologists and pediatric general surgeons perform extirpative renal surgery in children. We compared the contemporary performance and outcome of all-cause nephrectomy at pediatric hospitals as performed by pediatric urologists and pediatric general surgeons. We queried the Pediatric Health Information System to identify patients 0 to 18 years old who were treated with nephrectomy between 2004 and 2013 by pediatric urologists and pediatric general surgeons. Data points included age, gender, severity level, mortality risk, complications and length of stay. Patients were compared by APR DRG codes 442 (kidney and urinary tract procedures for malignancy) and 443 (kidney and urinary tract procedures for nonmalignancy). Pediatric urologists performed more all-cause nephrectomies. While pediatric urologists were more likely to operate on patients with benign renal disease, pediatric general surgeons were more likely to operate on children with malignancy. Patients on whom pediatric general surgeons operated had a higher average severity level and were at greater risk for mortality. After controlling for differences patients without malignancy operated on by pediatric urologists had a shorter length of stay, and fewer medical and surgical complications. There was no difference in length of stay, or medical or surgical complications in patients with malignancy. Overall compared to pediatric general surgeons more nephrectomies are performed by pediatric urologists. Short-term outcomes, including length of stay and complication rates, appear better in this data set in patients without malignancy who undergo nephrectomy by pediatric urologists but there is no difference in outcomes when nephrectomy is performed for malignancy. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Pediatric Salivary Gland Malignancies.

PubMed

Ord, Robert A; Carlson, Eric R

2016-02-01

Pediatric malignant salivary gland tumors are extremely rare. The percentage of malignant tumors is higher than that seen in adults, although the outcomes in terms of survival are better in pediatric patients. The mainstay of treatment is surgical excision with negative margins. This article reviews current concepts in demographics, etiology, management, and outcomes of malignant salivary tumors in children. Copyright © 2016 Elsevier Inc. All rights reserved.

THE DIFFERENTIAL ALGORITHM BETWEEN RHEUMATOLOGIC AND MALIGN DISEASES

PubMed Central

Këpuska, Arbnore Batalli; Spahiju, Lidvana; Bejiq, Ramush; Manqestena, Rufadije; Stavileci, Valbona; Ibraimi, Zana

2016-01-01

Objective: The aim of this study is to determine the differential algorithm between rheumatism and malignant diseases. For every pediatrician, to be warned when attending joint pain and child arthralgia and prevent and treat within time malignant diseases. Methods: Our case presented in Pediatric Clinic, was referred by Regional Hospital of Ferizaj with suspected diagnose of Febris Rheumatica and Arthralgia. The main complaint was joint pain. Initially the patient was admitted at Cardiology and Rheumatology department. Then after examinations was referred to Hemato-Oncology department. Hospitalized during the period from 12.12.2014 to 18.01.2015. Results: Bone marrow biopsy as terminal diagnostic tool reviled severe malignant hematologic disease, which was masked by clinical and lab findings as Febris Rheumatica. Conclusion: Arthralgia as one of child’s often complain, should have a special attention paid to, as it might be a warning sign for a lot of diseases. Steroid treatment should not be used before final diagnose of the disease and before rolling out hematologic etiology with peripheral blood smear. PMID:27147926

Sports in pediatric oncology: the role(s) of physical activity for children with cancer.

PubMed

Götte, Miriam; Taraks, Silke; Boos, Joachim

2014-03-01

Malignant disease and anticancer therapy dramatically affect daily life activities and participation in grassroots and high-performance sports. Specifically in childhood and adolescence such activities are relevant factors of individual development and social life. This review focuses on the inherent reduction of normal physical activity in pediatric oncology because this cutback additionally contributes to the level of burden of malignancies. Maintaining normality requires detailed analyses of disease-related and therapy-related restrictions and their justification. Relevant efforts should be stepped up to maintain physical activity levels during pediatric cancer therapy. Another aspect addresses direct therapeutic implications. Feasibility studies, nonrandomized as well as randomized investigations addressed therapeutic effects in acute hospital care, in bone marrow transplant settings, and in outpatient therapy. The overall summary shows positive effects on clinical and psychosocial outcome. Even if the basis of the data for children is still limited, there will be no doubt about a general impact of physical activity on acute side effects as well as late effects. In the areas of tension between context-related restrictions, the right to maintain normality wherever possible and the positive therapeutic and psychosocial perspectives of sports, strong efforts are needed to support physical activity wherever indicated, clarify contraindications, and overcome structural limitations.

New frontiers in pediatric allogeneic stem cell transplantation

PubMed Central

Talano, Julie-An M.; Pulsipher, Michael A.; Symons, Heather J.; Militano, Olga; Shereck, Evan B.; Giller, Roger H.; Hancock, Laura; Morris, Erin; Cairo, Mitchell S.

2015-01-01

The inaugural meeting of “New Frontiers in Pediatric Allogeneic Stem Cell Transplantation” organized by the Pediatric Blood and Transplant Consortium (PBMTC) was held at the American Society of Pediatric Hematology and Oncology Annual Meeting. This meeting provided an international platform for physicians and investigators active in the research and utilization of pediatric allogeneic stem cell transplantation (AlloSCT) in children and adolescents with malignant and non-malignant disease, to share information and develop future collaborative strategies. The primary objectives of the conference included: 1) to present advances in AlloSCT in pediatric ALL and novel pre- and post-immunotherapy; 2) to highlight new strategies in alternative allogeneic stem cell donor sources for children and adolescents with non-malignant hematological disorders; 3) to discuss timing of immune reconstitution after AlloSCT and methods of facilitating more rapid recovery of immunity; 4) to identify strategies of utilizing AlloSCT in pediatric myeloproliferative disorders (MPD); 5) to develop diagnostic and therapeutic approaches to hematological complications post pediatric AlloSCT; 6) to enhance the understanding of new novel cellular therapeutic approaches to pediatric malignant and non-malignant hematological disorders; and 7) to discuss optimizing drug therapy in pediatric recipients of AlloSCT. This paper will provide a brief overview of the conference. PMID:24820213

Tumor angiogenesis and its clinical significance in pediatric malignant liver tumor

PubMed Central

Sun, Xiao-Yi; Wu, Zai-De; Liao, Xiao-Feng; Yuan, Ji-Yan

2005-01-01

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD) count in pediatric malignant liver tumor and their clinical significances. METHODS: Fourteen children with malignant liver tumors including seven hepatocellular carcinomas (HCCs), five hepatoblastomas, one malignant mesenchymoma and one rhabdomyosarcoma were studied. Twelve adult HCC samples served as control group. All samples were examined with streptavidin-biotin peroxidase (SP) immunohistochemical staining for VEGF expression and MVD count. RESULTS: VEGF positive expression in all pediatric malignant liver tumors was significantly higher than that in adult HCC (0.4971±0.14 vs 0.4027±0.03, P<0.05). VEGF expression in pediatric HCC group was also markedly higher than that in adult HCC group (0.5665±0.10 vs 0.4027±0.03, P<0.01) and pediatric non-HCC group (0.5665±0.10 vs 0.4276±0.15, P<0.05). The mean value of MVD in pediatric malignant liver tumors was significantly higher than that in adult HCC (33.66±12.24 vs 26.52±4.38, P<0.05). Furthermore, MVD in pediatric HCC group was significantly higher compared to that in adult HCC group (36.94±9.28 vs 26.52±4.38, P<0.05), but there was no significant difference compared to the pediatric non-HCC group (36.94±9.28 vs 30.37±14.61, P>0.05). All 7 children in HCC group died within 2 years, whereas the prognosis in pediatric non-HCC group was better, in which two patients survived more than 5 years. CONCLUSION: Children with malignant liver tumors, especially with HCC, may have extensive angiogenesis that induces a rapid tumor growth and leads to a poor prognosis. PMID:15655835

Nutritional status among pediatric cancer patients: a comparison between hematological malignancies and solid tumors.

PubMed

Tah, Pei Chien; Nik Shanita, Safii; Poh, Bee Koon

2012-10-01

This study aimed to compare the nutritional status of pediatric patients with hematological malignancies and solid tumors. A total of 74 pediatric cancer patients were assessed for anthropometric status, biochemical profiles, and dietary intake. The prevalence of undernutrition was higher among patients with solid tumors as reflected in their lower dietary intakes of energy and nutrients compared with patients with hematological malignancies. Adequate dietary intake is important for pediatric cancer patients, but nurses need to pay more attention to the diets of patients with solid tumors as compared with those with hematological malignancies. © 2012, Wiley Periodicals, Inc.

3D Printed Pediatric Temporal Bone: A Novel Training Model.

PubMed

Longfield, Evan A; Brickman, Todd M; Jeyakumar, Anita

2015-06-01

Temporal bone dissection is a fundamental element of otologic training. Cadaveric temporal bones (CTB) are the gold standard surgical training model; however, many institutions do not have ready access to them and their cost can be significant: $300 to $500. Furthermore, pediatric cadaveric temporal bones are not readily available. Our objective is to develop a pediatric temporal bone model. Temporal bone model. Tertiary Children's Hospital. Pediatric patient model. We describe the novel use of a 3D printer for the generation of a plaster training model from a pediatric high- resolution CT temporal bone scan of a normal pediatric temporal bone. Three models were produced and were evaluated. The models utilized multiple colors (white for bone, yellow for the facial nerve) and were of high quality. Two models were drilled as a proof of concept and found to be an acceptable facsimile of the patient's anatomy, rendering all necessary surgical landmarks accurately. The only negative comments pertaining to the 3D printed temporal bone as a training model were the lack of variation in hardness between cortical and cancellous bone, noting a tactile variation from cadaveric temporal bones. Our novel pediatric 3D temporal bone training model is a viable, low-cost training option for previously inaccessible pediatric temporal bone training. Our hope is that, as 3D printers become commonplace, these models could be rapidly reproduced, allowing for trainees to print models of patients before performing surgery on the living patient.

GLUT1 expression in pediatric adrenocortical tumors: a promising candidate to predict clinical behavior.

PubMed

Pinheiro, Céline; Granja, Sara; Longatto-Filho, Adhemar; Faria, André M; Fragoso, Maria C B V; Lovisolo, Silvana M; Bonatelli, Murilo; Costa, Ricardo F A; Lerário, Antonio M; Almeida, Madson Q; Baltazar, Fátima; Zerbini, Maria C N

2017-09-08

Discrimination between benign and malignant tumors is a challenging process in pediatric adrenocortical tumors. New insights in the metabolic profile of pediatric adrenocortical tumors may contribute to this distinction, predict prognosis, as well as identify new molecular targets for therapy. The aim of this work is to characterize the expression of the metabolism-related proteins MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX in a series of pediatric adrenocortical tumors. A total of 50 pediatric patients presenting adrenocortical tumors, including 41 clinically benign and 9 clinically malignant tumors, were included. Protein expression was evaluated using immunohistochemistry in samples arranged in tissue microarrays. The immunohistochemical analysis showed a significant increase in plasma membrane expression of GLUT1 in malignant lesions, when compared to benign lesions ( p =0.004), being the expression of this protein associated with shorter overall and disease-free survival ( p =0.004 and p =0.001, respectively). Although significant differences were not observed for proteins other than GLUT1, MCT1, MCT4 and CD147 were highly expressed in pediatric adrenocortical neoplasias (around 90%). GLUT1 expression was differentially expressed in pediatric adrenocortical tumors, with higher expression in clinically malignant tumors, and associated with shorter survival, suggesting a metabolic remodeling towards a hyperglycolytic phenotype in this malignancy.

Pediatric cancer risk in association with birth defects: A systematic review

PubMed Central

Padda, Hannah; Feng, Qianxi; Partap, Sonia; Fowler, Susan A.; Druley, Todd E.

2017-01-01

Background Many epidemiological studies have examined associations between birth defects (BDs) and pediatric malignancy over the past several decades. Our objective was to conduct a systematic literature review of studies reporting on this association. Methods We used librarian-designed searches of the PubMed Medline and Embase databases to identify primary research articles on pediatric neoplasms and BDs. English language articles from PubMed and Embase up to 10/12/2015, and in PubMed up to 5/12/2017 following an updated search, were eligible for inclusion if they reported primary epidemiological research results on associations between BDs and pediatric malignancies. Two reviewers coded each article based on the title and abstract to identify eligible articles that were abstracted using a structured form. Additional articles were identified through reference lists and other sources. Results were synthesized for pediatric cancers overall and for nine major pediatric cancer subtypes. Results A total of 14,778 article citations were identified, of which 80 met inclusion criteria. Pediatric cancer risk was increased in most studies in association with BDs overall with some notable specific findings, including increased risks for CNS tumors in association with CNS abnormalities and positive associations between rib anomalies and several pediatric cancer types. Conclusions Some children born with BDs may be at increased risk for specific pediatric malignancy types. This work provides a foundation for future investigations that are needed to clarify specific BD types predisposing toward malignancy and possible underlying causes of both BDs and malignancy. PMID:28749971

Magnetic Resonance Imaging of Tumor Associated Macrophages: Clinical Translation.

PubMed

Aghighi, Maryam; Theruvath, Ashok Joseph; Pareek, Anuj; Pisani, Laura; Alford, Raphael; Muehe, Anne Monika; Sethi, Tarsheen K; Holdsworth, Samantha J; Hazard, Florette K; Gratzinger, Dita; Luna-Fineman, Sandra; Advani, Ranjana H; Spunt, Sheri L; Daldrup-Link, Heike E

2018-05-15

Tumor associated macrophages (TAM) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with non-invasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. In a first-in-patient , IRB-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (2 lymphoma, 3 bone sarcoma) underwent pre- and post-contrast MRI. Subsequently, 20 patients (10 lymphoma, 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24-48 hours after intravenous injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68+ and CD163+ TAM quantities on histopathology. Significant ferumoxytol tumor enhancement was noted on post-contrast scans compared to pre-contrast scans ( P = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density ( P < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68+ and CD163+ TAM ( P < 0.05). Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies. Copyright ©2018, American Association for Cancer Research.

Inhibiting Polo-like kinase 1 causes growth reduction and apoptosis in pediatric acute lymphoblastic leukemia cells

PubMed Central

Hartsink-Segers, Stefanie A.; Exalto, Carla; Allen, Matthew; Williamson, Daniel; Clifford, Steven C.; Horstmann, Martin; Caron, Huib N.; Pieters, Rob; Den Boer, Monique L.

2013-01-01

This study investigated Polo-like kinase 1, a mitotic regulator often over-expressed in solid tumors and adult hematopoietic malignancies, as a potential new target in the treatment of pediatric acute lymphoblastic leukemia. Polo-like kinase 1 protein and Thr210 phosphorylation levels were higher in pediatric acute lymphoblastic leukemia (n=172) than in normal bone marrow mononuclear cells (n=10) (P<0.0001). High Polo-like kinase 1 protein phosphorylation, but not expression, was associated with a lower probability of event-free survival (P=0.042) and was a borderline significant prognostic factor (P=0.065) in a multivariate analysis including age and initial white blood cell count. Polo-like kinase 1 was necessary for leukemic cell survival, since short hairpin-mediated Polo-like kinase 1 knockdown in acute lymphoblastic leukemia cell lines inhibited cell proliferation by G2/M cell cycle arrest and induced apoptosis through caspase-3 and poly (ADP-ribose) polymerase cleavage. Primary patient cells with a high Polo-like kinase 1 protein expression were sensitive to the Polo-like kinase 1-specific inhibitor NMS-P937 in vitro, whereas cells with a low expression and normal bone marrow cells were resistant. This sensitivity was likely not caused by Polo-like kinase 1 mutations, since only one new mutation (Ser335Arg) was found by 454-sequencing of 38 pediatric acute lymphoblastic leukemia cases. This mutation did not affect Polo-like kinase 1 expression or NMS-P937 sensitivity. Together, these results indicate a pivotal role for Polo-like kinase 1 in pediatric acute lymphoblastic leukemia and show potential for Polo-like kinase 1-inhibiting drugs as an addition to current treatment strategies for cases expressing high Polo-like kinase 1 levels. PMID:23753023

Bone healing in children.

PubMed

Lindaman, L M

2001-01-01

Just as pediatric fractures and bones are basically similar to adult fractures and bones, pediatric bone healing is basically similar to adult bone healing. They both go through the three same phases of inflammation, reparation, and remodeling. It is those differences between pediatric and adult bone, however, that affect the differences in the healing of pediatric bone. Because pediatric bone can fail in compression, less initial stability and less callus formation is required to achieve a clinically stable or healed fracture. The greater subperiosteal hematoma and the stronger periosteum all contribute to a more rapid formation of callous strong enough to render the fracture healed more rapidly than the adult. Genes and hormones that are necessary for the initial formation of the skeleton are the same as, or at least similar in most instances, to those necessary for the healing of fractures. This osteogenic environment of the pediatric bone means that these fracture healing processes are already ongoing in the child at the time of the fracture. In the adult, these factors must be reawakened, leading to the slower healing time in the adult. Once the fracture is healed, the still-growing pediatric bone can correct any "sins" of fracture alignment or angulation leaving the bone with no signs of having ever been broken. The final result is bone that is, in the child's words, "as good as new."

Pediatric oncology in Turkey.

PubMed

Kebudi, Rejin

2012-03-01

The survival of children with cancer has increased dramatically in the last decades, as a result of advances in diagnosis, treatment and supportive care. Each year in Turkey, 2500-3000 new childhood cancer cases are expected. According to the Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Societies Registry, about 2000 new pediatric cancer cases are reported each year. The population in Turkey is relatively young. One fourth of the population is younger than 15 years of age. According to childhood mortality, cancer is the fourth cause of death (7.2%) after infections, cardiac deaths and accidents. The major cancers in children in Turkey are leukemia (31%), lymphoma (19%), central nervous system (CNS) neoplasms (13%), neuroblastomas (7%), bone tumors (6.1%), soft tissue sarcomas (6%), followed by renal tumors, germ cell tumors, retinoblastoma, carcinomas-epithelial neoplasms, hepatic tumors and others. Lymphomas rank second in frequency as in many developing countries in contrast to West Europe or USA, where CNS neoplasms rank second in frequency. The seven-year survival rate in children with malignancies in Turkey is 65.8%. The history of modern Pediatric Oncology in Turkey dates back to the 1970's. Pediatric Oncology has been accepted as a subspecialty in Turkey since 1983. Pediatric Oncologists are all well trained and dedicated. All costs for the diagnosis and treatment of children with cancer is covered by the government. Education and infrastructure for palliative care needs improvement.

Role of apparent diffusion coefficients with diffusion-weighted magnetic resonance imaging in differentiating between benign and malignant bone tumors.

PubMed

Wang, Tingting; Wu, Xiangru; Cui, Yanfen; Chu, Caiting; Ren, Gang; Li, Wenhua

2014-11-29

Benign and malignant bone tumors can present similar imaging features. This study aims to evaluate the significance of apparent diffusion coefficients (ADC) in differentiating between benign and malignant bone tumors. A total of 187 patients with 198 bone masses underwent diffusion-weighted (DW) magnetic resonance (MR) imaging. The ADC values in the solid components of the bone masses were assessed. Statistical differences between the mean ADC values in the different tumor types were determined by Student's t-test. Histological analysis showed that 84/198 (42.4%) of the bone masses were benign and 114/198 (57.6%) were malignant. There was a significant difference between the mean ADC values in the benign and malignant bone lesions (P<0.05). However, no significant difference was found in the mean ADC value between non-ossifying fibromas, osteofibrous dysplasia, and malignant bone tumors. When an ADC cutoff value≥1.10×10(-3) mm2/s was applied, malignant bone lesions were excluded with a sensitivity of 89.7%, a specificity of 84.5%, a positive predictive value of 82.6%, and a negative predictive value of 95.3%. The combination of DW imaging with ADC quantification and T2-weighted signal characteristics of the solid components in lesions can facilitate differentiation between benign and malignant bone tumors.

New anti-angiogenic strategies in pediatric solid malignancies: agents and biomarkers of a near future.

PubMed

Taylor, Melissa; Rössler, Jochen; Geoerger, Birgit; Vassal, Gilles; Farace, Françoise

2010-07-01

Antiangiogenic strategies are affording considerable interest and have become a major milestone in therapeutics of various adult cancers. However, progress has been slow to expand such therapies to patients with pediatric solid malignancies. This review discusses the principal pathways for angiogenesis in pediatric solid malignancies and summarizes recent preclinical and clinical data on antiangiogenesis strategies in these tumors. The reader will gain state-of-the-art knowledge in the current advancements of antiangiogenic therapies in pediatric clinical trials in regard to supporting preclinical data, and in the status of potential biomarkers investigated for monitoring angiogenesis inhibitors. Mechanisms of resistance to antiangiogenic therapy will also be discussed. Finally, we describe our experience in the monitoring of circulating endothelial cells and progenitors and their potential role as biomarkers of metastatic disease and resistance to antiangiogenic therapies. Evaluation and development of antiangiogenesis protocols are starting and represent a crucial step in the management of pediatric solid malignancies today. Emphasis should be placed on the development of proper surrogate markers to monitor antiangiogenic activity and on the possible long-term effects of these therapies in a pediatric population.

Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies.

PubMed

Place, Andrew E; Goldsmith, Kelly; Bourquin, Jean-Pierre; Loh, Mignon L; Gore, Lia; Morgenstern, Daniel A; Sanzgiri, Yeshwant; Hoffman, David; Zhou, Ying; Ross, Jeremy A; Prine, Betty; Shebley, Mohamad; McNamee, Megan; Farazi, Thalia; Kim, Su Young; Verdugo, Maria; Lash-Fleming, Leanne; Zwaan, C Michel; Vormoor, Josef

2018-03-29

Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).

Treatment Option Overview (Osteosarcoma and Malignant Fibrous Histiocytoma of Bone)

MedlinePlus

... Treatment Research Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Treatment (PDQ®)–Patient Version General Information About Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Go to Health Professional Version Key Points Osteosarcoma ...

Bone Metabolism of the Patient with a Malignant Melanoma during the Entry Examination and the Check-up of Whole-body Bone Scintigraphy.

PubMed

Weissensteiner, Jaroslav; Babušíková, Eva

Malignant melanoma is a malignancy located predominantly in the skin and the incidence of melanoma increases. We compared the markers of bone metabolism - osteocalcin (OC), beta-carboxyterminal cross-linked telopeptide of type I collagen (β-CrossLaps, β-CTx) and tumour marker - human epididymis protein 4 (HE4) in the serum with finding during the entry examination and the check-up of whole-body bone scintigraphy of the patient with a malignant melanoma. Serum concentrations of OC, β-CTx, HE4 were determined in 1 patient (female, age 64 years) with malignant melanoma and correlated with the presence of equivocal bone metastases detected by whole-body bone scintigraphy (the entry examination and check-up after 6 months). Concentrations of bone metabolism markers decreased during six months and we observed progress in bone metastases. The change of the markers levels during the entry examination and the check-up of the whole-body bone scintigraphy with equivocal finding of bone metastases could be a sign of a possible initiating progression of malignant melanoma despite a clinically negative finding that does not prove the progression of the disease.

Skull infarction in a patient with malignant fibrous histiocytoma.

PubMed

Nagle, C E; Morayati, S J; LeDuc, M A

1987-09-01

The authors describe a case of a skull infarction initially suspected to be an isolated, remote metastasis in a patient diagnosed with soft tissue malignant fibrous histiocytoma. Osseous malignant fibrous histiocytoma has been reported to occur within a bone infarction but the presence of a benign bone infarction remote from a soft tissue malignant fibrous histiocytoma has not been reported previously. Bone infarctions and malignant fibrous histiocytomas are briefly reviewed.

Muscle-Bone Interactions in Pediatric Bone Diseases.

PubMed

Veilleux, Louis-Nicolas; Rauch, Frank

2017-10-01

Here, we review the skeletal effects of pediatric muscle disorders as well as muscle impairment in pediatric bone disorders. When starting in utero, muscle disorders can lead to congenital multiple contractures. Pediatric-onset muscle weakness such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, or spina bifida typically are associated with small diameter of long-bone shafts, low density of metaphyseal bone, and increased fracture incidence in the lower extremities, in particular, the distal femur. Primary bone diseases can affect muscles through generic mechanisms, such as decreased physical activity or in disease-specific ways. For example, the collagen defect underlying the bone fragility of osteogenesis imperfecta may also affect muscle force generation or transmission. Transforming growth factor beta released from bone in Camurati Engelman disease may decrease muscle function. Considering muscle-bone interactions does not only contribute to the understanding of musculoskeletal disorders but also can identify new targets for therapeutic interventions.

Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma

ClinicalTrials.gov

2018-06-28

Metastatic Ewing Sarcoma; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Bone Marrow; Metastatic Malignant Neoplasm in the Lung; Metastatic Peripheral Primitive Neuroectodermal Tumor of Bone; Peripheral Primitive Neuroectodermal Tumor of Soft Tissues

Patterns of Cancer in Kurdistan - Results of Eight Years Cancer Registration in Sulaymaniyah Province-Kurdistan-Iraq.

PubMed

Khoshnaw, Najmaddin; Mohammed, Hazha A; Abdullah, Dana A

2015-01-01

Cancer has become a major health problem associated with high mortality worldwide, especially in developing countries. The aim of our study was to evaluate the incidence rates of different types of cancer in Sulaymaniyah from January-2006 to January-2014. The data were compared with those reported for other middle east countries. This retrospective study depended on data collected from Hiwa hospital cancer registry unit, death records and histopathology reports in all Sulaymaniyah teaching hospitals, using international classification of diseases. A total of 8,031 cases were registered during the eight year period, the annual incidence rate in all age groups rose from 38 to 61.7 cases/100,000 population/year, with averages over 50 in males and 50.7 in females. The male to female ratio in all age groups were 0.98, while in the pediatric age group it was 1.33. The hematological malignancies in all age groups accounted for 20% but in the pediatric group around half of all cancer cases. Pediatric cancers were occluding 7% of total cancers with rates of 10.3 in boys and 8.7 in girls. The commonest malignancies by primary site were leukemia, lymphoma, brain, kidney and bone. In males in all age groups they were lung, leukaemia, lymphoma, colorectal, prostate, bladder, brain, stomach, carcinoma of unknown primary (CUP) and skin, while in females they were breast, leukaemia, lymphoma, colorectal, ovary, lung, brain, CUP, and stomach. Most cancers were increased with increasing age except breast cancer where decrease was noted in older ages. High mortality rates were found with leukemia, lung, lymphoma, colorectal, breast and stomach cancers. We here found an increase in annual cancer incidence rates across the period of study, because of increase of cancer with age and higher rates of hematological malignancies. Our study is valuable for Kurdistan and Iraq because it provides more accurate data about the exact patterns of cancer and mortality in our region.

[Telangiectatic osteosarcoma in an infant].

PubMed

Cepeda, María de Los Ángeles; Sosa, Ana Julia; Mora, Glenda

Osteosarcoma is one of the most common types of cancer in childhood and adolescence and it is the most common malignant bone tumor in this group of age. Osteosarcoma is frequently found in long bones of the extremities. There are very few cases described in children under 5 years of age, and according to this review, none in infants. The telangiectatic variant is uncommon, and there are no reported cases before preschool age. A 10-month-old female infant with a lithic tumor of the ninth right rib, which was classified after resection as a telangiectatic osteosarcoma, is presented. Telangiectatic osteosarcoma in the pediatric age is very uncommon. To date, the patient has presented good response to treatment, although the prognosis and survival of this condition is unknown. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma

PubMed Central

Redini, Françoise; Heymann, Dominique

2015-01-01

Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the “vicious cycle” concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable “niche” for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma. PMID:26779435

Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma.

PubMed

Redini, Françoise; Heymann, Dominique

2015-01-01

Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due to osteolysis. Osteoclast activation and subsequent bone resorption are responsible for the clinical features of bone tumors, including pain, vertebral collapse, and spinal cord compression. Based on the "vicious cycle" concept of tumor cells and bone resorbing cells, drugs, which target osteoclasts, may be promising agents as adjuvant setting for treating bone tumors, including Ewing sarcoma. There is also increasing evidence that cellular and molecular protagonists present in the bone microenvironment play a part in establishing a favorable "niche" for tumor initiation and progression. The purpose of this review is to discuss the potential therapeutic value of drugs targeting the bone tumor microenvironment in Ewing sarcoma. The first part of the review will focus on targeting the bone resorbing function of osteoclasts by means of bisphosphonates or drugs blocking the pro-resorbing cytokine receptor activator of NF-kappa B ligand. Second, the role of this peculiar hypoxic microenvironment will be discussed in the context of resistance to chemotherapy, escape from the immune system, or neo-angiogenesis. Therapeutic interventions based on these specificities could be then proposed in the context of Ewing sarcoma.

Setting up low-risk bone marrow transplantation for children with thalassemia may facilitate pediatric cancer care.

PubMed

Faulkner, Lawrence B

2013-07-01

In many South Asian countries there is shortage of centers providing care for pediatric malignancies. This report describes the experience of the Cure2Children Foundation (C2C) in supporting, both financially and professionally, the startup of two bone marrow transplant (BMT) centers, one in Pakistan and one in India, for the cure of transfusion-dependent thalassemia. Even though transplantation is generally considered as a more complex and advanced step relatively to basic pediatric cancer care, the authors argue that BMT for low-risk thalassemia patients with a matched sibling is a relatively simple procedure amenable to focused training. Since 2008 the C2C, an Italian Nongovernmental Organization (NGO), has supported a BMT network in Pakistan. The primary aim of this project was to assess feasibility, outcomes, and costs of matched-related BMT for thalassemia in young low-risk children employing a well established and quite tolerable strategy employed in Italy. This initiative relied primarily on focused training and task-shift strategies within a structured cooperation program. The initial success of that strategy led to its replication in India with 100 total BMTs performed over the past 4 years, 91 of which were for thalassemia major. Low-risk matched-related BMT in children younger than 5 years could deliver a 92% thalassemia-free survival with 100% performance score and no extensive chronic graft versus host disease (GVHD), for an average cost of 10,000 USD per BMT. Within an existing hospital facility, 50,000 USD were sufficient to renovate and fully equip a 2-3 bedded start up BMT unit capable of performing safe low-risk compatible marrow transplantation. In low resource settings matched-related low-risk BMT for thalassemia can be performed with outcomes comparable to richer countries and with a fraction of the costs. Within structured and intensive cooperation, good outcomes can be obtained from the very beginning. This observation may have important implications to increase access to cure for both nonmalignant and malignant.

The application of x-ray, computed tomography, and magnetic resonance imaging on 22 pediatric Langerhans cell histiocytosis patients with long bone involvement: A retrospective analysis.

PubMed

Zhang, Xiaojun; Zhou, Jing; Chai, Xuee; Chen, Guiling; Guo, Bin; Ni, Lei; Wu, Peng

2018-04-01

The studies focusing on x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) in pediatric Langerhans cell histiocytosis (LCH) patients were still rare. Therefore, we aimed to evaluate the application of x-ray, CT, and MRI in pediatric LCH patients with long bone involvement.Total 22 pediatric LCH patients were included in this study. The diagnosis of LCH was confirmed by pathological examination. All patients were followed up for 3 years. X-ray, CT, or MRI was performed and the results were recorded for further analyses.Among 22 pediatric patients, x-ray (n = 20), CT (n = 18), or MRI (n = 12) were used to scan the lesion on long bones affected by LCH. Femurs (n = 13, 38.24%), tibia (n = 11, 32.35%), humerus (n = 5, 14.71%), and radius (n = 4, 11.76%) were the most frequently affected anatomic sites. Ovoid or round radiolucent lesions, aggressive periosteal reaction, and swelling of surrounding soft tissues were characteristic image of long bones on x-ray, CT, and MRI in pediatric LCH.Femurs, tibia, humerus, and radius were the most commonly affected long bones of pediatric LCH. The application of x-ray, CT, and MRI on long bones could help with the diagnosis of pediatric LCH.

Outcome of bone recycling using liquid nitrogen as bone reconstruction procedure in malignant and recurrent benign aggressive bone tumour of distal tibia: A report of four cases.

PubMed

Gede, Eka Wiratnaya I; Ida Ayu, Arrisna Artha; Setiawan I Gn, Yudhi; Aryana Ign, Wien; I Ketut, Suyasa; I Ketut, Siki Kawiyana; Putu, Astawa

2017-01-01

Amputation still considered as primary choice of malignancy treatment in distal tibia. Bone recycling with liquid nitrogen for reconstruction following resection of malignant bone tumours offers many advantages. We presented four patients with osteosarcoma, Ewing sarcoma, adamantinoma and recurrent giant cell tumour over distal tibia. All of the patients underwent wide excision and bone recycling using liquid nitrogen as bone reconstruction. The mean functional Musculoskeletal Tumor Society (MSTS) score was 75% with no infection and local recurrent. The reconstruction provides good local control and functional outcome.

MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors

ClinicalTrials.gov

2018-03-30

Relapsed Pediatric Solid Tumors; Refractory Pediatric Solid Tumors; Tumors Located in Bone or Soft Tissue in Close Proximity to Bone; Rhabdomyosarcoma; Ewing Sarcoma; Osteosarcoma; Neuroblastoma; Wilms Tumor; Hepatic Tumor; Germ Cell Tumor; Desmoid Tumor

Association Between Prolonged Seizures and Malignant Middle Cerebral Artery Infarction in Children With Acute Ischemic Stroke.

PubMed

Andrade, Andrea; Bigi, Sandra; Laughlin, Suzanne; Parthasarathy, Sujatha; Sinclair, Adriane; Dirks, Peter; Pontigon, Ann Marie; Moharir, Mahendranath; Askalan, Rand; MacGregor, Daune; deVeber, Gabrielle

2016-11-01

Malignant middle cerebral artery infarct syndrome is a potentially fatal complication of stroke that is poorly understood in children. We studied the frequency, associated characteristics, and outcomes of this condition in children. Children, aged two months to 18 years with acute middle cerebral artery infarct diagnosed at our center between January 2005 and December 2012 were studied. Associations with malignant middle cerebral artery infarct syndrome were sought, including age, seizures, neurological deficit severity (Pediatric National Institute of Health Stroke Severity Score), stroke etiology, fever, blood pressure, blood glucose, infarct location, infarct volume (modified pediatric Alberta Stroke Program Early Computed Tomography Score), and arterial occlusion. Death and neurological outcomes were determined. Among 66 children with middle cerebral artery stroke, 12 (18%) developed malignant middle cerebral artery infarct syndrome, fatal in three. Prolonged seizures during the first 24 hours (odds ratio, 25.51; 95% confidence interval, 3.10 to 334.81; P = 0.005) and a higher Pediatric National Institute of Health Stroke Severity Score (odds ratio, 1.22; 95% confidence interval, 1.08 to 1.45; P = 0.006) were independently associated with malignant middle cerebral artery infarct syndrome. All children aged greater than two years with a Pediatric National Institute of Health Stroke Severity Score ≥8 and initial seizures ≥5 minutes duration developed malignant middle cerebral artery infarct syndrome (100%). Malignant middle cerebral artery infarct syndrome affects nearly one in five children with acute middle cerebral artery stroke. Children with higher Pediatric National Institute of Health Stroke Severity Scores and prolonged initial seizures are at greatly increased risk for malignant middle cerebral artery infarct syndrome. Children with middle cerebral artery infarcts warrant intensive neuroprotective management and close monitoring to enable early referral for hemicraniectomy surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors.

PubMed

Cairo, Mitchell S; Rocha, Vanderson; Gluckman, Eliane; Hale, Gregory; Wagner, John

2008-01-01

Allogeneic stem cell transplantation has been demonstrated to be curative in a wide variety of pediatric malignant and nonmalignant diseases, and can be traced back over 50 years ago to the original report of Thomas et al. HLA matched sibling donors have been the gold standard for pediatric recipients requiring allogeneic donors for both nonmalignant and malignant conditions. However, only 25% of potential pediatric recipients possesses an HLA-matched sibling donor, and the frequency is even less in those with genetic nonmalignant conditions because of genetically affected other siblings within the family. Therefore, 75% to 90% of potential pediatric recipients require alternative allogeneic donor cells for treatment of their underlying conditions. Potential alternative allogeneic donor sources include unrelated cord blood donors, unrelated adult donors, and haploidentical family donors. In this article we review the experience of both unrelated cord blood donor and haploidentical family donor transplants in selected pediatric malignant and nonmalignant conditions.

Bone scanning in severe external otitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levin, W.J.; Shary, J.H. 3d.; Nichols, L.T.

1986-11-01

Technetium99 Methylene Diphosphate bone scanning has been considered an early valuable tool to diagnose necrotizing progressive malignant external otitis. However, to our knowledge, no formal studies have actually compared bone scans of otherwise young, healthy patients with severe external otitis to scans of patients with clinical presentation of malignant external otitis. Twelve patients with only severe external otitis were studied with Technetium99 Diphosphate and were compared to known cases of malignant otitis. All scans were evaluated by two neuroradiologists with no prior knowledge of the clinical status of the patients. Nine of the 12 patients had positive bone scans withmore » many scans resembling those reported with malignant external otitis. Interestingly, there was no consistent correlation between the severity of clinical presentation and the amount of Technetium uptake. These findings suggest that a positive bone scan alone should not be interpreted as indicative of malignant external otitis.« less

Inhibition of Focal Adhesion Kinase (FAK) Leads to Abrogation of the Malignant Phenotype in Aggressive Pediatric Renal Malignancies

PubMed Central

Megison, Michael L.; Gillory, Lauren A.; Stewart, Jerry E.; Nabers, Hugh C.; Mrozcek-Musulman, Elizabeth; Beierle, Elizabeth A.

2014-01-01

Despite the tremendous advances in the treatment of childhood kidney tumors, there remain subsets of pediatric renal tumors that continue to pose a therapeutic challenge, mainly malignant rhabdoid kidney tumors and non-osseous renal Ewing sarcoma. Children with advanced, metastatic or relapsed disease have a disease-free survival rate under 30%. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is important in many facets of tumor development and progression. FAK has been found in other pediatric solid tumors and in adult renal cellular carcinoma, leading us to hypothesize that FAK would be present in pediatric kidney tumors and would impact their cellular survival. In the current study, we showed that FAK was present and phosphorylated in pediatric kidney tumor specimens. We also examined the effects of FAK inhibition upon G401 and SK-NEP-1 cell lines utilizing a number of parallel approaches to block FAK including RNAi and small molecule FAK inhibitors. FAK inhibition resulted in decreased cellular survival, invasion and migration, and increased apoptosis. Further, small molecule inhibition of FAK led to decreased tumor growth in a nude mouse SK-NEP-1 xenograft model. The findings from this study will help to further our understanding of the regulation of tumorigenesis in rare pediatric renal tumors, and may provide desperately needed novel therapeutic strategies and targets for these rare, but difficult to treat, malignancies. PMID:24464916

The effect of NACHRI children's hospital designation on outcome in pediatric malignant brain tumors.

PubMed

Donoho, Daniel A; Wen, Timothy; Liu, Jonathan; Zarabi, Hosniya; Christian, Eisha; Cen, Steven; Zada, Gabriel; McComb, J Gordon; Krieger, Mark D; Mack, William J; Attenello, Frank J

2017-08-01

OBJECTIVE Although current pediatric neurosurgery guidelines encourage the treatment of pediatric malignant brain tumors at specialized centers such as pediatric hospitals, there are limited data in support of this recommendation. Previous studies suggest that children treated by higher-volume surgeons and higher-volume hospitals may have better outcomes, but the effect of treatment at dedicated children's hospitals has not been investigated. METHODS The authors analyzed the Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) from 2000-2009 and included all patients undergoing a craniotomy for malignant pediatric brain tumors based on ICD-9-CM codes. They investigated the effects of patient demographics, tumor location, admission type, and hospital factors on rates of routine discharge and mortality. RESULTS From 2000 through 2009, 83.6% of patients had routine discharges, and the in-hospital mortality rate was 1.3%. In multivariate analysis, compared with children treated at an institution designated as a pediatric hospital by NACHRI (National Association of Children's Hospitals and Related Institutions), children receiving treatment at a pediatric unit within an adult hospital (OR 0.5, p < 0.01) or a general hospital without a designated pediatric unit (OR 0.4, p < 0.01) were less likely to have routine discharges. Treatment at a large hospital (> 400 beds; OR 1.8, p = 0.02) and treatment at a teaching hospital (OR 1.7, p = 0.02) were independently associated with greater likelihood of routine discharge. However, patients transferred between facilities had a significantly decreased likelihood of routine discharge (OR 0.5, p < 0.01) and an increased likelihood of mortality (OR 5.0, p < 0.01). Procedural volume was not associated with rate of routine discharge or mortality. CONCLUSIONS These findings may have implications for planning systems of care for pediatric patients with malignant brain tumors. The authors hope to motivate future research into the specific factors that may lead to improved outcomes at designated pediatric hospitals.

Pre-Clinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies

PubMed Central

Waters, Alicia M.; Stewart, Jerry E.; Atigadda, Venkatram R.; Mroczek-Musulman, Elizabeth; Muccio, Donald D.; Grubbs, Clinton J.; Beierle, Elizabeth A.

2016-01-01

Rare tumors of solid organs remain some of the most difficult pediatric cancers to cure. These difficult tumors include rare pediatric renal malignancies such as malignant rhabdoid kidney tumors (MRKT) and non-osseous renal Ewing sarcoma, and hepatoblastoma, a pediatric liver tumor that arises from immature liver cells. There are data in adult renal and hepatic malignancies demonstrating the efficacy of retinoid therapy. The investigation of retinoic acid therapy in cancer is not a new strategy, but the widespread adoption of this therapy has been hindered by toxicities. Our laboratory has been investigating a novel synthetic rexinoid, UAB30, which exhibits a more favorable side effect profile. In this current study, we hypothesized that UAB30 would diminish the growth of tumor cells from both rare renal and liver tumors in vitro and in vivo. We successfully demonstrated decreased cellular proliferation, invasion and migration, cell cycle arrest and increased apoptosis after treatment with UAB30. Additionally, in in vivo murine models of human hepatoblastoma or rare human renal tumors, there were significantly decreased tumor xenograft growth and increased animal survival after UAB30 treatment. UAB30 should further be investigated as a developing therapeutic in these rare and difficult to treat, pediatric solid organ tumors. PMID:26873726

Can diffusion-weighted imaging distinguish between benign and malignant pediatric liver tumors?

PubMed

Caro-Domínguez, Pablo; Gupta, Abha A; Chavhan, Govind B

2018-01-01

There are limited data on utility of diffusion-weighted imaging (DWI) in the evaluation of pediatric liver lesions. To determine whether qualitative and quantitative DWI can be used to differentiate benign and malignant pediatric liver lesions. We retrospectively reviewed MRIs in children with focal liver lesions to qualitatively evaluate lesions noting diffusion restriction, T2 shine-through, increased diffusion, hypointensity on DWI and apparent diffusion coefficient (ADC) maps, and intermediate signal on both, and to measure ADC values. Pathology confirmation or a combination of clinical, laboratory and imaging features, and follow-up was used to determine final diagnosis. We included 112 focal hepatic lesions in 89 children (median age 11.5 years, 51 female), of which 92 lesions were benign and 20 malignant. Interobserver agreement was almost perfect for both qualitative (kappa 0.8735) and quantitative (intraclass correlation coefficient [ICC] 0.96) diffusion assessment. All malignant lesions showed diffusion restriction. Most benign lesions other than abscesses were not restricted. There was significant association of qualitative restriction with malignancy and non-restriction with benignancy (Fisher exact test P<0.0001). Mean normalized ADC values of malignant lesions (1.23x10 -3  mm 2 /s) were lower than benign lesions (1.62x10 -3  mm 2 /s; Student's t-test, P<0.015). However, there was significant overlap of ADC between benign and malignant lesions, with wide range for each diagnosis. Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.63 for predicting malignancy using an ADC cut-off value of ≤1.20x10 -3  mm 2 /s, yielding a sensitivity of 78% and a specificity of 54% for differentiating malignant from benign lesions. Qualitative diffusion restriction in pediatric liver lesions is a good predictor of malignancy and can help to differentiate between benign and malignant lesions, in conjunction with conventional MR sequences. Even though malignant lesions demonstrated significantly lower ADC values than benign lesions, the use of quantitative diffusion remains limited in its utility for distinguishing them because of the significant overlap and wide ranges of ADC values.

Hematoxylin Bodies in Pediatric Bone Marrow Aspirates and Their Utility in the Diagnosis of Systemic Lupus Erythematosus.

PubMed

Xu, Min; Chisholm, Karen M; Fan, Guang; Stevens, Anne M; Rutledge, Joe C

2017-01-01

In our recent case report, the finding of lupus erythematosus (LE) cells in a bone marrow aspirate led to the diagnosis of systemic lupus erythematosus (SLE) and appropriate treatment, although the patient was not clinically suspected to have SLE. To determine whether LE cells are present in the bone marrow aspirates of SLE patients, but overlooked in routine bone marrow morphology review, bone marrow aspirates from 30 pediatric patients (15 with SLE and 15 with other diagnoses) evaluated by rheumatologists were reviewed. LE cells were found in the bone marrow aspirates of only 1 SLE patient and none in non-SLE patients. However, hematoxylin bodies were identified in 53% (8/15) of SLE patients. Neither hematoxylin bodies nor LE cells were found in the aspirates from patients with other disorders. Three additional pediatric patients identified prospectively were found to have hematoxylin bodies in the bone marrow aspirates. Although the diagnosis was not initially suspected, 2 of the 3 patients were subsequently diagnosed with SLE. All patients with hematoxylin bodies and SLE had antinuclear antibody titers ≥1:640 with a homogeneous staining pattern. In addition, bone marrow aspirates of 9 adult patients were reviewed, and neither LE cells nor hematoxylin bodies were identified. In summary, hematoxylin bodies were present in the bone marrow aspirates of many pediatric SLE patients, while LE cells were rare. The finding of hematoxylin bodies in pediatric bone marrow aspirates is a helpful and specific diagnostic clue that may lead to the diagnosis of SLE when other clinical features are nonspecific.

Pediatric Hodgkin lymphoma: biomarkers, drugs, and clinical trials for translational science and medicine.

PubMed

Nagpal, Poonam; Akl, Mohamed R; Ayoub, Nehad M; Tomiyama, Tatsunari; Cousins, Tasheka; Tai, Betty; Carroll, Nicole; Nyrenda, Themba; Bhattacharyya, Pritish; Harris, Michael B; Goy, Andre; Pecora, Andrew; Suh, K Stephen

2016-10-11

Hodgkin lymphoma (HL) is a lymphoid malignancy that is typically derived from germinal-center B cells. EBV infection, mutations in NF-κB pathway genes, and genetic susceptibility are known risk factors for developing HL. CD30 and NF-κB have been identified as potential biomarkers in pediatric HL patients, and these molecules may represent therapeutic targets. Although current risk adapted and response based treatment approaches yield overall survival rates of >95%, treatment of relapse or refractory patients remains challenging. Targeted HL therapy with the antibody-drug conjugate Brentuximab vedotin (Bv) has proven to be superior to conventional salvage chemotherapy and clinical trials are being conducted to incorporate Bv into frontline therapy that substitutes Bv for alkylating agents to minimize secondary malignancies. The appearance of secondary malignancies has been a concern in pediatric HL, as these patients are at highest risk among all childhood cancer survivors. The risk of developing secondary leukemia following childhood HL treatment is 10.4 to 174.8 times greater than the risk in the general pediatric population and the prognosis is significantly poorer than the other hematological malignancies with a mortality rate of nearly 100%. Therefore, identifying clinically valuable biomarkers is of utmost importance to stratify and select patients who may or may not need intensive regimens to maintain optimal balance between maximal survival rates and averting late effects. Here we discuss epidemiology, risk factors, staging, molecular and genetic prognostic biomarkers, treatment for low and high-risk patients, and the late occurrence of secondary malignancies in pediatric HL.

Malignancy and mortality in pediatric patients with inflammatory bowel disease: a multinational study from the porto pediatric IBD group.

PubMed

de Ridder, Lissy; Turner, Dan; Wilson, David C; Koletzko, Sibylle; Martin-de-Carpi, Javier; Fagerberg, Ulrika L; Spray, Christine; Sladek, Malgorzata; Shaoul, Ron; Roma-Giannikou, Eleftheria; Bronsky, Jiri; Serban, Daniela E; Cucchiara, Salvatore; Veres, Gabor; Ruemmele, Frank M; Hojsak, Iva; Kolho, Kaija L; Davies, Ieuan H; Aloi, Marina; Lionetti, Paolo; Veereman-Wauters, Gigi; Braegger, Christian P; Trindade, Eunice; Wewer, Anne V; Hauer, Almuthe; Levine, Arie

2014-02-01

The combination of the severity of pediatric-onset inflammatory bowel disease (IBD) phenotypes and the need for intense medical treatment may increase the risk of malignancy and mortality, but evidence regarding the extent of the problem is scarce. Therefore, the Porto Pediatric IBD working group of ESPGHAN conducted a multinational-based survey of cancer and mortality in pediatric IBD. A survey among pediatric gastroenterologists of 20 European countries and Israel on cancer and/or mortality in the pediatric patient population with IBD was undertaken. One representative from each country repeatedly contacted all pediatric gastroenterologists from each country for reporting retrospectively cancer and/or mortality of pediatric patients with IBD after IBD onset, during 2006-2011. We identified 18 cases of cancers and/or 31 deaths in 44 children (26 males) who were diagnosed with IBD (ulcerative colitis, n = 21) at a median age of 10.0 years (inter quartile range, 3.0-14.0). Causes of mortality were infectious (n = 14), cancer (n = 5), uncontrolled disease activity of IBD (n = 4), procedure-related (n = 3), other non-IBD related diseases (n = 3), and unknown (n = 2). The most common malignancies were hematopoietic tumors (n = 11), of which 3 were hepatosplenic T-cell lymphoma and 3 Ebstein-Barr virus-associated lymphomas. Cancer and mortality in pediatric IBD are rare, but cumulative rates are not insignificant. Mortality is primarily related to infections, particularly in patients with 2 or more immunosuppressive agents, followed by cancer and uncontrolled disease. At least 6 lymphomas were likely treatment-associated by virtue of their phenotype.

Primary Occipital Ewing's Sarcoma with Subsequent Spinal Seeding.

PubMed

Alqahtani, Ali; Amer, Roaa; Bakhsh, Eman

2017-01-01

Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing's sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT) imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4 vertebrae. Primary cranial Ewing's sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing's sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing's sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.

Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers.

PubMed

Kruger, Thomas E; Miller, Andrew H; Godwin, Andrew K; Wang, Jinxi

2014-02-01

The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, particularly bone sialoprotein (BSP) and osteopontin (OPN), exhibit multiple activities known to promote malignant cell proliferation, detachment, invasion, and metastasis of several osteotropic cancers. The expression level of BSP and OPN is elevated in a variety of human cancers, particularly those that metastasize preferentially to the skeleton. Recent studies suggest that the "osteomimicry" of malignant cells is not only conferred by transmembrane receptors bound by BSP and OPN, but includes the "switch" in gene expression repertoire typically expressed in cells of skeletal lineage. Understanding the role of BSP and OPN in tumor progression, altered pathophysiology of bone microenvironment, and tumor metastasis to bone will likely result in development of better diagnostic approaches and therapeutic regimens for osteotropic malignant diseases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The risk of malignancy among biologic-naïve pediatric psoriasis patients: A retrospective cohort study in a US claims database.

PubMed

Gu, Yun; Nordstrom, Beth L

2017-08-01

Little published literature exists regarding malignancy risk in pediatric psoriasis patients. To compare malignancy risk in biologic-naïve pediatric psoriasis patients with a matched pediatric population without psoriasis. This retrospective cohort study used IMS LifeLink Health Plan Claims data covering 1998-2008. Cancer incidence was compared with the US Surveillance, Epidemiology, and End Results (SEER) data using standardized incidence ratios (SIR), and between cohorts using Cox models. Among 9045 pediatric psoriasis patients and 77,206 comparators, 18 probable or highly probable cancers were identified. Pediatric psoriasis patients had a nonsignificantly lower incidence than comparators (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.05-3.54). The HR increased to 1.67 (95% CI 0.54-5.18) when cancer diagnosed during the first 90 days of follow-up was included. The pediatric psoriasis cohort had a significantly increased lymphoma rate compared with SEER (SIR 5.42, 95% CI 1.62-12.94), but no significant increase relative to the comparator cohort. Misclassification of disease and outcome might have occurred with patients in the claims database. Patients with pediatric psoriasis showed no significant increase in overall cancer risk compared with those without psoriasis. A potential increased risk for lymphoma was observed when compared with the general population. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

ClinicalTrials.gov

2017-09-05

Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

PET/CT in paediatric malignancies - An update

PubMed Central

Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga; Tewari, Anshu

2016-01-01

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging modality in adult oncological practice. Its role in childhood malignancies needs to be discussed as paediatric malignancies differ from adults in tumor subtypes and they have different tumor biology and FDG uptake patterns. This is also compounded by smaller body mass, dosimetric restrictions, and physiological factors that can affect the FDG uptake. It calls for careful planning of the PET study, preparing the child, the parents, and expertise of nuclear physicians in reporting pediatric positron emission tomography/computed tomography (PET/CT) studies. In a broad perspective, FDG-PET/CT has been used in staging, assessment of therapy response, identifying metastases and as a follow-up tool in a wide variety of pediatric malignancies. This review outlines the role of PET/CT in childhood malignancies other than hematological malignancies such as lymphoma and leukemia. PMID:27688605

Rare malignant pediatric tumors registered in the German Childhood Cancer Registry 2001-2010.

PubMed

Brecht, Ines B; Bremensdorfer, Claudia; Schneider, Dominik T; Frühwald, Michael C; Offenmüller, Sonja; Mertens, Rolf; Vorwerk, Peter; Koscielniak, Ewa; Bielack, Stefan S; Benesch, Martin; Hero, Barbara; Graf, Norbert; von Schweinitz, Dietrich; Kaatsch, Peter

2014-07-01

The German Childhood Cancer Registry (GCCR) annually registers approximately 2,000 children diagnosed with a malignant disease (completeness of registration >95%). While most pediatric cancer patients are diagnosed and treated according to standardized cooperative protocols of the German Society for Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk of not being integrated in the network including trials and reference centers. A retrospective analysis of all rare extracranial solid tumors reported to the GCCR 2001-2010 (age <18 years) was undertaken using a combination of the International Classification of Childhood Cancer (ICCC-3) and the International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting for <0.3% of all malignancies were defined as rare (approx. 6 cases/year and registered malignancy). According to this definition 1,189 rare extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were registered, among these 232 patients (19.5% of rare tumor cases), were not included in preexisting GPOH studies/registries. Within 10 years, the number of registered non-GPOH-trial patients with a rare tumor increased. Though most of the GCCR-registered patients with rare malignant tumors are treated within GPOH trials, there is a considerable number of patients that have been diagnosed and treated outside the structures of the GPOH. These patients should be reported to the recently founded German Pediatric Rare Tumor Registry (STEP). Active data accrual and the development of appropriate structures will allow for better registration and improvement of medical care in these patients. © 2014 Wiley Periodicals, Inc.

Low usage rate of banked sibling cord blood units in hematopoietic stem cell transplantation for children with hematological malignancies: implications for directed cord blood banking policies.

PubMed

Goussetis, Evgenios; Peristeri, Ioulia; Kitra, Vasiliki; Papassavas, Andreas C; Theodosaki, Maria; Petrakou, Eftichia; Spiropoulos, Antonia; Paisiou, Anna; Soldatou, Alexandra; Stavropoulos-Giokas, Catherine; Graphakos, Stelios

2011-02-15

Directed sibling cord blood banking is indicated in women delivering healthy babies who already have a sibling with a disease that is potentially treatable with an allogeneic cord blood transplant. We evaluated the effectiveness of a national directed cord blood banking program in sibling HLA-identical stem cell transplantation for hematological malignancies and the factors influencing the usage rate of the stored cord blood units. Fifty families were enrolled from which, 48 cord blood units were successfully collected and 2 collections failed due to damaged cord/placenta at delivery. Among enrolled families 4 children needed transplantation; however, only one was successfully transplanted using the collected cord blood unit containing 2×10(7) nucleated cells/kg in conjunction with a small volume of bone marrow from the same HLA-identical donor. Two children received grafts from matched unrelated donors because their sibling cord blood was HLA-haploidentical, while the fourth one received bone marrow from his HLA-identical brother, since cord blood could not be collected due to damaged cord/placenta at delivery. With a median follow-up of 6 years (range, 2-12) for the 9 remaining HLA-matched cord blood units, none from the prospective recipients needed transplantation. The low utilization rate of sibling cord blood in the setting of hematopoietic stem cell transplantation for pediatric hematological malignant diseases necessitates the development of directed cord blood banking programs that limit long-term storage for banked cord blood units with low probability of usage such as non-HLA-identical or identical to patients who are in long-term complete remission. Copyright © 2010 Elsevier Inc. All rights reserved.

Rapidly Growing Brtl/+ Mouse Model of Osteogenesis Imperfecta Improves Bone Mass and Strength with Sclerostin Antibody Treatment

PubMed Central

Sinder, Benjamin P.; Salemi, Joseph D.; Ominsky, Michael S.; Caird, Michelle S.; Marini, Joan C.; Kozloff, Kenneth M.

2014-01-01

Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk that presents most severely in children. Anti-resorptive bisphosphonates are frequently used to treat pediatric OI and controlled clinical trials have shown bisphosphonate therapy improves vertebral outcomes but has little benefit on long bone fracture rate. New treatments which increase bone mass throughout the pediatric OI skeleton would be beneficial. Sclerostin antibody (Scl-Ab) is a potential candidate anabolic therapy for pediatric OI and functions by stimulating osteoblastic bone formation via the canonical wnt signaling pathway. To explore the effect of Scl-Ab on the rapidly growing OI skeleton, we treated rapidly growing 3 week old Brtl/+ mice, harboring a typical heterozygous OI-causing Gly->Cys substitution on col1a1, for 5 weeks with Scl-Ab. Scl-Ab had anabolic effects in Brtl/+ and led to new cortical bone formation and increased cortical bone mass. This anabolic action resulted in improved mechanical strength to WT Veh levels without altering the underlying brittle nature of the material. While Scl-Ab was anabolic in trabecular bone of the distal femur in both genotypes, the effect was less strong in these rapidly growing Brtl/+ mice compared to WT. In conclusion, Scl-Ab was able to stimulate bone formation in a rapidly growing Brtl/+ murine model of OI, and represents a potential new therapy to improve bone mass and reduce fracture risk in pediatric OI. PMID:25445450

Cellular Mechanisms of Multiple Myeloma Bone Disease

PubMed Central

Oranger, Angela; Carbone, Claudia; Izzo, Maddalena; Grano, Maria

2013-01-01

Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulates and proliferates in the bone marrow. MM patients often develop bone disease that results in severe bone pain, osteolytic lesions, and pathologic fractures. These skeletal complications have not only a negative impact on quality of life but also a possible effect in overall survival. MM osteolytic bone lesions arise from the altered bone remodeling due to both increased osteoclast activation and decreased osteoblast differentiation. A dysregulated production of numerous cytokines that can contribute to the uncoupling of bone cell activity is well documented in the bone marrow microenvironment of MM patients. These molecules are produced not only by malignant plasma cells, that directly contribute to MM bone disease, but also by bone, immune, and stromal cells interacting with each other in the bone microenvironment. This review focuses on the current knowledge of MM bone disease biology, with particular regard on the role of bone and immune cells in producing cytokines critical for malignant plasma cell proliferation as well as in osteolysis development. Therefore, the understanding of MM pathogenesis could be useful to the discovery of novel agents that will be able to both restore bone remodelling and reduce tumor burden. PMID:23818912

Malignant Brain Tumours in Children : Present and Future Perspectives.

PubMed

Rutka, James T

2018-05-01

In contrast to many of the malignant tumors that occur in the central nervous system in adults, the management, responses to therapy, and future perspectives of children with malignant lesions of the brain hold considerable promise. Within the past 5 years, remarkable progress has been made with our understanding of the basic biology of the molecular genetics of several pediatric malignant brain tumors including medulloblastoma, ependymoma, atypical teratoid rhabdoid tumour, and high grade glioma/diffuse intrinsic pontine glioma. The recent literature in pediatric neuro-oncology was reviewed, and a summary of the major findings are presented. Meaningful sub-classifications of these tumors have arisen, placing children into discrete categories of disease with requirements for targeted therapy. While the mainstay of therapy these past 30 years has been a combination of central nervous system irradiation and conventional chemotherapy, now with the advent of high resolution genetic mapping, targeted therapies have emerged, and less emphasis is being placed on craniospinal irradiation. In this article, the present and future perspective of pediatric brain malignancy are reviewed in detail. The progress that has been made offers significant hope for the future for patients with these tumours.

Miscellaneous indications in bone scintigraphy: metabolic bone diseases and malignant bone tumors.

PubMed

Cook, Gary J R; Gnanasegaran, Gopinath; Chua, Sue

2010-01-01

The diphosphonate bone scan is ideally suited to assess many global, focal or multifocal metabolic bone disorders and there remains a role for conventional bone scintigraphy in metabolic bone disorders at diagnosis, investigation of complications, and treatment response assessment. In contrast, the role of bone scintigraphy in the evaluation of primary malignant bone tumors has reduced with the improvement of morphologic imaging, such as computed tomography and magnetic resonance imaging. However, an increasing role for (18)F-fluorodeoxyglucose positron emission tomography and positron emission tomography/computed tomography is emerging as a functional assessment at diagnosis, staging, and neoadjuvant treatment response assessment.

Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: A report from the Pediatric Heart Transplant Study (PHTS) group.

PubMed

Bock, Matthew J; Pahl, Elfriede; Rusconi, Paolo G; Boyle, Gerard J; Parent, John J; Twist, Clare J; Kirklin, James K; Pruitt, Elizabeth; Bernstein, Daniel

2017-08-01

We aimed to determine whether malignancy after pediatric HTx for ACM affects overall post-HTx survival. Patients <18y listed for HTx for ACM in the PHTS database between 1993 and 2014 were compared to those with DCM. A 2:1 matched DCM cohort was also compared. Wait-list and post-HTx survival, along with freedom from common HTx complications, were compared. Eighty subjects were listed due to ACM, whereas 1985 were listed for DCM. Although wait-list survival was higher in the ACM group, post-HTx survival was lower for the ACM cohort. Neither difference persisted in the matched cohort analysis. Primary cause of death in the ACM group was infection, which was higher than the DCM group. Malignancy rates were not different. All ACM malignancies were due to PTLD without primary cancer recurrence or SMN. Long-term graft survival after pediatric HTx for ACM is no different than for matched DCM peers, nor is there an increased risk of any malignancy. However, risk of infection and death from infection after HTx are higher in the ACM group. Further studies are needed to assess the effects of prior chemotherapy on susceptibility to infection in this group. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection and evaluation of normal and malignant cells using laser-induced fluorescence spectroscopy.

PubMed

Khosroshahi, Mohamad E; Rahmani, Mahya

2012-01-01

The aim of this research is to study the normalized fluorescence spectra (intensity variations and area under the fluorescence signal), relative quantum yield, extinction coefficient and intracellular properties of normal and malignant human bone cells. Using Laser-Induced Fluorescence Spectroscopy (LIFS) upon excitation of 405 nm, the comparison of emission spectra of bone cells revealed that fluorescence intensity and the area under the spectra of malignant bone cells was less than that of normal. In addition, the area ratio and shape factor were changed. We obtained two emission bands in spectra of normal cells centered at about 486 and 575 nm and for malignant cells about 482 and 586 nm respectively, which are most likely attributed to NADH and riboflavins. Using fluorescein sodium emission spectrum, the relative quantum yield of bone cells is numerically determined.

Stem cell mobilization and collection from pediatric patients and healthy children.

PubMed

Karakukcu, Musa; Unal, Ekrem

2015-08-01

Today, hematopoietic stem cell transplantation (HSCT) is a standard treatment for a variety of conditions in children, including certain malignancies, hemoglobinopathies, bone marrow failure syndromes, immunodeficiency and inborn metabolic disease. Two fundamentally different types of HSCT are categorized by the source of the stem cells. The first, autologous HSCT represents infusion of patient's own hematopoietic stem cells (HSCs) obtained from the patient; the second, allogeneic HSCT refers to the infusion of HSCs obtained from a donor via bone marrow harvest or apheresis. Bone marrow has been the typical source for HSCs for pediatric donors. Bone marrow harvest is a safe procedure mainly related to mild and transient side effects. Recently, a dramatically increased use of mobilized peripheral blood stem cells (PBSCs) in the autologous as well as allogeneic setting has been seen worldwide. There are limited data comparing mobilization regimens; also mobilization practices vary widely in children. The most commonly used approach includes granulocyte colony stimulating factor (G-CSF) at 10 mg/kg/day as a single daily dose for 4 days before the day of leukapheresis. G-CSF induced pain was less reported in children compared to adult donors. For the collection, there are several technical problems, derived from the size of the patient or donor, which must be considered before and during the apheresis. Vascular access, extracorporeal circuit volume, blood flow rates are the main limiting factors for PBSC collection in small children. Most children younger than 12 years require central vascular access for apheresis; line placement may require either general anesthesia or conscious sedation and many of the complications arise from the central venous catheter. In this review, we discuss that the ethical considerations and some principals regarding children serving as stem cell donors and the commonest sources of HSCs are presented in children, together with a discussion of how to collect and process these cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Proton density fat fraction (PDFF) MRI for differentiation of benign and malignant vertebral lesions.

PubMed

Schmeel, Frederic Carsten; Luetkens, Julian Alexander; Wagenhäuser, Peter Johannes; Meier-Schroers, Michael; Kuetting, Daniel Lloyd; Feißt, Andreas; Gieseke, Jürgen; Schmeel, Leonard Christopher; Träber, Frank; Schild, Hans Heinz; Kukuk, Guido Matthias

2018-06-01

To investigate whether proton density fat fraction (PDFF) measurements using a six-echo modified Dixon sequence can help to differentiate between benign and malignant vertebral bone marrow lesions. Sixty-six patients were prospectively enrolled in our study. In addition to conventional MRI at 3.0-Tesla including at least sagittal T2-weighted/spectral attenuated inversion recovery and T1-weighted sequences, all patients underwent a sagittal six-echo modified Dixon sequence of the spine. The mean PDFF was calculated using regions of interest and compared between vertebral lesions. A cut-off value of 6.40% in PDFF was determined by receiver operating characteristic curves and used to differentiate between malignant (< 6.40%) and benign (≥ 6.40%) vertebral lesions. There were 77 benign and 44 malignant lesions. The PDFF of malignant lesions was statistically significant lower in comparison with benign lesions (p < 0.001) and normal vertebral bone marrow (p < 0.001). The areas under the curves (AUC) were 0.97 for differentiating benign from malignant lesions (p < 0.001) and 0.95 for differentiating acute vertebral fractures from malignant lesions (p < 0.001). This yielded a diagnostic accuracy of 96% in the differentiation of both benign lesions and acute vertebral fractures from malignancy. PDFF derived from six-echo modified Dixon allows for differentiation between benign and malignant vertebral lesions with a high diagnostic accuracy. • Establishing a diagnosis of indeterminate vertebral lesions is a common clinical problem • Benign bone marrow processes may mimic the signal alterations observed in malignancy • PDFF differentiates between benign and malignant lesions with a high diagnostic accuracy • PDFF of non-neoplastic vertebral lesions is significantly higher than that of malignancy • PDFF from six-echo modified Dixon may help avoid potentially harmful bone biopsy.

Fine needle aspiration of thyroid nodules in the pediatric population: a 12-year cyto-histological correlation experience at North Shore-Long Island Jewish Health System.

PubMed

Lale, Seema A; Morgenstern, Nora N; Chiara, Sugrue; Wasserman, Patricia

2015-08-01

Diagnostic evaluation of thyroid nodules by FNA is used in the clinical management triage based on the knowledge of the rate of malignancy of each diagnostic category. The Bethesda System for Reporting Thyroid Cytopathology was published in 2007 by the National Cancer Institute (NCI). Using this classification, we studied our institution's experience in the pediatric population calculating the rate of malignancy for each diagnostic category, comparing our findings to our general patient population and that of the literature. 13,312 thyroid FNAs were performed at our institution between 1998 and 2010. 282 cases were from patients under 19 years of age. We reviewed and reclassified these cases using the new NCI categories, and pursued cytology-surgical follow-up. Of the 282 FNA cases, 20.92% (59) were classified as unsatisfactory (U), 48.22, % (136) benign (B), 2.12% (6) Atypia of undetermined significance (AUS), 14.18% (40) suspicious for follicular neoplasm (FN), 2.12% (6) suspicious for malignancy (SM) and 12.41% (35) positive for malignancy (P). The U-category was further classified into nondiagnostic (ND) 12.41% (35) and cysts (C) 8.51% (24). Seventy-four children had surgical follow-up. The rates of histologically confirmed malignancy were 10% in U (1/10), 0% in B (0/17), 50% in AUS (2/4), 39% in FN (7/18), 100% in SM (4/4) and 100% in P (24/24) categories respectively. Among the U category, malignancy rate was 0% for the ND category and 25% for the C category. To our knowledge, this is the first study to apply the NCI categories to the pediatric population. The rate of malignancy in the U category was only seen in the specimens with cystic component. AUS and FN categories had a higher malignancy rate (50 and 39% respectively) as compared with that of the general population (15 and 30% respectively). Given that the rates of malignancy are higher for cysts and AUS, the literature recommendation to "follow-up and repeat" may not apply to the pediatric population. Surgery may be reasonable in these categories instead. © 2015 Wiley Periodicals, Inc.

Acute lymphoblastic leukemia of childhood monitored by bacteriocin and flowcytometry.

PubMed

Musclow, C E; Farkas-Himsley, H; Weitzman, S S; Herridge, M

1987-04-01

Bacteriocin and flowcytometric analysis of 106 blood samples from children with acute lymphoblastic leukemia were correlated with clinical stages of disease. Bacteriocins interacted selectively with malignant, and not with normal, lymphocytes causing cell cycle perturbation which was rapidly and objectively recorded by the flowcytometer. The patients were grouped as: (A) newly-diagnosed (15); (B) early induction (11); (C) remission with viral infection (7); (D) remission (64); (E) bone marrow relapsed (5); (F) extramedullary relapsed (3); (G) non-malignant pediatric controls (8). Bacteriocin reacted usually with groups A, B, C, E and not with groups D, F and G. Repeated testing correlated well with the clinical status. Blood from 7 patients in remission and from 3 normal individuals, each with transient viral infection, reacted with bacteriocin. A quantitative correlation between peripheral blood blasts or surface markers for ALL and bacteriocin reactivity was not established. Unexpected results were obtained only in 13% (false-positive 11% and false-negative 3%). This test can be recommended for preliminary diagnosis and possibly prognosis of lymphoblastic leukemia and provides means of monitoring progress during chemotherapy.

Biomechanical Studies on Patterns of Cranial Bone Fracture Using the Immature Porcine Model.

PubMed

Haut, Roger C; Wei, Feng

2017-02-01

This review was prepared for the American Society of Mechanical Engineers Lissner Medal. It specifically discusses research performed in the Orthopaedic Biomechanics Laboratories on pediatric cranial bone mechanics and patterns of fracture in collaboration with the Forensic Anthropology Laboratory at Michigan State University. Cranial fractures are often an important element seen by forensic anthropologists during the investigation of pediatric trauma cases litigated in courts. While forensic anthropologists and forensic biomechanists are often called on to testify in these cases, there is little basic science developed in support of their testimony. The following is a review of studies conducted in the above laboratories and supported by the National Institute of Justice to begin an understanding of the mechanics and patterns of pediatric cranial bone fracture. With the lack of human pediatric specimens, the studies utilize an immature porcine model. Because much case evidence involves cranial bone fracture, the studies described below focus on determining input loading based on the resultant bone fracture pattern. The studies involve impact to the parietal bone, the most often fractured cranial bone, and begin with experiments on entrapped heads, progressing to those involving free-falling heads. The studies involve head drops onto different types and shapes of interfaces with variations of impact energy. The studies show linear fractures initiating from sutural boundaries, away from the impact site, for flat surface impacts, in contrast to depressed fractures for more focal impacts. The results have been incorporated into a "Fracture Printing Interface (FPI)," using machine learning and pattern recognition algorithms. The interface has been used to help interpret mechanisms of injury in pediatric death cases collected from medical examiner offices. The ultimate aim of this program of study is to develop a "Human Fracture Printing Interface" that can be used by forensic investigators in determining mechanisms of pediatric cranial bone fracture.

Rapidly growing Brtl/+ mouse model of osteogenesis imperfecta improves bone mass and strength with sclerostin antibody treatment.

PubMed

Sinder, Benjamin P; Salemi, Joseph D; Ominsky, Michael S; Caird, Michelle S; Marini, Joan C; Kozloff, Kenneth M

2015-02-01

Osteogenesis imperfecta (OI) is a heritable collagen-related bone dysplasia, characterized by brittle bones with increased fracture risk that presents most severely in children. Anti-resorptive bisphosphonates are frequently used to treat pediatric OI and controlled clinical trials have shown that bisphosphonate therapy improves vertebral outcomes but has little benefit on long bone fracture rate. New treatments which increase bone mass throughout the pediatric OI skeleton would be beneficial. Sclerostin antibody (Scl-Ab) is a potential candidate anabolic therapy for pediatric OI and functions by stimulating osteoblastic bone formation via the canonical Wnt signaling pathway. To explore the effect of Scl-Ab on the rapidly growing OI skeleton, we treated rapidly growing 3week old Brtl/+ mice, harboring a typical heterozygous OI-causing Gly→Cys substitution on col1a1, for 5weeks with Scl-Ab. Scl-Ab had anabolic effects in Brtl/+ and led to new cortical bone formation and increased cortical bone mass. This anabolic action resulted in improved mechanical strength to WT Veh levels without altering the underlying brittle nature of the material. While Scl-Ab was anabolic in trabecular bone of the distal femur in both genotypes, the effect was less strong in these rapidly growing Brtl/+ mice compared to WT. In conclusion, Scl-Ab was able to stimulate bone formation in a rapidly growing Brtl/+ murine model of OI, and represents a potential new therapy to improve bone mass and reduce fracture risk in pediatric OI. Copyright © 2014 Elsevier Inc. All rights reserved.

Myxoid malignant fibrous histiocytoma presenting as a midline nasal mass.

PubMed

DeRosa, Jaimie; Smit, Jeffrey R

2012-04-01

Myxoid malignant fibrous histiocytoma is a rare type of pediatric non-rhabdomyosarcoma soft-tissue sarcoma. The case of a 5-year-old girl is presented, highlighting the potential for multiple pitfalls and aberrant differential diagnoses that need to be identified for successful treatment of pediatric myxofibrosarcomas. An awareness of these tumors and a call for standardized postsurgical treatment protocols is necessary in order to successfully treat children with this disease.

Resection followed by vascularized bone autograft in patients with possible recurrence of malignant bone tumors after conservative treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Metaizeau, J.P.; Olive, D.; Bey, P.

1984-04-01

In conservative treatment of malignant bone tumors, assessment of the local condition is difficult. The radiological changes seen in the irradiated tumor and the frequent occurrence of pathological fractures at this site may give rise to the fear that the tumor has relapsed. Resection of the whole of the involved bone is the best way to assure adequate local control but the extent of the bone defect and the bad local conditions secondary to irradiation make reconstruction hazardous. In two patients (one with Ewing's sarcoma of the femur and one with osteogenic sarcoma of the humerus) the authors used amore » free, vascularized fibular graft for the reconstruction having obtained consolidation of the limb after resection of the irradiated tumor, with preservation of its function. The encouraging results obtained have suggested a conservative attitude as primary treatment of specific malignant bone tumors.« less

Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Childhood Langerhans Cell Histiocytosis; Histiocytic Sarcoma; Juvenile Xanthogranuloma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Refractory Central Nervous System Neoplasm; Refractory Childhood Malignant Germ Cell Tumor; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor

Dental management of a pediatric patient with Burkitt lymphoma: a case report.

PubMed

Padmanabhan, M Y; Pandey, R K; Kumar, Archana; Radhakrishnan, Aparna

2012-06-01

Recent advancements in the field of cancer diagnosis and chemotherapy have led to higher rates of survival for children with malignant tumors. More than 75% of pediatric patients diagnosed with malignancies survive more than 5 years. These advancements have resulted in additional responsibilities for dental professionals to diagnose, evaluate, prevent, stabilize, and manage the oral and dental problems that can compromise the quality of life of these children. This case report highlights the importance of professional and self-administered oral prophylactic measures and patient compliance in the successful oral rehabilitation of a pediatric patient with Burkitt lymphoma. © 2012 Special Care Dentistry Association and Wiley Periodicals, Inc.

[Benign bone tumors. General principles].

PubMed

Hillmann, A; Gösling, T

2014-10-01

Benign bone tumors and tumor-like lesions are much more frequent than malignant bone tumors among the total number of tumors of the skeleton. This article gives a presentation of the characteristics and treatment modalities of benign bone tumors. In this article in-house treatment principles are compared with those in the currently available literature. Benign bone tumors are frequently found incidentally; however, the term benign does not always signify that a purely observational role is needed. Benign bone tumors differ in their biological behavior and can be latent, active or aggressive which determines the treatment approach. Some benign bone tumors are just as aggressive locally as malignant tumors. The most important diagnostic feature is still conventional radiography and a thorough systematic analysis is necessary. Therapy options range from ignore, wait and see up to wide resection. In contrast to malignant tumors the radicalism of resection can be weighed against the accompanying local control and loss of function. The treatment of benign bone tumors depends on the histological type and the biological activity. Most benign bone tumors are diagnosed incidentally and do not necessitate any treatment.

High Prevalence of Vitamin D Deficiency in Patients with Bone Tumors.

PubMed

Horas, Konstantin; Maier, Gerrit; Jakob, Franz; Maus, Uwe; Kurth, Andreas; Jakuscheit, Axel; Rudert, Maximilian; Holzapfel, Boris Michael

2017-09-14

The aim of this study was to evaluate the prevalence of vitamin D deficiency in patients with different types of bone tumors and to elucidate whether or not there are differences in prediagnostic vitamin D levels in patients with malignant compared to benign bone tumors. Prediagnostic serum 25(OH)D levels of 105 consecutive patients that presented with bone tumors and tumor-like lesions to two Orthopedic Level I University Centers in Germany between 2011 and 2016 were measured on admission. We found an alarming and widespread rate of vitamin D deficiency in patients with bone tumors. Specifically, 83% of all patients had low vitamin D levels with a mean 25(OH)D level of 19.82 ng/ml. Notably, patients diagnosed with malignant bone tumors had significantly lower vitamin D levels compared to patients with benign bone lesions (p = 0.0008). In conclusion, it is essential to assess vitamin D levels in patients with tumors involving bone. In addition, there might be an association between vitamin D deficiency and the onset or course of primary malignant bone tumors.

Bone marrow metastasis of malignant melanoma in childhood arising within a congenital melanocytic nevus.

PubMed

Volejnikova, Jana; Bajciova, Viera; Sulovska, Lucie; Geierova, Marie; Buriankova, Eva; Jarosova, Marie; Hajduch, Marian; Sterba, Jaroslav; Mihal, Vladimir

2016-09-01

Malignant melanoma in childhood is infrequent and can arise within congenital melanocytic nevi. Spread of malignant melanoma to the bone marrow, especially in children, is extremely rare. Reported is a case of a 5-year-old boy with a congenital large melanocytic nevus of the head and neck who presented with a short history of low back and leg pain, fever and cervical lymphadenopathy. Despite regular follow-up by a dermatologist and plastic surgeon and repeatedly negative histology of previous partial excisions, diffuse bone marrow infiltration with malignant melanoma was diagnosed. The primary site was identified in the post-excision area. The disease progressed rapidly on ipilimumab immunotherapy and led to death at four months from the diagnosis. Surveillance is indispensable in children with a predisposition to melanoma and nonspecific symptoms such as bone pain, gait impairment or cytopenia, should always be taken into account.

Can physical activity improve peak bone mass?

PubMed

Specker, Bonny; Minett, Maggie

2013-09-01

The pediatric origin of osteoporosis has led many investigators to focus on determining factors that influence bone gain during growth and methods for optimizing this gain. Bone responds to bone loading activities by increasing mass or size. Overall, pediatric studies have found a positive effect of bone loading on bone size and accrual, but the types of loads necessary for a bone response have only recently been investigated in human studies. Findings indicate that responses vary by sex, maturational status, and are site-specific. Estrogen status, body composition, and nutritional status also may influence the bone response to loading. Despite the complex interrelationships among these various factors, it is prudent to conclude that increased physical activity throughout life is likely to optimize bone health.

Quantitative Evaluation of Segmentation- and Atlas-Based Attenuation Correction for PET/MR on Pediatric Patients.

PubMed

Bezrukov, Ilja; Schmidt, Holger; Gatidis, Sergios; Mantlik, Frédéric; Schäfer, Jürgen F; Schwenzer, Nina; Pichler, Bernd J

2015-07-01

Pediatric imaging is regarded as a key application for combined PET/MR imaging systems. Because existing MR-based attenuation-correction methods were not designed specifically for pediatric patients, we assessed the impact of 2 potentially influential factors: inter- and intrapatient variability of attenuation coefficients and anatomic variability. Furthermore, we evaluated the quantification accuracy of 3 methods for MR-based attenuation correction without (SEGbase) and with bone prediction using an adult and a pediatric atlas (SEGwBONEad and SEGwBONEpe, respectively) on PET data of pediatric patients. The variability of attenuation coefficients between and within pediatric (5-17 y, n = 17) and adult (27-66 y, n = 16) patient collectives was assessed on volumes of interest (VOIs) in CT datasets for different tissue types. Anatomic variability was assessed on SEGwBONEad/pe attenuation maps by computing mean differences to CT-based attenuation maps for regions of bone tissue, lungs, and soft tissue. PET quantification was evaluated on VOIs with physiologic uptake and on 80% isocontour VOIs with elevated uptake in the thorax and abdomen/pelvis. Inter- and intrapatient variability of the bias was assessed for each VOI group and method. Statistically significant differences in mean VOI Hounsfield unit values and linear attenuation coefficients between adult and pediatric collectives were found in the lungs and femur. The prediction of attenuation maps using the pediatric atlas showed a reduced error in bone tissue and better delineation of bone structure. Evaluation of PET quantification accuracy showed statistically significant mean errors in mean standardized uptake values of -14% ± 5% and -23% ± 6% in bone marrow and femur-adjacent VOIs with physiologic uptake for SEGbase, which could be reduced to 0% ± 4% and -1% ± 5% using SEGwBONEpe attenuation maps. Bias in soft-tissue VOIs was less than 5% for all methods. Lung VOIs showed high SDs in the range of 15% for all methods. For VOIs with elevated uptake, mean and SD were less than 5% except in the thorax. The use of a dedicated atlas for the pediatric patient collective resulted in improved attenuation map prediction in osseous regions and reduced interpatient bias variation in femur-adjacent VOIs. For the lungs, in which intrapatient variation was higher for the pediatric collective, a patient- or group-specific attenuation coefficient might improve attenuation map accuracy. Mean errors of -14% and -23% in bone marrow and femur-adjacent VOIs can affect PET quantification in these regions when bone tissue is ignored. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Biomarkers of Osteosarcoma, Chondrosarcoma, and Ewing Sarcoma.

PubMed

Evola, Francesco R; Costarella, Luciano; Pavone, Vito; Caff, Giuseppe; Cannavò, Luca; Sessa, Andrea; Avondo, Sergio; Sessa, Giuseppe

2017-01-01

Osteosarcoma is the most frequent malignant bone neoplasm, followed by chondrosarcoma and Ewing sarcoma. The diagnosis of bone neoplasms is generally made through histological evaluation of a biopsy. Clinical and radiological features are also important in aiding diagnosis and to complete the staging of bone cancer. In addition to these, there are several non-specific serological or specific molecular markers for bone neoplasms. In bone tumors, molecular markers increase the accuracy of the diagnosis and assist in subtyping bone tumors. Here, we review these markers and discuss their role in the diagnosis and prognosis of the three most frequent malignant bone neoplasms, namely osteosarcoma, chondrosarcoma, and Ewing sarcoma.

Diversity of Pubertal Development in Cartilage-Hair Hypoplasia; Two Illustrative Cases.

PubMed

Holopainen, Elina; Vakkilainen, Svetlana; Mäkitie, Outi

2018-08-01

Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia, including disproportionate short stature, hypoplastic hair, immunodeficiency, and increased risk of malignancies. Absent pubertal growth spurt and absent pubic hair complicate monitoring of pubertal development in these patients. Two CHH patients with delayed puberty and excessive growth failure are described. One of the girls had hypogonadotropic hypogonadism whereas the other had hyponormogonadotropic hypogonadism with no spontaneous pubertal development and slow response to estrogen therapy, both requiring permanent replacement therapy. Careful follow-up of pubertal development in individuals with CHH and other growth-restricting bone diseases is needed. In delayed pubertal development timely hormone therapy is essential to ensure maximal growth and well developed secondary sex characteristics. Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Strontium-85 Scanning of Suspected Bone Disease

PubMed Central

Parsons, Victor; Williams, Margery; Hill, David; Frost, Pamela; Lapham, Avril

1969-01-01

Strontium-85 scanning of suspected bone lesions in 81 patients has added to the criteria for the diagnosis of malignant and other lesions of bone. Of 46 patients with a previous history of malignant disease and skeletal symptoms negative radiological findings were recorded in 19, but nine of these had positive scans, eight of which when followed up over periods of up to four years proved to be metastatic. A similar prevalence of positive scans occurred in patients without a previous history of malignancy. Because of the anatomical localization of lesions made possible by this technique a tissue diagnosis was made in six patients, while fields of radiotherapy were altered in another seven. This technique can improve the management of patients with suspected bone disease. PMID:5761888

Ultrasound-guided core needle biopsy in diagnosis of abdominal and pelvic neoplasm in pediatric patients.

PubMed

Wang, Hailing; Li, Fangxuan; Liu, Juntian; Zhang, Sheng

2014-01-01

Ultrasound-guided core needle biopsy of abdominal and pelvic masses in adults has gained tremendous popularity. However, the application of the same treatment in children is not as popular because of apprehensions regarding inadequate tissues for the biopsy and accidental puncture of vital organs. Data of the application of ultrasound-guided core needle biopsy in 105 pediatric patients with clinically or ultrasound-diagnosed abdominopelvic masses were reviewed. Diagnostic procedures were conducted in our institution from May 2011 to May 2013. The biopsies were conducted on 86 malignant lesions and 19 benign lesions. 86 malignant tumors comprised neuroblastomas (30 cases), hepatoblastomas (15 cases), nephroblastomas (11 cases), and primitive neuroectodermal tumors/malignant small round cells (6 cases). Among malignant tumor cases, only a pelvic primitive neuroectodermal tumor did not receive a pathological diagnosis. Therefore, the biopsy accuracy was 98.8 % in malignant tumor. However, the biopsies for one neuroblastomas and one malignant small round cell tumor were inadequate for cytogenetic analysis. Therefore, 96.5 % of the malignant tumor patients received complete diagnosis via biopsy. 19 benign tumors comprised mature teratoma (10 cases), hemangioendothelioma (3 cases), paraganglioma (2 cases), and infection (2 cases). The diagnostic accuracy for benign neoplasm was 100 %. Five patients experienced postoperative complications, including pain (2 patients), bleeding from the biopsy site (2 patients), and wound infection (1 patient). Ultrasound-guided core needle biopsy is an efficient, minimally invasive, accurate, and safe diagnostic method that can be applied in the management of abdominal or pelvic mass of pediatric patients.

Subsequent Malignant Neoplasms in a Population-Based Cohort of Pediatric Cancer Patients: A Focus on the First 5 Years.

PubMed

Pole, Jason D; Gu, Lan Ying; Kirsh, Victoria; Greenberg, Mark L; Nathan, Paul C

2015-10-01

The purpose was to describe the development of subsequent malignant neoplasms (SMN) among a population-based cohort of pediatric cancer patients, with a focus on SMNs that occurred within the first 5 years from diagnosis. The cohort was identified from POGONIS, an active provincial registry. Cohort members were Ontario residents ages 0 to 14.9 years at primary diagnosis between January 1985 and December 2008. SMNs that developed <18 years were captured by POGONIS, whereas SMNs diagnosed later were identified through linkage. Cumulative incidence and standardized incidence ratios (SIR) were calculated, and proportional hazards models were estimated to examine factors associated with SMN development. A total of 7,920 patients were eligible. 2.4% (188/7,920) developed 197 SMNs. Mean follow-up time was 10.7 years (SD = 7.6 years; range, 0.0-26.4 years) with mean time to SMN of 8.5 years (SD = 6.3 years; range, 0.0-24.9 years). The SIR for the development of a SMN was 9.9 [95% confidence interval (CI), 8.6-11.4]. 40.6% of SMNs (80/197) developed within 5 years. Early SMNs were more likely to be leukemia and lymphoma. Factors associated with early SMN were primary diagnosis of a bone tumor (OR, 4.88; 95% CI, 1.52-15.60), exposure to radiotherapy (OR, 1.82; 95% CI, 1.02-3.22), and the highest dose of epipodophyllotoxin (OR, 3.74; 95% CI, 1.88-7.42). Over 40% of SMNs diagnosed in childhood cancer patients occurred in the first 5 years after diagnosis, suggesting a need for early and ongoing surveillance. The early development of certain SMNs reinforces the need for early and continued surveillance at all stages for pediatric cancer patients. ©2015 American Association for Cancer Research.

PERSPECTIVES ON CANCER STEM CELLS IN OSTEOSARCOMA

PubMed Central

Basu-Roy, Upal; Basilico, Claudio; Mansukhani, Alka

2012-01-01

Osteosarcoma is an aggressive pediatric tumor of growing bones that, despite surgery and chemotherapy, is prone to relapse. These mesenchymal tumors are derived from progenitor cells in the osteoblast lineage that have accumulated mutations to escape cell cycle checkpoints leading to excessive proliferation and defects in their ability to differentiate appropriately into mature bone-forming osteoblasts. Like other malignant tumors, osteosarcoma is often heterogeneous, consisting of phenotypically distinct cells with features of different stages of differentiation. The cancer stem cell hypothesis posits that tumors are maintained by stem cells and it is the incomplete eradication of a refractory population of tumor-initiating stem cells that accounts for drug resistance and tumor relapse. In this review we present our current knowledge about the biology of osteosarcoma stem cells from mouse and human tumors, highlighting new insights and unresolved issues in the identification of this elusive population. We focus on factors and pathways that are implicated in maintaining such cells, and differences from paradigms of epithelial cancers. Targeting of the cancer stem cells in osteosarcoma is a promising avenue to explore to develop new therapies for this devastating childhood cancer. PMID:22659734

Optimal Treatment of Malignant Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing

DTIC Science & Technology

2014-10-01

Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing 5a. CONTRACT NUMBER...in the fifth quarter of the award. 15. SUBJECT TERMS Fracture healing , bone healing , endochondral ossification, intramembranous ossification...of radiation on the two pathways of bone healing and propose an optimal method of surgical fracture repair for managing malignant osteoporotic

Non-malignant Fibrosing Tumors in the Pediatric Hand: A Clinicopathologic Case Review

PubMed Central

Baumholtz, Michael A.; Popek, Edwina; Schneider, Adam M.

2008-01-01

Non-malignant fibrosing tumors in the pediatric hand or juvenile fibromatoses are clinically challenging because of their relatively infrequent occurrence and because of the variety of names associated with these diseases. We conducted a review of a personal case series of pediatric patients with these tumors and discuss here the more common histologic types and clinical characteristics of the disease spectrum in the context of the available published literature. All histologic samples were reviewed by a single pathologist. Infantile myofibromatosis, fibrous hamartoma of infancy, juvenile aponeurotic fibromatosis, palmar fibromatosis (Dupuytren’s type), infantile digital fibromatosis (Reye’s tumor), fibroma of the tendon sheath, and melorheostosis represent the encountered lesions. PMID:19048350

Contrast-enhanced sonography in pediatrics.

PubMed

McCarville, M Beth

2011-05-01

Microbubble US contrast agents are composed of an outer shell of protein, phospholipid or polymer that encase air or perfluorocarbon gas. These contrast agents have been widely used in adult cardiology patients to improve endocardial border delineation and have been proved safe and well tolerated in this patient population. There is also a growing body of literature elucidating the value of contrast-enhanced sonography to distinguish benign from malignant liver lesions in adults and to characterize non-hepatic adult malignancies. Because these agents have not been approved for pediatric use in many countries, less is known of the value of contrast-enhanced sonography in children. In this review I will discuss several proven and potential pediatric applications of contrast-enhanced sonography.

Survivorship Care in Reducing Symptoms in Young Adult Cancer Survivors

ClinicalTrials.gov

2017-10-13

Breast Carcinoma; Cancer Survivor; Depression; Fatigue; Leukemia; Lymphoma; Malignant Bone Neoplasm; Malignant Digestive System Neoplasm; Malignant Female Reproductive System Neoplasm; Malignant Male Reproductive System Neoplasm; Pain; Sleep Disorder; Soft Tissue Sarcoma

Reconstruction of the mandible bone by treatment of resected bone with pasteurization.

PubMed

Uehara, Masataka; Inokuchi, Tsugio; Sano, Kazuo; Sumita, Yoshinori; Tominaga, Kazuhiro; Asahina, Izumi

2012-11-01

The results of long-term follow-up for reimplantation of the mandibular bone treated with pasteurization are reported. Mandibulectomy was performed for mandibular malignancy in 3 cases. The resected bones were subsequently reimplanted after treatment with pasteurization in 3 cases to eradicate tumor cells involved in the resected bone. Although postoperative infection was observed in 2 of 3 cases, reimplantation of the resected mandibular bone treated by pasteurization was finally successful. Ten to 22 years of follow-up was carried out. Pasteurization was able to devitalize tumor cells involved in the resected bone and to preserve bone-inductive activity. Reimplantation of pasteurization could be a useful strategy for reconstruction of the mandible in patients with mandibular malignancy.

[LiLa classification for paediatric long bone fractures. Intraobserver and interobserver reliability].

PubMed

Kamphaus, A; Rapp, M; Wessel, L M; Buchholz, M; Massalme, E; Schneidmüller, D; Roeder, C; Kaiser, M M

2015-04-01

There are two child-specific fracture classification systems for long bone fractures: the AO classification of pediatric long-bone fractures (PCCF) and the LiLa classification of pediatric fractures of long bones (LiLa classification). Both are still not widely established in comparison to the adult AO classification for long bone fractures. During a period of 12 months all long bone fractures in children were documented and classified according to the LiLa classification by experts and non-experts. Intraobserver and interobserver reliability were calculated according to Cohen (kappa). A total of 408 fractures were classified. The intraobserver reliability for location in the skeletal and bone segment showed an almost perfect agreement (K = 0.91-0.95) and also the morphology (joint/shaft fracture) (K = 0.87-0.93). Due to different judgment of the fracture displacement in the second classification round, the intraobserver reliability of the whole classification revealed moderate agreement (K = 0.53-0.58). Interobserver reliability showed moderate agreement (K = 0.55) often due to the low quality of the X-rays. Further differences occurred due to difficulties in assigning the precise transition from metaphysis to diaphysis. The LiLa classification is suitable and in most cases user-friendly for classifying long bone fractures in children. Reliability is higher than in established fracture specific classifications and comparable to the AO classification of pediatric long bone fractures. Some mistakes were due to a low quality of the X-rays and some due to difficulties to classify the fractures themselves. Improvements include a more precise definition of the metaphysis and the kind of displacement. Overall the LiLa classification should still be considered as an alternative for classifying pediatric long bone fractures.

An Approach for Determining Quantitative Measures for Bone Volume and Bone Mass in the Pediatric Spina Bifida Population

PubMed Central

Horenstein, Rachel E.; Shefelbine, Sandra J.; Mueske, Nicole M.; Fisher, Carissa L.; Wren, Tishya A.L.

2015-01-01

Background The pediatric spina bifida population suffers from decreased mobility and recurrent fractures. This study aimed to develop a method for quantifying bone mass along the entire tibia in youth with spina bifida. This will provide information about all potential sites of bone deficiencies. Methods Computed tomography images of the tibia for 257 children (n=80 ambulatory spina bifida, n=10 non-ambulatory spina bifida, n=167 typically developing) were analyzed. Bone area was calculated at regular intervals along the entire tibia length and then weighted by calibrated pixel intensity for density weighted bone area. Integrals of density weighted bone area were used to quantify bone mass in the proximal and distal epiphyses and diaphysis. Group differences were evaluated using analysis of variance. Findings Non-ambulatory children suffer from decreased bone mass in the diaphysis and proximal and distal epiphyses compared to ambulatory and control children (P≤0.001). Ambulatory children with spina bifida showed statistically insignificant differences in bone mass in comparison to typically developing children at these sites (P>0.5). Interpretation This method provides insight into tibial bone mass distribution in the pediatric spina bifida population by incorporating information along the whole length of the bone, thereby providing more information than dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. This method can be applied to any population to assess bone mass distribution across the length of any long bone. PMID:26002057

The Risk of Misdiagnosing the Primary Site Responsible for Bone Metastases in Patients With Chronic Lymphocytic Leukemia and a Second Primary Carcinoma

PubMed Central

Hatoum, Georges; Meshkin, Cyrus; Alkhunaizi, Sufana; Levene, Richard; Formoso-Onofrio, Julie

2015-01-01

Chronic lymphocytic leukemia (CLL) is a common malignancy which may coexist with other primary cancers. CLL is rarely the cause of solitary bone lesions; such lesions in the context of CLL are believed to result from either Richter’s transformation or metastasis from another primary malignancy. Renal cell carcinoma (RCC), on the other hand, is a malignancy which frequently metastasizes to bone and may cause an osteolytic solitary bone lesion. The origin of a solitary bone lesion in a patient with multiple potential primary malignancies has prognostic implications and affects treatment protocol, and as such must be diagnosed accurately. We describe a patient with CLL and a history of RCC who is found to have an incidental solitary bone lesion of the T11 vertebra. After two separate CT-guided biopsies revealed various lymphoid cell predominance and no evidence of RCC, treatment with low dose external beam radiation therapy (EBRT) was employed. Post-therapy MRI showed further propagation of the lesion. Surgical corpectomy was subsequently performed and postoperative pathology of the lesion was consistent with RCC. The patient was treated with bisphosphonates and a higher dose of EBRT. Our case illustrates the importance of surgical excisional biopsy for accurately diagnosing the primary source metastatic to the bone in a patient with CLL and another potential primary cancer. PMID:29147427

Systemic malignancies presenting as primary osteolytic lesion.

PubMed

Sirelkhatim, A; Kaiserova, E; Kolenova, A; Puskacova, J; Subova, Z; Petrzalkova, D; Banikova, K; Suvada, J; Sejnova, D

2009-01-01

The tumor formation may be the earliest manifestation preceeding other symptoms, signs and bone marrow evidence of systemic malignancy - leukemia/lymphoma. Here we present three cases of systemic malignancy in which bone lesions were the first manifested signs of the disease. All three cases were thought to be orthopedic cases and had been treated as so without genuing improvement. We would like to draw an attention to children who present with multifocal musculoskeletal pain and the importance of whole-body scaning. We describe interesting cases of diffuse large cell lymphoma and leukemia that initially presented as primary osteolytic bone lesion and discuss the differential diagnosis, literature review of non-Hodgkin's lymphoma arising in bone as the primary site (Tab. 1, Fig. 3, Ref. 18). Full Text (Free, PDF) www.bmj.sk.

Orthobiologics in Pediatric Sports Medicine.

PubMed

Bray, Christopher C; Walker, Clark M; Spence, David D

2017-07-01

Orthobiologics are biological substances that allow injured muscles, tendons, ligaments, and bone to heal more quickly. They are found naturally in the body; at higher concentrations they can aid in the healing process. These substances include autograft bone, allograft bone, demineralized bone matrix, bone morphogenic proteins, growth factors, stem cells, plasma-rich protein, and ceramic grafts. Their use in sports medicine has exploded in efforts to increase graft incorporation, stimulate healing, and get athletes back to sport with problems including anterior cruciate ligament ruptures, tendon ruptures, cartilage injuries, and fractures. This article reviews orthobiologics and their applications in pediatric sports medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Canine osteosarcoma: a naturally occurring disease to inform pediatric oncology.

PubMed

Fenger, Joelle M; London, Cheryl A; Kisseberth, William C

2014-01-01

Osteosarcoma (OSA) is the most common form of malignant bone cancer in children and dogs, although the disease occurs in dogs approximately 10 times more frequently than in people. Multidrug chemotherapy and aggressive surgical techniques have improved survival; however, new therapies for OSA are critical, as little improvement in survival times has been achieved in either dogs or people over the past 15 years, even with significant efforts directed at the incorporation of novel therapeutic approaches. Both clinical and molecular evidence suggests that human and canine OSA share many key features, including tumor location, presence of microscopic metastatic disease at diagnosis, development of chemotherapy-resistant metastases, and altered expression/activation of several proteins (e.g. Met, ezrin, phosphatase and tensin homolog, signal transducer and activator of transcription 3), and p53 mutations, among others. Additionally, canine and pediatric OSA exhibit overlapping transcriptional profiles and shared DNA copy number aberrations, supporting the notion that these diseases are similar at the molecular level. This review will discuss the similarities between pediatric and canine OSA with regard to histology, biologic behavior, and molecular genetic alterations that indicate canine OSA is a relevant, spontaneous, large animal model of the pediatric disease and outline how the study of naturally occurring OSA in dogs will offer additional insights into the biology and future treatment of this disease in both children and dogs. © The Author 2014. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Broken bones: common pediatric fractures--part I.

PubMed

Hart, Erin S; Albright, Maurice B; Rebello, Gleeson N; Grottkau, Brian E

2006-01-01

Musculoskeletal injuries are one of the most frequently encountered problems in pediatric practice, with fractures accounting for a surprisingly large percentage of these injuries. A fracture occurs when bone is subjected to more energy than it can absorb. Pediatric healthcare providers must have a good understanding of normal bone growth and development and must recognize common mechanisms of injury and fracture patterns seen in children. Nearly 20% of children who present with an injury have a fracture, and it is estimated that 42% of boys and 27% of girls will sustain a fracture during childhood (Wilkins, 1996). The immature skeleton has several unique properties that directly affect the management of fractures in children.

Pediatric Genomic Data Inventory (PGDI) Overview

Cancer.gov

About Pediatric cancer is a genetic disease that can largely differ from similar malignancies in an adult population. To fuel new discoveries and treatments specific to pediatric oncologies, the NCI Office of Cancer Genomics has developed a dynamic resource known as the Pediatric Genomic Data Inventory to allow investigators to more easily locate genomic datasets. This resource lists known ongoing and completed sequencing projects of pediatric cancer cohorts from the United States and other countries, along with some basic details and reference metadata.

Prevalence of vitamin D deficiency and insufficiency in children with osteopenia or osteoporosis referred to a pediatric metabolic bone clinic.

PubMed

Bowden, Sasigarn A; Robinson, Renee F; Carr, Roxane; Mahan, John D

2008-06-01

The purpose of this work was to determine the prevalence of vitamin D deficiency and insufficiency in children with osteopenia or osteoporosis and to evaluate the relationship between serum 25-hydroxyvitamin D levels and bone parameters, including bone mineral density. Serum 25-hydroxyvitamin D, 1,25 dihydroxyvitamin D, parathyroid hormone, and other bone markers, as well as bone mineral density, were obtained for 85 pediatric patients with primary osteoporosis (caused by osteogenesis imperfecta or juvenile idiopathic osteoporosis) and secondary osteopenia or osteoporosis caused by various underlying chronic illnesses. Pearson's correlation was used to assess the relationship between vitamin D levels and different bone parameters. Vitamin D insufficiency (defined as serum 25-hydroxyvitamin D <30 ng/mL) was observed in 80.0% of patients. Overt vitamin D deficiency (defined as serum 25-hydroxyvitamin D <10 ng/mL) was present in 3.5% of patients. Using a more recent definition for vitamin D deficiency in adults (defined as serum 25-hydroxyvitamin D <20 ng/mL), 21.1% of the patients had vitamin D deficiency. There was a significant inverse correlation between 25-hydroxyvitamin D and parathyroid hormone levels. There was a positive correlation between 1,25 dihydroxyvitamin D and parathyroid hormone, alkaline phosphatase, and urine markers for bone turnover. Vitamin D insufficiency was remarkably common in pediatric patients with primary and secondary osteopenia or osteoporosis. The inverse relationship between 25-hydroxyvitamin D and parathyroid hormone levels suggests a physiologic impact of insufficient vitamin D levels that may contribute to low bone mass or worsen the primary bone disease. We suggest that monitoring and supplementation of vitamin D should be a priority in the management of pediatric patients with osteopenia or osteoporosis.

Analysis of imaging characteristics of primary malignant bone tumors in children

PubMed Central

Sun, Yingwei; Liu, Xueyong; Pan, Shinong; Deng, Chunbo; Li, Xiaohan; Guo, Qiyong

2017-01-01

The present study aimed to investigate the imaging characteristics of primary malignant bone tumors in children. The imaging results of 34 children with primary malignant bone tumors confirmed by histopathological diagnosis between March 2008 and January 2014 were retrospectively analyzed. In total, 25 patients had osteosarcoma, with radiography and computed tomography (CT) showing osteolytic bone destruction or/and osteoblastic bone sclerosis, an aggressive periosteal reaction, a soft-tissue mass and cancerous bone. The tumors appeared as mixed magnetic resonance imaging (MRI) signals that were inhomogeneously enhanced. A total of 5 patients presented with Ewing sarcoma, with radiography and CT showing invasive bone destruction and a soft-tissue mass. Of the 5 cases, 2 showed a laminar periosteal reaction. The tumors were shown to have mixed low signal on T1-weighted images (T1WI) and high signal on T2-weighted images (T2WI); 1 case showed marked inhomogeneous enhancement. Another 3 patients exhibited chondrosarcoma. Of these cases, 1 was adjacent to the cortex of the proximal tibia, and presented with local cortical bone destruction and a soft-tissue mass containing scattered punctate and amorphous calcifications. MRI revealed mixed low T1 signal and high T2 signals. Another case was located in the medullary cavity of the distal femur, with radiography revealing a localized periosteal reaction. The tumor appeared with mixed MRI signals, and with involvement of the epiphysis and epiphyseal plates. Radiography and CT of the third case showed bone destruction in the right pubic ramus, with patchy punctate, cambered calcifications in the soft-tissue mass. MRI of the soft-tissue mass revealed isointensity on T1WI and heterogeneous hyperintensity on T2WI. Ossifications and the septum appeared as low T1WI and T2WI. Of the 34 patients, 1 patient presented with lymphoma involving the T12, L1 and L2 vertebrae. CT showed vertebral bone destruction, a soft-tissue mass and a compression fracture of L1. MRI showed a soft-tissue mass with low T1 signal and high T2 signal and marked inhomogeneous enhancement. Overall, osteosarcoma was the most common primary malignant bone tumor, followed by Ewing sarcoma, chondrosarcoma and lymphoma. Osteoblastic or osteolytic bone destruction, an invasive periosteal reaction, soft-tissue masses, a tumor matrix and inhomogeneous enhancement were important imaging features of malignant bone tumors. PMID:29113210

[Malignant T-cell lymphoma with osteomyelitis-like bone infiltration].

PubMed

Mittelmeier, H; Schmitt, O

1980-01-01

After a short review on the late literature, existing about various forms of acute lymphoblastic leucemias, it is reported on a rare case of malignant T-cell-Lymphoma with ostemyelitis-like, painfull bone infiltration. The clinical symptoms, as well as differential-diagnostic criterias to other leucemias are described.

Dental anomalies in pediatric patients with familial adenomatous polyposis.

PubMed

Septer, Seth; Bohaty, Brenda; Onikul, Robin; Kumar, Vandana; Williams, Karen B; Attard, Thomas M; Friesen, Craig A; Friesen, Lynn Roosa

2018-04-01

Familial adenomatous polyposis patients often present with non-malignant extra-intestinal manifestations which include dental anomalies that may be evident prior to the appearance of the colonic adenomas. The aims of this study were to describe the prevalence and type of dental anomalies and the relationships between gene mutations and dental anomalies in these patients. Twenty-two pediatric familial adenomatous polyposis patients and 46 controls, who were age and gender matched participated. Familial adenomatous polyposis patient's had a dental examination with panoramic radiograph and medical record review for age at diagnosis, the presence of the adenomatous polyposis coli gene mutation, and determination of other extra-intestinal manifestations on the body. The control group was identified from a retrospective chart review and selected if there was a current panoramic radiograph. The only significant difference between familial adenomatous polyposis patients and controls were the presence of jaw osteomas and sclerosis (p = .0001). Patients with a mutation in, or upstream of codon 1309 had a higher frequency of osteomas (77.8%) and jaw-bone sclerosis (44.4%), and 77% of these had at least one dental anomaly. This preliminary study showed an association between a genetic variant at, or upstream of codon 1309, and radiographic dental anomalies.

Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children

PubMed Central

Franca, Raffaella; Stocco, Gabriele; Favretto, Diego; Giurici, Nagua; Decorti, Giuliana; Rabusin, Marco

2015-01-01

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. Despite the great improvements in HSCT clinical practices over the last few decades, complications, such as graft vs. host disease (GVHD) and sinusoidal obstructive syndrome (SOS), are still largely unpredictable and remain the major causes of morbidity and mortality. Both donor and patient genetic background might influence the success of bone marrow transplantation and could at least partially explain the inter-individual variability in HSCT outcome. This review summarizes some of the recent studies on candidate gene polymorphisms in HSCT, with particular reference to pediatric cohorts. The interest is especially focused on pharmacogenetic variants affecting myeloablative and immunosuppressive drugs, although genetic traits involved in SOS susceptibility and transplant-related mortality are also reviewed. PMID:26266406

An epidemiological evaluation of pediatric long bone fractures - a retrospective cohort study of 2716 patients from two Swiss tertiary pediatric hospitals.

PubMed

Joeris, Alexander; Lutz, Nicolas; Wicki, Bárbara; Slongo, Theddy; Audigé, Laurent

2014-12-20

Children and adolescents are at high risk of sustaining fractures during growth. Therefore, epidemiological assessment is crucial for fracture prevention. The AO Comprehensive Injury Automatic Classifier (AO COIAC) was used to evaluate epidemiological data of pediatric long bone fractures in a large cohort. Data from children and adolescents with long bone fractures sustained between 2009 and 2011, treated at either of two tertiary pediatric surgery hospitals in Switzerland, were retrospectively collected. Fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF). For a total of 2716 patients (60% boys), 2807 accidents with 2840 long bone fractures (59% radius/ulna; 21% humerus; 15% tibia/fibula; 5% femur) were documented. Children's mean age (SD) was 8.2 (4.0) years (6% infants; 26% preschool children; 40% school children; 28% adolescents). Adolescent boys sustained more fractures than girls (p < 0.001). The leading cause of fractures was falls (27%), followed by accidents occurring during leisure activities (25%), at home (14%), on playgrounds (11%), and traffic (11%) and school accidents (8%). There was boy predominance for all accident types except for playground and at home accidents. The distribution of accident types differed according to age classes (p < 0.001). Twenty-six percent of patients were classed as overweight or obese - higher than data published by the WHO for the corresponding ages - with a higher proportion of overweight and obese boys than in the Swiss population (p < 0.0001). Overall, differences in the fracture distribution were sex and age related. Overweight and obese patients seemed to be at increased risk of sustaining fractures. Our data give valuable input into future development of prevention strategies. The AO PCCF proved to be useful in epidemiological reporting and analysis of pediatric long bone fractures.

A Pediatric Acute Promyelocytic Leukemia With a Rare Karyotype of ider(17)(q10)t(15;17) and Favorable Outcome: A Case Report.

PubMed

He, Yanli; Wang, Ping; Liang, Kaiwei; Chen, Xiangjun; Du, Wen; Li, Juan; Hu, Yanjie; Bai, Yan; Liu, Wei; Li, Xiaoqing; Jin, Runming; Zhang, Min; Zheng, Jine

2015-10-01

Acute promyelocytic leukemia (APL) is a specific malignant hematological disorder with a diagnostic hallmark of chromosome translocation t(15;17)(q22;q21). As a very rare secondary cytogenetic aberration in pediatric APL, ider(17q) (q10)t(15;17) was suggested to be a poor prognostic factor based on previous case reports.Here, we report a pediatric APL case with a rare karyotype of ider(17)(q10)t(15;17). Bone marrow aspiration, immunophenotyping, molecular biology, cytogenetic, and fluorescence in situ hybridization (FISH) analyses were performed at initial diagnosis and during the treatment.A 6-year-old boy was brought to our hospital with the chief complaint of bleeding gums twice and intermittent fever for 3 days in January 2013. He was diagnosed as low-risk APL according to the 2012 NCCN guideline on APL, with the expression of PML-RARA (bcr3 subtype) and the karyotype of 46,XY, der(15)t(15;17)(q22;q21),ider(17)(q10)t(15;17), which was further verified by FISH. The patient was treated through combination all-trans retinoic acid (ATRA) and arsenic with daunorubicin according to the 2012 NCCN guideline for APL. Continuous hematological completed remission (HCR) and major molecular remission (MMR) were achieved with normal karyotype for >28 months after induction chemotherapy.Different from previously reported cases, this pediatric APL patient with ider(17)(q10)t(15;17) displays favorable clinical outcomes, which might be related to the low-risk classification and arsenic treatment during the treatment. It suggests that ider(17)(q10)t(15;17) may not be the sole determinant for worse outcomes in pediatric APL and implies that more contributed factors should be considered for pediatric APL prognosis.

General Information about Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

MedlinePlus

... Other Myeloid Malignancies Treatment (PDQ®)–Patient Version General Information About Childhood Acute Myeloid Leukemia and Other Myeloid ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Musculoskeletal Imaging Findings of Hematologic Malignancies.

PubMed

Navarro, Shannon M; Matcuk, George R; Patel, Dakshesh B; Skalski, Matthew; White, Eric A; Tomasian, Anderanik; Schein, Aaron J

2017-01-01

Hematologic malignancies comprise a set of prevalent yet clinically diverse diseases that can affect every organ system. Because blood components originate in bone marrow, it is no surprise that bone marrow is a common location for both primary and metastatic hematologic neoplasms. Findings of hematologic malignancy can be seen with most imaging modalities including radiography, computed tomography (CT), technetium 99m ( 99m Tc) methylene diphosphonate (MDP) bone scanning, fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, and magnetic resonance (MR) imaging. Because of the diversity of imaging appearances and clinical behavior of this spectrum of disease, diagnosis can be challenging, and profound understanding of the underlying pathophysiologic changes and current treatment modalities can be daunting. The appearance of normal bone marrow at MR imaging and FDG PET/CT is also varied due to dynamic compositional changes with normal aging and in response to hematologic demand or treatment, which can lead to false-positive interpretation of imaging studies. In this article, the authors review the normal maturation and imaging appearance of bone marrow. Focusing on lymphoma, leukemia, and multiple myeloma, they present the spectrum of imaging findings of hematologic malignancy affecting the musculoskeletal system and the current imaging tools available to the radiologist. They discuss the imaging findings of posttreatment bone marrow and review commonly used staging systems and consensus recommendations for appropriate imaging for staging, management, and assessment of clinical remission. © RSNA, 2017.

Pathological fractures in children

PubMed Central

De Mattos, C. B. R.; Binitie, O.; Dormans, J. P.

2012-01-01

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated. PMID:23610658

Magnetic resonance imaging spectroscopy in pediatric atypical teratoid rhabdoid tumors of the brain.

PubMed

Bruggers, Carol S; Moore, Kevin

2014-08-01

Pediatric central nervous system (CNS) atypical teratoid rhabdoid tumors (ATRT) are highly malignant tumors characterized by SMARCB1 gene abnormalities. Despite chemoradiation responsiveness, most children die of disease. No imaging findings distinguish ATRT from other malignant brain tumors. This study sought to describe magnetic resonance spectroscopy (MRS) of childhood CNS ATRT and identify metabolite patterns for diagnosis and disease status monitoring. Data from 7 children diagnosed with CNS ATRT from 2007 to 2010, whose imaging included MRS, were retrospectively reviewed. Age at diagnosis ranged from 2.5 to 54 months. Tumors were large with calcium and cysts and avid gadolinium enhancement. All were isointense on T1-weighted imaging and mildly hyperintense on T2-weighted imaging. Short-TE MRS showed prominent lactate+lipid and choline, minimal N-acetyl acetate (NAA), and rarely minimal myoinositol and low creatine peaks. Long TE showed prominent choline, minimal NAA, and rarely low lactate peaks. The combination of prominent choline and lactate+lipids peaks, and generally absent NAA and myoinositol peaks by MRS in this panel of ATRT expands existing information and provides a potentially distinct metabolite profile from other malignant pediatric brain tumors, including medulloblastoma. Prospective, comparative quantitative MRS of ATRT with other pediatric CNS tumors is warranted.

International comparative study of childhood malignancy comparative study of pediatric malignancy between Kurume and Karachi (K-K Project 1991).

PubMed

Shakoor, A; Murakami, T; Yamashita, F

1991-01-01

A study was undertaken to compare Pediatric Malignancy at Kurume (Japan) and Karachi (Pakistan) with reference to international data collected over the years, in order to identify essential differences between developed and developing conditions and factors influencing the etio-pathogenesis of pediatric cancer. The study was retrospective encompassing all types of cancer in children over a period of three years i-e 1988-1990. Essential factors related to present study were: 1. The population of Karachi is about 10 million while that of Kurume is only half a million. 2. Socio-economic conditions: The average socio-economic condition of people in Karachi is poor while in Kurume it appears to be good. 3. Educational status: Only 25% people in Karachi are educated beyond middle class while Kurume reveals a 100% education up to high school level. 4. Environmental conditions: The environmental conditions of Kurume and surrounding areas are very clean and free from pollution, sewage problems and traffic hazards. Karachi and its surroundings on the other hand pose very serious air and water industries! It was concluded that whereas genetic predisposition predominates, the environmental conditions, educational and socio-economic status of a society immensely influence the pattern and trends of pediatric carcinogenesis.

Primary Ewing's Sarcoma of the Temporal Bone: A Rare Case Report and Literature Review.

PubMed

Gupta, Divya; Gulati, Achal; Purnima

2017-09-01

Ewing's sarcoma is a malignant, round cell tumor arising from the bones and primarily affecting children and adolescent, accounting for 3 % of all childhood malignancies. Although the long bones and the trunk are typically affected, rare cases of it involving isolated bones throughout the body have been reported. Involvement of the skull bones is rare, constituting 1-6 % of the total Ewing's sarcoma cases but those affecting the cranial bones are rarer still, constituting only 1 %. We describe an 8 months old infant having Ewing sarcoma, of the petrous and mastoid parts of temporal bone along with the occipital bone, whose clinical presentation mimicked mastoiditis with facial nerve palsy. We discuss the clinical and therapeutic course of an extensive primary Ewing sarcoma of the temporal bone, which was treated without performing surgery and review this entity's literature in detail.

Bone Lengthening in the Pediatric Upper Extremity.

PubMed

Farr, Sebastian; Mindler, Gabriel; Ganger, Rudolf; Girsch, Werner

2016-09-07

➤Bone lengthening has been used successfully for several congenital and acquired conditions in the pediatric clavicle, humerus, radius, ulna, and phalanges.➤Common indications for bone lengthening include achondroplasia, radial longitudinal deficiency, multiple hereditary exostosis, brachymetacarpia, symbrachydactyly, and posttraumatic and postinfectious growth arrest.➤Most authors prefer distraction rates of <1 mm/day for each bone in the upper extremity except the humerus, which can safely be lengthened by 1 mm/day.➤Most authors define success by the amount of radiographic bone lengthening, joint motion after lengthening, and subjective patient satisfaction rather than validated patient-related outcome measures.➤Bone lengthening of the upper extremity is associated with a high complication rate, with complications including pin-track infections, fixation device failure, nerve lesions, nonunion, fracture of regenerate bone, and joint dislocations. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Relationship of serum insulin-like growth factor I (IGF-I) with nutritional status in pediatric patients with malignant diseases--a single Romanian center experience.

PubMed

Chinceşan, Mihaela Ioana; Mărginean, Oana; Pitea, Ana-Maria; Dobreanu, Minodora

2013-10-01

The aim of this study was to analyze insulin-like growth factor I (IGF-I) serum level in pediatric patients with cancer compared with pediatric patients with nononcological diseases and to assess the relationship between IGF-I and nutritional status of oncological patients. From January 2009 to July 2012, we assessed 151 consecutively hospitalized patients in a tertiary emergency pediatric hospital. The patients were divided into two groups: group I, consisting of patients with malignant diseases (64 patients), and group II, the control group, consisting of 87 age- and gender-matched patients with different pediatric diseases. The anthropometric parameters (weight, height, body mass index, middle upper arm circumference (MUAC), and tricipital skinfold thickness (TST) and biochemical parameters (proteins, albumin, and total IGF-I) were comparatively evaluated at the diagnosis and after intensive chemotherapy in the malignant group. Anthropometric and biochemical parameters in group I were significantly different from those in group II for height, MUAC, TST, total proteins, and albumin (p < 0.05). Twenty-five out of 64 patients with malignant diseases and 5 out of 87 patients in the control group had malnutrition. IGF-I in patients with cancer was much lower than in the control group (median 48.3 ng/ml, range 25.00-662.00 ng/ml vs 129.00 ng/ml, range 25.00-745.00 ng/ml) (p = 0.014). We found a positive correlation between IGF-I, MUAC, and TST at the diagnosis of the malignant disease. Also, we identified positive correlations between IGF-I, protein, and albumin. Serum IGF-I levels in cancer patients were significantly lower at diagnosis than after chemotherapy (48.3 ng/ml, range 25.00-662.00 ng/ml vs 110.0 ng/ml, range 25.00-573.00 ng/ml; p = 0.04). IGF-I seems to be an accurate biochemical parameter used in malnutrition assessment of children with cancer. IGF-I correlated with the anthropometric parameters of the arm, serum protein, and albumin. These parameters most accurately characterize the nutritional status.

Ovarian masses in pediatric patients: a multicenter study of 98 surgical cases in Tunisia.

PubMed

Abid, I; Zouari, M; Jallouli, M; Sahli, S; Bouden, A; Ben Abdallah, R; Trabelsi, F; Jabloun, A; Charieg, A; Mrad, C; Marzouki, M; Mosbahi, S; Ezzi, A; Mootamri, R; Hamzaoui, M; Kaabar, N; Jlidi, S; Nouri, A; Mhiri, R

2018-03-01

Ovarian masses requiring surgical intervention are uncommon in the pediatric population. Our aim is to report results of a multicentric Tunisian study concerning the clinical practice and the management of pediatric ovarian masses and to identify the factors that are associated with ovarian preservation. Between January 2000 and December 2015, 98 pediatric patients (<14 years) were surgically treated for ovarian masses at the five pediatric surgery departments in Tunisia. Ninety-eight patients were included in this study. The mean age of the patients at time of surgery was 8.46 ± 4.87 years. Sixty-three ovarian masses (64.3%) were non-neoplastic lesions, 24 (24.5%) were benign tumors, and 11 (11.2%) were malignant neoplasms. Conservative surgery (ovarian-preserving surgery) was successfully performed in 72.4% of the benign lesions, whereas only three patients (27.3%) with malignant tumors underwent ovary-sparing tumor resection (p < .001). The mean diameter of the tumors in the patients who underwent oophorectomy was significantly larger than that in the patients who underwent conservative surgery (7.8 ± 3.9 cm vs. 5.7 ± 2.9 cm, respectively, p = .001). In our study, the risk factors for oophorectomy were a malignant pathology and large tumor size. In accordance with the Gynecologic Cancer Intergroup consensus, we recommend that surgical management of ovarian masses in children should be based on ovarian-preserving surgery.

Diagnostic value of apparent diffusion coefficients to differentiate benign from malignant vertebral bone marrow lesions.

PubMed

Balliu, E; Vilanova, J C; Peláez, I; Puig, J; Remollo, S; Barceló, C; Barceló, J; Pedraza, S

2009-03-01

The aim of this study is to evaluate the value of the apparent diffusion coefficient (ADC) obtained in diffusion-weighted (DW) MR sequences for the differentiation between malignant and benign bone marrow lesions. Forty-five patients with altered signal intensity vertebral bodies on conventional MR sequences were included. The cause of altered signal intensity was benign osteoporotic collapse in 16, acute neoplastic infiltration in 15, and infectious processes in 14; based on plain-film, CT, bone scintigraphy, conventional MR studies, biopsy or follow-up. All patients underwent isotropic DW MR images (multi-shot EPI, b values of 0 and 500 s/mm(2)). Signal intensity at DW MR images was evaluated and ADC values were calculated and compared between malignancy, benign edema and infectious spondylitis. Acute malignant fractures were hyperintense compared to normal vertebral bodies on the diffusion-weighted sequence, except in one patient with sclerotic metastases. Mean ADC value from benign edema (1.9+/-0.39 x 10(-3) mm(2)/s) was significantly (p<0.0001) higher than untreated metastasic lesions (0.9+/-1.3 x 10(-3)mm (2)/s). Mean ADC value of infectious spondilytis (0.96+/-0.49 x 10(-3) mm(2)/s) was not statistically (p>0.05) different from untreated metastasic lesions. ADC value was low (0.75 x 10(-3) mm(2)/s) in one case of subacute benign fracture. ADC values are a useful complementary tool to characterize bone marrow lesions, in order to distinguish acute benign fractures from malignant or infectious bone lesions. However, ADC values are not valuable in order to differentiate malignancy from infection.

Bayesian pretest probability estimation for primary malignant bone tumors based on the Surveillance, Epidemiology and End Results Program (SEER) database.

PubMed

Benndorf, Matthias; Neubauer, Jakob; Langer, Mathias; Kotter, Elmar

2017-03-01

In the diagnostic process of primary bone tumors, patient age, tumor localization and to a lesser extent sex affect the differential diagnosis. We therefore aim to develop a pretest probability calculator for primary malignant bone tumors based on population data taking these variables into account. We access the SEER (Surveillance, Epidemiology and End Results Program of the National Cancer Institute, 2015 release) database and analyze data of all primary malignant bone tumors diagnosed between 1973 and 2012. We record age at diagnosis, tumor localization according to the International Classification of Diseases (ICD-O-3) and sex. We take relative probability of the single tumor entity as a surrogate parameter for unadjusted pretest probability. We build a probabilistic (naïve Bayes) classifier to calculate pretest probabilities adjusted for age, tumor localization and sex. We analyze data from 12,931 patients (647 chondroblastic osteosarcomas, 3659 chondrosarcomas, 1080 chordomas, 185 dedifferentiated chondrosarcomas, 2006 Ewing's sarcomas, 281 fibroblastic osteosarcomas, 129 fibrosarcomas, 291 fibrous malignant histiocytomas, 289 malignant giant cell tumors, 238 myxoid chondrosarcomas, 3730 osteosarcomas, 252 parosteal osteosarcomas, 144 telangiectatic osteosarcomas). We make our probability calculator accessible at http://ebm-radiology.com/bayesbone/index.html . We provide exhaustive tables for age and localization data. Results from tenfold cross-validation show that in 79.8 % of cases the pretest probability is correctly raised. Our approach employs population data to calculate relative pretest probabilities for primary malignant bone tumors. The calculator is not diagnostic in nature. However, resulting probabilities might serve as an initial evaluation of probabilities of tumors on the differential diagnosis list.

[Pathological diagnosis of pediatric Burkitt lymphoma involving bone marrow].

PubMed

Sun, Qi; Chen, Zhenping; Liu, Enbin; Li, Zhanqi; Yang, Qingying; Sun, Fujun; Ma, Yue; Zhang, Hongju; Zhang, Peihong; Ru, Kun

2015-02-01

To investigate pathologic and differential diagnostic features of pediatric Burkitt lymphoma (BL). A total of 20 cases of pediatric BL were retrospectively reviewed for their clinical and pathologic profiles. Bone marrow aspiration specimens were available in all cases and bone marrow biopsies were available for immunohistochemical study in 18 cases. Flow cytometry study was available in 16 cases. MYC translocation by FISH method was performed in 11 cases. Atypical lymphocytes with cytoplasmic vacuoles were found in bone marrow smears in all 20 cases and peripheral blood films in all 19 available cases. The bone marrow biopsies showed infiltration by uniform medium-sized atypical lymphocytes with multiple small nucleoli but without the starry-sky pattern in all 18 cases. Immunohistochemistry showed the following results in all 18 cases: positive for CD20, PAX-5, CD10, CD34 and TdT, but negative for bcl-2 and CD3 with Ki-67 > 95%.Flow cytometry showed CD19+CD20+CD10+FMC7+CD22+TdT-CD3- in 16 cases, including κ+ in 8 cases, λ+ in 7 cases, and κ-λ- in 1 case. MYC gene rearrangement by FISH was observed in 10 of the 11 cases. The histopathology of BL is distinct, including atypical lymphocytes with cytoplasmic vacuoles in bone marrow aspirate, lack of starry-sky patternin bone marrow biopsy. Generally, the diagnosis should be made with a combined immunophenotype and FISH approach. Pediatric BL must be distinguished from DLBCL and B-cell lymphoma, unclassifiable, which has intermediate features between DLBCL and Burkitt lymphoma.

Study to Evaluate the Safety and Tolerability of IACS-010759 in Subjects With Advanced Solid Tumors and Lymphoma

ClinicalTrials.gov

2018-05-25

Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

Inflammatory myofibroblastic tumor: an entity of CT and MR imaging to differentiate from malignant tumors of the sinonasal cavity.

PubMed

Yan, Zhongyu; Wang, Yongzhe; Zhang, Zhengyu

2014-01-01

Inflammatory myofibroblastic tumor (IMT) is chronic inflammatory lesions of unknown origins. The preoperative diagnosis for tumors in the sinonasal cavity is difficult to distinguish between IMT and aggressive malignancy in most cases. The purpose of this study was to evaluate the imaging features of IMT distinguishing the 2 types of tumors. Computed tomography and magnetic resonance imaging were identified retrospectively with IMT in 14 cases and with aggressive malignancy in 38 cases in the sinonasal cavity proven by pathology. Imaging findings were evaluated, including the configuration, extent, margin, calcification, bone involvement, T1WI and T2WI signal intensity, and degree of enhancement. There was a significant difference between IMT and aggressive malignancy regarding the configuration, extension, calcification, bone change, signal intensity and homogeneous on T2-weighted imaging, and degree of enhancement (P < 0.05). Inflammatory myofibroblastic tumor and aggressive malignancy have some different imaging features that could be helpful in the differentiation between the lesions. Bone erosion with sclerosis, calcification when present, typically homogenous and never hyperintense of T2 appearance, and mild enhancement played an important role in differentiating sinonasal IMT from malignancies.

Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

PubMed Central

Shweikeh, Faris; Bukavina, Laura; Saeed, Kashif; Sarkis, Reem; Suneja, Aarushi; Sweiss, Fadi; Drazin, Doniel

2014-01-01

Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing's sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma), some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma), and a few after 36 months (chondrosarcoma and liposarcoma). Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing's sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas). Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease. PMID:24757391

Dual-fibular reconstruction of a massive tibial defect after Ewing's sarcoma resection in a pediatric patient with a vascular variation.

PubMed

Saridis, Alkis G; Megas, Panagiotis D; Georgiou, Christos S; Diamantakis, Georgios M; Tyllianakis, Minos E

2011-01-01

In the management of malignancies of the extremities, limb salvage procedures have recently taken on greater significance. For those patients under intense adjuvant chemotherapy and with massive bone loss, free vascularized fibular grafting is currently advocated as a reliable reconstructive option, maybe because of the controversial results of bone transport in similar situations. However, when there is a vascular abnormality of either the recipient or donor extremity, microsurgical procedures are not feasible, further limiting potential reconstructive alternatives. We present the case of a 13-year-old female patient with Ewing's sarcoma of the right tibia. Preoperative angiography showed that vascularity of the affected side depended totally on a single peroneal artery. The patient was treated initially with multiagent chemotherapy, followed by an excision of 23 cm. The defect was bridged by a gradual medial transportation of the ipsilateral fibula with the Ilizarov technique and strengthened by nonvascularized transfer of the contralateral fibula. Total external fixation time was 162 days. After the removal of the Ilizarov frame a walking cast was applied for another month. At 5 years postoperatively there was no recurrence of the malignancy. The patient had full weight-bearing ability on the affected limb, with preservation of the ankle and knee joints motion and without any limb length discrepancy or axial deformity. The functional outcome that was visible was graded excellent. Transverse distraction osteogenesis of the ipsilateral fibula performed well under chemotherapy, showing unproblematic callus formation. Supplemented with nonvascularized transfer of the contralateral fibula, provided a reconstructive option with biological affinity, sufficient biomechanical strength and durability, and with a decreased complication rate. This case report presents a viable option, especially in cases in which vascular abnormalities of either the donor or the recipient limb, combined with multiagent chemotherapy, restrict potential reconstructive alternatives. It also highlights why vascularized bone graft should not be regarded as a panacea for all situations in which a fibular graft is required. Level IV, case report.

Clinical Features of Adult Patients Admitted to Pediatric Wards in Japan.

PubMed

Michihata, Nobuaki; Matsui, Hiroki; Fushimi, Kiyohide; Yasunaga, Hideo

2015-10-01

Pediatricians generally need to treat adult patients who require long-term care for pediatric diseases. However, little is known about the characteristics of adult patients in pediatric wards. Using a national inpatient database, the aim of this study was to determine the clinical details of adult patients admitted to pediatric wards in Japanese acute-care hospitals. We extracted all inpatients aged ≥19 years who were admitted to pediatric departments in Japan from April 2012 to March 2013. We examined the patients' main diagnoses and the use of life-supporting home medical devices. Of 417,352 patients admitted to pediatric wards during the study period, we identified 4,729 (1.1%) adult patients. The major diagnoses of the adult patients were malignancy, congenital heart disease, epilepsy, and cerebral palsy. More than 35% of the patients with cerebral palsy had a tracheostomy tube, gastrostomy tube, home central venous alimentation, or home respirator. More than 20% of patients aged ≥40 years in pediatric wards had adult diseases, including ischemic heart diseases, cerebrovascular diseases, and adult malignancy. Many adult patients in pediatric wards had adult diseases. It is essential to establish a disease-oriented support system for adults with chronic conditions that originated in their childhood. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Design of the long-term observational cohort study with recombinant human growth hormone in Korean children: LG Growth Study

PubMed Central

Chung, Sochung; Yoo, Jae-Ho; Choi, Jin Ho; Rhie, Young-Jun; Chae, Hyun-Wook; Kim, Jae Hyun; Hwang, Il Tae; Shin, Choong Ho; Kim, Eun Young

2018-01-01

Purpose Regarding recombinant human growth hormone (rhGH) use in the pediatric population, no long-term follow-up data are available for Korean patients. To fill in the gap of knowledge, a registry study (LG Growth Study) was initiated to assess the safety and effectiveness of four types of rhGH products in real-life settings. Methods A total of 4,000 children will be registered and prospectively followed up at 6-month intervals until 2 years after epiphyseal closure to collect data on treatment and adverse events, with primary interest in malignancies and growth outcomes. Results As of 22 March 2017, approximately 50% (2,024) of the target number of patients have been included in the analysis set: growth hormone deficiency, 1,297 (64.1%); idiopathic short stature, 315 (15.6%); small for gestational age, 206 (10.2%); Turner syndrome, 197 (9.7%); and chronic renal failure, 9 (0.4%). At baseline, median age (years) was 8 (interquartile range [IQR], 5–11); 52% (1,048) were boys; and the majority were at Tanner stage I (83% based on breast/external genitalia, 97% on pubic hair). Median height standard deviation score was -2.26 (IQR, -2.69 to -2.0), and median bone age delay (years) was -1.46 (IQR, -2.26 to -0.78). Conclusions This registry study will provide the opportunity to assess the risk of malignancies as well as the general safety data in Korean pediatric patients receiving rhGH. In addition, the long-term effectiveness of rhGH and comparative data between different disease entities will provide practical insight on the standard rhGH treatment. PMID:29609449

NIH scientists map gene changes driving tumors in common pediatric soft-tissue cancer

Cancer.gov

Scientists have mapped the genetic changes that drive tumors in rhabdomyosarcoma, a pediatric soft-tissue cancer, and found that the disease is characterized by two distinct genotypes. The genetic alterations identified in this malignancy could be useful

A study report of 174 units of placental umbilical cord whole blood transfusion in 62 patients as a rich source of fetal hemoglobin supply in different indications of blood transfusion.

PubMed

Bhattacharya, N; Mukherijee, K; Chettri, M K; Banerjee, T; Mani, U; Bhattacharya, S

2001-01-01

In the animal kingdom, even herbivorous animals swallow the placenta after the birth of the baby (for example, the cow). In the human system, we do not know about the proper utilization of the placenta and membranes although there are suggestions regarding this on the basis of research on placental umbilical cord blood stem cells as an alternative to bone marrow transplantation. In this present series of placental umbilical cord whole blood transfusions, we wanted to examine the safety aspect of other components of cord blood transfusion, e.g., fetal RBC, growth factors and cytokine filled plasma, etc., in different indications of blood transfusion, from the pediatric to the geriatric age group, in malignant and non-malignant disorders affecting our patients. One hundred and seventy-four units of umbilical cord whole blood were collected aseptically from the umbilical vein after caesarean section in standard pediatric blood transfusion bags, after the removal of the baby from the operative field and after confirming the stable condition of the mother. The volume of cord blood varied from 50 ml to 140 ml with a mean of 86 ml+/-16 ml. The cord blood was transfused immediately (within three days of collection) to 62 patients from nine years to 78 years of age, of whom 32 were suffering from varying stages and grades of malignancy from 1 April 1999 till date i.e., 11 Aug 2000, after obtaining adequate consent and following the precautions of standard blood transfusion protocol. The remaining 30 patients included patients suffering from thalassemia major, aplastic anemia, systemic lupus erythematosus, chronic renal failure, rheumatoid arthritis, ankylosing spondylitis and a geriatric group of patients with benign prostatic hypertrophy. All have tolerated the procedure without any immunological or non-immunological reactions. On the basis of our experience with 174 units of placental umbilical cord whole blood transfusion in malignant and non-malignant conditions (within three days of collection and preservation at 1-6 degrees C in a refrigerator), we are of the opinion that this is a safe transfusion protocol which takes advantage of the safety of nature's finest biological sieve, i.e., the placenta, as an alternative to adult whole blood transfusion. It also has the advantage of a higher oxygen carrying capacity of fetal hemoglobin in addition to many growth factors and other cytokine filled cord blood plasma along with its hypoantigenicity.

Pediatric solid organ transplantation and osteoporosis: a descriptive study on bone histomorphometric findings.

PubMed

Tamminen, Inari S; Valta, Helena; Jalanko, Hannu; Salminen, Sari; Mäyränpää, Mervi K; Isaksson, Hanna; Kröger, Heikki; Mäkitie, Outi

2014-08-01

Organ transplantation may lead to secondary osteoporosis in children. This study characterized bone histomorphometric findings in pediatric solid organ transplant recipients who were assessed for suspected secondary osteoporosis. Iliac crest biopsies were obtained from 19 children (7.6-18.8 years, 11 male) who had undergone kidney (n = 6), liver (n = 9), or heart (n = 4) transplantation a median 4.6 years (range 0.6-16.3 years) earlier. All patients had received oral glucocorticoids at the time of the biopsy. Of the 19 patients, 21 % had sustained peripheral fractures and 58 % vertebral compression fractures. Nine children (47 %) had a lumbar spine BMD Z-score below -2.0. Histomorphometric analyses showed low trabecular bone volume (< -1.0 SD) in 6 children (32 %) and decreased trabecular thickness in 14 children (74 %). Seven children (37 %) had high bone turnover at biopsy, and low turnover was found in 6 children (32 %), 1 of whom had adynamic bone disease. There was a great heterogeneity in the histological findings in different transplant groups, and the results were unpredictable using non-invasive methods. The observed changes in bone quality (i.e. abnormal turnover rate, thin trabeculae) rather than the actual loss of trabecular bone, might explain the increased fracture risk in pediatric solid organ transplant recipients.

[Is ultrasound equal to X-ray in pediatric fracture diagnosis?].

PubMed

Moritz, J D; Hoffmann, B; Meuser, S H; Sehr, D H; Caliebe, A; Heller, M

2010-08-01

Ultrasound is currently not established for the diagnosis of fractures. The aim of this study was to compare ultrasound and X-ray beyond their use solely for the identification of fractures, i. e., for the detection of fracture type and dislocation for pediatric fracture diagnosis. Limb bones of dead young pigs served as a model for pediatric bones. The fractured bones were examined with ultrasound, X-ray, and CT, which served as the gold standard. 162 of 248 bones were fractured. 130 fractures were identified using ultrasound, and 148 using X-ray. There were some advantages of X-ray over ultrasound in the detection of fracture type (80 correct results using X-ray, 66 correct results using ultrasound). Ultrasound, however, was superior to X-ray for dislocation identification (41 correct results using X-ray, 51 correct results using ultrasound). Both findings were not statistically significant after adjustment for multiple testing. Ultrasound not only has comparable sensitivity to that of X-ray for the identification of limb fractures but is also equally effective for the diagnosis of fracture type and dislocation. Thus, ultrasound can be used as an adequate alternative method to X-ray for pediatric fracture diagnosis. Georg Thieme Verlag KG Stuttgart, New York.

Transpalatal distraction for the management of maxillary constriction in pediatric patients.

PubMed

Adolphs, Nicolai; Ernst, Nicole; Hoffmeister, Bodo; Raguse, Jan-Dirk

2015-01-01

The management of severe maxillary constriction can be challenging. For that purpose surgically assisted maxillary expansion by transpalatal distraction (TPD) can typically be recommended after skeletal maturity. However in selected cases bone borne transpalatal distraction devices can contribute to improve maxillary constriction considerably earlier already during mixed dentition. To assess the possibility of bone borne transpalatal distraction in pediatric patients. Clinical paper. Since 2010 TPD has been applied to six pediatric patients during mixed dentition when severe maxillary constriction was present and conventional orthodontic widening has already failed. Individually selected devices (Surgitec, Belgium) were inserted in general anaesthesia and distraction was performed according to well known parameters. Maxillary constriction could be improved in all six patients without any drawbacks by bone borne devices during mixed dentition. Skeletal conditions were obviously improved for subsequent orthodontic or orthognathic therapy without functional impairment. Follow-up is up to 36 months after device removal. Transpalatal Distraction is recommendable in selected pediatric patients if massive growth disturbance is present or has to be expected. TPD allows for individually adapted maxillary expansion by selection and positioning of appropriate devices in combination with intraoperative testing of maxillary movements and controlled bone removal.

Improving Care in Pediatric Neuro-oncology Patients: An Overview of the Unique Needs of Children With Brain Tumors.

PubMed

Fischer, Cheryl; Petriccione, Mary; Donzelli, Maria; Pottenger, Elaine

2016-03-01

Brain tumors represent the most common solid tumors in childhood, accounting for almost 25% of all childhood cancer, second only to leukemia. Pediatric central nervous system tumors encompass a wide variety of diagnoses, from benign to malignant. Any brain tumor can be associated with significant morbidity, even when low grade, and mortality from pediatric central nervous system tumors is disproportionately high compared to other childhood malignancies. Management of children with central nervous system tumors requires knowledge of the unique aspects of care associated with this particular patient population, beyond general oncology care. Pediatric brain tumor patients have unique needs during treatment, as cancer survivors, and at end of life. A multidisciplinary team approach, including advanced practice nurses with a specialty in neuro-oncology, allows for better supportive care. Knowledge of the unique aspects of care for children with brain tumors, and the appropriate interventions required, allows for improved quality of life. © The Author(s) 2015.

TAK228 With Carbo and Taxol in Advanced Malignancies

ClinicalTrials.gov

2018-03-12

Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

A Rare Case of Pure Erythroid Sarcoma in a Pediatric Patient: Case Report and Literature Review

PubMed Central

Tarín, Fabián; Niveiro, María; Tasso, María; Alda, Olga; Verdú, José J.; De Paz, Francisco; López, Silvia; Del Cañizo, María; Such, Esperanza; Barragán, Eva; Martirena, Fernanda

2017-01-01

We describe an exceptional case of erythroid sarcoma in a pediatric patient as a growing orbital mass with no evidence of morphologic bone marrow involvement, who was finally diagnosed of pure erythroid sarcoma based on histopathology and flow cytometry criteria. We discuss the contribution of standardized eight-color flow cytometry as a rapid and reliable diagnostic method. The use of normal bone marrow databases allowed us to identify small aberrant populations in bone marrow and later confirm the diagnosis in the neoplastic tissue. PMID:29261159

A Rare Case of Pure Erythroid Sarcoma in a Pediatric Patient: Case Report and Literature Review.

PubMed

Manresa, Pablo; Tarín, Fabián; Niveiro, María; Tasso, María; Alda, Olga; López, Francisco; Sarmiento, Héctor; Verdú, José J; De Paz, Francisco; López, Silvia; Del Cañizo, María; Such, Esperanza; Barragán, Eva; Martirena, Fernanda

2017-12-20

We describe an exceptional case of erythroid sarcoma in a pediatric patient as a growing orbital mass with no evidence of morphologic bone marrow involvement, who was finally diagnosed of pure erythroid sarcoma based on histopathology and flow cytometry criteria. We discuss the contribution of standardized eight-color flow cytometry as a rapid and reliable diagnostic method. The use of normal bone marrow databases allowed us to identify small aberrant populations in bone marrow and later confirm the diagnosis in the neoplastic tissue.

Increases in IGF-1 After Anti-TNF-α Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease.

PubMed

DeBoer, Mark D; Lee, Arthur M; Herbert, Kirabo; Long, Jin; Thayu, Meena; Griffin, Lindsay M; Baldassano, Robert N; Denson, Lee A; Zemel, Babette S; Denburg, Michelle R; Herskovitz, Rita; Leonard, Mary B

2018-03-01

Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits. Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor α (TNF-α) therapy in pediatric and adolescent CD. Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12-month visit. IGF-1 levels at baseline and 10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral quantitative computed tomography (pQCT) measures of bone and muscle at baseline and 12 months after initiation of anti-TNF-α therapy. Outcomes were expressed as sex-specific z scores. IGF-1 z scores increased from a median (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10 weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as greater estradiol z scores (in girls), was significantly associated with greater IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) z scores were low at baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001) over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical area. Adjustment for changes in muscle mass markedly attenuated the associations between IGF-1 levels and bone outcomes. Short-term improvements in IGF-1 z scores predicted recovery of bone and muscle outcomes following initiation of anti-TNF-α therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.

Bone changes in hypercalcemia of malignancy in dogs.

PubMed

Norrdin, R W; Powers, B E

1983-08-15

Bone was collected for trabecular bone morphometry from 6 dogs with hypercalcemia of malignancy. Five of the dogs had lymphosarcoma and 1 had an anal sac apocrine gland carcinoma with vertebral metastases. Parathyroid gland weights varied around normal, with those for 1 dog being slightly low and those for another dog being moderately increased. As a group, the dogs had decreased bone volume, with increased resorption surfaces and increased numbers of osteoclasts. In 4 dogs, osteoid seams and osteoblasts were limited in extent and this distinguished them from dogs with hyperparathyroidism. Although most dogs had received corticosteroids, chemotherapy, or radiation treatment, the bone changes in these dogs were similar to 1 dog that had not received treatment. Also, the changes could not be related to uremia or renal mineralization that had developed in 2 of the dogs. Two of the dogs had somewhat greater amounts of osteoid-covered surface and slightly widened osteoid seams, ie, findings more like those of hyperparathyroidism. One of these dogs had anal sac apocrine gland carcinoma and the other had lymphosarcoma in which there was invasion of the bone cortex at the sampling site. It was concluded that bone remodeling changes do occur in hypercalcemia of malignancy and that these changes are varied and often are not those of hyperparathyroidism.

FROM ANEURYSMAL BONE CYST TO TELANGIECTATIC OSTEOSARCOMA WITH METASTASIS IN INGUINAL LYMPH NODES - CASE REPORT.

PubMed

Janevska, Vesna; Spasevska, Liljana; Samardziski, Milan; Nikodinovskai, Violeta; Zhivadinovik, Julija; Trajkovskai, Elizabeta

2015-01-01

Aneurysmal bone cyst is a benign bone lesion composed of blood filled cystic cavities lined by fibrous septa. Its malignant transformation of is a rare event. We report a case of a lesion in the second metatarsal bone in a 29-year-old male, presented as a slight swelling of the right foot. After the curettage had been done, the diagnosis of aneurysmal bone cyst was made but the recurrence occurred 4 years later. The biopsy of the recurrent tumor showed compact neoplastic tissue consistent with diagnosis of giant cell tumor with malignancy. The malignant component was recognized as a high grade sarcoma with osteoid production. A tumor mass with the whole II metatarsal bone was extirpated and a resected part of fibula was transplanted. A year later, another recurrence occurred, an amputation was performed and a teleangiectatic osteosarcoma with ingvinal lymph nodes metastases was diagnosed. No other tumor mass was confirmed, either clinically or by imaging techniques at the time of his third operation. He died 4 months later with multiple pulmonary metastases. We emphasize the importance of team work in order to achieve the accurate diagnosis, highlighting careful radiological examinations, good sampling and awareness of unusual cases in bone tumor pathology.

Ultrasound of pediatric breast masses: what to do with lumps and bumps.

PubMed

Valeur, Natalie S; Rahbar, Habib; Chapman, Teresa

2015-10-01

The approach to breast masses in children differs from that in adults in many ways, including the differential diagnostic considerations, imaging algorithm and appropriateness of biopsy as a means of further characterization. Most pediatric breast masses are benign, either related to breast development or benign neoplastic processes. Biopsy is rarely needed and can damage the developing breast; thus radiologists must be familiar with the imaging appearance of common entities so that biopsies are judiciously recommended. The purpose of this article is to describe the imaging appearances of the normally developing pediatric breast as well as illustrate the imaging findings of a spectrum of diseases, including those that are benign (fibroadenoma, juvenile papillomatosis, pseudoangiomatous stromal hyperplasia, gynecomastia, abscess and fat necrosis), malignant (breast carcinoma and metastases), and have variable malignant potential (phyllodes tumor).

An update on childhood bone health: mineral accrual, assessment and treatment.

PubMed

Sopher, Aviva B; Fennoy, Ilene; Oberfield, Sharon E

2015-02-01

To update the reader's knowledge about the factors that influence bone mineral accrual and to review the advances in the assessment of bone health and treatment of bone disorders. Maternal vitamin D status influences neonatal calcium levels, bone mineral density (BMD) and bone size. In turn, BMD z-score tends to track in childhood. These factors highlight the importance of bone health as early as fetal life. Dual-energy x-ray absorptiometry is the mainstay of clinical bone health assessment in this population because of the availability of appropriate reference data. Recently, more information has become available about the assessment and treatment of bone disease in chronically ill pediatric patients. Bone health must become a health focus starting prenatally in order to maximize peak bone mass and to prevent osteoporosis-related bone disease in adulthood. Vitamin D, calcium and weight-bearing activity are the factors of key importance throughout childhood in achieving optimal bone health as BMD z-score tracks through childhood and into adulthood. Recent updates of the International Society for Clinical Densitometry focus on the appropriate use of dual-energy x-ray absorptiometry in children of all ages, including children with chronic disease, and on the treatment of pediatric bone disease.

Alcohol Devitalization and Replantation for Primary Malignant Bone Tumors of the Knee Joint

PubMed Central

ZHANG, Xihai; CHEN, Ge; WANG, Jun; TANG, Lian; YIN, Yiran

2017-01-01

Background: This paper is aimed at studying the therapeutic effects of in situ replantation of alcohol-devitalized bone segments to treat malignant bone tumors of the knee joint. Methods: We retrospectively analyzed clinical data for 45 patients from January 2013 to January 2016 who underwent replantation following alcohol-devitalization of bone segments and 40 who underwent prosthesis implantation. The two groups were comparable in basal clinical biometric data, including gender, age, tumor type and location, Enneking staging, and maximum tumor diameter. Radical tumor resection was combined with neoadjuvant chemotherapy following the two-implantation procedures. Results: The median follow-up time was 25 months, and the outcomes were compared. We found no differences in the length of bone lesions, surgery time, intraoperative blood loss, amount of postoperative drainage, and perioperative complications, which were just three for each method. We also found no significant differences in limb function scores, internal fixation imaging scores, tumor-free survival rate, and overall survival rate between the two groups. Replantation following alcohol-devitalization of tumor-bearing bone segment demonstrated similar clinical outcomes compared with prosthesis implantation in the treatment of primary malignant bone tumors of the knee joint. Conclusion: Both therapies enjoy good application safety and effectiveness. Because alcohol devitalization is inexpensive and easy to apply in the clinic, it should be considered a preferred method in the treatment of bone tumors. PMID:29308374

Orthobiologics in Pediatric Orthopedics.

PubMed

Murphy, Robert F; Mooney, James F

2017-07-01

Orthobiologics are biologic devices or products used in orthopedic surgery to augment or enhance bone formation. The use of orthobiologics in pediatric orthopedics is less frequent than in other orthopedic subspecialties, mainly due to the naturally abundant healing potential and bone formation in children compared with adults. However, orthobiologics are used in certain situations in pediatric orthopedics, particularly in spine and foot surgery. Other uses have been reported in conjunction with specific procedures involving the tibia and pelvis. The use of bioabsorable implants to stabilize children's fractures is an emerging concept but has limited supporting data. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression of receptor activator of nuclear factor kappa-B ligand (RANKL) in neoplasms of dogs and cats.

PubMed

Barger, Anne M; Fan, Timothy M; de Lorimier, Louis-Philippe; Sprandel, Ian T; O'Dell-Anderson, Kristen

2007-01-01

Receptor activator of nuclear factor kappa-B (RANK), RANK-ligand (RANKL), and the soluble decoy receptor osteoprotegerin (OPG) form a key axis modulating osteoclastogenesis. In health, RANKL-expressing bone stromal cells and osteoblasts activate osteoclasts through RANK ligation, resulting in homeostatic bone resorption. Skeletal tumors of dogs and cats, whether primary or metastatic, may express RANKL and directly induce malignant osteolysis. Bone malignancies of dogs and cats may express RANKL, thereby contributing to pathologic bone resorption and pain. Furthermore, relative RANKL expression in bone tumors may correlate with radiographic characteristics of bone pathology. Forty-two dogs and 6 cats with spontaneously-occurring tumors involving bones or soft tissues were evaluated. A polyclonal anti-human RANKL antibody was validated for use in canine and feline cells by flow cytometry and immunocytochemistry. Fifty cytologic specimens were collected from bone and soft tissue tumors of 48 tumor-bearing animals and assessed for RANKL expression. In 15 canine osteosarcoma (OSA) samples, relative RANKL expression was correlated with radiographic characteristics of bone pathology. Expression of RANKL by neoplastic cells was identified in 32/44 canine and 5/6 feline tumor samples. In 15 dogs with OSA, relative RANKL expression did not correlate with either radiographic osteolysis or bone mineral density as assessed by dual energy x-ray absorptiometry. In dogs and cats, tumors classically involving bone and causing pain, often may express RANKL. Confirming RANKL expression in tumors is a necessary step toward the rational institution of novel therapies targeting malignant osteolysis via RANKL antagonism.

Simultaneous whole body 18F-fluorodeoxyglucose positron emission tomography magnetic resonance imaging for evaluation of pediatric cancer: Preliminary experience and comparison with 18F-fluorodeoxyglucose positron emission tomography computed tomography

PubMed Central

Pugmire, Brian S; Guimaraes, Alexander R; Lim, Ruth; Friedmann, Alison M; Huang, Mary; Ebb, David; Weinstein, Howard; Catalano, Onofrio A; Mahmood, Umar; Catana, Ciprian; Gee, Michael S

2016-01-01

AIM: To describe our preliminary experience with simultaneous whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography and magnetic resonance imaging (PET-MRI) in the evaluation of pediatric oncology patients. METHODS: This prospective, observational, single-center study was Health Insurance Portability and Accountability Act-compliant, and institutional review board approved. To be eligible, a patient was required to: (1) have a known or suspected cancer diagnosis; (2) be under the care of a pediatric hematologist/oncologist; and (3) be scheduled for clinically indicated 18F-FDG positron emission tomography-computed tomography (PET-CT) examination at our institution. Patients underwent PET-CT followed by PET-MRI on the same day. PET-CT examinations were performed using standard department protocols. PET-MRI studies were acquired with an integrated 3 Tesla PET-MRI scanner using whole body T1 Dixon, T2 HASTE, EPI diffusion-weighted imaging (DWI) and STIR sequences. No additional radiotracer was given for the PET-MRI examination. Both PET-CT and PET-MRI examinations were reviewed by consensus by two study personnel. Test performance characteristics of PET-MRI, for the detection of malignant lesions, including FDG maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin), were calculated on a per lesion basis using PET-CT as a reference standard. RESULTS: A total of 10 whole body PET-MRI exams were performed in 7 pediatric oncology patients. The mean patient age was 16.1 years (range 12-19 years) including 6 males and 1 female. A total of 20 malignant and 21 benign lesions were identified on PET-CT. PET-MRI SUVmax had excellent correlation with PET-CT SUVmax for both benign and malignant lesions (R = 0.93). PET-MRI SUVmax > 2.5 had 100% accuracy for discriminating benign from malignant lesions using PET-CT reference. Whole body DWI was also evaluated: the mean ADCmin of malignant lesions (780.2 + 326.6) was significantly lower than that of benign lesions (1246.2 + 417.3; P = 0.0003; Student’s t test). A range of ADCmin thresholds for malignancy were evaluated, from 0.5-1.5 × 10-3 mm2/s. The 1.0 × 10-3 ADCmin threshold performed best compared with PET-CT reference (68.3% accuracy). However, the accuracy of PET-MRI SUVmax was significantly better than ADCmin for detecting malignant lesions compared with PET-CT reference (P < 0.0001; two-tailed McNemar’s test). CONCLUSION: These results suggest a clinical role for simultaneous whole body PET-MRI in evaluating pediatric cancer patients. PMID:27028112

Simultaneous whole body (18)F-fluorodeoxyglucose positron emission tomography magnetic resonance imaging for evaluation of pediatric cancer: Preliminary experience and comparison with (18)F-fluorodeoxyglucose positron emission tomography computed tomography.

PubMed

Pugmire, Brian S; Guimaraes, Alexander R; Lim, Ruth; Friedmann, Alison M; Huang, Mary; Ebb, David; Weinstein, Howard; Catalano, Onofrio A; Mahmood, Umar; Catana, Ciprian; Gee, Michael S

2016-03-28

To describe our preliminary experience with simultaneous whole body (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and magnetic resonance imaging (PET-MRI) in the evaluation of pediatric oncology patients. This prospective, observational, single-center study was Health Insurance Portability and Accountability Act-compliant, and institutional review board approved. To be eligible, a patient was required to: (1) have a known or suspected cancer diagnosis; (2) be under the care of a pediatric hematologist/oncologist; and (3) be scheduled for clinically indicated (18)F-FDG positron emission tomography-computed tomography (PET-CT) examination at our institution. Patients underwent PET-CT followed by PET-MRI on the same day. PET-CT examinations were performed using standard department protocols. PET-MRI studies were acquired with an integrated 3 Tesla PET-MRI scanner using whole body T1 Dixon, T2 HASTE, EPI diffusion-weighted imaging (DWI) and STIR sequences. No additional radiotracer was given for the PET-MRI examination. Both PET-CT and PET-MRI examinations were reviewed by consensus by two study personnel. Test performance characteristics of PET-MRI, for the detection of malignant lesions, including FDG maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin), were calculated on a per lesion basis using PET-CT as a reference standard. A total of 10 whole body PET-MRI exams were performed in 7 pediatric oncology patients. The mean patient age was 16.1 years (range 12-19 years) including 6 males and 1 female. A total of 20 malignant and 21 benign lesions were identified on PET-CT. PET-MRI SUVmax had excellent correlation with PET-CT SUVmax for both benign and malignant lesions (R = 0.93). PET-MRI SUVmax > 2.5 had 100% accuracy for discriminating benign from malignant lesions using PET-CT reference. Whole body DWI was also evaluated: the mean ADCmin of malignant lesions (780.2 + 326.6) was significantly lower than that of benign lesions (1246.2 + 417.3; P = 0.0003; Student's t test). A range of ADCmin thresholds for malignancy were evaluated, from 0.5-1.5 × 10(-3) mm(2)/s. The 1.0 × 10(-3) ADCmin threshold performed best compared with PET-CT reference (68.3% accuracy). However, the accuracy of PET-MRI SUVmax was significantly better than ADCmin for detecting malignant lesions compared with PET-CT reference (P < 0.0001; two-tailed McNemar's test). These results suggest a clinical role for simultaneous whole body PET-MRI in evaluating pediatric cancer patients.

Bone marrow necrosis secondary to imatinib usage, mimicking spinal metastasis on magnetic resonance imaging and FDG-PET/CT.

PubMed

Aras, Yavuz; Akcakaya, Mehmet Osman; Unal, Seher N; Bilgic, Bilge; Unal, Omer Faruk

2012-01-01

Imatinib mesylate has become the treatment of choice for gastrointestinal stromal tumors (GISTs) and has made a revolutionary impact on survival rates. Bone marrow necrosis is a very rare adverse event in malignant GIST. Bone metastases are also rarely encountered in the setting of this disease. The authors report on a patient with malignant GIST who developed a bone lesion, mimicking spinal metastasis on both MR imaging and FDG-PET/CT. Corpectomy and anterior fusion was performed, but the pathology report was consistent with bone marrow necrosis. Radiological and clinical similarities made the distinction between metastasis and bone marrow necrosis challenging for the treating physicians. Instead of radical surgical excision, more conservative methods such as percutaneous or endoscopic bone biopsies may be more useful for pathological confirmation, even though investigations such as MR imaging and FDG-PET/CT indicate metastatic disease.

Respiratory syncytial virus infection in infants with acute leukemia: a retrospective survey of the Japanese Pediatric Leukemia/Lymphoma Study Group.

PubMed

Hatanaka, Michiki; Miyamura, Takako; Koh, Katsuyoshi; Taga, Takashi; Tawa, Akio; Hasegawa, Daisuke; Kajihara, Ryosuke; Adachi, Souichi; Ishii, Eiichi; Tomizawa, Daisuke

2015-12-01

Respiratory syncytial virus (RSV) can cause life-threatening complications of lower respiratory tract infection (LRTI) in young children with malignancies, but reports remain limited. We performed a retrospective nationwide survey to clarify the current status of RSV disease among infants with hematological malignancies. Clinical course, treatment, and outcome of patients with hematological malignancies who suffered from RSV infections at the age of <24 months during anti-tumor therapy from April 2006 to March 2009 were investigated by sending a questionnaire to all member institutions of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG). Twelve patients with acute leukemia were identified as having experienced RSV disease. The primary diseases were acute myeloid leukemia (n = 8) and acute lymphoblastic leukemia (n = 4). RSV infection occurred pre- or during induction therapy (n = 8) and during consolidation therapy (n = 4). Eight patients developed LRTI, four of whom had severe pneumonia or acute respiratory distress syndrome; these four patients died despite receiving intensive care. In our survey, the prognosis of RSV disease in pediatric hematological malignancies was poor, and progression of LRTI in particular was associated with high mortality. In the absence of RSV-specific therapy, effective prevention and treatment strategies for severe RSV disease must be investigated.

Early Non Invasive Ventilation and Hematological Malignancies

ClinicalTrials.gov

2018-01-03

Hematological Malignancies; Chronic Hypoxemic Respiratory Failure; Blood And Marrow Transplantation; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

HIV-associated hematologic malignancies: Experience from a Tertiary Cancer Center in India.

PubMed

Reddy, Rakesh; Gogia, Ajay; Kumar, Lalit; Sharma, Atul; Bakhshi, Sameer; Sharma, Mehar C; Mallick, Saumyaranjan; Sahoo, Ranjit

2016-01-01

Data on HIV associated hematologic malignancies is sparse from India. This study attempts to analyze the spectrum and features of this disease at a tertiary cancer center in India. Retrospective study from case records of patients registered with a diagnosis of hematologic malignancy and HIV infection between January 2010 and June 2015. Thirteen cases of HIV associated hematologic malignancies were identified, six of them pediatric. HIV diagnosis was concurrent to diagnosis of cancer in 12 and preceded it in one of them. ECOG PS at presentation was >1 in all of them. All patients, except one, had B symptoms. Six of the patients had bulky disease and six are stage 4. Predominant extranodal disease was seen in 67% of them. NHL accounted for 10 of 13 patients and DLBCL-Germinal center was the most common subtype. Mean CD4+ cell count was 235/μL (range, 32-494). HAART could be given along with chemotherapy to 11 patients. Two-thirds of patients received standard doses of therapy. Chemo-toxicity required hospitalization in 58%. CR was achieved in 45% and 36% had progressive disease with first-line therapy. At the time of last follow up, 3 patients were alive with responsive disease, 2 in CR and 1 in PR. None of the pediatric patients were long time responders. These malignancies were of advanced stage and higher grade. Goal of therapy, in the HAART era, is curative. Pediatric patients had dismal outcome despite good chemotherapy and HAART. There is an urgent need to improve data collection for HIV related cancers in India.

Malignant external otitis: early scintigraphic detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strashun, A.M.; Nejatheim, M.; Goldsmith, S.J.

1984-02-01

Pseudomonas otitis externa in elderly diabetics may extend aggressively to adjacent bone, cranial nerves, meninges, and vessels, leading to a clinical diagnosis of ''malignant'' external otitis. Early diagnosis is necessary for successful treatment. This study compares the findings of initial radiographs, thin-section tomography of temporal bone, CT scans of head and neck, technetium-99m methylene diphosphonate (MDP) and gallium-67 citrate scintigraphy, and single-photon emission computed tomography (SPECT) for detection of temporal bone osteomylitis in ten patients fulfilling the clinical diagnostic criteria of malignant external otitis. Skull radiographs were negative in all of the eight patients studied. Thin-section tomography was positive inmore » one of the seven patients studied using this modality. CT scanning suggested osteomyelitis in three of nine patients. Both Tc-99m and Ga-67 citrate scintigraphy were positive in 10 of 10 patients. These results suggest that technetium and gallium scintigraphy are more sensitive than radiographs and CT scans for early detection of malignant external otitis.« less

Survival and endogenous colony formation in irradiated mice grafted with normal or infectious mononucleosis bone marrow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louwagie, A. C.; Verwilghen, R. L.

1973-07-01

Mice were exposed to 850 or 975 rad of whole-body radiation; three hr later mice were given normal human bone marrow, infectious mononucleosis bone marrow, or cells from malignant blood diseases. The surviving mice were killed at day 9 and the spleen nodules were counted. Some mice were also given antihuman antilymphocytic serum (ALS). In mice exposed to 975 rad, the highest survival was observed in mice grafted with infectious mononucleosis bone marrow, while none of the animals grafted with cells from malignant blood diseases survived 9 days. In mice exposed to 850 rad, grafting of normal or infectious mononucleosismore » bone marrow markedly decreased the survival. Endogenous spleen colonies were induced in all animals grafted with normal or infectious mononucleosis bone marrow. (HLW)« less

Clinical utility of (18)F-fluoride PET/CT in benign and malignant bone diseases.

PubMed

Li, Yuxin; Schiepers, Christiaan; Lake, Ralph; Dadparvar, Simin; Berenji, Gholam R

2012-01-01

(18)F labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT, there is renewed interest in using (18)F-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that (18)F fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to (99m)Tc based bone scintigraphy. National Oncologic PET Registry (NOPR) has expanded coverage for (18)F sodium fluoride PET scans since February 2011 for the evaluation of osseous metastatic disease. In this article, we reviewed the pharmacological characteristics of sodium fluoride, as well as the clinical utility of PET/CT using (18)F-fluoride in both benign and malignant bone disorders. Published by Elsevier Inc.

Malignant bone tumors (other than Ewing's): clinical practice guidelines for diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas (GEIS).

PubMed

Redondo, Andrés; Bagué, Silvia; Bernabeu, Daniel; Ortiz-Cruz, Eduardo; Valverde, Claudia; Alvarez, Rosa; Martinez-Trufero, Javier; Lopez-Martin, Jose A; Correa, Raquel; Cruz, Josefina; Lopez-Pousa, Antonio; Santos, Aurelio; García Del Muro, Xavier; Martin-Broto, Javier

2017-12-01

Primary malignant bone tumors are uncommon and heterogeneous malignancies. This document is a guideline developed by the Spanish Group for Research on Sarcoma with the participation of different specialists involved in the diagnosis and treatment of bone sarcomas. The aim is to provide practical recommendations with the intention of helping in the clinical decision-making process. The diagnosis and treatment of bone tumors requires a multidisciplinary approach, involving as a minimum pathologists, radiologists, surgeons, and radiation and medical oncologists. Early referral to a specialist center could improve patients' survival. The multidisciplinary management of osteosarcoma, chondrosarcoma, chordoma, giant cell tumor of bone and other rare bone tumors is reviewed in this guideline. Ewing's sarcoma will be the focus of a separate guideline because of its specific biological, clinical and therapeutic features. Each statement has been accompanied by the level of evidence and grade of recommendation on the basis of the available data. Surgical excision is the mainstay of treatment of a localized bone tumor, with various techniques available depending on the histologic type, grade and location of the tumor. Chemotherapy plays an important role in some chemosensitive subtypes (such as high-grade osteosarcoma). In other subtypes, historically considered chemoresistant (such as chordoma or giant cell tumor of bone), new targeted therapies have emerged recently, with a very significant efficacy in the case of denosumab. Radiation therapy is usually necessary in the treatment of chordoma and sometimes of other bone tumors.

A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics medulloblastoma.

PubMed

Ho, Evangeline S Q; Barrett, Sarah A; Mullaney, Laura M

2017-08-01

Craniospinal irradiation (CSI) is the standard radiation therapy treatment for medulloblastoma. Conventional CSI photon therapy (Photon-CSI) delivers significant dose to surrounding normal tissue (NT). Research into pediatric CSI with proton therapy (Proton-CSI) has increased, with the aim of exploiting the potential to reduce NT dose and associated post-treatment complications. This review aims to compare treatment outcomes of pediatric medulloblastoma patients between Proton- and Photon-CSI treatments. A search and review of studies published between 1990 and 2016 comparing pediatric (2-18 years) medulloblastoma Proton- and Photon-CSI in three aspects - normal organ sparing and target coverage; normal organ dysfunction and second malignancy risks - was completed. Fifteen studies were selected for review and the results were directly compared. Proton-CSI reported improved out-of-field organ sparing while target coverage improvements were inconsistent. Normal organ dysfunction risks were predicted to be lower following Proton-CSI. Secondary malignancy risks (SMRs) were generally lower with Proton-CSI based on several different risk models. Proton-CSI conferred better treatment outcomes than Photon-CSI for pediatric medulloblastoma patients. This review serves to compare the current literature in the absence of long-term data from prospective studies.

Study to Evaluate the Safety and Tolerability of Avelumab in Combination With Other Anti-Cancer Therapies in Patients With Advanced Malignancies

ClinicalTrials.gov

2018-04-27

Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Neoplasms of Uncertain or Unknown Behavior

Fourth near-infrared optical window for assessment of bone and other tissues

NASA Astrophysics Data System (ADS)

Sordillo, Diana C.; Sordillo, Laura A.; Sordillo, Peter P.; Alfano, Robert R.

2016-02-01

Recently, additional near-infrared (NIR) optical windows beyond the conventional first therapeutic window have been utilized for deep tissue imaging through scattering media. Biomedical applications using a second optical window (1100 to 1300 nm) and a third (1600 to 1870 nm) are emerging. A fourth window (2100 to 2300 nm) has been largely ignored due to high water absorption and a lack of high sensitivity imaging detectors and ultrafast laser sources. In this study, optical properties of bone in this fourth NIR optical window, were investigated. Results were compared to those seen at the first, second and third windows, and are consistent with our previous work on malignant and benign breast and prostate tissues. Bone and malignant tissues showed highest uptake in the third and fourth windows. As collagen is a major chromophore with prominent spectral peaks between 2100 and 2300 nm, it may be that the fourth optical window is particularly useful for studying tissues with a higher collagen content, such as bone or malignant tumors.

Clinical trial for patients with relapsed/refractory B-cell malignancies now recruiting | Center for Cancer Research

Cancer.gov

B-cell lymphomas are blood cancers that affect B-cells, white blood cells that develop and mature in bone marrow in the core of most bones. Mark Roschewski, M.D., of the Lymphoid Malignancies Branch is leading a study of a new treatment for B-cell lymphomas that have not responded to radiation and chemotherapy. Read more...

Bone marrow-derived CD13+ cells sustain tumor progression: A potential non-malignant target for anticancer therapy.

PubMed

Dondossola, Eleonora; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2014-01-01

Non-malignant cells found within neoplastic lesions express alanyl (membrane) aminopeptidase (ANPEP, best known as CD13), and CD13-null mice exhibit limited tumor growth and angiogenesis. We have recently demonstrated that a subset of bone marrow-derived CD11b + CD13 + myeloid cells accumulate within neoplastic lesions in several murine models of transplantable cancer to promote angiogenesis. If these findings were confirmed in clinical settings, CD11b + CD13 + myeloid cells could become a non-malignant target for the development of novel anticancer regimens.

A skeletal case of hypertrophic osteoarthropathy from the Canary Islands dating from 1000 BP.

PubMed

González-Reimers, Emilio; Trujillo-Mederos, Aioze; Machado-Calvo, Manuel; Castañeyra-Ruiz, María; Ordóñez, Alejandra C; Arnay-de-la-Rosa, Matilde

2015-12-01

A left tibia, the distal right tibia, and the proximal four fifths of the right ulna and radius, probably belonging to an adult prehispanic man (antiquity of ≈1000 years BP) were found among commingled bone remains in a collective burial cave of the island of El Hierro, in the Canary Archipelago. All four bones show an intense periosteal bone formation, encrusting the preserved cortical bone of the diaphyses. Differential diagnosis include melorheostosis, syphilis, and leprosy, although the most likely diagnosis is hypertrophic osteoarthropathy, which is usually associated with lung neoplasm or non-malignant diseases leading to chronic hypoxemia. The marked bone proliferation, possibly due to a chronic condition, suggests that possibly the underlying illness was a non-malignant one. Copyright © 2015 Elsevier Inc. All rights reserved.

Pediatric oncologic endosurgery.

PubMed

Boo, Yoon Jung; Goedecke, Jan; Muensterer, Oliver J

2017-08-01

Despite increasing popularity of minimal-invasive techniques in the pediatric population, their use in diagnosis and management of pediatric malignancy is still debated. Moreover, there is limited evidence to clarify this controversy due to low incidence of each individual type of pediatric tumor, huge diversity of the disease entity, heterogeneity of surgical technique, and lack of well-designed studies on pediatric oncologic minimal-invasive surgery. However, a rapid development of medical instruments and technologies accelerated the current trend toward less invasive surgery, including oncologic endosurgery. The aim of this article is to review current literatures about the application of the minimal-invasive approach for pediatric tumors and to give an overview of the current status, indications, individual techniques, and future perspectives.

What Is a Pediatric Rheumatologist?

MedlinePlus

... Life Medical Home Health Insurance Pediatric Specialists Family Dynamics ... Content Article Body If your child has complaints of pain in the musculoskeletal system (joints, muscles, bones, or tendons), other symptoms of ...

Mathematical modeling of bone marrow--peripheral blood dynamics in the disease state based on current emerging paradigms, part I.

PubMed

Afenya, Evans K; Ouifki, Rachid; Camara, Baba I; Mundle, Suneel D

2016-04-01

Stemming from current emerging paradigms related to the cancer stem cell hypothesis, an existing mathematical model is expanded and used to study cell interaction dynamics in the bone marrow and peripheral blood. The proposed mathematical model is described by a system of nonlinear differential equations with delay, to quantify the dynamics in abnormal hematopoiesis. The steady states of the model are analytically and numerically obtained. Some conditions for the local asymptotic stability of such states are investigated. Model analyses suggest that malignancy may be irreversible once it evolves from a nonmalignant state into a malignant one and no intervention takes place. This leads to the proposition that a great deal of emphasis be placed on cancer prevention. Nevertheless, should malignancy arise, treatment programs for its containment or curtailment may have to include a maximum and extensive level of effort to protect normal cells from eventual destruction. Further model analyses and simulations predict that in the untreated disease state, there is an evolution towards a situation in which malignant cells dominate the entire bone marrow - peripheral blood system. Arguments are then advanced regarding requirements for quantitatively understanding cancer stem cell behavior. Among the suggested requirements are, mathematical frameworks for describing the dynamics of cancer initiation and progression, the response to treatment, the evolution of resistance, and malignancy prevention dynamics within the bone marrow - peripheral blood architecture. Copyright © 2016 Elsevier Inc. All rights reserved.

Intercalary frozen autograft for reconstruction of malignant bone and soft tissue tumours.

PubMed

Zekry, Karem M; Yamamoto, Norio; Hayashi, Katsuhiro; Takeuchi, Akihiko; Higuchi, Takashi; Abe, Kensaku; Taniguchi, Yuta; Alkhooly, Ali Zein A A; Abd-Elfattah, Ahmed Saleh; Fouly, Ezzat H; Ahmed, Adel Refaat; Tsuchiya, Hiroyuki

2017-07-01

In 1999, we developed a technique using frozen autografts-tumour-containing bone treated with liquid nitrogen-for the reconstruction of malignant bone tumours. The purpose of this study was to evaluate the functional and oncological outcomes of frozen autografts for intercalary reconstruction of malignant bones and soft tissue tumours. This retrospective study was designed to assess 34 patients of mean age 35 (range, 6-79) years. The mean follow-up period was 62 (24-214) months. The median length of the frozen autografts was 138.4 ± 60.39 (50-290) mm. Postsurgically, 20 patients remained disease-free, seven patients survived with no evidence of disease, five patients were alive with disease, and two patients died of disease. The five- and ten-year survival rates of the frozen autografts were 91.2% and the mean International Society of Limb Salvage score was 90%. Complete bony union was achieved in 97% of the patients. There were five cases of nonunion, six cases of fracture, two cases of deep infection and four cases of local recurrence. Utilizing intercalary frozen autografts for patients with a nonosteolytic primary or secondary bone tumour without involvement of the subchondral bone is a good alternative treatment, because it is a straightforward biological technique and can provide excellent limb function.

Guided bone regeneration: A novel approach in the treatment of pediatric dentoalveolar trauma

PubMed Central

Murthy, Prashanth Sadashiva; Shivamallu, Avinash Bettahalli; Deshmukh, Seema; Nandlal, Bhojraj; Thotappa, Srilatha K.

2015-01-01

Traumatic injuries in the primary dentition pose major challenges for management. This emergency treatment requires proper planning so as to achieve favorable results. Trauma causing severe dentoalveolar injuries, especially in children, needs an interdisciplinary approach so as to retain normal functional anatomy for that age. This article describes a clinical innovative technique, which utilizes a resorbable membrane in management of pediatric dentoalveolar trauma. The membrane was shaped to cover the multiple alveolar bone fracture, thereby favoring the healing of the bone defects. The use of this resorbable membrane maintained a secluded space for the bone growth and prevented overgrowth of the soft tissue in the region of the defect. This resulted in uneventful healing leading to well-maintained functional bone contour, which further favored the esthetic rehabilitation as well as protected the underlying permanent tooth buds. PMID:26005471

Novel therapies in benign and malignant bone diseases.

PubMed

Rachner, Tilman D; Hadji, Peyman; Hofbauer, Lorenz C

2012-06-01

With an ageing population and improving cancer therapies, the two most common benign and malignant bone diseases, osteoporosis and bone metastases, will continue to affect an increasing number of patients. Our expanding knowledge of the molecular processes underlying these conditions has resulted in novel bone targets that are currently being explored in clinical trials. Clearly, the approval of denosumab, a monoclonal antibody directed against RANKL, has just marked the beginning of a new era for bone therapy with several additional new therapies lining up for clinical approval in the coming years. Potential agents targeting the osteoclast include cathepsin K, currently in phase 3 trials, and src inhibitors. Amongst anabolic agents, inhibitors of the Wnt-inhibitor sclerostin and dickkopf-1 are promising in clinical trials. Here, we will provide a comprehensive overview of the most promising agents currently explored for the treatment of bone diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

Bisphosphonate Treatment for Children With Disabling Conditions

PubMed Central

Boyce, Alison M.; Tosi, Laura L.; Paul, Scott M.

2014-01-01

Fractures are a frequent source of morbidity in children with disabling conditions. The assessment of bone density in this population is challenging, because densitometry is influenced by dynamic forces affecting the growing skeleton and may be further confounded by positioning difficulties and surgical hardware. First-line treatment for pediatric osteoporosis involves conservative measures, including optimizing the management of underlying conditions, maintaining appropriate calcium and vitamin D intake, encouraging weight-bearing physical activity, and monitoring measurements of bone mineral density. Bisphosphonates are a class of medications that increase bone mineral density by inhibiting bone resorption. Although bisphosphonates are commonly prescribed for treatment of adult osteoporosis, their use in pediatric patients is controversial because of the lack of long-term safety and efficacy data. PMID:24368091

Advanced Ultrasonic Tomograph of Children's Bones

NASA Astrophysics Data System (ADS)

Lasaygues, Philippe; Lefebvre, Jean-Pierre; Guillermin, Régine; Kaftandjian, Valérie; Berteau, Jean-Philippe; Pithioux, Martine; Petit, Philippe

This study deals with the development of an experimental device for performing ultrasonic computed tomography (UCT) on bone in pediatric degrees. The children's bone tomographs obtained in this study, were based on the use of a multiplexed 2-D ring antenna (1 MHz and 3 MHz) designed for performing electronic and mechanical scanning. Although this approach is known to be a potentially valuable means of imaging objects with similar acoustical impedances, problems arise when quantitative images of more highly contrasted media such as bones are required. Various strategies and various mathematical procedures for modeling the wave propagation based on Born approximations have been developed at our laboratory, which are suitable for use with pediatric cases. Inversions of the experimental data obtained are presented.

A metastatic glomus jugulare tumor. A temporal bone report

DOE Office of Scientific and Technical Information (OSTI.GOV)

El Fiky, F.M.; Paparella, M.M.

The clinicopathologic findings in the temporal bone of a patient with a highly malignant metastasizing glomus jugulare tumor are reported. The patient exhibited all the symptoms of primary malignant tumors of the ear, including facial paralysis, otorrhea, pain, hearing loss, tinnitus, dizziness, and vertigo. He was treated with cobalt irradiation followed by radium implant in the ear canal for a residual tumor; then a left-sided radical mastoidectomy was performed.

To Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors

ClinicalTrials.gov

2018-04-23

Neuroblastoma; Rhabdomyosarcoma; Ewing's Sarcoma; Ewing's Tumor; Sarcoma, Ewing's; Sarcomas, Epitheliod; Sarcoma, Soft Tissue; Sarcoma, Spindle Cell; Melanoma; Malignant Melanoma; Clinical Oncology; Oncology, Medical; Pediatrics, Osteosarcoma; Osteogenic Sarcoma; Osteosarcoma Tumor; Sarcoma, Osteogenic; Tumors; Cancer; Neoplasia; Neoplasm; Histiocytoma; Fibrosarcoma; Dermatofibrosarcoma

Clinical hypnosis versus cognitive behavioral training for pain management with pediatric cancer patients undergoing bone marrow aspirations.

PubMed

Liossi, C; Hatira, P

1999-04-01

A randomized controlled trial was conducted to compare the efficacy of clinical hypnosis versus cognitive behavioral (CB) coping skills training in alleviating the pain and distress of 30 pediatric cancer patients (age 5 to 15 years) undergoing bone marrow aspirations. Patients were randomized to one of three groups: hypnosis, a package of CB coping skills, and no intervention. Patients who received either hypnosis or CB reported less pain and pain-related anxiety than did control patients and less pain and anxiety than at their own baseline. Hypnosis and CB were similarly effective in the relief of pain. Results also indicated that children reported more anxiety and exhibited more behavioral distress in the CB group than in the hypnosis group. It is concluded that hypnosis and CB coping skills are effective in preparing pediatric oncology patients for bone marrow aspiration.

Is the European pediatric medicine regulation working for children and adolescents with cancer?

PubMed

Vassal, Gilles; Geoerger, Birgit; Morland, Bruce

2013-03-15

The European Pediatric Medicine Regulation was launched in 2007 to provide better medicines for children. Five years later, the number of new anticancer drugs in early development in the pediatric population remains low, and most children with cancer are still largely denied access to innovative drugs in Europe, as compared with the United States. We analyzed individual pediatric investigation plan (PIP) and waiver decisions for oncology drugs and all oncology drugs that have been approved for marketing authorization since 2007 in Europe. Among the 45 approved PIPs, 33% concern leukemias and lymphomas, 29% solid tumors, 13% brain tumors, and 20% a drug for supportive care. No specific PIP exists for life-threatening diseases such as high-risk neuroblastoma, whereas there are several PIPs in extremely rare malignancies in children and adolescents such as gastrointestinal stromal tumor, melanoma, thyroid cancer, and chronic myeloid leukemia. This paradoxical situation is due to approval of a PIP being driven by the adult indication. Twenty-six of 28 authorized new oncology drugs have a potentially relevant mechanism of action for pediatric malignancies, but 50% have been waived because the adult condition does not occur in children. The most striking example is crizotinib. Implementation of the pediatric regulation should no longer be driven by the adult indication but should be guided instead by the biology of pediatric tumors and the mechanism of action of a drug. This change will be achievable through voluntary PIPs submitted by Pharma or revocation of the oncology class waiver list.

Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; BRAF NP_004324.2:p.V600X; Ependymoma; Ewing Sarcoma; Hepatoblastoma; Histiocytosis; Langerhans Cell Histiocytosis; Malignant Germ Cell Tumor; Malignant Glioma; Osteosarcoma; Peripheral Primitive Neuroectodermal Tumor; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Rhabdomyosarcoma; Soft Tissue Sarcoma; Wilms Tumor

Chondromyxoid fibroma of the pubic ramus: a case report and literature review.

PubMed

Arıkan, Murat; Toğral, Güray; Yıldırım, Ahmet; Aktaş, Erdem

2016-01-01

Chondromyxoid fibromas (CMF) are benign cartilaginous bone tumors which are found most frequently in the metaphyses of long bones. They comprise less than 1% of primary bone neoplasms. We report an interesting incidental case of a 43-year-old woman with a CMF of the left pubic ramus, presenting with complaints of gradual onset of left groin pain over a period of 2 years. According to radiological examination, a malign chondroid bone tumor was excluded, and histopathological examination confirmed the diagnosis of CMF. The patient underwent aggressive curettage and bone grafting 6 years ago. Pelvic bones are encountered as rare localizations for CMFs. Pubic ramus is accepted as an exceptional site for this benign bone tumor of cartilaginous origin. To our knowledge, no any other CMF case in this localization has been reported in the literature. In atypical regions such as the pelvis and pubic ramus, CMF must be considered for differential diagnosis of malign tumors.

[Adjuvant cryosurgery in the treatment of unicameral bone cysts].

PubMed

Tena-Sanabria, Mario Edgar; Hernández-Hernández, Melissa Jesús; Tena-González, Mario Edgar; Mejía-Aranguré, Juan Manuel

2014-01-01

Multiple treatments have been used for the unicameral bone cyst lesion, such as steroid application, multiple perforations, bone curettages, partial resection and bone grafting. The purpose of this study was to describe the evolution of children with unicameral bone cyst who were treated with cryosurgery as coadjuvant therapy. Cross-sectional descriptive study over the period between January 2001 and December 2006. Twelve patients were studied and treated at the Pediatric Orthopedics Department of the Pediatrics Hospital at the Centro Médico Nacional Siglo XXI. Twelve patients were analyzed; all of them were treated with curettage, cryotherapy and bone grafting. In 7 patients, the lesions were located in the humerus (58.3 %), in 3 in the tibia (25 %), in 1 in the ilio-ischiopubic branch (8.3 %), and in 1 in the clavicle (8.3 %). Follow-up ranged from 12 to 36 months. Bone healing required 2 to 3 months after the surgery; the response was complete in 9 (75 %) patients and partial in 3 (25 %). Function was restored in all cases, without recurrences. Cryosurgery as an adjuvant treatment and autologous or homologous bone grafting prevented local recurrence of unicameral bone cyst lesions, favored bone healing and allowed for a full range of motion functionality without complications.

Growth, body composition, and bone density following pediatric liver transplantation.

PubMed

Sheikh, Amin; Cundy, Tim; Evans, Helen Maria

2018-04-24

Patients transplanted for cholestatic liver disease are often significantly fat-soluble vitamin deficient and malnourished pretransplant, with significant corticosteroid exposure post-transplant, with increasing evidence of obesity and metabolic syndrome post-LT. Our study aimed to assess growth, body composition, and BMD in patients post-pediatric LT. Body composition and bone densitometry scans were performed on 21 patients. Pre- and post-transplant anthropometric data were analyzed. Bone health was assessed using serum ALP, calcium, phosphate, and procollagen-1-N-peptide levels. Median ages at transplant and at this assessment were 2.7 and 10.6 years, respectively. Physiological markers of bone health, median z-scores for total body, and lumbar spine aBMD were normal. Bone area was normal for height and BMAD at L3 was normal for age, indicating, respectively, normal cortical and trabecular bone accrual. Median z-scores for weight, height, and BMI were 0.6, -0.9, 1.8 and 0.6, 0.1, 0.8 pre- and post-transplant, respectively. Total body fat percentages measured on 21 body composition scans revealed 2 underweight, 7 normal, 6 overweight, and 6 obese. Bone mass is preserved following pediatric LT with good catch-up height. About 52% of patients were either overweight/obese post-transplant, potentially placing them at an increased risk of metabolic syndrome and its sequelae in later life. BMI alone is a poor indicator of nutritional status post-transplant. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Relationship between plasma fibroblast growth factor-23 concentration and bone mineralization in children with renal failure on peritoneal dialysis.

PubMed

Wesseling-Perry, Katherine; Pereira, Renata C; Wang, Hejing; Elashoff, Robert M; Sahney, Shobha; Gales, Barbara; Jüppner, Harald; Salusky, Isidro B

2009-02-01

Fibroblast growth factor (FGF)-23 is produced in bone, and circulating levels are markedly elevated in patients with end-stage kidney disease, but the relationship between plasma levels of FGF-23 and bone histology in dialysis patients with secondary hyperparathyroidism is unknown. The aim of the study was to evaluate the correlation between plasma levels of FGF-23 and bone histology in pediatric patients with end-stage kidney disease who display biochemical evidence of secondary hyperparathyroidism. We performed a cross-sectional analysis of the relationship between plasma FGF-23 levels and bone histomorphometry. The study was conducted in a referral center. Participants consisted of forty-nine pediatric patients who were treated with maintenance peritoneal dialysis and who had serum PTH levels (1st generation Nichols assay) greater than 400 pg/ml. There were no interventions. Plasma FGF-23 levels and bone histomorphometry were measured. No correlation existed between values of PTH and FGF-23. Bone formation rates correlated with PTH (r = 0.44; P < 0.01), but not with FGF-23. Higher FGF-23 concentrations were associated with decreased osteoid thickness (r = -0.49; P < 0.01) and shorter osteoid maturation time (r = -0.48; P < 0.01). High levels of FGF-23 are associated with improved indices of skeletal mineralization in dialyzed pediatric patients with high turnover renal osteodystrophy. Together with other biomarkers, FGF-23 measurements may indicate skeletal mineralization status in this patient population.

Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children's Oncology Group.

PubMed

Pollack, Ian F; Hamilton, Ronald L; Burger, Peter C; Brat, Daniel J; Rosenblum, Marc K; Murdoch, Geoffrey H; Nikiforova, Marina N; Holmes, Emiko J; Zhou, Tianni; Cohen, Kenneth J; Jakacki, Regina I

2010-09-01

Aberrant activation of Akt is a common finding in adult malignant gliomas, resulting in most cases from mutations or deletions involving PTEN, which allows constitutive Akt phosphorylation. In contrast, we have previously reported that pediatric malignant gliomas, which are morphologically similar to lesions arising in adults, have a substantially lower incidence of genomic alterations of PTEN. The objective of this study was to determine whether Akt activation was also an uncommon finding in childhood malignant gliomas and whether this feature was associated with survival. To address this issue, we examined the frequency of Akt activation, determined by overexpression of the activated phosphorylated form of Akt (Se(473)) on immunohistochemical analysis, in a series of 53 childhood malignant gliomas obtained from newly diagnosed patients treated on the Children's Oncology Group ACNS0126 and 0423 studies. The relationship between Akt activation and p53 overexpression, MIB1 labeling, and tumor histology was evaluated. The association between Akt activation and survival was also assessed. Overexpression of activated Akt was observed in 42 of 53 tumors, far in excess of the frequency of PTEN mutations we have previously observed. There was no association between Akt activation and either histology, p53 overexpression, or MIB1 proliferation indices. Although tumors that lacked Akt overexpression had a trend toward more favorable event-free survival and overall survival (p = 0.06), this association reflected that non-overexpressing tumors were significantly more likely to have undergone extensive tumor removal, which was independently associated with outcome. Activation of Akt is a common finding in pediatric malignant gliomas, although it remains uncertain whether this is an independent adverse prognostic factor. In view of the frequency of Akt activation, the evaluation of molecularly targeted therapies that inhibit this pathway warrants consideration for these tumors.

Prevalence of Demodex folliculorum and Demodex brevis in childhood malnutrition and malignancy.

PubMed

Kaya, Sadik; Selimoglu, Mukadder Ayse; Kaya, Ozlem Aycan; Ozgen, Unsal

2013-02-01

Hair follicle mites, Demodex folliculorum and Demodex brevis, are known to accompany immune-deficiency states, however no study so far has investigated their presence in malnutrition. In this study we aimed to determine the prevalence of those mites in childhood malnutrition, malignancy and risk factors. One hundred children with malnutrition, 31 children with malignancy and 63 children without any chronic disease and infection were included in this study. History, physical examination, anthropometric measurements and routine laboratory findings were recorded. Demodex spp. were investigated by standard superficial skin biopsies. Demodex was found in 25 patients (25%), 10 patients (32.3%), and one patient (1.6%) among malnutrition, malignancy, and control groups, respectively (P = 0.001). By using multilogistic regression binary method, it was found that malnutrition, malignancy and low socioeconomic level increased the risk 17.37 times (P = 0.006), 27.29 times (P = 0.002), and 2.3 times (P = 0.037), respectively. Of 22 children who were evaluated after 6 months, 13 (59.1%) were negative for Demodex. In 11 (84.6%) of those 13, nutritional status was improved. Demodex was detected in approximately in one-quarter and one-third of children with malnutrition and malignancy, respectively. Eliminating the cause of immunosuppression, such as poor nutritional status, seems also to be an effective method for eliminating Demodex. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).

PubMed

Audigé, Laurent; Slongo, Theddy; Lutz, Nicolas; Blumenthal, Andrea; Joeris, Alexander

2017-04-01

Background and purpose - The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF) describes the localization and morphology of fractures, and considers severity in 2 categories: (1) simple, and (2) multifragmentary. We evaluated simple and multifragmentary fractures in a large consecutive cohort of children diagnosed with long bone fractures in Switzerland. Patients and methods - Children and adolescents treated for fractures between 2009 and 2011 at 2 tertiary pediatric surgery hospitals were retrospectively included. Fractures were classified according to the AO PCCF. Severity classes were described according to fracture location, patient age and sex, BMI, and cause of trauma. Results - Of all trauma events, 3% (84 of 2,730) were diagnosed with a multifragmentary fracture. This proportion was age-related: 2% of multifragmentary fractures occurred in school-children and 7% occurred in adolescents. In patients diagnosed with a single fracture only, the highest percentage of multifragmentation occurred in the femur (12%, 15 of 123). In fractured paired radius/ulna bones, multifragmentation occurred in 2% (11 of 687); in fractured paired tibia/fibula bones, it occurred in 21% (24 of 115), particularly in schoolchildren (5 of 18) and adolescents (16 of 40). In a multivariable regression model, age, cause of injury, and bone were found to be relevant prognostic factors of multifragmentation (odds ratio (OR) > 2). Interpretation - Overall, multifragmentation in long bone fractures in children was rare and was mostly observed in adolescents. The femur was mostly affected in single fractures and the lower leg was mostly affected in paired-bone fractures. The clinical relevance of multifragmentation regarding growth and long-term functional recovery remains to be determined.

Systemic rhabdomyosarcoma presenting as leukemia: case report with ultrastructural study and reviews.

PubMed

Huntrakoon, M; Callaway, L A; Vergara, G G

1987-08-01

A 20-year-old white male was initially suspected clinically and pathologically of having an acute lymphoblastic leukemic process because of fatigue, severe anemia, thrombocytopenia, a leuko-erythroblastic peripheral blood picture, and a diffusely infiltrated bone marrow. Subsequent review of the bone marrow material indicated cytologic features consistent with either an embryonal, undifferentiated small cell mesenchymal malignancy or reticulo-endothelial malignancy. Ultimately, the electron microscopic (EM) study of the tumor proved to be diagnostic of rhabdomyosarcoma. An extensive search for a primary site of rhabdomyosarcoma did not show any lesion, although the genitourinary region was clinically suspected. The clinical course was a rapidly downhill one with extensive bone and CNS involvement. The patient died 5 months later. An autopsy permit was not obtained. This case emphasizes the occasional tendency of rhabdomyosarcoma to masquerade as a hematopoietic malignancy at the time of presentation and the usefulness of EM study in confirming a diagnosis.

Ewing's sarcoma of the cranial vault: a case report.

PubMed

Feki, Jihene; Guermazi, Zeineb; Kammoun, Brahim; Khanfir, Afef; Toumi, Nabil; Boudawara, Tahiya; Boudawara, Zaher; Daoud, Jamel; Frikha, Mounir

2017-12-01

Ewing's sarcoma is a malignant tumor that mainly affects young patients. It represents 10% of primary malignant tumors of the bone and 3% of malignant tumors of the child. Cranial localization is extremely rare representing less than 1% of all the localizations. We report a case of a 10-year-old girl who presented with an intracranial hypertension syndrome with left parietal mass of progressive installation. The X-ray skull showed a lytic lesion with irregular margins involving the left parietal bone. Brain magnetic resonance imaging revealed extensive parietal bone destruction involving both the inner and outer tables. The girl was operated in emergency. Histological examination concluded to Ewing's Sarcoma. The resection was incomplete (R1). The girl received induction's chemotherapy. The cerebral scanner evaluation showed no abnormalities. Then, she received consolidation's chemotherapy with concomitant local radiation therapy. Currently, the girl is in complete remission with a seven-month decline.

Malignant adenomyoepithelioma of breast masquerading as soft tissue lytic lesion of right iliac bone: a rare entity.

PubMed

R, Kalyani; Murthy V, Srinivas

2014-09-01

Adenomyoepithelioma (AME) of breast is a low grade malignant biphasic tumour, usually seen in elderly women as a firm, well circumscribed tumour having both glandular and myoepithelial cells. The cells may show atypical features. The tumour may harbour foci of carcinoma which may be epithelial type, myoepithelial type, both or of metaplastic cells. The behaviour is hard to predict as it can be treated by local excision, recurrence is known or it can present with distant metastasis and hence the prognosis. We present a case of 50-year-old women who presented with right iliac bone lytic lesion diagnosed as metastatic deposits. Past history revealed that patient was diagnosed and treated for AME of right breast seven years back. The metastatic deposits also showed features of adenomyoepithelioma. Hence, a diagnosis of malignant AME deposits in right iliac bone was made.

[Multiple long bone fractures in a child with pycnodysostosis. A case report].

PubMed

Rojas, Paula I; Niklitschek, Nathia E; Sepúlveda, Matías F

2016-06-01

Fractures are an important entity to consider in pediatric patients. There are certain diseases in which bones fracture with a minimal trauma. Pycnodysostosis is an autosomal recessive unusual type of cráneo metaphyseal dysplasia, that presents frequently as fracture in a pathological bone. A 9 year old caucasian female, diagnosed with pycnodysostosis, was admitted with a right femur fracture as a result of a low energy trauma. Radiographic studies showed bilateral femur fractures, proximal fracture and non-union in antecurvatum of the left tibia. Pycnodysostosis is a rare disease, generally diagnosed at an early age by growth restriction, frequent fractures or fractures with low energy trauma. Therapy alternatives are limited, and no permanent cure has been developed. If a patient has dysmorphic facial features and fractures in a pathological bone, it is important to suspect bone dysplasia, such as pycnodysostosis and its differential diagnoses. Sociedad Argentina de Pediatría.

Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with Tomotherapy HDA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Eun Young, E-mail: eyhan@uams.edu; Kim, Dong-Wook; Zhang, Xin

It is important to minimize the radiation dose delivered to healthy tissues in pediatric cancer treatment because of the risk of secondary malignancies. Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ) delivery mode. The purpose of this study was to evaluate its dosimetric effect on the pediatric cancer cases. We included 6 pediatric cases in this study. The dose profiles and plan statistics—target dose conformity, uniformity, organ-at-risk (OAR) mean dose, beam-on time, and integral dose—were compared for each case. Consequently,more » the target dose coverage and uniformity were similar for different jaw settings. The OAR dose sparing depended on its relative location to the target and disease sites. For example, in the head and neck cancer cases, the brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3 Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric cases could be critical to reduce a probability of a secondary malignancy.« less

Pediatric maxillary fractures.

PubMed

Yu, Jack; Dinsmore, Robert; Mar, Philip; Bhatt, Kirit

2011-07-01

Pediatric craniofacial structures differ from those of adults in many ways. Because of these differences, management of pediatric craniofacial fractures is not the same as those in adults. The most important differences that have clinical relevance are the mechanical properties, craniofacial anatomy, healing capacity, and dental morphology. This article will review these key differences and the management of pediatric maxillary fractures. From the mechanical properties' perspective, pediatric bones are much more resilient than adult bones; as such, they undergo plastic deformation and ductile failure. From the gross anatomic perspective, the relative proportion of the cranial to facial structures is much larger for the pediatric patients and the sinuses are not yet developed. The differences related to dentition and dental development are more conical crowns, larger interdental spaces, and presence of permanent tooth buds in the pediatric population. The fracture pattern, as a result of all the above, does not follow the classic Le Fort types. The maxillomandibular fixation may require circum-mandibular wires, drop wires, or Ivy loops. Interfragmentary ligatures using absorbable sutures play a much greater role in these patients. The use of plates and screws should take into consideration the future development with respect to growth centers and the location of the permanent tooth buds. Pediatric maxillary fractures are not common, require different treatments, and enjoy better long-term outcomes.

Nationwide population-based study reveals increased malignancy risk in taiwanese liver transplant recipients.

PubMed

Tsai, Yung Fong; Chen, Hsiu Pin; Liu, Fu Chao; Liu, Shih Hao; Chen, Chun Yu; Cheng, Chih Wen; Lin, Jr-Rung

2016-12-13

Post-transplant malignancy is a major cause of late mortality for liver transplant recipients (LTRs). This nationwide population-based cohort study investigated the cancer type, incidence, and risk factors associated with post-transplant malignancies in 2938 Taiwanese LTRs who underwent transplantation between 1998 and 2012. Data from the National Health Insurance Research Database were extracted on the basis of the International Classification of Disease, Ninth Revision, Clinical Modification codes. Among these patients, 284 post-transplant malignancies were diagnosed. These included 99 de novo malignancies among 98 patients, yielding a standardized incidence ratio of 2.17 (95% CI, 1.76 to 2.64) compared to the general population. The most common malignancies were infection related liver cancer (19.39%), oropharyngeal cancer (19.39%), non-Hodgkin's lymphoma (9.18%), and esophageal cancer (5.10%), as well as non-infection-related prostate cancer (6.12%). Patients with recurrent malignancies had the highest mortality. Furthermore, 186 recurrent malignancies relapsed, and the commonly affected organs were the liver (83.33%), lung (4.84%), bone and bone marrow (4.30%), and intrahepatic bile ducts (2.69%). Old age, the male sex, liver cirrhosis, hepatitis B, peptic ulcer, diabetes mellitus, and pre-existing cancer were all risk factors associated with post-transplant malignancies. Recipients with biliary atresia or urea cycle metabolism disorders were protected from post-transplant malignancies. Our data revealed a significantly increased risk of malignancies in Taiwanese LTRs and suggest implementation of a careful malignancy-surveillance program and immunosuppression-minimizing strategy for high-risk patients.

Osteosarcoma and MFH of Bone Treatment (PDQ®)—Patient Version

Cancer.gov

Osteosarcoma and malignant fibrous histiocytoma (MFH) of the bone treatment usually involves surgery to remove the tumor. Chemotherapy, radiation therapy, and/or targeted therapy may also be used. Learn more about osteosarcoma and MFH of bone in this expert-reviewed summary.

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma

PubMed Central

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P. Leif; Camaschella, Clara; Campanella, Alessandro

2015-01-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. PMID:25715406

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma.

PubMed

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P Leif; Camaschella, Clara; Campanella, Alessandro

2015-06-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. Copyright© Ferrata Storti Foundation.

A case of dedifferentiated chondrosarcoma arising in the cricoid cartilage that mimicked an aneurysmal bone cyst.

PubMed

Chen, Lixiao; Yu, Ziwei; Jiang, Rui; Dong, Pin; Shen, Bin; Li, Yu

2018-03-01

Dedifferentiated chondrosarcoma of the larynx is a rare and highly malignant tumor. We present the report of a 59-year-old man with dedifferentiated laryngeal chondrosarcoma, which was difficult to diagnose even under microscopic examination. The original diagnosis was an aneurysmal bone cyst, and the final diagnosis was established only after careful consideration of the imaging, surgical, and microscopic findings. In clinical practice, there are many similarities between dedifferentiated chondrosarcoma and aneurysmal bone cysts. Furthermore, it is difficult to identify dedifferentiated laryngeal chondrosarcoma with a giant-cell malignant mesenchymal component. This report describes our experience and discusses this phenomenon.

Skeletal malignancies among beagles injected with 241Am.

PubMed

Lloyd, R D; Taylor, G N; Angus, W; Miller, S C; Boecker, B B

1994-02-01

Seventy skeletal malignancies in 44 dogs were identified among 117 beagles injected as young adults with graded dosages of approximately 0.07 to 104 kBq 241Am kg-1 and maintained for lifetime observation. All of these tumors were osteosarcomas except four fibrosarcomas of bone and four chondrosarcomas of bone. Of these 117 animals, 114 survived beyond the minimum age (of 2.79 y) for radiation-induced bone cancer, and all are now dead. An expression was derived that described the dependence of percent occurrence of bone sarcoma on skeletal radiation dose of A = 0.76 + 30D, where A = percent of dogs with skeletal malignancy within any dosage group, D = average skeletal dose (< 3 Gy) at 1 y before death (average skeletal dose was calculated to the presumed start of tumor growth, which we have taken to be 1 y before death), and 0.76 represents the lifetime percent malignant bone tumor response among 132 suitable control dogs in our colony not given any radioactivity. All dosage groups with skeletal doses of > 3 Gy at 1 y before death exhibited close to 100% occurrence and appeared to be beyond the region of linearity. Therefore, they were excluded from the derivation of this expression. Similar analysis of corresponding data for beagles given 226Ra as young adults, excluding the two highest dosage groups in which the bone tumor response was approximately 100%, yielded the expression, A = 0.76 + 4.7D, (D < 20 Gy). A ratio of the coefficients in these two expressions indicates the effectiveness at low radiation doses for bone-cancer induction of 241Am relative to 226Ra, or (30 +/- 2.6)(4.7 +/- 0.47)-1 = 6 +/- 0.8. This compares to the relative effectiveness at low radiation doses that was obtained earlier for a 239Pu:226Ra toxicity ratio of about 16 +/- 5.

L-MTP-PE and zoledronic acid combination in osteosarcoma: preclinical evidence of positive therapeutic combination for clinical transfer

PubMed Central

Biteau, Kevin; Guiho, Romain; Chatelais, Mathias; Taurelle, Julien; Chesneau, Julie; Corradini, Nadège; Heymann, Dominique; Redini, Françoise

2016-01-01

Osteosarcoma, the most frequent malignant primary bone tumor in pediatric patients is characterized by osteolysis promoting tumor growth. Lung metastasis is the major bad prognosis factor of this disease. Zoledronic Acid (ZA), a potent inhibitor of bone resorption is currently evaluated in phase III randomized studies in Europe for the treatment of osteosarcoma and Ewing sarcoma. The beneficial effect of the liposomal form of Muramyl-TriPeptide-Phosphatidyl Ethanolamine (L-mifamurtide, MEPACT®), an activator of macrophage populations has been demonstrated to eradicate lung metastatic foci in osteosarcoma. The objective of this study was to evaluate the potential therapeutic benefit and the safety of the ZA and L-mifamurtide combination in preclinical models of osteosarcoma, as a prerequisite before translation to patients. The effects of ZA (100 μg/kg) and L-mifamurtide (1 mg/kg) were investigated in vivo in xenogeneic and syngeneic mice models of osteosarcoma, at clinical (tumor proliferation, spontaneous lung metastases development), radiological (bone microarchitecture by microCT analysis), biological and histological levels. No interference between the two drugs could be observed on ZA-induced bone protection and on L-mifamurtide-induced inhibition of lung metastasis development. Unexpectedly, ZA and L-mifamurtide association induced an additional and in some cases synergistic inhibition of primary tumor progression. L-mifamurtide has no effect on tumor proliferation in vitro or in vivo, and macrophage population was not affected at the tumor site whatever the treatment. This study evidenced for the first time a significant inhibition of primary osteosarcoma progression when both drugs are combined. This result constitutes a first proof-of-principle for clinical application in osteosarcoma patients. PMID:27152244

Shoulder arthrodesis with a reconstruction plate

PubMed Central

Byeon, Hwa Kyo

2008-01-01

From 1995 to 2005, arthrodesis with a reconstruction plate was performed for eight shoulders. The average follow-up period was 44 months. The indications for shoulder arthrodesis were joint destruction as a sequel of tuberculous arthritis, malignant bone tumour, pyogenic arthritis, failed arthrodesis and paralysis of the brachial plexus. The evaluation criteria included bony union and pain. Two cases of malignant tumour required an homologous bone graft due to severe bone deficit—a fracture that occurred in the distal part of the arthrodesed shoulder after removing the plate. With the exception of these two cases, severe pain or other complications did not occur in any other case. Shoulder arthrodesis with a reconstruction plate was judged to be a useful method for glenohumeral salvage in cases without severe bone deficit. Further, additional treatment methods should be considered to prevent fracture that may occur as a result of severe bone deficit. PMID:18716728

Malignant lymphoma incidentally diagnosed due to the perforation of the small intestine caused by a fish bone: A case report.

PubMed

Hiraki, Masatsugu; Miyoshi, Atsushi; Anegawa, Go; Kubo, Hiroshi; Ikeda, Osamu; Ohira, Keiichi; Azama, Shinya; Kido, Shinichi; Mori, Daisuke; Aibe, Hitoshi; Tanaka, Toshiya; Kitahara, Kenji; Sato, Seiji

2017-01-01

The ingestion of a foreign body is relatively common. However, it rarely results in the perforation of gastrointestinal tract. We herein report an unusual case of malignant lymphoma incidentally diagnosed after the perforation of the small intestine by a fish bone. A 90-year-old woman was admitted to our hospital because of abdominal pain and vomiting. Abdominal computed tomography demonstrated free air and ascites in the abdominal cavity. In the pelvic cavity, a radiopaque linear shadow about 35mm in diameter was shown in the small intestine, and the stricture was exposed to the abdominal cavity. Therefore, a diagnosis of perforation of the small intestine due to ingestion of a foreign body and panperitonitis was made. Emergent laparotomy was performed. The intraoperative findings revealed perforation of the small intestine with a fish bone in the jejunum. Local inflammation at the perforation site was seen, and circulated wall thickness was observed at the distal side of the jejunum. Partial resection of the jejunum and anastomosis of jejuno-jejunostomy was performed. A pathological examination and immunohistochemical study of the resected specimen resulted in a diagnosis of malignant lymphoma of follicular lymphoma Grade 1. It is very difficult to identify the existence malignancy accompanied with gastrointestinal perforation with ingestion of a foreign body. In cases suspected of involving malignancy, careful observation during surgery is needed in order to avoid missing the accompanying malignancy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Computer-aided designed, three dimensional-printed hemipelvic prosthesis for peri-acetabular malignant bone tumour.

PubMed

Wang, Baichuan; Hao, Yongqiang; Pu, Feifei; Jiang, Wenbo; Shao, Zengwu

2018-03-01

Prosthetic reconstruction may be a promising treatment for peri-acetabular malignant bone tumour; however, it is associated with a high complication rate. Therefore, prosthetic design and approach of prosthetic reconstruction after tumour resection warrant study. We retrospectively analyzed 11 patients with peri-acetabular malignant bone tumours treated by personalized 3D-printed hemipelvic prostheses after en bloc resection between 2015 and 2016. Pre-operative and post-operative pain at rest was assessed according to a 10-cm VAS score. The results of functional improvement were evaluated using the MSTS-93 score at the final follow-up. We also analyzed tumour recurrence, metastases, and complications associated with the reconstruction procedure. All patients were observed for six to 24 months with an average follow-up of 15.5 months. One patient had occasional pain of the involved hip at the final follow-up (VAS, pre vs. post 8 months: 3 vs. 2). The mean MSTS-93 score was 19.2 (range, 13-25). Hip dislocation was detected in two patients, while delayed wound healing occurred in one patient. One patient with mesenchymal chondrosarcoma had a left iliac bone metastasis. Local tumour recurrence was not observed. Reconstruction of bony defect after tumour resection using personalized 3D-printed hemipelvic prostheses can obtain acceptable functional results without severe complications. Based on previous reports and our results, we believe that reconstruction arthroplasty using 3D-printed hemipelvic prostheses will provide a promising alternative for those patients with peri-acetabular malignant bone tumours. Level IV, therapeutic study.

Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency.

PubMed

Sanchez, Lauren A; Maggadottir, Solrun Melkorka; Pantell, Matthew S; Lugar, Patricia; Rundles, Charlotte Cunningham; Sullivan, Kathleen E

2017-08-01

Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older). Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups. After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients. These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for continued longitudinal study of pediatric and early-onset CVID patients to further characterize accrual of features over time.

Epidemiology of pediatric bone fractures across age groups: Analysis of a pediatric population at an outpatient clinic in the Southwest region of Puerto Rico.

PubMed

Ortiz-Fullana, Jose; Valentín, Pablo; Ramírez, Norman

2016-01-01

Background: Gender disparities in pediatric fracture events has been well-documented however, less is known about racial disparities. The aim of this study is to investigate the epidemiology of pediatric bone fractures in a Hispanic population. This is a retrospective cross-sectional analysis of patient’s records from a Pediatric Orthopeadic outpatient clinic in the Southwest region of Puerto Rico during a 1-year span (August 2014 – August 2015). Differences in sex, BMI, health insurance coverage, parental educational level and employment status, mechanism of fracture, fracture site, and seasonality were investigated among three age classes (pre-school children, school children and adolescents). The sample consited of 243 subjects (0-21 y/o) sustaining a fracture of any extremity within the study period. Boys were at a higher risk of having a fracture event and as age increased, the male/female ratio also increased. The mean BMI was 18.0 kg/m2, with the highest in the school children age group (20.3 kg/m2). Slighlty more than half of the subjects (55.7%) benefitted from public health insurance coverage. The typical father was a laborer with a high school diploma, while the mother had a high school diploma but was unemployed There was a tendency for the children to suffer a bone fracture while at school (49.4%), followed by fractures at home (34.6%). In both the pre-school and school children groups, the upper extremity was more frequently involved (66.7% and 63.9%, respectively) in fracture events. Finally, there was very little variation in the seasonality of fracture events. This study provided valuable epidemiological information about pediatric bone fractures within a Hispanic population. It may contribute to the development and implementation of educational and preventive strategies appropriate to age and sex-differences.

Primary Ewing's Sarcoma of the temporal bone in an infant.

PubMed

Goudarzipour, Kourosh; Shamsian, Shahin; Alavi, Samin; Nourbakhsh, Kazem; Aghakhani, Roxana; Eydian, Zahra; Arzanian, Mohammad Taghi

2015-04-01

Introduction : Ewing's sarcoma is the second most common primary malignant tumor of bone found in children after Osteosarcoma. It accounts for 4-9% of primary malignant bone tumors and it affects bones of the skull or face in only 1-4% of cases. Hence it rarely affects the head and neck. Subject and Method : In this case report, we describe a case of primary Ewing's sarcoma occurring in the temporal bone. The tumor was surgically excised, and the patient underwent chemotherapy for ten months. Results : Neither recurrence nor distant metastasis was noted in these 10 months after surgery but about 18 months after surgery our patient was expired. Conclusion : Although the prognosis of Ewing's sarcoma is generally poor because of early metastasis to the lungs and to other bones, a review of the article suggested that Ewing's sarcoma occurring in the skull can often be successfully managed by intensive therapy with radical excision and chemotherapy. This result was supported by the case reported here.

Occurrence of metastases in beagles with skeletal malignancies induced by internal irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lloyd, R.D.; Angus, W.; Taylor, G.N.

1994-03-01

Metastases from malignant bone tumors often are responsible for the fatal effects of these cancers. Characteristics of primary skeletal malignancies in beagles injected with bone-seeking radionuclides were studied by Thurman (1971) and summarized by Thurman et al. (1971). There were 212 tumors in 186 of these dogs for which we subsequently received information on bone tumor metastases. Evaluation of bone and soft tissue slides from these animals allowed us to compare parameters reported previously with the occurrence of grossly apparent bone tumor metastases. Data included growth-rate of the primary tumor, volume of the primary tumor at death, sex of themore » animal, growth period of the primary tumor, degree of calcification of the primary tumor, skeletal location of the primary tumor, cumulative radiation dose to the skeleton, dose equivalent to the skeleton, and year of death. For most of the comparisons, no significant differences could be established between dogs with and without metastases. However, tumor volume at death appeared to be correlated with probability of metastasis (p < 0.05), with the larger tumors being associated with higher rates of metastasis. Comparisons of dogs with and without metastases as a function of tumor growth-rate did not, for the most part, yield significantly different results between groups. 10 refs., 11 tabs.« less

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF)

PubMed Central

Audigé, Laurent; Slongo, Theddy; Lutz, Nicolas; Blumenthal, Andrea; Joeris, Alexander

2017-01-01

Background and purpose The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF) describes the localization and morphology of fractures, and considers severity in 2 categories: (1) simple, and (2) multifragmentary. We evaluated simple and multifragmentary fractures in a large consecutive cohort of children diagnosed with long bone fractures in Switzerland. Patients and methods Children and adolescents treated for fractures between 2009 and 2011 at 2 tertiary pediatric surgery hospitals were retrospectively included. Fractures were classified according to the AO PCCF. Severity classes were described according to fracture location, patient age and sex, BMI, and cause of trauma. Results Of all trauma events, 3% (84 of 2,730) were diagnosed with a multifragmentary fracture. This proportion was age-related: 2% of multifragmentary fractures occurred in school­children and 7% occurred in adolescents. In patients diagnosed with a single fracture only, the highest percentage of multifragmentation occurred in the femur (12%, 15 of 123). In fractured paired radius/ulna bones, multifragmentation occurred in 2% (11 of 687); in fractured paired tibia/fibula bones, it occurred in 21% (24 of 115), particularly in schoolchildren (5 of 18) and adolescents (16 of 40). In a multivariable regression model, age, cause of injury, and bone were found to be relevant prognostic factors of multifragmentation (odds ratio (OR) > 2). Interpretation Overall, multifragmentation in long bone fractures in children was rare and was mostly observed in adolescents. The femur was mostly affected in single fractures and the lower leg was mostly affected in paired-bone fractures. The clinical relevance of multifragmentation regarding growth and long-term functional recovery remains to be determined. PMID:27882814

Circadian and seasonal variation of malignant arrhythmias in a pediatric and congenital heart disease population.

PubMed

Stephenson, Elizabeth A; Collins, Kathryn K; Dubin, Anne M; Epstein, Michael R; Hamilton, Robert M; Kertesz, Naomi J; Alexander, Mark E; Cecchin, Frank; Triedman, John K; Walsh, Edward P; Berul, Charles I

2002-10-01

Recent studies in adult populations have revealed seasonal variation in the frequency of acute cardiovascular events, including life-threatening arrhythmias, demonstrating increased events during winter and early spring. Trends in the time of day that arrhythmias occur also were noted. We sought to establish whether pediatric and young adult congenital heart disease implantable cardioverter defibrillator (ICD) recipients have circadian or seasonal variability in shock frequency, similar to adult populations. Data from ICD patients at six pediatric centers in North America were analyzed to assess the timing of life-threatening arrhythmias. The populations consisted of children and adults with congenital heart disease and ICDs placed for malignant arrhythmias. Data were considered in 46 patients who received appropriate therapy (total 139 episodes) for ventricular tachycardia or ventricular fibrillation. Multiple variables were analyzed, including time of day, day of week, and month of year. In contrast to previously studied adult patients, fewer events occurred in the early morning (7.5%), with the most therapies occurring between 6 P.M. and midnight (35%). An increased frequency of therapies was observed in the fall and winter (September-January), representing 60% of all appropriate shocks. Unlike adult populations, Mondays did not have an increased frequency of malignant arrhythmias. Pediatric and adult congenital heart disease populations have moderate seasonal and 24-hour variation in ICD event rate, with some distinctly different peaks than those seen in typical adult ICD populations. These findings suggest circadian variation in arrhythmia vulnerability that may differ from conventional occupational, physical, or emotional stressors. (J Cardiovasc Electrophysiol, Vol. 13, pp.

Diagnostic performance of 18F-FDG PET/CT and whole-body diffusion-weighted imaging with background body suppression (DWIBS) in detection of lymph node and bone metastases from pediatric neuroblastoma.

PubMed

Ishiguchi, Hiroaki; Ito, Shinji; Kato, Katsuhiko; Sakurai, Yusuke; Kawai, Hisashi; Fujita, Naotoshi; Abe, Shinji; Narita, Atsushi; Nishio, Nobuhiro; Muramatsu, Hideki; Takahashi, Yoshiyuki; Naganawa, Shinji

2018-06-01

Recent many studies have shown that whole body "diffusion-weighted imaging with background body signal suppression" (DWIBS) seems a beneficial tool having higher tumor detection sensitivity without ionizing radiation exposure for pediatric tumors. In this study, we evaluated the diagnostic performance of whole body DWIBS and 18 F-FDG PET/CT for detecting lymph node and bone metastases in pediatric patients with neuroblastoma. Subjects in this retrospective study comprised 13 consecutive pediatric patients with neuroblastoma (7 males, 6 females; mean age, 2.9 ± 2.0 years old) who underwent both 18 F-FDG PET/CT and whole-body DWIBS. All patients were diagnosed as neuroblastoma on the basis of pathological findings. Eight regions of lymph nodes and 17 segments of skeletons in all patients were evaluated. The images of 123 I-MIBG scintigraphy/SPECT-CT, bone scintigraphy/SPECT, and CT were used to confirm the presence of lymph node and bone metastases. Two radiologists trained in nuclear medicine evaluated independently the uptake of lesions in 18 F-FDG PET/CT and the signal-intensity of lesions in whole-body DWIBS visually. Interobserver difference was overcome through discussion to reach a consensus. The sensitivities, specificities, and overall accuracies of 18 F-FDG PET/CT and whole-body DWIBS were compared using McNemer's test. Positive predictive values (PPVs) and negative predictive values (NPVs) of both modalities were compared using Fisher's exact test. The total numbers of lymph node regions and bone segments which were confirmed to have metastasis in the total 13 patients were 19 and 75, respectively. The sensitivity, specificity, overall accuracy, PPV, and NPV of 18 F-FDG PET/CT for detecting lymph node metastasis from pediatric neuroblastoma were 100, 98.7, 98.9, 95.0, and 100%, respectively, and those for detecting bone metastasis were 90.7, 73.1, 80.3, 70.1, and 91.9%, respectively. In contrast, the sensitivity, specificity, overall accuracy, PPV, and NPV of whole-body DWIBS for detecting bone metastasis from pediatric neuroblastoma were 94.7, 24.0, 53.0, 46.4 and 86.7%, respectively, whereas those for detecting lymph node metastasis were 94.7, 85.3, 87.2, 62.1, and 98.5%, respectively. The low specificity, overall accuracy, and PPV of whole-body DWIBS for detecting bone metastasis were due to a high incidence of false-positive findings (82/108, 75.9%). The specificity, overall accuracy, and PPV of whole-body DWIBS for detecting lymph node metastasis were also significantly lower than those of 18 F-FDG PET/CT for detecting lymph node metastasis, although the difference between these 2 modalities was less than that for detecting bone metastasis. The specificity, overall accuracy, and PPV of whole-body DWIBS are significantly lower than those of 18 F-FDG PET/CT because of a high incidence of false-positive findings particularly for detecting bone metastasis, whereas whole-body DWIBS shows a similar level of sensitivities for detecting lymph node and bone metastases to those of 18 F-FDG PET/CT. DWIBS should be carefully used for cancer staging in children because of its high incidence of false-positive findings in skeletons.

Rationale and Design of a Phase 1 Clinical Trial to Evaluate HSV G207 Alone or with a Single Radiation Dose in Children with Progressive or Recurrent Malignant Supratentorial Brain Tumors.

PubMed

Waters, Alicia M; Johnston, James M; Reddy, Alyssa T; Fiveash, John; Madan-Swain, Avi; Kachurak, Kara; Bag, Asim K; Gillespie, G Yancey; Markert, James M; Friedman, Gregory K

2017-03-01

Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors. G207 is a genetically engineered HSV-1 lacking genes essential for replication in normal brain cells. Safety has been established in preclinical investigations involving intracranial inoculation in the highly HSV-sensitive owl monkey (Aotus nancymai), and in three adult phase 1 trials in recurrent/progressive high-grade gliomas. No dose-limiting toxicities were seen in the adult studies and a maximum tolerated dose was not reached. Approximately half of the 35 treated adults had radiographic or neuropathologic evidence of response at a minimum of one time point. Preclinical studies in pediatric brain tumor models indicate that a variety of pediatric tumor types are highly sensitive to killing by G207. This clinical protocol outlines a first in human children study of intratumoral inoculation of an oncolytic virus via catheters placed directly into recurrent or progressive supratentorial malignant tumors.

Pediatric mandibular fractures.

PubMed

Thaller, S R; Mabourakh, S

1991-06-01

In spite of curiosity, facial fractures, particularly mandibular fractures, in the pediatric age group embrace only a modest proportion of facial fractures that occur within the general population. Several large series report an overall incidence of approximately 1% of all facial bone fractures. A considerable volume of literature has been generated describing the pattern of injury and treatment modalities for pediatric facial bone fractures. At our institution, which is an extremely busy university-based regional trauma center, we have witnessed a persistent escalation in the number of patients requiring repair of their facial bone fractures. During the period of January 1989 through January 1990, we treated a total of 204 patients for repair of mandible fractures. An analysis of the records of this group revealed only 3 patients who were younger than 4 years of age and 2 additional patients younger than 8 years. There were another 10 patients 17 years and younger, for a total incidence of 0.08%. Additionally, we found that within this seemingly small group, there was a surprisingly high incidence of severe, associated injuries.

Bone marrow failure in childhood: central pathology review of a nationwide registry.

PubMed

Ito, Masafumi

2017-01-01

Refractory cytopenia of childhood (RCC) was proposed as a provisional entity in the 2008 WHO classification of myelodysplastic syndromes (MDS). It is defined as a childhood MDS featuring persistent cytopenia without increase blasts in bone marrow (BM) or peripheral blood (PB). Because the majority of RCC cases feature hypocellularity and pancytopenia, it is quite challenging to differentiate RCC from acquired aplastic anemia (AA) and many kinds of inherited bone marrow failure syndromes (IBMFS). Diagnosis of RCC requires BM histology of characteristic features such as isolated erythroid islet with left shift, abnormal localization and micromegakaryocytes. The Japanese Society of Pediatric Hematology/Oncology has opened the central registry review system since 2009 to evaluate childhood cases of bone marrow failure (BMF). It has reviewed cytology and BM pathology of all registered BMF cases, which number more than 1,700. In the evaluation of BMF, BM pathology is important to assess the mechanism of hematopoiesis. Pathological dysplasia should be differentiated from cytological dysplasia. A central review system is important for rare diseases, such as pediatric BMF. Standardization of pathological diagnosis should be established upon consensus findings, descriptions, and diagnostic approaches. In this review, the pathology of pediatric BMF syndromes is summarized.

Complementary roles of tumour specific PET tracer ¹⁸F-FAMT to ¹⁸F-FDG PET/CT for the assessment of bone metastasis.

PubMed

Morita, Motoho; Higuchi, Tetsuya; Achmad, Arifudin; Tokue, Azusa; Arisaka, Yukiko; Tsushima, Yoshito

2013-10-01

The usefulness of (18)F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [(18)F]-3-fluoro-alpha-methyl tyrosine ((18)F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of (18)F-FAMT PET/CT to complement (18)F-FDG PET/CT in the evaluation of bone metastasis. This retrospective study included 21 patients with bone metastases of various cancers who had undergone both (18)F-FDG and (18)F-FAMT PET/CT within 1 month of each other. (18)F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the (18)F-FAMT in the corresponding lesions were evaluated. A total of 72 (18)F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. (18)F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P < 0.01). Bone metastatic lesions of oesophageal cancer showed the highest average of (18)F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher (18)F-FAMT uptake than those of adenocarcinoma. No significant difference in (18)F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of (18)F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that (18)F-FAMT uptake was confirmed by (18)F-FDG uptake suggests that (18)F-FAMT PET/CT has the potential to complement (18)F-FDG PET/CT for the detection of bone metastases.

Pediatric temporal bone fractures: A case series.

PubMed

Waissbluth, S; Ywakim, R; Al Qassabi, B; Torabi, B; Carpineta, L; Manoukian, J; Nguyen, L H P

2016-05-01

Temporal bone fractures are relatively common findings in patients with head trauma. The aim of this study was to evaluate the characteristics of temporal bone fractures in the pediatric population. Retrospective case series. Tertiary care pediatric academic medical center. The medical records of patients aged 18 years or less diagnosed with a temporal bone fracture at the Montreal Children's Hospital from January 2000 to August 2014 were reviewed. Patient demographics, clinical presentation, mechanism of injury and complications were analyzed. Imaging studies and audiograms were also evaluated. Out of 323 patients presenting to the emergency department with a skull fracture, 61 presented with a temporal bone fracture. Of these, 5 presented with bilateral fractures. 47 patients had associated fractures, and 3 patients deceased. We observed a male to female ratio of 2.8:1, and the average age was 9.5 years. Motor vehicle accidents were the primary mechanism of injury (53%), followed by falls (21%) and bicycle or skateboard accidents (10%). The most common presenting signs included hemotympanum, decreased or loss of consciousness, facial swelling and nausea and vomiting. 8 patients had otic involvement on computed tomography scans, and 30 patients had documented hearing loss near the time of accident with a majority being conductive hearing loss. 17 patients underwent surgical management of intracranial pressure. In children, fractures of the temporal bone were most often caused by motor vehicle accidents and falls. It is common for these patients to have associated fractures. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Overview of Pediatric Testicular Tumors in Korea

PubMed Central

Chung, Jae Min

2014-01-01

Prepubertal testicular tumors are rare compared with postpubertal testicular tumors. The incidence of prepubertal testicular tumors peaks at 2 years of age, tapers off after 4 years of age, and then begins to rise again at puberty. Prepubertal and postpubertal testicular tumors show many differences, including the typical tumor histology, molecular biological differences, and the malignant potential of tumors at different ages. Pediatric testicular tumors are classified as benign or malignant on the basis of their clinical behavior and histologically are divided into germ cell and gonadal stromal (nongerm cell) tumors. Many histological and biological studies have further confirmed the distinct nature of prepubertal and postpubertal testicular tumors. These differences have led to various management strategies for prepubertal and postpubertal tumors. Because overall about 75% of prepubertal testicular tumors are benign, a testis-sparing approach is becoming more common in children. Orchiectomy and observation with very selective use of chemotherapy has become the standard approach when a malignant tumor is identified. Retroperitoneal lymph node dissection and radiation therapy play very limited roles. PMID:25512812

An Alternative Method of Intermaxillary Fixation for Simple Pediatric Mandible Fractures.

PubMed

Farber, Scott J; Nguyen, Dennis C; Harvey, Alan A; Patel, Kamlesh B

2016-03-01

Mandibular fractures represent a substantial portion of facial fractures in the pediatric population. Pediatric mandibles differ from their adult counterparts in the presence of mixed dentition. Avoidance of injury to developing tooth follicles is critical. Simple mandibular fractures can be treated with intermaxillary fixation (IMF) using arch bars or bone screws. This report describes an alternative to these methods using silk sutures and an algorithm to assist in treating simple mandibular fractures in the pediatric population. A retrospective chart review was performed and the records of 1 surgeon were examined. Pediatric patients who underwent treatment for a mandibular fracture in the operating room from 2011 to 2015 were identified using Common Procedural Terminology codes. Data collected included age, gender, type of fracture, type of treatment used, duration of fixation, and presence of complications. Five patients with a mean age of 6.8 years at presentation were identified. Fracture types were unilateral fractures of the condylar neck (n = 3), bilateral fractures of the condylar head (n = 1), and a unilateral fracture of the condylar head with an associated parasymphyseal fracture (n = 1). IMF was performed in 4 patients using silk sutures, and bone screw fixation was performed in the other patient. No post-treatment complications or malocclusion were reported. Average duration of IMF was 18.5 days. An algorithm is presented to assist in the treatment of pediatric mandibular fractures. Silk suture fixation is a viable and safe alternative to arch bars or bone screws for routine mandibular fractures. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

A Multicenter, Randomized Clinical Trial of a Cognitive Remediation Program for Childhood Survivors of a Pediatric Malignancy

ERIC Educational Resources Information Center

Butler, Robert W.; Copeland, Donna R.; Fairclough, Diane L.; Mulhern, Raymond K.; Katz, Ernest R.; Kazak, Anne E.; Noll, Robert B.; Patel, Sunita K.; Sahler, Olle Jane Z.

2008-01-01

Survivors of childhood cancer whose malignancy and/or treatment involved the central nervous system may demonstrate a consistent pattern of neurocognitive deficits. The present study evaluated a randomized clinical trial of the Cognitive Remediation Program (CRP). Participants were 6- to 17-year-old survivors of childhood cancer (N = 161; 35%…

Pre-operative simulation of pediatric mastoid surgery with 3D-printed temporal bone models.

PubMed

Rose, Austin S; Webster, Caroline E; Harrysson, Ola L A; Formeister, Eric J; Rawal, Rounak B; Iseli, Claire E

2015-05-01

As the process of additive manufacturing, or three-dimensional (3D) printing, has become more practical and affordable, a number of applications for the technology in the field of pediatric otolaryngology have been considered. One area of promise is temporal bone surgical simulation. Having previously developed a model for temporal bone surgical training using 3D printing, we sought to produce a patient-specific model for pre-operative simulation in pediatric otologic surgery. Our hypothesis was that the creation and pre-operative dissection of such a model was possible, and would demonstrate potential benefits in cases of abnormal temporal bone anatomy. In the case presented, an 11-year-old boy underwent a planned canal-wall-down (CWD) tympano-mastoidectomy for recurrent cholesteatoma preceded by a pre-operative surgical simulation using 3D-printed models of the temporal bone. The models were based on the child's pre-operative clinical CT scan and printed using multiple materials to simulate both bone and soft tissue structures. To help confirm the models as accurate representations of the child's anatomy, distances between various anatomic landmarks were measured and compared to the temporal bone CT scan and the 3D model. The simulation allowed the surgical team to appreciate the child's unusual temporal bone anatomy as well as any challenges that might arise in the safety of the temporal bone laboratory, prior to actual surgery in the operating room (OR). There was minimal variability, in terms of absolute distance (mm) and relative distance (%), in measurements between anatomic landmarks obtained from the patient intra-operatively, the pre-operative CT scan and the 3D-printed models. Accurate 3D temporal bone models can be rapidly produced based on clinical CT scans for pre-operative simulation of specific challenging otologic cases in children, potentially reducing medical errors and improving patient safety. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Malignant external otitis: The diagnostic value of bone scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ostfeld, E.; Aviel, A.; Pelet, D.

1981-06-01

Technetium99m Methylene Diphosphate bone scintigraphy (BS) of the skull was performed in three patients with malignant external otitis (MEO). Pathological uptake of the radioisotope in the mastoid region was found during the early stages of MEO updating radiologic findings. The extent of the radioisotope accumulation during the early stages of MEO indicates that the actual tissue damage exceeds the clinical estimation. The follow-up BS findings correlate well with the clinical course of MEO indicating either healing or extension to the base of skull.

Dermoscopy of benign and malignant neoplasms in the pediatric population.

PubMed

Haliasos, Helen C; Zalaudek, Iris; Malvehy, Josep; Lanschuetzer, Christoph; Hinter, Helmut; Hofmann-Wellenhof, Rainer; Braun, Ralph; Marghoob, Ashfaq A

2010-12-01

Dermoscopy is a noninvasive technique that enables visualization of subsurface colors and structures within the skin that are imperceptible to the naked eye. The dermatoscope allows the physician to examine both the macroscopic and microscopic primary morphology of skin lesions, identify subtle clinical clues, confirm naked-eye clinical diagnoses, and monitor treatment progress while posing little threat to the young patient. Dermoscopic findings have been formulated into diagnostic criteria that assist experienced clinicians in differentiating benign and malignant neoplasms. In this review, clinical morphology of melanocytic nevi and melanoma in the pediatric population is examined and the relevant dermoscopic findings and histopathologic correlates that aid in the diagnosis and management of these lesions are described. Copyright © 2010. Published by Elsevier Inc.

Analysis of risk factors for central venous catheter-related complications: a prospective observational study in pediatric patients with bone sarcomas.

PubMed

Abate, Massimo Eraldo; Sánchez, Olga Escobosa; Boschi, Rita; Raspanti, Cinzia; Loro, Loretta; Affinito, Domenico; Cesari, Marilena; Paioli, Anna; Palmerini, Emanuela; Ferrari, Stefano

2014-01-01

The incidence of central venous catheter (CVC)-related complications reported in pediatric sarcoma patients is not established as reports in available literature are limited. The analysis of risk factors is part of the strategy to reduce the incidence of CVC complications. The objective of this study was to determine the incidence of CVC complications in children with bone sarcomas and if defined clinical variables represent a risk factor. During an 8-year period, 155 pediatric patients with bone sarcomas were prospectively followed up for CVC complications. Incidence and correlation with clinical features including gender, age, body mass index, histology, disease stage, and use of thromboprophylaxis with low-molecular-weight heparin were analyzed. Thirty-three CVC complications were recorded among 42 687 CVC-days (0.77 per 1000 CVC-days). No correlation between the specific clinical variables and the CVC complications was found. A high incidence of CVC-related sepsis secondary to gram-negative bacteria was observed. The analysis of CVC complications and their potential risk factors in this sizable and relatively homogeneous pediatric population with bone sarcomas has led to the implementation of a multimodal approach by doctors and nurses to reduce the incidence and morbidity of the CVC-related infections, particularly those related to gram-negative bacteria. As a result of this joint medical and nursing study, a multimodal approach that included equipping faucets with water filters, the reeducation of doctors and nurses, and the systematic review of CVC protocol was implemented.

Are oral and maxillofacial surgery residents being adequately trained to care for pediatric patients?

PubMed

Abramowicz, Shelly; Kaban, Leonard B; Wurtzel, Andrew S; Roser, Steven M

2017-09-01

To evaluate whether current oral and maxillofacial surgery (OMS) residents are receiving adequate training and experience to perform specific surgical procedures and anesthesia for pediatric patients. A 17-question survey was sent electronically to fellows of the American Academy of Craniomaxillofacial Surgeons. Descriptive data for individual surgeons, their associated residency programs, and the quantity of specific pediatric procedures they performed were collected. Resident case load for inpatient and outpatient procedures and overall experience in medical, surgical, and anesthetic management of pediatric OMS patients were explored. Surveys were sent to 110 active fellows; 64 completed the questionnaire (58%). There were 59 male fellows and 5 female fellows, with a mean age of 50.4 years. Of those, 68.8% practice in an academic setting. Specifically, 93.8% take after-hours emergency calls covering adult and pediatric patients and 98.4% have admitting privileges at a children's hospital or a pediatric unit in an adult hospital. Their affiliated residency programs include required rotations in pediatrics or pediatric subspecialties. In their opinion, >90% of graduating OMS residents have the appropriate skill set to perform dentoalveolar procedures, outpatient anesthesia, orthognathic procedures, and alveolar bone grafts. However, residents have limited ability to reconstruct pediatric ramus-condyle unit with a costochondral graft. Results of this study indicate that, in the opinion of the respondents, graduates of OMS residency programs have adequate training to perform dentoalveolar procedures, outpatient anesthesia, orthognathic surgery, and alveolar bone grafts in pediatric procedures, but have limited experience with reconstruction of pediatric ramus-condyle unit via costochondral graft. Copyright © 2017 Elsevier Inc. All rights reserved.

A genome-wide scan identifies variants in NFIB associated with metastasis in patients with osteosarcoma

PubMed Central

Mirabello, Lisa; Koster, Roelof; Moriarity, Branden S.; Spector, Logan G.; Meltzer, Paul S.; Gary, Joy; Machiela, Mitchell J.; Pankratz, Nathan; Panagiotou, Orestis A.; Largaespada, David; Wang, Zhaoming; Gastier-Foster, Julie M.; Gorlick, Richard; Khanna, Chand; de Toledo, Silvia Regina Caminada; Petrilli, Antonio S.; Patiño-Garcia, Ana; Sierrasesúmaga, Luis; Lecanda, Fernando; Andrulis, Irene L.; Wunder, Jay S.; Gokgoz, Nalan; Serra, Massimo; Hattinger, Claudia; Picci, Piero; Scotlandi, Katia; Flanagan, Adrienne M.; Tirabosco, Roberto; Amary, Maria Fernanda; Halai, Dina; Ballinger, Mandy L.; Thomas, David M.; Davis, Sean; Barkauskas, Donald A.; Marina, Neyssa; Helman, Lee; Otto, George M.; Becklin, Kelsie L.; Wolf, Natalie K.; Weg, Madison T.; Tucker, Margaret; Wacholder, Sholom; Fraumeni, Joseph F.; Caporaso, Neil E.; Boland, Joseph F.; Hicks, Belynda D.; Vogt, Aurelie; Burdett, Laurie; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Savage, Sharon A.

2015-01-01

Metastasis is the leading cause of death in osteosarcoma patients, the most common pediatric bone malignancy. We conducted a multi-stage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified a SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P=1.2×10−9, OR 2.43, 95% CI 1.83–3.24). The risk allele was significantly associated with lowered NFIB expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. Additionally, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in Nfib, and had lowered Nfib expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis, and that NFIB is an osteosarcoma metastasis susceptibility gene. PMID:26084801

Single-cell whole exome and targeted sequencing in NPM1/FLT3 positive pediatric acute myeloid leukemia.

PubMed

Walter, Christiane; Pozzorini, Christian; Reinhardt, Katarina; Geffers, Robert; Xu, Zhenyu; Reinhardt, Dirk; von Neuhoff, Nils; Hanenberg, Helmut

2018-02-01

The small portion of leukemic stem cells (LSCs) in acute myeloid leukemia (AML) present in children and adolescents is often masked by the high background of AML blasts and normal hematopoietic cells. The aim of the current study was to establish a simple workflow for reliable genetic analysis of single LSC-enriched blasts from pediatric patients. For three AMLs with mutations in nucleophosmin 1 and/or fms-like tyrosine kinase 3, we performed whole genome amplification on sorted single-cell DNA followed by whole exome sequencing (WES). The corresponding bulk bone marrow DNAs were also analyzed by WES and by targeted sequencing (TS) that included 54 genes associated with myeloid malignancies. Analysis revealed that read coverage statistics were comparable between single-cell and bulk WES data, indicating high-quality whole genome amplification. From 102 single-cell variants, 72 single nucleotide variants and insertions or deletions (70%) were consistently found in the two bulk DNA analyses. Variants reliably detected in single cells were also present in TS. However, initial screening by WES with read counts between 50-72× failed to detect rare AML subclones in the bulk DNAs. In summary, our study demonstrated that single-cell WES combined with bulk DNA TS is a promising tool set for detecting AML subclones and possibly LSCs. © 2017 Wiley Periodicals, Inc.

Distribution of skeletal malignancies in beagles injected with 239Pu citrate.

PubMed

Lloyd, R D; Taylor, G N; Angus, W; Miller, S C; Bruenger, F W; Jee, W S

1994-04-01

The distribution of skeletal malignancies among our beagles injected with 239Pu as young adults roughly seems to follow the distribution of skeletal mass and skeletal 239Pu. These findings are similar to those we reported previously for a group of dogs given 26Ra. Although there were differences in tumor distribution between the animals given 226Ra and those given 239Pu, most of them were not statistically significant; however, the radium dogs seemed to show a greater sensitivity to bone tumor origin in the tibia, while there may have been a tendency among the plutonium dogs toward increased relative sensitivity in the scapula, lumbar vertebrae, sacrum, and ribs. In contrast, the most common site for the formation of naturally-occurring bone malignancy in the dog is the distal radius. Perhaps there were too few tumors and too few dogs to establish statistical significance. A correlation between tumor location and at least two anatomical-physiological factors in the skeleton indicated that these two factors (site-specific bone turnover rate and percent of red marrow at the site, which is correlated with vascularity) may influence the appearance of malignancies both individually and in combination. Except for the femur, there appeared to be no difference between the relative distribution of skeletal malignancies of low-level (30 Bq-2 Bq kg-1 injected) and high-level (3-122 kBq kg-1) dogs. Distribution of bone tumors between the axial and appendicular skeleton was 50% vs. 50% for 239Pu (42 and 42), but it was 39% axial vs. 61% appendicular (22 and 35, respectively) for dogs given 226Ra. This difference was not significant (p > 0.2).

Osteochondroma of the Scapula with Accessory Nerve (XI) Compression.

PubMed

Beauchamp-Chalifour, Philippe; Pelet, Stéphane

2018-01-01

Osteochondroma is the most common benign bone tumor and is characterized as a cartilage-capped bony stalk. This lesion usually develops from the growth plate of long bones. Most osteochondromas are asymptomatic. Neurovascular compressions or cosmetic issues can occur in specific locations. Malignant transformation is extremely rare, and MRI can help evaluate these lesions. Symptomatic mass and malignancy features are the main surgical indications. Uncommonly, an osteochondroma can develop from flat bones. We present the case of a 25-year-old patient with a right scapula osteochondroma causing an accessory nerve compression. The mass was surgically removed, and the diagnosis was confirmed. The patient fully recovered at the latest 3-year follow-up visit.

A suspected malignancy in osteolytic bone tumour of the thumb

PubMed Central

Mattiassich, Georg; Ensat, Florian; Hager, Martina; Wechselberger, Gottfried

2012-01-01

A 75-year-old male patient was referred to our institution owing to a painful and gradually developing lesion of the thumb with suspicious malignancy. The patient was suffering from a swollen, red, tender left thumb for 3 months. An old scar at the finger pulp could be traced from an old minor trauma. The x-ray revealed an osteolytic lesion in the terminal phalanx of the non-dominant hand that raised concerns of malignancy. Additional investigations such as ultrasound, CT-scan and MRI have been performed to get better insight to the lesion. After performing a biopsy, no malignant cells were found. Owing to the local destroying effect of the lesion and the clinical signs of the patient, the lesion was excised in total. The histopathological evaluation confirmed the tumour as a rare intraosseous epidermoid cyst. A bone graft after resection was not needed. The postoperative follow-up of the patient was uneventful. PMID:23109418

78 FR 76507 - Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-17

... blast (immature) cells in the peripheral blood or bone marrow is 10 percent or greater. We propose this... evaluate cancer treatment by bone marrow or stem cell transplantation, including transplantation using stem... evaluate cancers treated with bone marrow or stem cell transplantation, including transplantation using...

Translating genomic discoveries to the clinic in pediatric oncology.

PubMed

Glade Bender, Julia; Verma, Anupam; Schiffman, Joshua D

2015-02-01

The present study describes the recent advances in the identification of targetable genomic alterations in pediatric cancers, along with the progress and associated challenges in translating these findings into therapeutic benefit. Each field within pediatric cancer has rapidly and comprehensively begun to define genomic targets in tumors that potentially can improve the clinical outcome of patients, including hematologic malignancies (leukemia and lymphoma), solid malignancies (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), and brain tumors (gliomas, ependymomas, and medulloblastomas). Although each tumor has specific and sometimes overlapping genomic targets, the translation to the clinic of new targeted trials and precision medicine protocols is still in its infancy. The first clinical tumor profiling studies in pediatric oncology have demonstrated feasibility and patient enthusiasm for the personalized medicine paradigm, but have yet to demonstrate clinical utility. Complexities influencing implementation include rapidly evolving sequencing technologies, tumor heterogeneity, and lack of access to targeted therapies. The return of incidental findings from the germline also remains a challenge, with evolving policy statements and accepted standards. The translation of genomic discoveries to the clinic in pediatric oncology continues to move forward at a brisk pace. Early adoption of genomics for tumor classification, risk stratification, and initial trials of targeted therapeutic agents has led to powerful results. As our experience grows in the integration of genomic and clinical medicine, the outcome for children with cancer should continue to improve.

Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with Tomotherapy HDA.

PubMed

Han, Eun Young; Kim, Dong-Wook; Zhang, Xin; Penagaricano, Jose; Liang, Xiaoying; Hardee, Matthew; Morrill, Steve; Ratanatharathorn, Vaneerat

2015-01-01

It is important to minimize the radiation dose delivered to healthy tissues in pediatric cancer treatment because of the risk of secondary malignancies. Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ) delivery mode. The purpose of this study was to evaluate its dosimetric effect on the pediatric cancer cases. We included 6 pediatric cases in this study. The dose profiles and plan statistics—target dose conformity, uniformity, organ-at-risk (OAR) mean dose, beam-on time, and integral dose—were compared for each case. Consequently, the target dose coverage and uniformity were similar for different jaw settings. The OAR dose sparing depended on its relative location to the target and disease sites. For example, in the head and neck cancer cases, the brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3 Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric cases could be critical to reduce a probability of a secondary malignancy. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

The role of 18F-FDG PET/CT in pediatric lymph-node acute lymphoblastic leukemia involvement.

PubMed

Cistaro, Angelina; Saglio, Francesco; Asaftei, Sebastian; Fania, Piercarlo; Berger, Massimo; Fagioli, Franca

2011-01-01

In pediatric oncology, positron emission tomography/computed tomography (PET/CT) is emerging as an essential diagnostic tool in characterizing suspicious neoplastic lesions and staging malignant diseases. Most studies regarding the possible role of FDG-PET/CT in the management of acute lymphoblastic leukemia (ALL) patients are limited to adults. Here we report a pediatric patient with recurrent ALL, in which FDG-PET/CT was used both to define more precisely the cause of lymphadenopathy and to assess the effect of the second-line therapy.

Animal models for bone tissue engineering and modelling disease

PubMed Central

Griffin, Michelle

2018-01-01

ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-13

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kunos, Charles A., E-mail: charles.kunos@UHhospitals.org; Debernardo, Robert; Radivoyevitch, Tomas

Purpose: To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies. Methods and Materials: A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile,more » 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates. Results: In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women. Conclusions: Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.« less

"A day in my life" photography project: the silent voice of pediatric bone marrow transplant patients.

PubMed

Breitwieser, Carrie L; Vaughn, Lisa M

2014-01-01

A photovoice project was conducted with pediatric bone marrow transplant (BMT) patients to examine their coping skills and interpretation of their experience during a BMT, especially when hospitalized. We also wanted to determine how photovoice could be used within a pediatric BMT unit. Sixteen children (ages 4-14) and 2 young adults (ages 22 and 25) from a pediatric BMT unit participated in the project. Six BMT outpatients participated in the data analysis and evaluation phase. Fourteen clinical staff evaluated the impact of the project on their practice. Three primary themes emerged from the pre- and post-BMT photos, accompanying detailed notes, and BMT outpatient analysis of the photos: (a) BMT is "torture," (b) BMT is "time slipping away," and (c) BMT requires normalization, comfort, distraction, and support. BMT patients and staff concluded that photovoice helped express and release emotions regarding the challenges of BMT. BMT staff noted that the results of this project reminded them of the importance of being patient-centered and mindful of patient experience and the therapeutic relationship. © 2014 by Association of Pediatric Hematology/Oncology Nurses.

Focal fluorine-18 fluorodeoxyglucose-avid lesions without computed tomography correlate at whole-body positron emission tomography-computed tomography in oncology patients: how often are they malignant?

PubMed

Kumar, Rahi; Hawkins, Randall A; Yeh, Benjamin M; Wang, Zhen Jane

2011-09-01

To retrospectively evaluate the rate of malignancy of focal fluorine-18 fluorodeoxyglucose (18F-FDG)-avid lesions without computed tomography (CT) correlate at whole-body positron emission tomography (PET)-CT in oncology patients, because better defining these abnormalities could potentially lead to improved patient management algorithms that rely on PET-CT for detection, staging, and treatment monitoring of malignancies. We performed a computer search of all PET-CT studies performed at our institution from 2006 to 2009, and identified 87 studies with findings of focal 18F-FDG-avid lesions without correlate at CT. The rate of malignancy of such lesions was determined by reviewing findings at follow-up imaging or by clinical or histopathological follow-up. Rates of malignancy were categorized and compared by lesion location and by the type of primary malignancy. The most common locations for focal 18F-FDG-avid lesions without CT correlate were: lymph node location (without visible lymph nodes; 27/87), bone (21/87), soft tissue (17/87), liver (9/87), and gastrointestinal tract (8/87). Forty-one percent (36/87) of the focal FDG-avid lesions without CT correlate were malignant (either metastatic disease or a second malignancy) at follow-up (mean follow-up: 5 months, range: 1-25 months). Focal FDG-avid lesions in lymph node location and in bone without CT correlate had higher rates of malignancy (56%, 15/27 and 52%, 11/21, respectively) than lesions in all other locations (26%, 10/39, P=0.028). In 15 of 87 cases, the only significant finding at PET-CT was an FDG-avid lesion without CT correlate. Of those, 53% (8/15) was positive for malignancy. There were no significant differences in the rates of malignancy for the focal FDG-avid lesions without CT correlate when stratified by the type of primary malignancy in this series. Focal FDG avid lesions without CT correlate were malignant in 41% of cases in our series of oncology patients. Lesions in lymph node location and in bones had the highest rates of malignancy. Knowledge of the patterns and risk of malignancy of focal FDG-avid lesions without CT correlate in oncology patients may facilitate the management of oncology patients with such lesions on PET-CT, and could lead to an improved interpretation of PET-CT scans by imaging specialists.

Selumetinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; BRAF Gene Mutation; GNA11 Gene Mutation; GNAQ Gene Mutation; Histiocytosis; HRAS Gene Mutation; KRAS Gene Mutation; NF1 Gene Mutation; NRAS Gene Mutation; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma

Complications and risk factors of infection in pediatric hemato-oncology patients with totally implantable access ports (TIAPs).

PubMed

Nam, So-Hyun; Kim, Dae-Yeon; Kim, Seong-Chul; Kim, In-Koo

2010-04-01

Totally implantable access ports (TIAPs) are widely used in pediatric hematology-oncology patients. We investigated the incidence of complications, causes of TIAP removal, and risk factors for infection. We retrospectively analyzed the clinical, demographic, and surgical characteristics in 225 pediatric hematology-oncology patients implanted with 238 TIAPs between January 2004 and December 2005. Except for 20 patients lost to follow-up, the mean maintenance period was 724.8 +/- 500.6 days (range: 17-2,124). Mechanical complications occurred in seven patients (2.9%). The causes of TIAP removal were termination of use in 130 patients (59.6%), death from primary disease with TIAP in situ in 35 (14.7%), infection in 35 (14.7%), and obstruction in 4 (1.8%). Early infections occurred in nine patients at mean 37.77 +/- 16.44 days (range: 17-56). Late infections occurred in 26 patients at mean 334.5 +/- 257.82 days (range: 68-997). Univariate analysis showed that the risk factors of early infection were re-implantation (P = 0.022) and long operation time (P = 0.045). The risk factors of late infection were ANC <500/mm(3) (P = 0.011) and platelet count <50,000/mm(3) (P < 0.001). In multivariate analysis, re-implantation was a significant risk factor of early infection (P = 0.033, OR 4.528) and low platelet count (<50,000/mm(3)) was the independent risk factor for late infection (P = 0.005, OR 4.24). Correct procedure and careful use decreases the incidence of early infection and leads to the prevention of re-implantation. Initial thrombocytopenia was attributable to bone marrow suppression caused by hematologic malignancies or severe infection. Thus, this condition is of value in predicting late infection.

Characteristics of long-term live-donor pediatric renal transplant survivors: a single-center experience.

PubMed

El-Husseini, Amr A; Foda, Mohamed A; Osman, Yasser M; Sobh, Mohamed A

2006-05-01

To study the characteristics and the predictors of survival observed in our pediatric live-donor renal transplant recipients with an allograft that functioned for more than 10 yr. One hundred fifteen children underwent renal transplantation between 1976 and 1995. Of these, 30 had functioning allografts for more than 10 yr (range, 11-18). The patients included 18 males and 12 females, with a mean age at transplantation of 13 yr (range, 5-18). Characteristics of the patients, data on graft survival, and determinants of outcome were obtained by reviewing all medical charts. At most recent follow-up (January 2005), the mean daily dose of azathioprine was 1.2 mg/kg (range, 1-2) and that of prednisone was 0.16 mg/kg (range, 0.1-0.2). Mean creatinine clearance was 72 mL/min per 1.73 m(2) (range, 45-112). Acute rejection occurred in 14 (47%) patients. Seven patients had one episode, five had two episodes, and two had three episodes of acute rejection. Three patients (10%) developed malignancy. A substantial proportion of patients (44%) were short, with a height standard deviation score (SDS) less than -1.88, which is below the third percentile for age and gender. One quarter of the patients, more commonly the females, were obese. Other complications included osteoporosis in 16 (53%) patients, avascular bone necrosis in four (13%), post-transplantation diabetes mellitus in three (10%), and hypertension in 18 (60%). Twelve (40%) patients were married and 27% had children post-transplantation. The independent determinants of long-term graft survival were acute rejection and post-transplant hypertension. Despite good renal function, long-term pediatric renal transplant survivors are at risk of significant morbidity. The determinants of long-term graft survival are acute rejection and post-transplant hypertension.

Case report of an 11-year-old child with a nonfunctional malignant pheochromocytoma.

PubMed

Holwitt, Dana; Neifeld, James; Massey, Gita; Lanning, David

2007-11-01

Pheochromocytoma is an unusual cause of surgical hypertension and is extremely rare in the pediatric population. We present a case of a hypertension-producing malignant pheochromocytoma in an 11-year-old, which was initially unresectable. The tumor responded partially to aggressive chemotherapy and was completely resected. This approach highlights the importance of multidisciplinary care for patients with large pheochromocytomas.

Italian Multicenter Study on Accuracy of 18F-FDG PET/CT in Assessing Bone Marrow Involvement in Pediatric Hodgkin Lymphoma.

PubMed

Cistaro, Angelina; Cassalia, Laura; Ferrara, Cinzia; Quartuccio, Natale; Evangelista, Laura; Bianchi, Maurizio; Fagioli, Franca; Bisi, Gianni; Baldari, Sergio; Zanella, Alessandro; Pillon, Marta; Zucchetta, Pietro; Burei, Marta; Sala, Alessandra; Guerra, Luca; Guglielmo, Priscilla; Burnelli, Roberta; Panareo, Stefano; Scalorbi, Federica; Rambaldi, Ilaria; Piccardo, Arnoldo; Garaventa, Alberto; Familiari, Demetrio; Fornito, Maria Concetta; Lopci, Egesta; Mascarin, Maurizio; Altini, Corinna; Ferrari, Cristina; Perillo, Teresa; Santoro, Nicola; Borsatti, Eugenio; Rubini, Giuseppe

2018-06-01

The present study investigated the utility of fluorine-18 ( 18 F) fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in newly diagnosed pediatric Hodgkin lymphoma (HL). A total of 224 pediatric patients with HL underwent 18 F-FDG PET/CT at staging. BMB or follow-up imaging was used as the standard of reference for the evaluation of BMI. 18 F-FDG PET/CT was negative for BMI in 193 cases. Of the 193 patients, the findings for 16 were originally reported as doubtful and later interpreted as negative for BMI, with negative findings on follow-up imaging and BMB. At BMB, 1 of the 16 patients (6.25%) had BMI. Of the 193 patients, 192 (99.48%) had negative BMB findings. Thus, the 18 F-FDG PET/CT findings were truly negative for 192 patients and falsely negative for 1 patient for BMI. 18 F-FDG PET/CT showed high diagnostic performance in the evaluation of BMI in pediatric HL. Thus, BMB should be ideally reserved for patients presenting with doubtful 18 F-FDG PET/CT findings for BMI. Copyright © 2018 Elsevier Inc. All rights reserved.

Is it safe to preserve the deltoid when resecting the proximal humerus for a primary malignant bone tumour? A comparative study.

PubMed

Cladière-Nassif, V; Bourdet, C; Audard, V; Babinet, A; Anract, P; Biau, D

2017-09-01

Resection of the proximal humerus for the primary malignant bone tumour sometimes requires en bloc resection of the deltoid. However, there is no information in the literature which helps a surgeon decide whether to preserve the deltoid or not. The aim of this study was to determine whether retaining the deltoid at the time of resection would increase the rate of local recurrence. We also sought to identify the variables that persuade expert surgeons to choose a deltoid sparing rather than deltoid resecting procedure. We reviewed 45 patients who had undergone resection of a primary malignant tumour of the proximal humerus. There were 29 in the deltoid sparing group and 16 in the deltoid resecting group. Imaging studies were reviewed to assess tumour extension and soft-tissue involvement. The presence of a fat rim separating the tumour from the deltoid on MRI was particularly noted. The cumulative probability of local recurrence was calculated in a competing risk scenario. There was no significant difference (adjusted p = 0.89) in the cumulative probability of local recurrence between the deltoid sparing (7%, 95% confidence interval (CI) 1 to 20) and the deltoid resecting group (26%, 95% CI 8 to 50). Patients were more likely to be selected for a deltoid sparing procedure if they presented with a small tumour (p = 0.0064) with less bone involvement (p = 0.032) and a continuous fat rim on MRI (p = 0.002) and if the axillary nerve could be identified (p = 0.037). A deltoid sparing procedure can provide good local control after resection of the proximal humerus for a primary malignant bone tumour. A smaller tumour, the presence of a continuous fat rim and the identification of the axillary nerve on pre-operative MRI will persuade surgeons to opt for a deltoid resecting procedure. Cite this article: Bone Joint J 2017;99-B:1244-9. ©2017 The British Editorial Society of Bone & Joint Surgery.

Indications of Carbon Ion Therapy at CNAO

NASA Astrophysics Data System (ADS)

Orecchia, Roberto; Rossi, Sandro; Fossati, Piero

2009-03-01

CNAO will be a dual center capable of providing therapeutic beams of protons and carbon ions with maximum energy of 400 MeV/u. At the beginning, it will be equipped with three treatment rooms with fixed horizontal and vertical beam lines. In a subsequent phase, two more rooms with a rotating gantry are foreseen. An active spot scanning dose delivery system will be employed. Initially, 80% of the treatments will be carried out with carbon ions. All patients will be treated within clinical trials to assess carbon ion indications with an evidence-based methodology. Seven disease-specific working groups have been developed: lung tumors, liver tumors, sarcomas, head and neck tumors, central nervous system lesions, eye tumors and pediatric tumors. The last two groups will be treated mainly with protons. In the first phase, CNAO will focus on head and neck cancers, treating inoperable, residual or recurrent malignant salivary gland tumors, mucosal melanoma, adenocarcinoma and unfavorably located SCC (nasal and paranasal sinuses). Carbon ions will be employed as a boost in the treatment of locally advanced, poor prognosis, SCC of the hypopharynx and tongue base. Bone and soft tissue sarcomas of the extremity will be treated with a limb-sparing approach, and trunk sarcomas will be treated with exclusive or post-operative irradiation. Skull base tumors (chordoma and chondrosarcoma), recurrent or malignant meningioma and glial tumors will be treated with carbon ions. After sufficient expertise has been gained in coping with organ motion, CNAO will start treating thoracic and abdominal targets. HCC will be treated in inoperable patients with one or more lesions that can be included in a single CTV. Early stage NSCLC will be treated. In the second phase, two more groups on gynecological malignancies and digestive tumors (esophageal cancer, rectal cancer, pancreatic cancer) will be created.

Extracorporeal irradiation for malignant bone tumors.

PubMed

Hong, A; Stevens, G; Stalley, P; Pendlebury, S; Ahern, V; Ralston, A; Estoesta, E; Barrett, I

2001-06-01

Extracorporeal irradiation (ECI) has been used selectively in the management of primary malignant bone tumors since 1996. We report our techniques for ECI and the short-term oncologic and orthopedic outcomes. Sixteen patients with primary malignant bone tumors were treated with ECI from 1996 to 2000. The median age was 14 years. The histologic diagnoses were Ewing's sarcoma (11), osteosarcoma (4) and chondrosarcoma (1). The treated sites were femur (7), tibia (4), humerus (2), ilium (2), and sacrum (1). Following induction chemotherapy in Ewing's sarcomas and osteosarcoma, en bloc resection of the tumor and tumor-bearing bone was performed. A single dose of 50 Gy was delivered to the bone extracorporeally using either a linear accelerator (9 cases) or a blood product irradiator (7 cases). The orthopedic outcome was recorded using a standard functional scale. At a median follow-up of 19.5 months, there were no cases of local recurrence or graft failure. One patient required amputation due to chronic osteomyelitis. For the 10 patients with follow-up greater than 18 months, the functional outcomes were graded good to excellent. The short-term oncologic and orthopedic results are encouraging and suggest that ECI provides a good alternative for reconstruction in limb conservative surgery in selected patients. This technique should only be used in a multidisciplinary setting, where careful follow-up is available to assess the long-term outcomes.

Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative.

PubMed

Pashankar, Farzana; Hale, Juliet P; Dang, Ha; Krailo, Mark; Brady, William E; Rodriguez-Galindo, Carlos; Nicholson, James C; Murray, Matthew J; Bilmire, Deborah F; Stoneham, Sara; Arul, G Suren; Olson, Thomas A; Stark, Daniel; Shaikh, Furqan; Amatruda, James F; Covens, Allan; Gershenson, David M; Frazier, A Lindsay

2016-01-15

There is a debate regarding the management of ovarian immature teratomas (ITs). In adult women, postoperative chemotherapy is standard except for stage I, grade 1 disease, whereas surgery alone is standard in pediatric patients. To determine the role of chemotherapy, a pooled analysis of pediatric and adult clinical trials was conducted. Data from 7 pediatric trials and 2 adult trials were merged in the Malignant Germ Cell International Collaborative data set. Four trials included patients with newly diagnosed pure ovarian ITs and were selected (Pediatric Oncology Group/Children's Cancer Group Intergroup Study (INT 0106), Second UKCCSG Germ Cell Tumor Study (GC2), Gynecologic Oncology Group (GOG 0078 and GOG 0090). Adult and pediatric trials were analyzed separately. The primary outcome measures were event-free survival (EFS) and overall survival (OS). One hundred seventy-nine patients were included (98 pediatric patients and 81 adult patients). Ninety pediatric patients were treated with surgery alone, whereas all adult patients received chemotherapy. The 5-year EFS and OS were 91% and 99%, respectively, for the pediatric cohort and 87% and 93%, respectively, for the adults. There were no relapses in grade 1 patients, regardless of the stage or age. Only 1 adult patient with a grade 2 IT relapsed. Among grade 3 patients, the 5-year EFS was 0.92 (0.72-0.98) for stage I/II and 0.52 (0.22-0.75) for stage III in the pediatric cohort (P = .005) and 0.91 (0.69-0.98) for stage I/II and 0.65 (0.39-0.83) for stage III/IV in the adult cohort (P = .01). Postoperative chemotherapy did not decrease relapses in the pediatric cohort. The grade was the most important risk factor for relapse in ovarian ITs. Among grade 3 patients, the stage was significantly associated with relapse. Adjuvant chemotherapy did not decrease relapses in the pediatric cohort; its role in adults remains unresolved. Cancer 2016;122:230-237. © 2015 American Cancer Society. © 2015 American Cancer Society.

Tumours of bones and joints

PubMed Central

Misdorp, W.; Van Der Heul, R. O.

1976-01-01

Tumours of bones and joints are not infrequent in dogs but are rare in other domestic animals. In the dog, most bone tumours are malignant; osteosarcomas are by far the most frequently encountered tumours, especially in giant breeds and boxers. The following main categories of bone tumour are described: bone-forming, cartilage-forming, giant cell, marrow, vascular, miscellaneous, metastatic, unclassified, and tumour-like lesions. The tumours of joints and related structures are classified as synovial sarcomas, fibroxanthomas, and malignant giant cell tumour of soft tissues. ImagesFig. 21Fig. 22Fig. 23Fig. 24Fig. 17Fig. 18Fig. 19Fig. 20Fig. 29Fig. 30Fig. 31Fig. 32Fig. 33Fig. 34Fig. 35Fig. 36Fig. 25Fig. 26Fig. 27Fig. 28Fig. 1Fig. 2Fig. 3Fig. 4Fig. 37Fig. 38Fig. 39Fig. 40Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086157

Cancer of the nasal cavity in the pediatric population.

PubMed

Benoit, Margo McKenna; Bhattacharyya, Neil; Faquin, William; Cunningham, Michael

2008-01-01

The purpose of this work was to investigate the clinical manifestations and diagnostic range of malignant entities presenting as a nasal mass in the pediatric population. A retrospective cohort analysis was conducted at a specialty hospital and a tertiary care university hospital. Patients aged between birth and 18 years and diagnosed with a malignancy that arose within the nasal cavity between the years 1991 and 2006 were included. This institution-specific patient group was compared with a similar cohort of patients extracted from the national Surveillance Epidemiology and End Results database. The main outcome measures were the incidence, presentation, and diagnoses of nasal cancer presenting in this population. Sixteen patients with nasal malignancies presented institutionally in the defined pediatric age group. Patient age at the time of diagnosis ranged from 7 months to 17 years, with a slight male predominance. The main presenting symptoms were unilateral nasal congestion and ophthalmologic complaints. The median time from presentation to diagnosis was 7 weeks; patients who presented with nonspecific complaints, such as nasal obstruction, headache, and fatigue, were given a diagnosis, on average, later than those who presented with focal manifestations. Nationwide, 47 patients were identified from the Surveillance Epidemiology and End Results database. In both subject groups, the most common diagnoses were rhabdomyosarcoma (37.5% institutionally and 23% in the Surveillance Epidemiology and End Results group) and esthesioneuroblastoma (25% institutionally and 28% Surveillance Epidemiology and End Results). In the Surveillance Epidemiology and End Results cohort, the overall mean survival rate was 188 months. Nasal cancer in the pediatric population often presents with nonspecific signs and symptoms, and a high index of suspicion is necessary for a timely diagnosis. Soft tissue sarcomas are expectedly common. The relative high frequency of esthesioneuroblastoma is particularly noteworthy.

Staphylococcus aureus infections in pediatric oncology patients: high rates of antimicrobial resistance, antiseptic tolerance and complications.

PubMed

McNeil, J Chase; Hulten, Kristina G; Kaplan, Sheldon L; Mahoney, Donald H; Mason, Edward O

2013-02-01

: Patients with malignancies represent a population at high risk for drug-resistant infections. We sought to determine the clinical spectrum and molecular epidemiology of Staphylococcus aureus infections in pediatric oncology patients followed at Texas Children's Hospital (Houston, TX). Furthermore, we determined the prevalence of the chlorhexidine resistance gene qacA/B from isolates in this unique population. : Patients with a history of malignancy and a culture-proven S. aureus infection were identified from 2001 to 2011. Antibiotic susceptibility, pulsed-field gel electrophoresis and detection of qacA/B by polymerase chain reaction were performed on all isolates. Medical records for all patients were reviewed. : During the study period, 213 isolates were identified from 179 patients with malignancies. Thirty-one percent of the isolates were methicillin-resistant S. aureus. The most common infectious diagnosis was bacteremia (85/213 [39.9%], with 72/85 [84.7%] being catheter-associated). Thirteen patients with bacteremia were found to have pulmonary nodules at the time of presentation; only S. aureus was found in tissue in 5 of the 6 patients who underwent lung biopsy. After 2007, 18.2% of isolates were qacA/B positive with a steady increase in prevalence every year (χ for trend P = 0.04). : S. aureus is a significant cause of morbidity and mortality in pediatric oncology patients at Texas Children's Hospital. In addition to the more well-known clinical manifestations, this pathogen can also be associated with pulmonary nodules. Furthermore, the prevalence of S. aureus isolates carrying antiseptic resistance genes increased in this population. Additional clinical and molecular studies and surveillance among pediatric oncology patients are warranted to further explore these findings.

Expandable endoprostheses in malignant bone tumors in children: indications and limitations.

PubMed

Baumgart, Rainer; Lenze, Ulrich

2009-01-01

Expandable endoprostheses can be an option after resection of malignant bone tumors of the lower extremity in children and adolescents not only to bridge the resultant surgical defect but also to correct a residual limb length discrepancy. Small intramedullary diameter and short residual bone segments, as well as stress-shielding, are intrinsic technical limitations of fully implantable reconstructive devices. As a consequence, until recently, repeated operative interventions to reconstruct the limb and compensate for subsequent absence of growth within the affected limb were required to compensate for continued growth of the contralateral limb. Innovative expandable endoprosthetic devices are now available to help achieve equal limb length at maturity. One common device is a conventional endoprosthesis that is lengthened using a telescopic module, whereas the "bioexpandable" system lengthens the remaining bone using a lengthening nail as a modular part of the endoprosthesis. Both systems are equipped with motor drives that electromagnetic waves activate transcutaneously. One advantage of the "bioexpandable" endoprosthesis is that with sequential lengthening, the proportion of residual bone shaft to prosthesis length increases, thereby diminishing host bone-endoprosthetic lever arm forces.

Consensus and controversy regarding osteoporosis in the pediatric population.

PubMed

Bachrach, Laura Keyes

2007-09-01

To review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence. The medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis. Childhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass-variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise-associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients. Bone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood.

Nuclear scanning in necrotizing progressive ''malignant'' external otitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parisier, S.C.; Lucente, F.E.; Som, P.M.

1982-09-01

The usefulness of radionuclear scanning in the treatment of 18 patients with necrotizing progressive ''malignant'' external otitis is discussed. A Tc 99-m bone scan, a valuable test since results are positive in early cases of osteomyelitis of the temporal bone and base of skull, showed increased uptake in all 18 patients. In 6 patients, Ga-67 citrate scans were obtained at the start of therapy and at 5-6 week intervals thereafter. The serial gallium scans were useful in evaluating the effectiveness of therapy since the uptake decrease with control of infection.

Bone marrow-derived CD13+ cells sustain tumor progression

PubMed Central

Dondossola, Eleonora; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2014-01-01

Non-malignant cells found within neoplastic lesions express alanyl (membrane) aminopeptidase (ANPEP, best known as CD13), and CD13-null mice exhibit limited tumor growth and angiogenesis. We have recently demonstrated that a subset of bone marrow-derived CD11b+CD13+ myeloid cells accumulate within neoplastic lesions in several murine models of transplantable cancer to promote angiogenesis. If these findings were confirmed in clinical settings, CD11b+CD13+ myeloid cells could become a non-malignant target for the development of novel anticancer regimens. PMID:25339996

Optimal Treatment of Malignant Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing

DTIC Science & Technology

2015-10-01

stiffness, or a partial snap with lower yield force and stiffness (Figure 4). Three dimensional micro CT analysis around fracture Figure 3. (a-b... fractures with plate fixation on both sides and irradiation on the left while the contralateral limb serves as a non-radiated internal control. The...AWARD NUMBER: W81XWH-13-1-0430 TITLE: Optimal Treatment of Malignant Long Bone Fracture : Influence of Method of Repair and External Beam

Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

ClinicalTrials.gov

2018-04-20

Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yingbin; School of Life Science, Southwest University, Chongqing 400715; Cai, Shaoxi, E-mail: sxcai@cqu.edu.cn

2010-12-10

Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA)more » selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.« less

Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

PubMed

Tucunduva, Luciana; Volt, Fernanda; Cunha, Renato; Locatelli, Franco; Zecca, Marco; Yesilipek, Akif; Caniglia, Maurizio; Güngör, Tayfun; Aksoylar, Serap; Fagioli, Franca; Bertrand, Yves; Addari, Maria Carmen; de la Fuente, Josu; Winiarski, Jacek; Biondi, Andrea; Sengeloev, Henrik; Badell, Isabel; Mellgren, Karin; de Heredia, Cristina Díaz; Sedlacek, Petr; Vora, Ajay; Rocha, Vanderson; Ruggeri, Annalisa; Gluckman, Eliane

2015-04-01

Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD. © 2014 John Wiley & Sons Ltd.

Differences in the Onset and Severity of Symptoms of Malignant Hyperthermia with Different Inhalational Anesthetics

DTIC Science & Technology

1999-10-01

patients had also received succinylcholine (Fu, Scharf, Mangar & Miller, 1996;Michalek- Sauberer , Fricker, Gradwohl, & Gilly, 1997). The case reported...In the case reported by Michaelek- Sauberer and colleagues (1997), a pediatric patient received desflurane. After 90 minutes of surgery, the...Malignant Hyperthermia 61 biopsy (Fu et al., 1996; Michalek- Sauberer et al., 1997). In both case reports, there was a wide

Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma.

PubMed

Liang, Chao; Li, Fangfei; Wang, Luyao; Zhang, Zong-Kang; Wang, Chao; He, Bing; Li, Jie; Chen, Zhihao; Shaikh, Atik Badshah; Liu, Jin; Wu, Xiaohao; Peng, Songlin; Dang, Lei; Guo, Baosheng; He, Xiaojuan; Au, D W T; Lu, Cheng; Zhu, Hailong; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge

2017-12-01

Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment. However, a major bottleneck to achieve the therapeutic potential of the CRISPR/Cas9 is the lack of in vivo tumor-targeted delivery systems. Here, we screened an OS cell-specific aptamer (LC09) and developed a LC09-functionalized PEG-PEI-Cholesterol (PPC) lipopolymer encapsulating CRISPR/Cas9 plasmids encoding VEGFA gRNA and Cas9. Our results demonstrated that LC09 facilitated selective distribution of CRISPR/Cas9 in both orthotopic OS and lung metastasis, leading to effective VEGFA genome editing in tumor, decreased VEGFA expression and secretion, inhibited orthotopic OS malignancy and lung metastasis, as well as reduced angiogenesis and bone lesion with no detectable toxicity. The delivery system simultaneously restrained autocrine and paracrine VEGFA signaling in tumor cells and could facilitate translating CRISPR-Cas9 into clinical cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

NCI, NHLBI/PBMTC First International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: The Need for Pediatric Specific Long Term Follow-up Guidelines

PubMed Central

Pulsipher, Michael A.; Skinner, Roderick; McDonald, George B.; Hingorani, Sangeeta; Armenian, Saro H.; Cooke, Kenneth R.; Gracia, Clarisa; Petryk, Anna; Bhatia, Smita; Bunin, Nancy; Nieder, Michael L.; Dvorak, Christopher C.; Sung, Lillian; Sanders, Jean E.; Kurtzberg, Joanne; Baker, K. Scott

2012-01-01

Existing standards for screening and management of late effects occurring in children who have undergone hematopoietic cell transplantation (HCT) include recommendations from pediatric cancer networks and consensus guidelines from adult-oriented transplantation societies applicable to all recipients of HCT. While these approaches have significant merit, they are not pediatric-HCT focused and they do not address post-HCT challenges faced by children with complex non-malignant disorders. In this article we discuss the strengths and weaknesses of current published recommendations and conclude that pediatric-specific guidelines for post-HCT screening and management would be beneficial to the long-term health of these patients and would promote late-effects research in this field. Our panel of late effects experts also provides recommendations for follow up and therapy of selected post-HCT organ and endocrine complications in pediatric patients. PMID:22248713

Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation

PubMed Central

Pereira, Renata C.; Valta, Helena; Tumber, Navdeep; Salusky, Isidro B.; Jalanko, Hannu

2015-01-01

Background Bone fragility is common post solid organ transplantation but little is known about bone pathology on a tissue level. Abnormal osteocytic protein expression has been linked to compromised bone health in chronic kidney disease (CKD) and immunosuppressant medications may impact osteocyte function. Methods Transiliac bone biopsies were obtained from 22 pediatric solid organ allograft recipients (average age 15.6 years) an average of 6.3 ± 1.2 years after transplantation and from 12 pediatric pre-dialysis CKD patients (average age 13.2 years). Histomorphometry and immunohistochemistry for FGF23, DMP1, sclerostin, and osteopontin were performed on all biopsies. Results FGF23 and sclerostin were increased in transplant recipients relative to non-transplant CKD, regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher GFR. Bone DMP1 expression was higher in liver or heart than in kidney recipients, concomitant with higher serum phosphate values. Osteopontin expression was higher in CKD than in transplant recipients (p<0.01). Bone FGF23 and sclerostin correlated directly (r = 0.38, p<0.05); bone FGF23 expression and osteoid thickness correlated inversely (r = - 0.46, p<0.01). Conclusions Solid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation. PMID:26390291

Altered Osteocyte-Specific Protein Expression in Bone after Childhood Solid Organ Transplantation.

PubMed

Pereira, Renata C; Valta, Helena; Tumber, Navdeep; Salusky, Isidro B; Jalanko, Hannu; Mäkitie, Outi; Wesseling Perry, Katherine

2015-01-01

Bone fragility is common post solid organ transplantation but little is known about bone pathology on a tissue level. Abnormal osteocytic protein expression has been linked to compromised bone health in chronic kidney disease (CKD) and immunosuppressant medications may impact osteocyte function. Transiliac bone biopsies were obtained from 22 pediatric solid organ allograft recipients (average age 15.6 years) an average of 6.3 ± 1.2 years after transplantation and from 12 pediatric pre-dialysis CKD patients (average age 13.2 years). Histomorphometry and immunohistochemistry for FGF23, DMP1, sclerostin, and osteopontin were performed on all biopsies. FGF23 and sclerostin were increased in transplant recipients relative to non-transplant CKD, regardless of the type of allograft received and despite, in the case of liver and heart recipients, a higher GFR. Bone DMP1 expression was higher in liver or heart than in kidney recipients, concomitant with higher serum phosphate values. Osteopontin expression was higher in CKD than in transplant recipients (p<0.01). Bone FGF23 and sclerostin correlated directly (r = 0.38, p<0.05); bone FGF23 expression and osteoid thickness correlated inversely (r = - 0.46, p<0.01). Solid-organ transplantation is associated with increased FGF23 and sclerostin expression. The contribution of these findings to compromised bone health post transplantation warrants further evaluation.

Development of Clostridium septicum gas gangrene as an adverse effect of clindamycin-induced Clostridium difficile infection in a pediatric patient.

PubMed

Kiser, Casey J; Urish, Kenneth L; Boateng, Henry A

2014-09-01

Clostridium myonecrosis or gas gangrene is a life-threatening infection characterized by either traumatic or atraumatic etiology. It has been widely described in patients with traumatic open wounds and in immunocompromised patients, including malignancy. A third source can result from natural flora in the gastrointestinal tract after bowel ischemia. This is a rare occurrence and is even less commonly described in the pediatric population. We present a pediatric patient who developed Clostridium septicum myonecrosis as an iatrogenic complication from clindamycin-induced Clostridium difficile ischemic colitis.

The bone mineral content alterations in pediatric patients medicated with levetiracetam, valproic acid, and carbamazepine.

PubMed

Serin, Hepsen Mine; Koç, Zehra Pınar; Temelli, Berfin; Esen, İhsan

2015-10-01

The negative effect of antiepileptic drugs on bone health has been previously documented. However, which antiepileptic drug is safer in regard to bone health is still questionable. Our aims were to investigate the bone mineral density alterations in pediatric patients who receive antiepileptic medication for a minimum of two years and to compare the results of these drugs. Fifty-nine patients (32 males, 27 females; mean age: 8.6±4.6years) and a control group (13 males, 7 females; mean age: 7.6±3.3years) were included in the study. The patients were receiving necessarily the same antiepileptic drugs (AEDs) for at least two years, and none of the patients had mental retardation or cerebral palsy. The patients were divided into three groups: group 1 (patients receiving levetiracetam (LEV), n=20), group 2 (patients receiving carbamazepine (CBZ), n=11), and group 3 (patients receiving valproic acid (VPA), n=28). Plasma calcium (Ca), phosphorus (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), vitamin D levels, and bone mineral density (BMD) values of femur and vertebras (L1-4) and z-scores (comparative results of BMD values of the patients with the age- and gender-matched controls in device database) of the groups were compared. The differences between P, PTH, ALP and age, Ca and BMD results, and vitamin D levels of the patients in all four groups was not statistically significant according to Kruskal-Wallis test (p>0.05). The z-score levels of all the patient and control groups were also not statistically significantly different compared with each other. In contrast to previous reports in pediatric patients, our study has documented that there is not a considerable bone loss in patients receiving long-term AED medication. Although levetiracetam has been proposed as bone-protecting medication, we did not observe any difference between AEDs regarding bone mineral density after two years of treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhanced anti-tumor activity and safety profile of targeted nano-scaled HPMA copolymer-alendronate-TNP-470 conjugate in the treatment of bone malignances

PubMed Central

Segal, Ehud; Pan, Huaizhong; Benayoun, Liat; Kopečková, Pavla; Shaked, Yuval; Kopeček, Jindčrich; Satchi-Fainaro, Ronit

2015-01-01

Bone neoplasms, such as osteosarcoma, exhibit a propensity for systemic metastases resulting in adverse clinical outcome. Traditional treatment consisting of aggressive chemotherapy combined with surgical resection, has been the mainstay of these malignances. Therefore, bone-targeted non-toxic therapies are required. We previously conjugated the aminobisphosphonate alendronate (ALN), and the potent anti-angiogenic agent TNP-470 with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer. HPMA copolymer-ALN-TNP-470 conjugate exhibited improved anti-angiogenic and anti-tumor activity compared with the combination of free ALN and TNP-470 when evaluated in a xenogeneic model of human osteosarcoma. The immune system has major effect on toxicology studies and on tumor progression. Therefore, in this manuscript we examined the safety and efficacy profiles of the conjugate using murine osteosarcoma syngeneic model. Toxicity and efficacy evaluation revealed superior anti-tumor activity and decreased organ-related toxicities of the conjugate compared with the combination of free ALN plus TNP-470. Finally, comparative anti-angiogenic activity and specificity studies, using surrogate biomarkers of circulating endothelial cells (CEC), highlighted the advantage of the conjugate over the free agents. The therapeutic platform described here may have clinical translational relevance for the treatment of bone-related angiogenesis-dependent malignances. PMID:21429572

Hot topics in parenteral nutrition. A review of the use of glutamine supplementation in the nutritional support of patients undergoing bone-marrow transplantation and traditional cancer therapy.

PubMed

Crowther, Mark

2009-08-01

The relationship between glutamine and malignancy can be traced back to the 1950s and the requirement for glutamine for malignant-cell growth in culture. Later studies demonstrated an association between the rate of proliferation of the malignant cells and glutamine usage. The excessive use of glutamine by malignant cells was seen as an opportunity for the development of a treatment using glutamine analogues, but unfortunately excessive toxicity was observed during clinical studies. In animal models glutamine supplementation, initially thought to increase tumour growth, actually causes tumour regression as a result of improved immune clearance of the tumour and appears to reduce the severity of the side effects of chemo- and radiotherapy. This finding led to human studies in both traditional cancer therapy and bone-marrow transplantation, which are reviewed here. Unfortunately, the majority of the studies performed are small and have poor methodological reporting. There is clinical heterogeneity in terms of routes of administration, dosing schedules, chemotherapy regimens and diseases. Studies of glutamine in non-bone-marrow transplantation chemo- and/or radiotherapy treatment suggest a possible trend towards reductions in objective mucositis but no effect on subjective symptoms. There is no evidence for its effect on other clinical outcomes. For bone-marrow transplantation there appears to be some benefit from oral glutamine in reducing mucositis and graft v. host disease, while intravenous glutamine may reduce infections but at the expense of an increased relapse rate. Good-quality studies are required in this area.

Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; ALK Fusion Protein Expression; ALK Gene Mutation; ALK Gene Translocation; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Histiocytosis; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Refractory Central Nervous System Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; ROS1 Fusion Positive; ROS1 Gene Mutation; ROS1 Gene Translocation

LIN28 expression in malignant germ cell tumors down-regulates let-7 and increases oncogene levels

PubMed Central

Murray, Matthew J.; Saini, Harpreet K.; Siegler, Charlotte A.; Hanning, Jennifer E.; Barker, Emily M.; van Dongen, Stijn; Ward, Dawn M.; Raby, Katie L.; Groves, Ian J.; Scarpini, Cinzia G.; Pett, Mark R.; Thornton, Claire M.; Enright, Anton J.; Nicholson, James C.; Coleman, Nicholas

2013-01-01

Despite their clinico-pathologic heterogeneity, malignant germ-cell-tumors (GCTs) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of down-regulation of the let-7 family of tumor-suppressor microRNAs in malignant-GCTs. Microarray results from pediatric and adult samples (n=45) showed that LIN28, the negative-regulator of let-7 biogenesis, was abundant in malignant-GCTs, regardless of patient age, tumor site or histologic subtype. Indeed, a strong negative-correlation existed between LIN28 and let-7 levels in specimens with matched datasets. Low let-7 levels were biologically significant, since the sequence complementary to the 2-7nt common let-7 seed ‘GAGGUA’ was enriched in the 3′untranslated regions of mRNAs up-regulated in pediatric and adult malignant-GCTs, compared with normal gonads (a mixture of germ cells and somatic cells). We identified 27 mRNA targets of let-7 that were up-regulated in malignant-GCT cells, confirming significant negative-correlations with let-7 levels. Among 16 mRNAs examined in a largely independent set of specimens by qRT-PCR, we defined negative-associations with let-7e levels for six oncogenes, including MYCN, AURKB, CCNF, RRM2, MKI67 and C12orf5 (when including normal control tissues). Importantly, LIN28 depletion in malignant-GCT cells restored let-7 levels and repressed all of these oncogenic let-7 mRNA targets, with LIN28 levels correlating with cell proliferation and MYCN levels. Conversely, ectopic expression of let-7e was sufficient to reduce proliferation and down-regulate MYCN, AURKB and LIN28, the latter via a double-negative feedback loop. We concluded that the LIN28/let-7 pathway has a critical pathobiological role in malignant-GCTs and therefore offers a promising target for therapeutic intervention. PMID:23774216

Biomedical technology transfer. Applications of NASA science and technology

NASA Technical Reports Server (NTRS)

Harrison, D. C.

1980-01-01

Ongoing projects described address: (1) intracranial pressure monitoring; (2) versatile portable speech prosthesis; (3) cardiovascular magnetic measurements; (4) improved EMG biotelemetry for pediatrics; (5) ultrasonic kidney stone disintegration; (6) pediatric roentgen densitometry; (7) X-ray spatial frequency multiplexing; (8) mechanical impedance determination of bone strength; (9) visual-to-tactile mobility aid for the blind; (10) Purkinje image eyetracker and stabilized photocoalqulator; (11) neurological applications of NASA-SRI eyetracker; (12) ICU synthesized speech alarm; (13) NANOPHOR: microelectrophoresis instrument; (14) WRISTCOM: tactile communication system for the deaf-blind; (15) medical applications of NASA liquid-circulating garments; and (16) hip prosthesis with biotelemetry. Potential transfer projects include a person-portable versatile speech prosthesis, a critical care transport sytem, a clinical information system for cardiology, a programmable biofeedback orthosis for scoliosis a pediatric long-bone reconstruction, and spinal immobilization apparatus.

Trauma to the Pediatric Temporomandibular Joint.

PubMed

Bae, Sam S; Aronovich, Sharon

2018-02-01

Management of pediatric condylar fractures presents a unique challenge because the developing mandible provides limited available bone for fixation and primary teeth preclude the use of typical closed reduction techniques. The available literature is reviewed with regard to closed and open treatment approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Classification, imaging, biopsy and staging of osteosarcoma

PubMed Central

Kundu, Zile Singh

2014-01-01

Osteosarcoma is the most common primary osseous malignancy excluding malignant neoplasms of marrow origin (myeloma, lymphoma and leukemia) and accounts for approximately 20% of bone cancers. It predominantly affects patients younger than 20 years and mainly occurs in the long bones of the extremities, the most common being the metaphyseal area around the knee. These are classified as primary (central or surface) and secondary osteosarcomas arising in preexisting conditions. The conventional plain radiograph is the best for probable diagnosis as it describes features like sun burst appearance, Codman's triangle, new bone formation in soft tissues along with permeative pattern of destruction of the bone and other characteristics for specific subtypes of osteosarcomas. X-ray chest can detect metastasis in the lungs, but computerized tomography (CT) scan of the thorax is more helpful. Magnetic resonance imaging (MRI) of the lesion delineates its extent into the soft tissues, the medullary canal, the joint, skip lesions and the proximity of the tumor to the neurovascular structures. Tc99 bone scan detects the osseous metastases. Positron Emission Tomography (PET) is used for metastatic workup and/or local recurrence after resection. The role of biochemical markers like alkaline phosphatase and lactate dehydrogenase is pertinent for prognosis and treatment response. The biopsy confirms the diagnosis and reveals the grade of the tumor. Enneking system for staging malignant musculoskeletal tumors and American Joint Committee on Cancer (AJCC) staging systems are most commonly used for extremity sarcomas. PMID:24932027

Sclerostin Antibody Improves Skeletal Parameters in a Brtl/+ Mouse Model of Osteogenesis Imperfecta†

PubMed Central

Sinder, Benjamin P.; Eddy, Mary M.; Ominsky, Michael S; Caird, Michelle S.; Marini, Joan C.; Kozloff, Kenneth M.

2012-01-01

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although anti-resorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials showed improved vertebral parameters but equivocal effects on long-bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly->Cys substitution in col1a1. Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in Brtl/+ and WT mice, leading to improved bone mass and reduced long-bone fragility. Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. PMID:22836659

International longitudinal pediatric reference standards for bone mineral content.

PubMed

Baxter-Jones, Adam D G; Burrows, Melonie; Bachrach, Laura K; Lloyd, Tom; Petit, Moira; Macdonald, Heather; Mirwald, Robert L; Bailey, Don; McKay, Heather

2010-01-01

To render a diagnosis pediatricians rely upon reference standards for bone mineral density or bone mineral content, which are based on cross-sectional data from a relatively small sample of children. These standards are unable to adequately represent growth in a diverse pediatric population. Thus, the goal of this study was to develop sex and site-specific standards for BMC using longitudinal data collected from four international sites in Canada and the United States. Data from four studies were combined; Saskatchewan Paediatric Bone Mineral Accrual Study (n=251), UBC Healthy Bones Study (n=382); Penn State Young Women's Health Study (n=112) and Stanford's Bone Mineral Accretion study (n=423). Males and females (8 to 25 years) were measured for whole body (WB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) BMC (g). Data were analyzed using random effects models. Bland-Altman was used to investigate agreement between predicted and actual data. Age, height, weight and ethnicity independently predicted BMC accrual across sites (P<0.05). Compared to White males, Asian males had 31.8 (6.8) g less WB BMC accrual; Hispanic 75.4 (28.2) g less BMC accrual; Blacks 82.8 (26.3) g more BMC accrual with confounders of age, height and weight controlled. We report similar findings for the PF and FN. Models for females for all sites were similar with age, height and weight as independent significant predictors of BMC accrual (P<0.05). We provide a tool to calculate a child's BMC Z-score, accounting for age, size, sex and ethnicity. In conclusion, when interpreting BMC in pediatrics we recommend standards that are sex, age, size and ethnic specific. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Automatic segmentation of bones from digital hand radiographs

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Taira, Ricky K.; Shim, Hyeonjoon; Keaton, Patricia

1995-05-01

The purpose of this paper is to develop a robust and accurate method that automatically segments phalangeal and epiphyseal bones from digital pediatric hand radiographs exhibiting various stages of growth. The algorithm uses an object-oriented approach comprising several stages beginning with the most general objects to be segmented, such as the outline of the hand from background, and proceeding in a succession of stages to the most specific object, such as a specific phalangeal bone from a digit of the hand. Each stage carries custom operators unique to the needs of that specific stage which will aid in more accurate results. The method is further aided by a knowledge base where all model contours and other information such as age, race, and sex, are stored. Shape models, 1-D wrist profiles, as well as an interpretation tree are used to map model and data contour segments. Shape analysis is performed using an arc-length orientation transform. The method is tested on close to 340 phalangeal and epiphyseal objects to be segmented from 17 cases of pediatric hand images obtained from our clinical PACS. Patient age ranges from 2 - 16 years. A pediatric radiologist preliminarily assessed the results of the object contours and were found to be accurate to within 95% for cases with non-fused bones and to within 85% for cases with fused bones. With accurate and robust results, the method can be applied toward areas such as the determination of bone age, the development of a normal hand atlas, and the characterization of many congenital and acquired growth diseases. Furthermore, this method's architecture can be applied to other image segmentation problems.

Cost effective use of audiograms after pediatric temporal bone fractures.

PubMed

Frisenda, Julia L; Schroeder, James W; Ryan, Maura E; Valika, Taher S; Billings, Kathleen R

2015-11-01

To identify the relationship of pediatric temporal fractures to the incidence and type of hearing loss present. To analyze the timing and utility of audiometric testing in children with temporal bone fractures. Retrospective case series of 50 pediatric patients with temporal bone fractures who were treated at an urban, tertiary care children's hospital from 2008 to 2014. A statistical analysis of predictors of hearing loss after temporal bone fracture was performed. Fifty-three fractures (69.7%) in 50 patients involved the petrous portion of the temporal bone. The mean age of patients was 7.13 years, and 39 (73.6%) were male. A fall was the most common mechanism of injury in 28 (52.8%) patients, followed by crush injury (n=14, 26.2%), and vehicular trauma (n=10, 18.9%). All otic capsule violating fractures were associated with a sensorineural hearing loss (n=4, 7.5%, p=0.002). Three of four otic capsule sparing fractures were associated with ossicular dislocation, with a corresponding mixed or conductive hearing loss on follow up audiometric testing. The majority of otic capsule sparing fracture patients (n=19/43, 44.2%) who had follow up audiograms had normal hearing, and those with otic capsule violating fractures were statistically more likely to have persistent hearing loss than those with otic capsule sparing fractures (p=0.01). Patients with otic capsule violating fractures or those with ossicular disruption are at higher risk for persistent hearing loss. Cost-saving may be accrued by selecting only those patients at high risk for persistent hearing loss for audiometric testing after temporal bone fractures. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Transformation in pretreatment manifestations of Gaucher disease type 1 during two decades of alglucerase/imiglucerase enzyme replacement therapy in the International Collaborative Gaucher Group (ICGG) Gaucher Registry

PubMed Central

Batista, Julie L.; Andersson, Hans C.; Balwani, Manisha; Burrow, Thomas Andrew; Charrow, Joel; Kaplan, Paige; Khan, Aneal; Kishnani, Priya S.; Kolodny, Edwin H.; Rosenbloom, Barry; Scott, C. Ronald; Weinreb, Neal

2017-01-01

Abstract This study tests the hypothesis that the prevalence of severe clinical manifestations in Gaucher disease type 1 (GD1) patients at the time of treatment initiation has changed since alglucerase/imiglucerase enzyme replacement therapy (ERT) was approved in the United States (US) in 1991. US alglucerase/imiglucerase‐treated GD1 patients from the International Collaborative Gaucher Group Gaucher Registry clinicaltrials.gov NCT00358943 were stratified by age at ERT initiation (<18, 18 to <50, ≥50 years), era of ERT initiation (1991‐1995, 1996‐2000, 2001‐2005, 2006‐2009), and splenectomy status pre‐ERT. Prevalence of splenectomy decreased dramatically across the eras among all age groups. Bone manifestations were more prevalent in splenectomized patients than non‐splenectomized patients in all age groups. Prevalence of bone manifestations differed across eras in certain age groups: non‐splenectomized patients had a lower prevalence of ischemic bone events (pediatric patients) and bone crisis (pediatric patients and adults 18 to <50 years) in later eras; splenectomized adult (18 to <50 years) patients had a lower prevalence of ischemic bone events and bone crisis in later eras. Over two decades after the introduction of ERT, the prevalence of splenectomy and associated skeletal complications has declined dramatically. Concomitantly, the interval between diagnosis and initiation of ERT has decreased, most strikingly in pediatric patients who have the most severe disease. Together, these findings suggest that since the introduction of alglucerase/imiglucerase ERT, optimal standard of care has become established in the US to prevent destructive complications of GD1. PMID:28569047

Hemangioma of the rib showing a relatively high 18F-FDG uptake: a case report with a literature review

PubMed Central

Emori, Makoto; Terashima, Yoshinori; Hasegawa, Tadashi; Shimizu, Junya; Nagoya, Satoshi; Yamashita, Toshihiko

2017-01-01

Hemangioma of the rib is a rare benign tumor that is often difficult to distinguish from malignant bone tumors. Rib hemangioma often shows bony disruption with a slight cortical disruption, extraosseous lesion, and expanded bone on computed tomography (CT). We report the case of a 68-year-old man with atypical rib hemangioma with a slight cortical disruption and no expanded bone. The tumor showed relatively high 18FDG-uptake on positron emission tomography (PET)/CT. Rib hemangioma often shows higher 18FDG-uptake. PET/CT may not provide useful information for distinguishing rib hemangioma from a malignant tumor. Close observation without surgical resection may be feasible if the tumor is diagnosed as a rib hemangioma by biopsy. PMID:28959457

Pancreatic islet autotransplantation for nonmalignant and malignant indications.

PubMed

Tanhehco, Yvette C; Weisberg, Stuart; Schwartz, Joseph

2016-03-01

The standard therapy for patients with chronic pancreatitis (CP) and severe abdominal pain is total pancreatectomy (TP) followed by islet autotransplantation (IAT) to prevent the development of brittle diabetes. In adult patients, narcotic independence is achieved in up to 73% of patients 1 to 5 years after transplantation whereas insulin independence is achieved in up to 40% of patients 1 to 2 years after transplantation. Pediatric patients have shown similar outcomes for narcotic independence (up to 79%) but better outcomes for insulin independence (up to 56% 1 year after transplantation). The quality of life of both adult and pediatric patients improved significantly after TP-IAT using the Medical Outcomes Study SF-36 survey. IAT after pancreatectomy is also performed for patients with benign and malignant disease of the pancreas. The limited studies in this patient population suggest that IAT may be potentially beneficial for carefully selected patients when sufficient numbers of islet cells can be isolated. Further studies involving a larger number of patients are needed to determine the risks and benefits of IAT in patients with malignancy. The feasibility of IAT depends on the availability of a laboratory that can isolate the pancreatic islet cells. An on-site laboratory is the traditional model; however, remote processing of pancreatic islets has been reported to result in successful outcomes. This review discusses the outcomes of adult and pediatric autologous pancreatic islet cell transplantation for CP and pancreatic tumors as well as laboratory processing of pancreatic islet cells. © 2015 AABB.

Radionuclide evaluation of free vascularized bone graft viability. [/sup 99m/Tc-methylene diphosphonate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lisbona, R.; Rennie, W.R.J.; Daniel, R.K.

1980-02-01

Free vascularized bone grafting is a new technique applied to the reconstructive surgery of long bones affected by aggressive benign or malignant processes, as well as traumatic deficiencies. These bone lesions may be treated by en bloc excision and replacement with fibular segments or osteocutaneous flaps from the groin isolated on their vascular pedicle. Microvascular anastomosis of the pedicle at the recipient site is necessary. Radionuclide bone imaging is unique in the assessment of the free vascularized bone graft because postoperative graft uptake of radiopharmaceutical reflects patent anastomoses and segmental bone viability.

Differences in the Onset and Severity of Symptoms of Malignant Hyperthermia With Different Inhalational Anesthetics

DTIC Science & Technology

1999-10-01

also received succinylcholine (Fu, Scharf, Mangar & Miller, 1996;Michalek- Sauberer , Fricker, Gradwohl, & Gilly, 1997). The case reported by Fu and...the case reported by Michaelek- Sauberer and colleagues (1997), a pediatric patient received desflurane. After 90 minutes of surgery, the patient s...Malignant Hyperthermia 61 biopsy (Fu et al., 1996; Michalek- Sauberer et al., 1997). In both case reports, there was a wide variability of

Somatic and Germline TP53 Alterations in Second Malignant Neoplasms from Pediatric Cancer Survivors.

PubMed

Sherborne, Amy L; Lavergne, Vincent; Yu, Katharine; Lee, Leah; Davidson, Philip R; Mazor, Tali; Smirnoff, Ivan V; Horvai, Andrew E; Loh, Mignon; DuBois, Steven G; Goldsby, Robert E; Neglia, Joseph P; Hammond, Sue; Robison, Leslie L; Wustrack, Rosanna; Costello, Joseph F; Nakamura, Alice O; Shannon, Kevin M; Bhatia, Smita; Nakamura, Jean L

2017-04-01

Purpose: Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants, we analyzed germline and SMN samples from pediatric cancer survivors. Experimental Design: We performed whole-exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in 37 pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without any history of a familial cancer predisposition syndrome but known to have developed SMNs. Results: WES revealed TP53 mutations involving p53's DNA-binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53- mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53- coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in 6 patients and a synonymous SNP A639G in 4 others, resulting in 10 of 37 evaluable patients (27%) harboring a germline TP53 variant. Conclusions: Currently, germline TP53 is not routinely assessed in patients with pediatric cancer. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive posttreatment monitoring. Clin Cancer Res; 23(7); 1852-61. ©2016 AACR . ©2016 American Association for Cancer Research.

Somatic and germline TP53 alterations in second malignant neoplasms from pediatric cancer survivors

PubMed Central

Sherborne, Amy L.; Lavergne, Vincent; Yu, Katharine; Lee, Leah; Davidson, Philip R.; Mazor, Tali; Smirnoff, Ivan; Horvai, Andrew; Loh, Mignon; DuBois, Steven G.; Goldsby, Robert E.; Neglia, Joseph; Hammond, Sue; Robison, Leslie L.; Wustrack, Rosanna; Costello, Joseph; Nakamura, Alice O.; Shannon, Kevin; Bhatia, Smita; Nakamura, Jean L.

2016-01-01

Purpose Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants we analyzed germline and SMN samples from pediatric cancer survivors. Experimental Design We performed whole exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in thirty-seven pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without history of a familial cancer predisposition syndrome but known to have developed SMNs. Results WES revealed TP53 mutations involving p53’s DNA binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53 mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53 coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in six patients and a synonymous single nucleotide polymorphism A639G in four others, resulting in ten out of 37 evaluable patients (27%) harboring a germline TP53 variant. Conclusions Currently, germline TP53 is not routinely assessed in pediatric cancer patients. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive post-treatment monitoring. PMID:27683180

Diagnosis of malignant change in Paget's disease by Tl-201.

PubMed

Colarinha, P; Fonseca, A T; Salgado, L; Vieira, M R

1996-04-01

Scintigraphy using Tc-99m MDP and Tl-201 was performed in a patient with polyostotic Paget's disease and sarcomatous degeneration in the right iliac bone. Tc-99m MDP imaging showed abnormal uptake in both types of lesions. Tl-201 imaging showed increased uptake in the sarcomatous lesion and absent uptake in pagetic lesions. This result supports the idea that Tl-201 scintigraphy may have a potential role to play in the differentiation of Paget's disease from malignancy. To the authors' knowledge, Tl-201 has never been reported for the detection of sarcomatous change of pagetic bone.

Dangerous blind tracheal intubation attempt due to fiberscope non-availability in a pediatric patient with retropharyngeal abscess caused by a large fish bone.

PubMed

Li, Bi-Lian; Xu, Ying-Yi; Jiang, Yan-Fang; Liu, Wen-Xing; Kuang, Xiao-Hua; Ni, Jin

2015-01-01

In China, foods containing bones are sometimes fed to young infants. Occasionally, this practice results in bone aspiration and retropharyngeal abscess, a potentially life-threatening infection in the deep space of the neck that can compromise the airway. The main concern in managing patients with retropharyngeal abscess is airway management. In China, not all hospitals and operating rooms are equipped with fiberscopes, particularly pediatric-size fiberscopes. Emergency airway management can be dangerous when a fiberscope is unavailable. We present the case of a 21-month-old baby girl with a retropharyngeal abscess secondary to fish bone ingestion. During an attempted blind tracheal intubation due to fiberscope non-availability, the abscess ruptured, and the pus released from it obstructed the airway. The patient was successfully treated despite the inadequate resources and dangerous complication. We recommend a detailed preoperative airway assessment and preparation for fiberscopic tracheal intubation in such patients to prevent this dangerous complication.

Malignant transformation of a unicameral bone cyst in a cat.

PubMed

Berger, Björn; Brühschwein, Andreas; Eddicks, Lina; Meyer-Lindenberg, Andrea

2016-04-01

A unicameral bone cyst in the proximal humerus of a 3-year-old Norwegian forest cat was diagnosed by dynamic contrast-enhanced magnetic resonance imaging, surgical exploration, and histopathology. Surgical curettage and incorporation of bone cement led to full recovery. An osteosarcoma developed at the surgical site 17 months later. Thoracic radiographs showed pulmonary lesions consistent with metastasis.

Malignant transformation of a unicameral bone cyst in a cat

PubMed Central

Berger, Björn; Brühschwein, Andreas; Eddicks, Lina; Meyer-Lindenberg, Andrea

2016-01-01

A unicameral bone cyst in the proximal humerus of a 3-year-old Norwegian forest cat was diagnosed by dynamic contrast-enhanced magnetic resonance imaging, surgical exploration, and histopathology. Surgical curettage and incorporation of bone cement led to full recovery. An osteosarcoma developed at the surgical site 17 months later. Thoracic radiographs showed pulmonary lesions consistent with metastasis. PMID:27041754

A rare case of primary bone lymphoma mimicking a pelvic abscess

PubMed Central

Al Wattar, BH; Mohanty, K

2011-01-01

Primary bone lymphoma (PBL) is a rare, malignant, neoplastic disorder of the skeleton that accounts for less than 5% of all primary bone tumours. We present an extremely rare case of PBL mimicking a pelvic abscess around the sacroiliac joint, which has never been reported in the medical literature, and discuss learning points highlighted from this case. PMID:22004625

European Union pediatric legislation jeopardizes worldwide, timely future advances in the care of children with cancer.

PubMed

Rose, Klaus

2014-02-01

Diagnosis of childhood cancer is no longer an automatic death sentence, but it has not lost all of its horror. Drugs, surgery, radiation, and clinical trials have advanced our capacity to handle these cancers, but pediatric cancers still face challenges. Pediatric pharmaceutical legislation was introduced in the United States in 1997 and has triggered many clinical trials that have helped us better understand what drugs do to a child's body and vice versa. Following the US precedence, the European Union introduced its own legislation. The US legislation was designed to generate additional pediatric data and balances between mandatory requirements and voluntary incentives. The US legislation was designed to mandate full registration of all new drugs for children whenever there is any potential pediatric use. The purpose of this article is to discuss unintended negative consequences of the legislation of the European Medicines Agency (EMA). We analyzed the effects of the EU pediatric legislation with respect to the history of the emergence of modern drugs, pediatric clinical pharmacology, and the development of drugs for pediatric malignancies. No new drug can be registered in the European Union without a detailed pediatric investigation plan (PIP) approved by the EMA's Pediatric Committee (PDCO). This has moved the discussion of the pediatric aspects of drug development to an earlier stage and has increased public awareness. It also has brought industry and pediatric oncologists closer together. However, in a review of >100 PDCO PIP decisions in childhood cancer, we found a lack of balance between the legitimate desire to include children in drug development and the common sense needed in the complex worlds of drug development and pediatric oncology. Many decisions appeared to have been based on both exaggerated assumptions about the frequency of childhood malignancies and the feasibility of the clinical trials proposed. Pharmaceutical companies are being forced into long-term commitments to clinical trials before efficacy in adults has been demonstrated. Pediatric clinical oncology trials are being driven by regulatory "tunnel vision" and not by therapeutic benevolence, epidemiologic data, or feasibility. As a result, children with cancer are being monopolized for PDCO-triggered, often unfeasible trials that are not always in their best interests and seldom produce useful therapies. Because clinical trials are global, this affects children with cancer worldwide. Until now, carefully worded concerns about these negative consequences have been published in specialty journals. It is time to start a broader debate on how to move forward. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Radiation therapy in the neonate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Littman, P.; D'Angio, G.J.

Radiation therapy (RT) is frequently used in the management of children with cancer, but neonatal neoplasms are rare. Newborns represent 1.5% of the children with malignant diseases in the Tumor Registry at the Children's Hospital of Philadelphia over the last 30 years. Thus, occasionally the pediatrics radiation therapist must consider treating the very young infant. The specific radiation effects on growth and development must be weighed in reaching a therapeutic decision. All children are vulnerable to the late effects of radiation therapy, but the neonates may be more susceptible because of the immaturity of important organs such as the brain,more » lung, liver, kidney, and bone. In general, radiation therapy, should be avoided during the first several weeks of life because of the potential increased sensitivity of the liver and kidneys during that period. If radiation therapy is used at all during infancy, the benefits must be weighed against the possibility of significant late effects. Increasing knowledge of pediatric neoplasms has shown that some tumors (such as mesoblastic nephroma) require no treatment except for surgical excision; and other tumors, such as Stage IV-S neuroblastoma, may require very little treatment. In those tumors that require radiation therapy, the use of chemotherapy may allow reduction of the radiation dose. Furthermore, alterations of time-dose-fractionation schemes and careful attention to tumor volume with the use of special techniques, such as ''shrinking fields,'' may decrease the late adverse effects of treatment.« less

Factors that increase diagnostic yield of surgical lung biopsy in pediatric oncology patients.

PubMed

Acker, Shannon N; Gonzales, Danielle; Ross, James T; Dishop, Megan K; Deterding, Robin R; Partrick, David A

2015-09-01

Recent data demonstrate that surgical lung biopsy in immunocompromised children, including oncology patients, alters therapy in only 50% of cases. We hypothesized that there are factors identifiable preoperatively which can predict the patients who will or will not benefit from surgical biopsy. We reviewed the medical records of all children with malignancy who underwent surgical lung biopsy between 2004 and 2013 at a single institution, excluding those children who had previously undergone a solid organ or bone marrow transplant. Eighty lung wedge biopsies were performed (median age 13 years, IQR 5.25-16; 63% male, n=50) 53 (66%) of which led to a change in patient management. The majority of biopsies were performed to diagnose a new mass or differentiate infection from metastases (mass group) (n=68, 85%), and 12 biopsies (15%) were performed to diagnose a known infection for antibiotic guidance (infection group). Children in the infection group were more likely to be febrile preoperatively, were more likely to be an inpatient preoperatively, and had a lower absolute neutrophil count at the time of biopsy. Patients in the infection group had higher postoperative mortality rates and higher rates of major complications. In pediatric oncology patients, surgical lung biopsy has a lower diagnostic yield and higher complication rate when performed for antibiotic guidance. Prior to proceeding with biopsy in this high-risk patient population, surgeons and oncologists should carefully weigh the potential risks and benefits. Copyright © 2015 Elsevier Inc. All rights reserved.

Another duel in the sun: weighing the balances between sun protection, tanning beds, and malignant melanoma.

PubMed

Roberts, Daniel J; Hornung, Carlton A; Polk, Hiram C

2009-07-01

The purpose of this report is to put the dueling factors of risk and prevention for melanoma in perspective for the thoughtful pediatric specialist to facilitate preteen preventive health counseling. We examined the rate of malignant melanoma among Kentucky residents and compared this rate with indicators of tanning bed prevalence in a large metropolitan area and sunscreen sales from a major distributor. We obtained malignant melanoma annual incidence data from the Kentucky Cancer Registry, which recorded Kentucky population incidence rates over the years 1995 to 2004. The rates reflected 2 malignant melanoma classifications: pre-invasive cancer only, or both invasive and noninvasive cancers combined. The age-adjusted incidence rate per hundred thousand for combined invasive and pre-invasive malignant melanoma swelled from 21.9 in 1995 to 31.3 in 2004. The respective invasive-only malignant melanoma incidence rates increased less dramatically, from 17.3 to 20.7, during this same 10-year time period. Since 1983, the number of separate tanning bed businesses increased from 1 in 1983 to 119 by the mid-1990s, and then declined to about 74 separate businesses by 2003. Sunscreen sales data is uneven between states and is currently inconclusive. Although current data cannot draw a precise link between melanoma and the use of tanning beds, the associated risk is implicit, as the ultraviolet A (UVA) and ultraviolet B (UVB) radiation in tanning bed usage is a well-established melanoma risk factor. In advising patients, the pediatric specialist should consider that melanoma rates are poised as a balance of some known risk factors and a few potential preventive factors.

Evaluation of intraperitoneal vincristine in malignant peritoneal effusion.

PubMed

Bairy, K L; Sanath, S; Jagetia, G C; Somayaji, S N; Vidyasagar, M S; Baliga, M S

2003-07-01

The efficacy and safety of intraperitoneal administration of vincristine sulphate was determined in mice bearing Ehrlich ascitic carcinoma. The tumor bearing animals were administered with 0.5 mg/kg body weight (b.wt) of freshly prepared vincristine sulphate intraperitoneally on day 6 after tumor transplantation followed by drug administration once daily 5 days a week consecutively. The observations regarding the survival, alteration in the volume of peritoneal fluid, increase in life span and pathological changes in the liver, kidney, gastrointestinal tract and bone tissues were made. The vincristine sulphate treatment reduced the malignant cell population significantly and there were no significant changes in the histological picture of liver, kidney, bone, except the intestine, where atropy of villi demonstrating nests and cords of uniform small round cells were observed. Our experimental data suggests that intraperitoneal administration of vincristine is beneficial in malignant peritoneal effusion.

A novel NF1 mutation in a Chinese patient with giant café-au-lait macule in neurofibromatosis type 1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

PubMed

Tong, H-X; Li, M; Zhang, Y; Zhu, J; Lu, W-Q

2012-08-29

Neurofibromatosis type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder that is characterized by multiple café-au-lait, skinfold freckling, Lisch nodules, and neurofibromas. Mutations in the NF1 gene, which encodes the neurofibromin protein, have been identified as the pathogenic gene of NF1. In this study, we present a clinical and molecular study of a Chinese patient with giant café-au-lait in NF1. The patient showed >6 café-au-lait spots on the body, axillary freckling, and multiple subcutaneous neurofibromas. He also had a malignant peripheral nerve sheath tumor and bone abnormalities. The germline mutational analysis of the NF1 gene revealed a novel missense mutation in exon 13. It is a novel heterozygous nucleotide G>A transition at position 2241 of the NF1 gene. We found no mutation in malignant peripheral nerve sheath tumor DNA from this patient. This expands the database for NF1 gene mutations in NF1. Its absence in the normal chromosomes suggests that it is responsible for the NF1 phenotype. To our knowledge, this is the first case of giant café-au-lait macule in NF1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

Bone marrow in pediatric patients with Hodgkin's disease.

PubMed

Khan, Fauzia Shafi; Hasan, Rabiya Fayyaz

2012-01-01

Hodgkin's disease is a malignant process of lymphoreticular system that constitutes 6% of childhood cancers Accurate staging of lymphoma is the basis for rational therapeutic planning and assessment of the presence or absence of marrow involvement is a basic part of the staging evaluation. The objective of this study was to determine the incidence of marrow infiltration in paediatric patients with Hodgkin's disease and to ascertain its morphological spectrum in the marrow. The study included 85 paediatric patients with diagnosed Hodgkin's disease seen at The Children's Hospital/Institute of Child Health, Lahore, from January 2010 to December 2011, referred to haematology department for bone marrow biopsies. Ages ranged between two years to fourteen years with an average age of seven years, the male female ratio being 13:1. Mixed cellularity was the commonest histological type present in 66 (78%) cases. The presenting feature common in all cases was superficial lymphadenopathy followed by hepatomegaly in 17 (20%) cases and splenomegaly in 16 (19%). All the marrow aspirates were negative for infiltration. Trephine biopsies revealed marrow infiltration in 9 (10.5%). Five (56%) cases had bilateral while 4 (44%) had unilateral involvement. Pattern of infiltration was diffuse in 8 (89%) and focal in one (11%) trephines. Increased marrow fibrosis was present in eight (89%) cases. Diagnostic Reed Sternberg cells were identified in only one case and the mononuclear variants were present in six cases and atypical cells were present in two cases in these immunohistochemistry for CD15 and CD30 was performed which was positive. Granulomas in one and lymphoid aggregates were present in two trephine biopsies otherwise negative for Hodgkin's infiltration. Bone marrow infiltration was present in 10.5% cases, immunohistochemistry was used to confirm infiltration in two cases, the pattern of infiltration being diffuse in majority (89%).

Surgical success of boomerang-shaped chondroperichondrial graft in pediatric chronic otitis media cases.

PubMed

Dundar, Riza; Kulduk, Erkan; Soy, Fatih Kemal; Aslan, Mehmet; Yukkaldiran, Ahmet; Guler, Osman Kadir; Ozbay, Can

2015-06-01

To reveal the success of boomerang-shaped chondroperichondrial graft (BSCPG) in pediatric chronic otitis media cases. A total of 43 pediatric patients (age 7-16 years) who had undergone type 1 tympanoplasty with the diagnosis of chronic otitis media between March 2010 and March 2013 were included in this retrospective study. The main outcome measures were the graft success rate and level of hearing improvement. Graft intake success rate was 90.7%. Mean preoperative and postoperative air-bone gap values were 20.51 ± 4.34 dB SPL and 9.32 ± 5.64 dB SPL, respectively (p < 0.001). Mean preoperative and postoperative pure tone average values were 28.6 ± 3.52 and 12.24 ± 5.22 respectively (p < 0.001). Air-bone gap was improved to ≤ 10 dB in 38 (88.37%) patients during the postoperative period. Boomerang-shaped chondroperichondrial grafting technique seems to be a successful alternative in the management of pediatric chronic otitis media cases. It has relatively higher grade graft success rate. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A fatal case of bone marrow embolism of unknown cause masquerading clinically as dengue shock syndrome.

PubMed

Selvi, Subramanian Kalaivani; Kar, Rakhee; Vadivelan, Mehalingam; Subrahmanyam, Dharanipragada Krishna Suri

2012-01-01

Bone marrow fat embolism usually occurs following multiple bone fractures, intraosseous surgical procedures, following vigorous cardiac resuscitation, ecclampsia, sickle cell anemia, malignancies, etc. We present a case of 70-year-old male who presented with fever, cough with expectoration, respiratory distress, altered sensorium, hypotension and thrombocytopenia, and diagnosed to have dengue shock syndrome and expired within 1 day of admission. Postmortem lung biopsy revealed bone marrow fat embolism.

Esthetic and functional reconstruction after parotidectomy in pediatric patients - A case series.

PubMed

Bryant, Lucas M; Cognetti, David; Baker, Adam; Roy, Sudeep; Johnston, Douglas R; Curry, Joseph; Krein, Howard

2015-12-01

Parotidectomy is a mainstay of treatment for benign and malignant parotid lesions in children and adults. Depending on surgical methods used and tumor size, parotidectomy may result in significant facial disfigurement as well as functional challenges. We describe a series of four pediatric patients, ages 13-16 who presented to our clinic with a parotid mass. All patients underwent parotidectomy with immediate reconstruction by local tissue rearrangement or free fat graft. Esthetic and functional reconstruction after parotidectomy is not well described in pediatric otolaryngology literature. A review of current literature and description of reconstructive methods is included. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Diagnosis of malignant hypertension with ocular examination: a child case.

PubMed

Yıldırım, Adnan; Mehmet Türkcü, Fatih; Yüksel, Harun; Sahin, Alparslan; Cınar, Yasin; Caça, Ihsan

2014-01-01

A 12-year-old female patient was admitted to our clinic complaining about low vision. Bilateral optic disc edema, macular star, and preretinal hemorrhages were found in fundoscopic examination. In fundus fluorescein angiography, massive leakage in the late phase was seen in the optic nerve head and macular area. These findings were compatible with high-grade hypertensive retinopathy. The patient consulted with pediatrics and a diagnosis of vesicourethral reflux and malignant hypertension was made.

[Periosteal reactions in bone tumors (author's transl)].

PubMed

Heuck, F

1979-08-01

Morphology of solid, lamellar and spicular periosteal reactions of benign and malignant primary and metastatic bone tumors in x-ray-pictures with regard to common and specific characteristics of different bone tumors is presented. The specific behaviour of the periosteum itself and of the subperiosteal region as an expression of the reactive biodynamics in skeletal neoplasia is demonstrated; and the diagnostic value of the radiograph is explained. The possibilities but also the limitations of sophisticated radiologic image analysis in establishing a differential diagnosis and a diagnosis of bone tumors and other bone lesions are discussed.

Targeting interleukin-11 receptor in leukemia and lymphoma: A functional ligand-directed study and hematopathology analysis of patient-derived specimens

PubMed Central

Karjalainen, Katja; Jaalouk, Diana E.; Bueso-Ramos, Carlos; Bover, Laura; Sun, Yan; Kuniyasu, Akihiko; Driessen, Wouter H. P.; Cardó-Vila, Marina; Rietz, Cecilia; Zurita, Amado J.; O’Brien, Susan; Kantarjian, Hagop M.; Cortes, Jorge E.; Calin, George A.; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2015-01-01

Purpose The interleukin-11 receptor (IL-11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here we evaluated the IL-11R as a candidate therapeutic target in human leukemia and lymphoma. Experimental Design and Results First, we show that the IL-11R protein is expressed in a variety of human leukemia- and lymphoma derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, while expression is absent from non-malignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11) specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL-11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analog with an apparent improved anti-leukemia cell profile. Conclusion These results indicate (i) that the IL-11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases. PMID:25779950

From notochord formation to hereditary chordoma: the many roles of Brachyury.

PubMed

Nibu, Yutaka; José-Edwards, Diana S; Di Gregorio, Anna

2013-01-01

Chordoma is a rare, but often malignant, bone cancer that preferentially affects the axial skeleton and the skull base. These tumors are both sporadic and hereditary and appear to occur more frequently after the fourth decade of life; however, modern technologies have increased the detection of pediatric chordomas. Chordomas originate from remnants of the notochord, the main embryonic axial structure that precedes the backbone, and share with notochord cells both histological features and the expression of characteristic genes. One such gene is Brachyury, which encodes for a sequence-specific transcription factor. Known for decades as a main regulator of notochord formation, Brachyury has recently gained interest as a biomarker and causative agent of chordoma, and therefore as a promising therapeutic target. Here, we review the main characteristics of chordoma, the molecular markers, and the clinical approaches currently available for the early detection and possible treatment of this cancer. In particular, we report on the current knowledge of the role of Brachyury and of its possible mechanisms of action in both notochord formation and chordoma etiogenesis.

Embryonal rhabdomyosarcoma in the maxillary sinus with orbital involvement in a pediatric patient: Case report

PubMed Central

de Melo, Ana Carolina Rodrigues; Lyra, Tácio Candeia; Ribeiro, Isabella Lima Arrais; da Paz, Alexandre Rolim; Bonan, Paulo Rogério Ferreti; de Castro, Ricardo Dias; Valença, Ana Maria Gondim

2017-01-01

This report presents a case of embryonal rhabdomyosarcoma (eRMS) located in the left maxillary sinus and invading the orbital cavity in a ten-year-old male patient who was treated at a referral hospital. The images provided from the computed tomography showed a heterogeneous mass with soft-tissue density, occupying part of the left half of the face inside the maxillary sinus, and infiltrating and destroying the bone structure of the maxillary sinus, left orbit, ethmoidal cells, nasal cavity, and sphenoid sinus. An analysis of the histological sections revealed an undifferentiated malignant neoplasm infiltrating the skeletal muscle tissue. The immunohistochemical analysis was positive for the antigens: MyoD1, myogenin, desmin, and Ki67 (100% positivity in neoplastic cells), allowing the identification of the tumour as an eRMS. The treatment protocol included initial chemotherapy followed by radiotherapy and finally surgery. The total time of the treatment was nine months, and in 18-mo of follow-up period did not show no local recurrences and a lack of visual impairment. PMID:29291204

Magnetic resonance imaging and computerized tomography in malignant external otitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gherini, S.G.; Brackmann, D.E.; Bradley, W.G.

1986-05-01

In malignant external otitis (MEO), determining the anatomic extent of disease and evaluating the physiologic response to therapy remain a problem. Magnetic resonance imaging (MRI) has recently become available in limited clinical settings. Four patients with MEO were evaluated using MRI, computerized tomography (CT), technetium-99 (Tc-99) bone scanning, and gallium-67 citrate (Ga-67 citrate) scanning. MRI is superior to CT, Tc-99 bone scanning, and Ga-67 citrate scanning in evaluating the anatomic extent of soft tissue changes in MEO. MRI alone cannot be relied upon to determine the physiologic response to therapy. MRI can, however, serve as a valuable guide to themore » interpretation of Tc-99 bone and Ga-67 citrate scans, and in this respect, MRI is extremely useful in the treatment of MEO.« less

Antifungal susceptibility and pathogenic potential of environmental isolated filamentous fungi compared with colonizing agents in immunocompromised patients.

PubMed

Teixeira, A B A; Silva, M; Lyra, L; Luz, E A; Uno, J; Takada, H; Miyaji, M; Nishimura, K; Schreiber, A Z

2005-09-01

Infection is a major cause of morbidity and mortality in bone marrow transplant recipients and in patients with hematological malignancies. The source of infection is almost always endogenous flora or the hospital environment. The present study evaluated bone marrow transplant recipients and patients with hematological malignancies colonized and/or infected with filamentous fungi. During 1 year, environmental air samples were also taken from the bone marrow transplant unit by a modification of gravity air-setting plate (GASP) methodology. Fusarium spp. were the most prevalent genus in the fall and Cladosporium spp. in the winter. Clinically isolated strains grew better at 37 degrees C than environmental strains. According to NCCLS M-38P methods, environmental Aspergillus strains showed higher MICs to miconazol and itraconazol, and clinical Fusarium strains were less susceptible to fluconazole.

The efficacy of routine use of recombinant human bone morphogenetic protein-2 in occipitocervical and atlantoaxial fusions of the pediatric spine: a minimum of 12 months' follow-up with computed tomography.

PubMed

Sayama, Christina; Hadley, Caroline; Monaco, Gina N; Sen, Anish; Brayton, Alison; Briceño, Valentina; Tran, Brandon H; Ryan, Sheila L; Luerssen, Thomas G; Fulkerson, Daniel; Jea, Andrew

2015-07-01

OBJECT The purpose of this study focusing on fusion rate was to determine the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) use in posterior instrumented fusions of the craniocervical junction in the pediatric population. The authors previously reported the short-term (mean follow-up 11 months) safety and efficacy of rhBMP-2 use in the pediatric age group. The present study reports on their long-term results (minimum of 12 months' follow-up) and focuses on efficacy. METHODS The authors performed a retrospective review of 83 consecutive pediatric patients who had undergone posterior occipitocervical or atlantoaxial spine fusion at Texas Children's Hospital or Riley Children's Hospital during the period from October 2007 to October 2012. Forty-nine patients were excluded from further analysis because of death, loss to follow-up, or lack of CT evaluation of fusion at 12 or more months after surgery. Fusion was determined by postoperative CT scan at a minimum of 12 months after surgery. The fusion was graded and classified by a board-certified fellowship-trained pediatric neuroradiologist. Other factors, such as patient age, diagnosis, number of vertebral levels fused, use of allograft or autograft, dosage of bone morphogenetic protein (BMP), and use of postoperative orthosis, were recorded. RESULTS Thirty-four patients had a CT scan at least 12 months after surgery. The average age of the patients at surgery was 8 years, 1 month (range 10 months-17 years). The mean follow-up was 27.7 months (range 12-81 months). There were 37 fusion procedures in 34 patients. Solid fusion (CT Grade 4 or 4-) was achieved in 89.2% of attempts (33 of 37), while incomplete fusion or failure of fusion was seen in 10.8%. Based on logistic regression analysis, there was no significant association between solid fusion and age, sex, BMP dose, type of graft material, use of postoperative orthosis, or number of levels fused. Three of 34 patients (8.8%) required revision surgery. CONCLUSIONS Despite the large number of adult studies reporting positive effects of BMP on bone fusion, our long-term outcomes using rhBMP-2 in the pediatric population suggest that rates of fusion failure are higher than observed in contemporary adult and pediatric reports of occipitocervical and atlantoaxial spine fusions.

Roles of Vitamins D and K, Nutrition, and Lifestyle in Low-Energy Bone Fractures in Children and Young Adults.

PubMed

Karpiński, Michał; Popko, Janusz; Maresz, Katarzyna; Badmaev, Vladimir; Stohs, Sidney J

2017-07-01

The research on skeletal system health in children and young adults, while recognizing the important role of calcium and vitamin D, goes beyond these nutritional standards. This review focuses on the role of vitamin K in combination with vitamin D and other factors in bone health. The current understanding is that maintaining bone health and prevention of low-energy fractures in any pediatric population includes nutritional factors combined with an active lifestyle. Calcium, vitamin D, and vitamin K supplementation contribute independently and collectively to bone health. The beneficial role of vitamin K, particularly vitamin K2 as menaquinone-7 (MK-7), in bone and cardiovascular health is reasonably well supported scientifically, with several preclinical, epidemiological, and clinical studies published over the last decade. Osteocalcin and matrix-Gla (glutamate-containing) protein (MGP) exemplify vitamin K-dependent proteins involved in building bone matrix and keeping calcium from accumulating in the arterial walls, respectively. An important part of the mechanism of vitamin K involves carboxylation and posttranslational activation of the family of vitamin K-dependent proteins, which prevent expression of pro-inflammatory factors and support improvement in bone mineral concentration, bone mineral density, and the quality of bone matrix. Understanding the combined approach to a healthy skeletal system in children and young adults, including the roles of vitamins D and K, calcium, healthy diet, and exercise, is particularly important in view of reports of subclinical insufficiency of vitamins D and K in otherwise healthy pediatric populations with low-energy bone fractures.

Evaluation of the Reliability and Validity of the Crawford Classification of Congenital Tibial Dysplasia

DTIC Science & Technology

2007-12-01

Month 1): a. Train a research coordinator to identify potential radiographs at pediatric orthopedic hospital. b. Have conference call with...JR. Delayed autogenous bone graft in the treatment of congenital pseudarthrosis. J Bone Joint Surg Am 1949;31:23. 8. Rudicel S. The orthopaedic

77 FR 41792 - Prospective Grant of Co-Exclusive License: The Development of Human Anti-CD22 Monoclonal...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-16

... hematological malignancies such as hairy cell leukemia, chronic lymphocytic leukemia and pediatric acute lymphoblastic leukemia, and autoimmune disease such as lupus and Sjogren's syndrome. The specific antibodies...

77 FR 9678 - Prospective Grant of Exclusive License: The Development of Human Anti-CD22 Monoclonal Antibodies...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

... hematological malignancies such as hairy cell leukemia, chronic lymphocytic leukemia and pediatric acute lymphoblastic leukemia, and autoimmune disease such as lupus and Sjogren's syndrome. The specific antibodies...

Medulloblastoma | Office of Cancer Genomics

Cancer.gov

The Medulloblastoma Project was developed to apply newly emerging genomic methods towards the discovery of novel genetic alterations in medulloblastoma (MB). MB is the most common malignant brain tumor in children, accounting for approximately 20% of all pediatric brain tumors.

Surveillance of bloodstream infections in pediatric cancer centers – what have we learned and how do we move on?

PubMed Central

Simon, Arne; Furtwängler, Rhoikos; Graf, Norbert; Laws, Hans Jürgen; Voigt, Sebastian; Piening, Brar; Geffers, Christine; Agyeman, Philipp; Ammann, Roland A.

2016-01-01

Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI). Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients’ safety during intensive treatment. The great majority of all pediatric cancer patients (about 85%) have a long-term central venous access catheter in use (type Broviac or Port; CVAD). Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD-associated BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined. PMID:27274442

Surveillance of bloodstream infections in pediatric cancer centers - what have we learned and how do we move on?

PubMed

Simon, Arne; Furtwängler, Rhoikos; Graf, Norbert; Laws, Hans Jürgen; Voigt, Sebastian; Piening, Brar; Geffers, Christine; Agyeman, Philipp; Ammann, Roland A

2016-01-01

Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI). Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients' safety during intensive treatment. The great majority of all pediatric cancer patients (about 85%) have a long-term central venous access catheter in use (type Broviac or Port; CVAD). Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD-associated BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined.

Risk for Health Care-Associated Bloodstream Infections in Pediatric Oncology Patients With Various Malignancies.

PubMed

Thurman, Cara B; Abbott, Maura; Liu, Jinfang; Larson, Elaine

This was a retrospective cohort study to identify the rates, predictors, and outcomes of health care-associated bloodstream infections (HA-BSI) among children with solid tumors, lymphoma, lymphoid leukemia, and myeloid leukemia. The study population included 4500 children ≤18 years old at a pediatric hospital in New York City from 2006 to 2014. A total of 147 HA-BSI cases were identified; using multivariable logistic regression modeling, children with a hematologic diagnosis (lymphoma, lymphoid leukemia, myeloid leukemia) were at greater risk for HA-BSI than those with a solid tumor diagnosis (all P values <.0001). The odds of mortality for patients with HA-BSI were 6.98 (95% confidence interval 3.02-16.10) times that of those without HA-BSI. Although malignancy type was identified as risk factor for HA-BSI, there was no significant difference in overall mortality from HA-BSI by tumor type ( P = .51).

Hydroxyapatite ceramic implants for cranioplasty in children: a single-center experience.

PubMed

Zaccaria, Laura; Tharakan, Sasha Job; Altermatt, Stefan

2017-02-01

The use of hydroxyapatite ceramic (HAC) implants for the treatment of skull defects in pediatric patients started 2010 at our institution. Ceramic implants facilitate osteoblast migration and therefore optimize osteointegration with the host bone. The purpose of this study is to report a single-center experience with this treatment modality. A retrospective review of all patients from July 2010 through June 2014 undergoing a cranioplasty using hydroxyapatite ceramic implant and managed at a single institution was performed. Indication for cranioplasty, the hospital course, and follow-up were reviewed. Bone density was measured in Hounsfield Units (HU) and osteointegration was calculated using Mimics Software® (Mimics Innovation Suite v17.0 Medical, Materialize, Leuven, Belgium). Over the 4-year period, six patients met criteria for the study. Five patients had an osteointegration of nearly 100%. One patient had an incomplete osteointegration with a total bone-implant contact area of 69%. The mean bone density was 2800 HU (2300-3000 HU). Bone density alone is estimated to have a Hounsfield value between 400 and 2000 HU depending on the body region and bone quality. There were no major complications, and the patients were highly satisfied with the esthetical result. Hydroxyapatite ceramic implants for cranioplasty in pediatric patients are a good choice for different indications. The implants show excellent osteointegration and esthetical results.

Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Deleterious ATM Gene Mutation; Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Deleterious RAD51C Gene Mutation; Deleterious RAD51D Gene Mutation; Histiocytosis; Low Grade Glioma; Malignant Glioma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Wilms Tumor

Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; FGFR1 Gene Mutation; FGFR2 Gene Mutation; FGFR3 Gene Mutation; FGFR4 Gene Mutation; Histiocytosis; Low Grade Glioma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Wilms Tumor

Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.

PubMed

Fontebasso, Adam M; Jabado, Nada

2015-01-01

Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.

Trauma of facial skeleton in children: An indian perspective.

PubMed

Karim, Tanweer; Khan, Arshad Hafeez; Ahmed, Syed Saeed

2010-06-01

Both children and adults are subject to similar types of injuries but fractures of facial bones in children are relatively uncommon. The aim of this study was to evaluate the epidemiology of facial bone fractures among children of <12 years, their management and outcome in an Indian city. This retrospective study included children of <12 years of age with facial bone fractures admitted over a span of 3 years. In order to compare our results we reviewed the existing literature related to pediatric facial bone fractures. A total of 45 children were admitted for facial bone fractures. Forty (89%) of them were above 5 years of age and male to female ratio was 2:1. About 53.33% of these injuries were because of fall from height. Mandible fracture was the most common facial bone fracture among admitted patients. Symphysis and para-symphysis was the commonest site of mandibular fractures, seen in 49% cases. Majority of these fractures were managed by Inter-maxillary fixation and inter-osseous wiring. Mini-plates were used for widely displaced compound fractures. For un-displaced fractures observation alone was sufficient. Mandible is the commonest facial bone fracture in children, more often caused by accidental fall from height. The high osteogenic potential of pediatric mandible allows non-surgical management to be successful in an increased proportion of younger patients.

Pediatric hematology in Poland: past and present.

PubMed

Boguslawska-Jaworska, J

1994-01-01

Pediatric hematology/oncology gradually developed in Poland in the beginning of the 20th century. The first pediatric hematology books written by M. Erlich were published in 1918 and 1924. In 1939, Jan Raszek-Rosenbusch was the first to use the intramedullary route of injection of living bone marrow cells in children suffering from lymphatic leukemia. The national cooperative chemotherapy group in Poland was formed in 1974. The studies carried out by the group in children with leukemia and lymphoma are documented by publications in international journals.

Aneurysmal bone cyst of the scapula. A case report.

PubMed

Megas, Panagiotis; Papathanassiou, Zafiria G; Kasimatis, George; Papachristou, Dionysios J

2009-10-01

Aneurysmal bone cyst (ABC) is an uncommon, benign but locally destructive bone lesion of unknown origin. Differential diagnosis can be challenging as it shares common radiological and pathological features with other benign and malignant bone lesions. The degree of diagnostic difficulty grows even more when an unusual location has to be taken into account. We report a rare and challenging case of a large primary ABC located at the scapula of a young male, who was surgically treated with subtotal removal of the scapula.

Activation of the germ-cell potential of human bone marrow-derived cells by a chemical carcinogen

PubMed Central

Liu, Chunfang; Ma, Zhan; Xu, Songtao; Hou, Jun; Hu, Yao; Yu, Yinglu; Liu, Ruilai; Chen, Zhihong; Lu, Yuan

2014-01-01

Embryonic/germ cell traits are common in malignant tumors and are thought to be involved in malignant tumor behaviors. The reasons why tumors show strong embryonic/germline traits (displaced germ cells or gametogenic programming reactivation) are controversial. Here, we show that a chemical carcinogen, 3-methyl-cholanthrene (3-MCA), can trigger the germ-cell potential of human bone marrow-derived cells (hBMDCs). 3-MCA promoted the generation of germ cell-like cells from induced hBMDCs that had undergone malignant transformation, whereas similar results were not observed in the parallel hBMDC culture at the same time point. The malignant transformed hBMDCs spontaneously and more efficiently generated into germ cell-like cells even at the single-cell level. The germ cell-like cells from induced hBMDCs were similar to natural germ cells in many aspects, including morphology, gene expression, proliferation, migration, further development, and teratocarcinoma formation. Therefore, our results demonstrate that a chemical carcinogen can reactivate the germline phenotypes of human somatic tissue-derived cells, which might provide a novel idea to tumor biology and therapy. PMID:24998261

Magnetic resonance imaging of the nose and paranasal sinuses.

PubMed Central

Lloyd, G A

1989-01-01

Seventy-five patients with a wide range of sinus disease have been investigated by magnetic resonance (MR): these included congenital conditions, allergic and inflammatory sinus disease, fungus infections, and the necrotizing granulomata. In addition, a variety of benign and malignant tumours have been examined, and in the more recent sinus malignancies the paramagnetic contrast agent, Gadolinium (Gd) DTPA (Schering Health Care) has been used. This experience of magnetic resonance scanning has shown that it is superior to computed tomography in demonstrating the extent of malignant disease in the nose and sinuses; most especially when Gd DTPA is used, reaching an accuracy of over 96% by biopsy correlation. An additional advantage of this technique is the wide coverage of the head and neck for the assessment of malignant disease, provided by direct 3 plane imaging and the multislice facility. The main disadvantage of magnetic resonance of the sinuses is the poor demonstration of calcification and bone. For this reason the MR scans may need to be augmented by high resolution CT performed specifically to show bone detail. Images Figure 2. Figure 3. PMID:2926770

Self healing hemophilic pseudotumor of the mandible in a 5-year-old boy, an interesting and rare finding: Case report and review.

PubMed

Prasad, Ruchika Keshaw; Siva, B; Rajpal, Jaisika; Singh, Ankur

2016-01-01

Hemophilic pseudotumor (PT) is a very rare complication of hemophilia consisting of a chronic, encapsulated, hemorrhagic fluid collection occurring both in the soft tissues and/or bone. Radiological features of osseous hemophilic PT are nonspecific and mimic several other benign or malignant bone tumors or infectious processes. Although the diagnosis is usually made on the location of the lesion and by the knowledge of the underlying disease, the radiologist should be aware of the imaging characteristics, in order to avoid misinterpretation as a malignant tumor, as biopsy of these lesions is contraindicated.

Correlation of Acute and Late Brainstem Toxicities With Dose-Volume Data for Pediatric Patients With Posterior Fossa Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanda, Ronica H., E-mail: rhazari@emory.edu; Ganju, Rohit G.; Schreibmann, Edward

Purpose: Radiation-induced brainstem toxicity after treatment of pediatric posterior fossa malignancies is incompletely understood, especially in the era of intensity modulated radiation therapy (IMRT). The rates of, and predictive factors for, brainstem toxicity after photon RT for posterior fossa tumors were examined. Methods and Materials: After institutional review board approval, 60 pediatric patients treated at our institution for nonmetastatic infratentorial ependymoma and medulloblastoma with IMRT were included in the present analysis. Dosimetric variables, including the mean and maximum dose to the brainstem, the dose to 10% to 90% of the brainstem (in 10% increments), and the volume of the brainstemmore » receiving 40, 45, 50, and 55 Gy were recorded for each patient. Acute (onset within 3 months) and late (>3 months of RT completion) RT-induced brainstem toxicities with clinical and radiographic correlates were scored using Common Terminology Criteria for Adverse Events, version 4.0. Results: Patients aged 1.4 to 21.8 years underwent IMRT or volumetric arc therapy postoperatively to the posterior fossa or tumor bed. At a median clinical follow-up period of 2.8 years, 14 patients had developed symptomatic brainstem toxicity (crude incidence 23.3%). No correlation was found between the dosimetric variables examined and brainstem toxicity. Vascular injury or ischemia showed a strong trend toward predicting brainstem toxicity (P=.054). Patients with grade 3 to 5 brainstem toxicity had undergone treatment to significant volumes of the posterior fossa. Conclusion: The results of the present series demonstrate a low, but not negligible, risk of brainstem radiation necrosis for pediatric patients with posterior fossa malignancies treated with IMRT. No specific dose-volume correlations were identified; however, modern treatment volumes might help limit the incidence of severe toxicity. Additional work investigating inherent biologic sensitivity might also provide further insight into this clinical problem.« less

A case of McCune-Albright syndrome associated with pituitary GH adenoma: therapeutic process and autopsy.

PubMed

Liu, Fuyi; Li, Wenting; Yao, Yong; Li, Guilin; Yang, Yi; Dou, Wanchen; Zhong, Dingrong; Wang, Lin; Zhu, Xiangdong; Hu, Hua; Zhang, Jianmin; Wang, Renzhi; Chen, Gao

2011-01-01

McCune-Albright syndrome (MAS) is a clinical syndrome with low incidence, and its concurrence with pituitary GH adenoma is rare. Little of the history, treatment and outcome has been studied. Follow-up of a 37-year-old male patient of MAS associated with pituitary GH adenoma was performed continuously recording the disease development and the treatment process until death, after which an autopsy was performed. Radiation therapy (RT) efficaciously controlled GH hypersecretion, however, it may have been the cause of the malignant transformation of the dysplastic bone tissue, which eventually caused brain hernia and death; autopsy demonstrated that the cranium had significant thickening (as much as 10 cm), the pathological diagnosis was fibrous dysplasia of bone associated with chondrosarcoma; and undifferentiated chondrosarcoma with malignant fibrous histocytoma subtype in the sellar region; nodular goiter with the thyroid gland, one nodus was pathologically demonstrated as papillary carcinoma. GH adenoma, present in a patient with MAS, might be cured by RT; but the risk of malignant transformation of the dysplastic bone tissue in the field of irradiation make it controversial. Lessons from the case reported here told us that we should take great caution when recommending RT for patients like this.

Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma; Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma; Malignant Glioma; NTRK1 Fusion Positive; NTRK2 Fusion Positive; NTRK3 Fusion Positive; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Solid Neoplasm; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Refractory Central Nervous System Neoplasm; Refractory Childhood Malignant Germ Cell Tumor; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; Wilms Tumor

PI3K/mTOR Inhibitor LY3023414 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)

ClinicalTrials.gov

2018-06-18

Advanced Malignant Solid Neoplasm; Ann Arbor Stage III Non-Hodgkin Lymphoma; Ann Arbor Stage IV Non-Hodgkin Lymphoma; Malignant Glioma; Recurrent Central Nervous System Neoplasm; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Solid Neoplasm; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Central Nervous System Neoplasm; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Solid Neoplasm; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Rhabdoid Tumor; Stage III Osteosarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Osteosarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Osteosarcoma AJCC v7; Stage IVB Osteosarcoma AJCC v7; TSC1 Gene Mutation; TSC2 Gene Mutation; Wilms Tumor

Pediatric inflammatory bowel disease and bone health.

PubMed

Mascarenhas, Maria R; Thayu, Meena

2010-08-01

Childhood and adolescence are important periods for bone development. Any disease that affects bone health has the potential to affect the bones not only in the short term but also later in life. Bone health abnormalities in patients with inflammatory bowel disease are being increasingly recognized. Screening the at-risk patient is important so that appropriate treatments can be instituted. Treatment options are limited to vitamin D and calcium supplementation, control of underlying disease activity, and appropriate physical activity. The role of bisphosphonates in these patients needs to be better studied, and treatment with bisphosphonates may be considered for some patients in consultation with a bone health expert.

Distinctive Epstein-Barr virus variants associated with benign and malignant pediatric pathologies: LMP1 sequence characterization and linkage with other viral gene polymorphisms.

PubMed

Lorenzetti, Mario Alejandro; Gantuz, Magdalena; Altcheh, Jaime; De Matteo, Elena; Chabay, Paola Andrea; Preciado, María Victoria

2012-03-01

The ubiquitous Epstein-Barr virus (EBV) is related to the development of lymphoma and is also the etiological agent for infectious mononucleosis (IM). Sequence variations in the gene encoding LMP1 have been deeply studied in different pathologies and geographic regions. Controversial results propose the existence of tumor-related variants, while others argued in favor of a geographical distribution of these variants. Reports assessing EBV variants in IM were performed in adult patients who displayed multiple variant infections. In the present study, LMP1 variants in 15 pediatric patients with IM and 20 pediatric patients with EBV-associated lymphomas from Argentina were analyzed as representatives of benign and malignant infections in children, respectively. A 3-month follow-up study of LMP1 variants in peripheral blood cells and in oral secretions of patients with IM was performed. Moreover, an integrated linkage analysis was performed with variants of EBNA1 and the promoter region of BZLF1. Similar sequence polymorphisms were detected in both pathological conditions, IM and lymphoma, but these differ from those previously described in healthy donors from Argentina and Brazil. The results suggest that certain LMP1 polymorphisms, namely, the 30-bp deletion and high copy number of the 33-bp repeats, are associated with EBV-related pathologies, either benign or malignant, instead of just being tumor related. Additionally, this is the first study to describe the Alaskan variant in EBV-related lymphomas that previously was restricted to nasopharyngeal carcinomas from North America.

Distinctive Epstein-Barr Virus Variants Associated with Benign and Malignant Pediatric Pathologies: LMP1 Sequence Characterization and Linkage with Other Viral Gene Polymorphisms

PubMed Central

Gantuz, Magdalena; Altcheh, Jaime; De Matteo, Elena; Chabay, Paola Andrea; Preciado, María Victoria

2012-01-01

The ubiquitous Epstein-Barr virus (EBV) is related to the development of lymphoma and is also the etiological agent for infectious mononucleosis (IM). Sequence variations in the gene encoding LMP1 have been deeply studied in different pathologies and geographic regions. Controversial results propose the existence of tumor-related variants, while others argued in favor of a geographical distribution of these variants. Reports assessing EBV variants in IM were performed in adult patients who displayed multiple variant infections. In the present study, LMP1 variants in 15 pediatric patients with IM and 20 pediatric patients with EBV-associated lymphomas from Argentina were analyzed as representatives of benign and malignant infections in children, respectively. A 3-month follow-up study of LMP1 variants in peripheral blood cells and in oral secretions of patients with IM was performed. Moreover, an integrated linkage analysis was performed with variants of EBNA1 and the promoter region of BZLF1. Similar sequence polymorphisms were detected in both pathological conditions, IM and lymphoma, but these differ from those previously described in healthy donors from Argentina and Brazil. The results suggest that certain LMP1 polymorphisms, namely, the 30-bp deletion and high copy number of the 33-bp repeats, are associated with EBV-related pathologies, either benign or malignant, instead of just being tumor related. Additionally, this is the first study to describe the Alaskan variant in EBV-related lymphomas that previously was restricted to nasopharyngeal carcinomas from North America. PMID:22205789

Usefulness of Tc-99m MDP spine SPECT imaging in differentiating malignant from benign lesions in cancer patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryu, J.S.; Moon, D.H.; Shin, M.J.

1994-05-01

Solitary or a few spinal abnormalities on planar bone scan pose a dilemma in cancer patients. The purpose of this study was to evaluate the usefulness of spine SPECT imaging in differential diagnosis of malignant and benign lesion. Subjects were 54 adult patients with solitary or a few equivocal vertebral lesions on planar bone scan. Spine SPECT imaging was obtained by a triple head SPECT system (TRIAD, Trionix). The final diagnoses were based on data from biopsy, other imaging studies, or minimum 1 year of follow up. Two blind observers reviewed the planar image first, then both planar and SPECTmore » images. The uptake patterns on SPECT images were analyzed, and the diagnostic performance was evaluated by the ROC analysis. Thirty three lesions of 22 patients were malignant, and 60 lesions of 32 patients were benign. Common characteristic patterns of malignant lesions were focal or segmental hot uptake in the body, hot uptake in the body and pedicle, and cold defect with surrounding hot uptake in the vertebra. Whereas marginal protruding hot uptakes in endplate, and hot uptakes in facet joints were benign. The ROC analysis showed that SPECT improved the diagnostic performance (the area under the ROC curve of two observers for planar image 0.903 and 0.791, for the combination of planar and SPECT : 0.950 and 0.976). In conclusion, the uptake pattern recognition in spine SPECT provides useful information for differential diagnosis of malignant and benign lesions in vertebra. Spine SPECT is a valuable complement in cancer patients with inconclusive findings on planar bone scan.« less

Osteosarcoma and MFH of Bone Treatment (PDQ®)—Health Professional Version

Cancer.gov

Osteosarcoma and malignant fibrous histiocytoma (MFH) of bone are most successfully treated with a combination of systemic chemotherapy and complete resection of all clinically detectable disease. Get detailed information about the presentation, diagnosis, genomics, prognosis and treatment of osteosarcoma and MFH in this summary for clinicians.

The challenging aspects of managing adolescents and young adults with Hodgkin's lymphoma.

PubMed

Jachimowicz, Ron D; Engert, Andreas

2014-01-01

Cancer in the adolescent and young adult (AYA) is the second leading cause of nonaccidental death with hematological malignancies spiking during this period. Treatment of AYAs with hematological malignancies usually follows either pediatric or adult protocols with sufficient information lacking on subgroup analyses regarding course and outcome. In this review we will outline up-to-date treatment possibilities for AYAs diagnosed with Hodgkin's lymphoma. Early and late toxicities will be addressed and future directions of research suggested. © 2014 S. Karger AG, Basel.

Histone deacetylases (HDAC) in physiological and pathological bone remodelling.

PubMed

Cantley, M D; Zannettino, A C W; Bartold, P M; Fairlie, D P; Haynes, D R

2017-02-01

Histone deacetylases (HDACs) 2 play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi) 3 that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are also currently being studied for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes. Selective isozyme-specific inhibitors currently being developed against class I HDACs (1, 2, 3 and 8) and class II HDACs (4, 5, 6, 7, 9 and 10) will be valuable tools for elucidating the roles played by individual HDACs in different physiological and pathological settings. Isozyme-specific HDACi promise to have greater efficacy and reduced side effects, as required for treating chronic disease over extended periods of time. This article reviews the current understanding of roles for individual HDAC isozymes and effects of HDACi on bone cells, (osteoblasts, osteoclasts and osteocytes), in relation to bone remodelling in conditions characterised by pathological bone loss, including periodontitis, rheumatoid arthritis and myeloma bone disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Using canine osteosarcoma as a model to assess efficacy of novel therapies: can old dogs teach us new tricks?

PubMed

Rodriguez, Carlos O

2014-01-01

Since its domestication more than 10,000 years ago, the dog has been the animal that most intimately shares our work and homelife. Interestingly, the dog also shares many of our diseases including cancer such as osteosarcoma. Like the human, osteosarcoma is the most common bone malignancy of the dog and death from pulmonary metastasis is the most common outcome. The incidence of this spontaneous bone neoplasm occurs ten times more frequently that it does so in children with about 8,000-10,000 cases estimated to occur in dogs in the USA. Because there is no "standard of care" in veterinary medicine, the dog can also serve us by being a model for this disease in children. Although the most common therapy for the dog with osteosarcoma is amputation followed by chemotherapy, not all owners choose this route. Consequently, novel therapeutic interventions can be attempted in the dog with or without chemotherapy that could not be done in humans with osteosarcoma due to ethical concerns. This chapter will focus on the novel therapies in the dog that have been reported or are in veterinary clinical trials at the author's institution. It is hoped that collaboration between veterinary oncologists and pediatric oncologists will lead to the development of novel therapies for (micro- or macro-) metastatic osteosarcoma that improve survival and might ultimately lead to a cure in both species.

Radiation dose optimization in pediatric temporal bone computed tomography: influence of tube tension on image contrast and image quality.

PubMed

Nauer, Claude Bertrand; Zubler, Christoph; Weisstanner, Christian; Stieger, Christof; Senn, Pascal; Arnold, Andreas

2012-03-01

The purpose of this experimental study was to investigate the effect of tube tension reduction on image contrast and image quality in pediatric temporal bone computed tomography (CT). Seven lamb heads with infant-equivalent sizes were scanned repeatedly, using four tube tensions from 140 to 80 kV while the CT-Dose Index (CTDI) was held constant. Scanning was repeated with four CTDI values from 30 to 3 mGy. Image contrast was calculated for the middle ear as the Hounsfield unit (HU) difference between bone and air and for the inner ear as the HU difference between bone and fluid. The influence of tube tension on high-contrast detail delineation was evaluated using a phantom. The subjective image quality of eight middle and inner ear structures was assessed using a 4-point scale (scores 1-2 = insufficient; scores 3-4 = sufficient). Middle and inner ear contrast showed a near linear increase with tube tension reduction (r = -0.94/-0.88) and was highest at 80 kV. Tube tension had no influence on spatial resolution. Subjective image quality analysis showed significantly better scoring at lower tube tensions, with highest image quality at 80 kV. However, image quality improvement was most relevant for low-dose scans. Image contrast in the temporal bone is significantly higher at low tube tensions, leading to a better subjective image quality. Highest contrast and best quality were found at 80 kV. This image quality improvement might be utilized to further reduce the radiation dose in pediatric low-dose CT protocols.

Pulmonary complications in patients with haematological malignancies treated at a respiratory ICU.

PubMed

Ewig, S; Torres, A; Riquelme, R; El-Ebiary, M; Rovira, M; Carreras, E; Raño, A; Xaubet, A

1998-07-01

Patients with haematological malignancies developing severe pulmonary complications have a poor outcome, especially after bone-marrow transplantation (BMT). We studied the aetiology, the yield of different diagnostic tools, as well as the outcome and prognostic factors in the corresponding population admitted to our respiratory intensive care unit (RICU). Overall, 89 patients with haematological malignancies and pulmonary complications treated within a 10 yr period were included. The underlying malignancies were predominantly acute leukaemia and chronic myeloid leukaemia (66/89, 74%). Fifty-two of 89 (58%) patients were bone marrow recipients. An aetiological diagnosis could be obtained in 61/89 (69%) of cases. The aetiology was infectious in 37/89 (42%) and noninfectious in 24/89 (27%). Blood cultures and cytological examinations of bronchoalveolar lavage fluid were the diagnostic tools with the highest yield (13/43 (30%) and 13/45 (29%) positive results, respectively). Necropsy results were coincident with results obtained during the lifetime in 43% of cases with infectious and 60% with noninfectious aetiologies. Overall mortality was 70/89 (79%), and 47/52 (90%) in transplant recipients. The requirement of mechanical ventilation, BMT, and an interval <90 days of BMT prior to ICU admission were independent adverse prognostic factors. The outcome in this patient population was uniformly poor. It was worst in bone marrow recipients developing pulmonary complications <90 days after transplantation and requiring mechanical ventilation. Decisions about intensive care unit admission and mech-anical ventilation should seriously consider the dismal prognosis of these patients.

Multiple primary Ewing’s sarcomas in cerebral cranium of a child: a case report and review of the literature

PubMed Central

Wang, Dawei; Guo, Zongze

2015-01-01

Ewing’s sarcoma is the second most common pediatric bone tumor. Primary Ewing’s sarcoma occurring in the cerebral cranium is exceptionally rare, with only one reported case of multiple tumor lesions in adolescence to date. We report a case of a 5-year-old male patient with multiple primary Ewing’s sarcomas associated with the cranial bones, the first pediatric case report to date. We also review 71 cases Ewing’s sarcoma involving intracranial extension. The purpose of this article is to provide data concerning the clinical and therapeutic course of multiple primary Ewing’s sarcomas in associated with cerebral cranium. PMID:26261672

Cystic fibrous dysplasia in the long bone.

PubMed

Bahk, Won-Jong; Kang, Yong-Koo; Rhee, Seung-Koo; Chung, Yang-Guk; Lee, An-Hee; Bahk, Yong-Whee

2007-10-01

Prominent osteolysis associated with "ground glass" density of fibrous dysplasia may indicate cystic change or sarcomatous transformation. This complication has been reported only sporadically in the long bones. This article presents clinical, radiographic, and pathologic findings, and outcome of simple curettage and bone graft observed in a series of 8 patients with prominent cystic fibrous dysplasia of the long bone. Magnetic resonance imaging features provide a basis for separation of benign cystic change from malignant transformation. However, biopsy is necessary to distinguish nonspecific cystic degeneration from secondary aneurysmal bone cyst. Simple curettage with allo-chip-bone graft is an effective treatment for cystic fibrous dysplasia.

18F-fluorodeoxyglucose imaging of primary malignant pericardial mesothelioma with concurrent pericardial and pleural effusions and bone metastasis: A case report.

PubMed

Li, Xiaohui; Lu, Rugang; Zhao, Youcai; Wang, Feng; Shao, Guoqiang

2018-06-01

Primary malignant pericardial mesothelioma (PMPM) is an aggressive tumor that originates from the mesothelial cells of the pericardium. PMPM with extensive atrial infiltration and bone metastasis is extremely rare. The diagnosis and staging of PMPM based on anatomical imaging may be difficult when concurrent pericardial and pleural effusions are present. A 28-year-old man presented with progressive chest pain. Concurrent pericardial and pleural effusions were identified on computed tomography. On echocardiography, mild thickening and adhesions of the pericardium with the right ventricle and atrium were observed. 18 F-fluorodeoxyglucose (FDG) metabolism imaging revealed increased accumulation in the pericardium and adjacent right atrium. Ring-shaped radioactivity aggregation and bone destruction in the sacrum were demonstrated on 18 F-FDG and 99m Tc-methyl diphosphonate imaging. The diagnosis of PMPM was subsequently confirmed by pathology. The patient survived for >1.5 years with comprehensive treatment.

Hypercalcaemia and hypocalcaemia: finding the balance.

PubMed

Body, Jean-Jacques; Niepel, Daniela; Tonini, Giuseppe

2017-05-01

The balance between bone formation and resorption may be disrupted in patients with cancer, leading either to increased bone resorption, calcium release, and possibly hypercalcaemia, or to increased bone formation, sequestration of calcium, and possibly hypocalcaemia. In adults, hypercalcaemia of malignancy is most common in patients with tumours that produce factors that induce osteoclast activation and enhance bone resorption. Impaired renal function and increased renal tubular calcium resorption may further affect calcium levels. Inhibitors of bone resorption, first the bisphosphonates and, later, denosumab, have been shown to be effective in hypercalcaemia treatment. Bisphosphonates (which are administered intravenously) are approved for hypercalcaemia of malignancy and are the current mainstay of treatment, whereas denosumab (which is administered subcutaneously) may offer an option for patients who do not respond to bisphosphonates or suffer from renal insufficiency. TREATMENT AND PREVENTION: Hypocalcaemia is most common in patients with prostate cancer and osteoblastic bone metastases, but can occur in patients with a variety of tumour types who are receiving inhibitors of bone resorption. While patients often respond to calcium and vitamin D supplementation, prevention should be the aim; at-risk patients should be identified before starting treatment with inhibitors of bone resorption, be closely monitored during at least the first few months of treatment, and receive concomitant calcium and vitamin D supplementation unless hypercalcaemia is present. Both hypercalcaemia and hypocalcaemia can be serious if left untreated. It is therefore important that patients with cancer are closely monitored and receive adequate prevention and treatment measures to maintain normal blood calcium levels.

Standard of Care for Neuropsychological Monitoring in Pediatric Neuro-Oncology: Lessons From the Children's Oncology Group (COG).

PubMed

Walsh, Karin S; Noll, Robert B; Annett, Robert D; Patel, Sunita K; Patenaude, Andrea F; Embry, Leanne

2016-02-01

As the mortality of pediatric cancers has decreased, focus on neuropsychological morbidities of treatment sequelae have increased. Neuropsychological evaluations are essential diagnostic tools that assess cognitive functioning and neurobiological integrity. These tests provide vital information to support ongoing medical care, documenting cognitive morbidity and response to interventions. We frame standards for neuropsychological monitoring of pediatric patients with CNS malignancy or who received cancer-directed therapies involving the CNS and discuss billing for these services in the United States in the context of clinical research. We describe a cost-effective, efficient model of neuropsychological monitoring that may increases access to neuropsychological care. © 2015 Wiley Periodicals, Inc.

Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease -- can it differentiate bone infarcts from acute osteomyelitis?

PubMed

Delgado, Jorge; Bedoya, Maria A; Green, Abby M; Jaramillo, Diego; Ho-Fung, Victor

2015-12-01

Children with sickle cell disease (SCD) are at risk of bone infarcts and acute osteomyelitis. The clinical differentiation between a bone infarct and acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR images have been proposed as a potential tool to differentiate bone infarcts from osteomyelitis. To evaluate the reliability of unenhanced T1-W fat-saturated MRI for differentiation between bone infarcts and acute osteomyelitis in children with SCD. We retrospectively reviewed the records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9 years) with SCD and acute bone pain who underwent MR imaging including unenhanced T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were reviewed by a pediatric hematologist with training in infectious diseases to determine a clinical standard to define the presence or absence of osteomyelitis. A pediatric radiologist reviewed all MR imaging and was blinded to clinical information. Based on the signal intensity in T1-W fat-saturated images, the children were further classified as positive for osteomyelitis (low bone marrow signal intensity) or positive for bone infarct (high bone marrow signal intensity). Based on the clinical standard, 5 children were classified as positive for osteomyelitis and 26 children as positive for bone infarct (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat-saturated imaging was not significant for the differentiation between bone infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging parameters on unenhanced MRI proved reliable in differentiating these diagnoses. The bone marrow signal intensity on unenhanced T1-W fat-saturated MR images is not a reliable criterion to differentiate bone infarcts from osteomyelitis in children.

Costal chondrosarcoma requiring differential diagnosis from metastatic tumor.

PubMed

Matsuoka, Katsunari; Ueda, Mitsuhiro; Miyamoto, Yoshihiro

2017-02-01

Although chondrosarcoma is a common malignant bone tumor, cases arising in the rib are relatively rare. We experienced a case of chondrosarcoma arising in the right 10th rib during follow-up after lung cancer surgery. Although the finding of an osteolytic mass suggested a metastatic bone tumor, 18F-fluorodeoxyglucose positron-emission tomography demonstrated low fluorodeoxyglucose uptake, and a primary bone tumor was suspected. The bone tumor was resected and diagnosed as chondrosarcoma. Four years after resection, there has been no recurrence or metastasis. Positron-emission tomography was useful for differential diagnosis between a chondrosarcoma and a metastatic bone tumor.

Pediatric head and neck masses.

PubMed

Gujar, Sachin; Gandhi, Dheeraj; Mukherji, Suresh K

2004-04-01

Most neck masses in the pediatric head and neck region are benign. Congenital, developmental, and inflammatory lesions make up most of the masses in the pediatric head and neck. For example, neck masses due to inflammatory lymphadenitis are common in children because of the frequency of upper respiratory tract infections. Although many of the malignant tumors in children are found in the head and neck, they account for only a small portion of the neck masses. The choice of the imaging modality is based on a number of factors, several of which are unique to the pediatric population. Although the bulk of disease entities are adequately evaluated by CT, MRI can provide additional vital information in many cases. MRI provides better soft tissue characterization than CT, has multiplanar capabilities. In this article, we will attempt to provide an overview of conditions that present as neck masses.

Hemoglobin Threshold for Blood Transfusion in a Pediatric Intensive Care Unit.

PubMed

Chegondi, Madhuradhar; Sasaki, Jun; Raszynski, André; Totapally, Balagangadhar R

2016-07-01

To evaluate the hemoglobin threshold for red cell transfusion in children admitted to a pediatric intensive care unit (PICU). Retrospective chart review study. Tertiary care PICU. Critically ill pediatric patients requiring blood transfusion. No intervention. We analyzed the charts of all children between 1 month and 21 years of age who received packed red blood cell (PRBC) transfusions during a 2-year period. The target patients were identified from our blood bank database. For analysis, the patients were subdivided into four groups: acute blood loss (postsurgically, trauma, or acute gastrointestinal bleeding from other causes), hematologic (hematologic malignancies, bone marrow suppression, hemolytic anemia, or sickle cell disease), unstable (FiO 2 > 0.6 and/or on inotropic support), and stable groups. We also compared the pre-transfusion hemoglobin threshold in all unstable patients with that of all stable patients. A total of 571 transfusion episodes in 284 patients were analyzed. 28% (n = 160) of transfusions were administered to patients in the acute blood loss group, 36% (n = 206) to hematologic patients, 17% (n = 99) to unstable patients, and 18% (n = 106) to stable patients. The mean pre-transfusion hemoglobin (± SD) in all children as well as in the acute blood loss, hematologic, unstable and stable groups was 7.3 ± 1.20, 7.83 ± 1.32, 6.97 ± 1.31, 7.96 ± 1.37, 7.31 ± 1.09 g/dl, respectively. The transfusion threshold for acute blood loss and unstable groups was higher compared to hematologic and stable groups (p < 0.001; ANOVA with multiple comparisons). The mean pre-transfusion hemoglobin threshold for stable and unstable patients among all groups was 7.3 ± 1.3 and 7.9 ± 1.3 (p < 0.0001), respectively. The observed mortality rate was higher among children who received transfusion compared to other children admitted to PICU. The hemoglobin threshold for transfusion varied according to clinical conditions. Overall, the hemoglobin threshold for transfusion was 7.3 ± 1.20 g/dl.

Antimicrobial Stewardship Barriers and Goals in Pediatric Oncology and Bone Marrow Transplantation: A Survey of Antimicrobial Stewardship Practitioners.

PubMed

Wolf, Joshua; Sun, Yilun; Tang, Li; Newland, Jason G; Gerber, Jeffrey S; Van Dyke, Christie J; Hymes, Saul R; Yu, Diana; Carias, Delia C; Bryant, Penelope A

2016-03-01

We undertook a cross-sectional survey of antimicrobial stewardship clinicians in North America and Australasia regarding practices, goals, and barriers to implementation of stewardship for pediatric oncology patients. Goals and barriers were similar regardless of clinician or institutional characteristics and geographic location. Strategies addressing these factors could help optimize antimicrobial use.

Purification of Bone Marrow Clonal Cells from Patients with Myelodysplastic Syndrome via IGF-IR

PubMed Central

He, Qi; Chang, Chun-Kang; Xu, Feng; Zhang, Qing-Xia; Shi, Wen-Hui; Li, Xiao

2015-01-01

Malignant clonal cells purification can greatly benefit basic and clinical studies in myelodysplastic syndrome (MDS). In this study, we investigated the potential of using type 1 insulin-like growth factor receptor (IGF-IR) as a marker for purification of malignant bone marrow clonal cells from patients with MDS. The average percentage of IGF-IR expression in CD34+ bone marrow cells among 15 normal controls was 4.5%, 70% of which also express the erythroid lineage marker CD235a. This indicates that IGF-IR mainly express in erythropoiesis. The expression of IGF-IR in CD34+ cells of 55 MDS patients was significantly higher than that of cells from the normal controls (54.0 vs. 4.5%). Based on the pattern of IGF-IR expression in MDS patients and normal controls, sorting of IGF-IR-positive and removal of CD235a-positive erythroid lineage cells with combination of FISH detection were performed on MDS samples with chromosomal abnormalities. The percentage of malignant clonal cells significantly increased after sorting. The enrichment effect was more significant in clonal cells with a previous percentage lower than 50%. This enrichment effect was present in samples from patients with +8, 5q-/-5, 20q-/-20 or 7q-/-7 chromosomal abnormalities. These data suggest that IGF-IR can be used as a marker for MDS bone marrow clonal cells and using flow cytometry for positive IGF-IR sorting may effectively purify MDS clonal cells. PMID:26469401

NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Endocrine Challenges--Thyroid Dysfunction, Growth Impairment, Bone Health, & Reproductive Risks

PubMed Central

Dvorak, Christopher C.; Gracia, Clarisa R.; Sanders, Jean E.; Cheng, Edward Y.; Baker, K. Scott; Pulsipher, Michael A.; Petryk, Anna

2011-01-01

The endocrine system is highly susceptible to damage by high-dose chemotherapy and/or irradiation prior to hematopoietic cell transplantation (HCT) during childhood. The specific endocrine organs most affected by HCT include the thyroid gland, the pituitary, and the gonads. In addition, hormones that support development and stability of the skeletal system are also affected. Insufficiency of thyroid hormone is one of the most common late sequelae of HCT, and occurs more often in young children. Deficiency in the pituitary’s production of growth hormone is a problem of unique concern to the pediatric population. The reproductive risks of HCT depend on the patient’s gender and pubertal status at the time of HCT. Pubertal or gonadal failure frequently occurs, especially in females. Infertility risks for both genders remain high, while methods of fertility preservation are limited in all but post-pubertal males. Bone health post-HCT can be compromised by low bone mineral density as well as avascular necrosis, but the data on both problems in the pediatric HCT population are limited. In this paper, the current state of knowledge, gaps in that knowledge, and recommendations for future research are addressed in detail for each of these systems. PMID:22005649

Epidemiological data and case load spectrum of patients presenting to bone and soft tissue disease management group at a tertiary cancer center.

PubMed

Gulia, A; Puri, A; Chorge, S; Panda, P K

2016-01-01

This study was conducted to know the spectrum and number of bone and soft tissue (BST) tumors presenting to our institute. We needed to assess the gap between the number of patients seen and infrastructure available, and based on this information, help formulate guidelines for optimum utilization of resources and to provide best possible evidence-based cancer care. This is a prospective observational study (epidemiological). This study included all new patients seen in BST-disease management group (DMG) in the year 2010. An audit form was devised to capture all the relevant information. A comparison of our data with other national and international studies was also done. Out of total 31,951 new patients registered at our institute, 2007 patients availed BST-DMG services. Sixty percent were bone tumors and 36% were soft tissue tumors. In bone tumor, 66% were malignant, 15% were benign, and 19% were non-neoplastic. Osteosarcoma (43%) was the most common malignant tumor followed by primitive neuroectodermal tumor/Ewing's (27%) and chondrosarcoma (11%). Giant cell tumor was the most common benign bone tumor. Eighty-one percent of all soft tissue lesions were malignant, of which 75% were of mesenchymal origin and 25% were of cutaneous origin. This is an attempt to document the epidemiology of musculoskeletal tumors presenting to our institution while guiding the institute to frame and implement disease-specific protocols and generate further research questions. Continued data collection and follow-up can provide valuable information on long-term survival and treatment-related toxicities. This data (within limitations) may be extrapolated to national level to identify the need for infrastructure and human resources.

[Hematologic malignancies in pregnancy].

PubMed

Doubek, R; Petrovová, D; Kalvodová, J; Doubek, M

2009-04-01

To summarize available data concerning hematologic malignancies in pregnancy. Review article. Department of Obstetrics and Gynekology, Fakulty of Medicine, Masaryk University and University Hospital Brno. Compilation of published data from scientific literature. Cancer complicating pregnancy is a rare coexistence. The incidence is approximately 1 in 1,000 pregnancies. The most frequent hematologic malignant tumor is Hodgkin's lymphoma, leukemia is less frequent and myeloproliferative diseases complicating pregnancy are sporadic coexistence. Symptoms of these deseases are often nonspecific and disguised in pregnancy, then the diagnosis can be late. It is imperative that a multidisciplinary team involving hematooncologist and obstetrician (pediatric specialist) care for patient with hematologic malignancies. Cleary, every patient have to know whole prognosis and all risk factors of treatment. Optimum timing of delivery is after 36th week of pregnancy (when chemotherapy is ended more than two weeks ago). We prefer vaginal delivery to caesarean section.

Curcumin deteriorates trabecular and cortical bone in mice bearing metastatic Lewis lung carcinoma

USDA-ARS?s Scientific Manuscript database

Bone is a major target of metastasis for many malignancies; curcumin has been studied for its role in cancer prevention including early phase clinical trials for its efficacy and safe use with cancer patients. The present study investigated the effects of dietary supplementation with curcumin (2% a...

Indications of Carbon Ion Therapy at CNAO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orecchia, Roberto; European Institute of Oncology, via Ripamonti 435, Milano 20141; CNAO National Centre for Oncological Hadrontherapy, Via Caminadella 16, Milano 20123

2009-03-10

CNAO will be a dual center capable of providing therapeutic beams of protons and carbon ions with maximum energy of 400 MeV/u. At the beginning, it will be equipped with three treatment rooms with fixed horizontal and vertical beam lines. In a subsequent phase, two more rooms with a rotating gantry are foreseen. An active spot scanning dose delivery system will be employed. Initially, 80% of the treatments will be carried out with carbon ions. All patients will be treated within clinical trials to assess carbon ion indications with an evidence-based methodology. Seven disease-specific working groups have been developed: lungmore » tumors, liver tumors, sarcomas, head and neck tumors, central nervous system lesions, eye tumors and pediatric tumors. The last two groups will be treated mainly with protons. In the first phase, CNAO will focus on head and neck cancers, treating inoperable, residual or recurrent malignant salivary gland tumors, mucosal melanoma, adenocarcinoma and unfavorably located SCC (nasal and paranasal sinuses). Carbon ions will be employed as a boost in the treatment of locally advanced, poor prognosis, SCC of the hypopharynx and tongue base. Bone and soft tissue sarcomas of the extremity will be treated with a limb-sparing approach, and trunk sarcomas will be treated with exclusive or post-operative irradiation. Skull base tumors (chordoma and chondrosarcoma), recurrent or malignant meningioma and glial tumors will be treated with carbon ions. After sufficient expertise has been gained in coping with organ motion, CNAO will start treating thoracic and abdominal targets. HCC will be treated in inoperable patients with one or more lesions that can be included in a single CTV. Early stage NSCLC will be treated. In the second phase, two more groups on gynecological malignancies and digestive tumors (esophageal cancer, rectal cancer, pancreatic cancer) will be created.« less

Novel therapeutic approaches in chondrosarcoma.

PubMed

Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

2017-03-01

Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

Cervical Spine Aneurysmal Bone Cysts in the Pediatric Population: A Systematic Review of the Literature.

PubMed

Protas, Matthew; Jones, Lydia W; Sardi, Juan Pablo; Fisahn, Christian; Iwanaga, Joe; Oskouian, Rod J; Tubbs, R Shane

2017-01-01

Cervical spine aneurysmal bone cysts (ABCs) in pediatric patients have not been thoroughly studied. Using PubMed and Google Scholar, a systematic review of the literature was conducted for publications that included patients aged ≤15 years with a confirmed diagnosis of ABC in the cervical spine. Thirty-five studies with a total of 71 patients met the inclusion criteria. Nearly 80% of patients presented with neck or shoulder pain. The axis was the level most frequently involved (34.28%), followed by C5 (24.28%). Posterior elements were most likely to be affected (88.46%) while exclusive involvement of the body was uncommon. To our knowledge, this is the first systematic review of the literature regarding ABCs of the cervical spine in a pediatric population. Spinal ABCs are rarely found in the cervical region, and their treatment remains challenging due to their location, vascularization, and a high overall recurrence rate even with surgical resection. © 2017 S. Karger AG, Basel.

Factors affecting bone mineral mass loss after lower-limb fractures in a pediatric population.

PubMed

Ceroni, Dimitri; Martin, Xavier; Kherad, Omar; Salvo, Davide; Dubois-Ferrière, Victor

2015-06-01

The purpose of this study was to assess the effects of the durations of cast immobilization and non-weight-bearing periods, and decreases in vigorous physical activity (VPA) on bone mineral parameters in a pediatric population treated for a lower-limb fracture. Fifty children and teenagers who had undergone a cast-mediated immobilization for a leg or ankle fracture were prospectively recruited. The durations of cast immobilization and non-weight-bearing periods were recorded for each participant. Dual-energy x-ray absorptiometry scans were performed at the time of fracture treatment (baseline) and at cast removal. Physical activity during cast immobilization was assessed using accelerometers. A strong negative correlation was found between the total duration of cast immobilization and decreases in both calcaneal bone mineral density (BMD) (r=-0.497) and total lower-limb bone mineral content (BMC) (r=-0.405). A strong negative correlation was also noted between the durations of the non-weight-bearing periods and alterations in calcaneal BMD (r=-0.420). No apparent correlations were found between lower BMD and BMC and decreased VPA. Bone mineral loss was correlated to the total duration of cast immobilization for all measurement sites on the affected leg, whereas it was only correlated to the durations of non-weight-bearing periods for calcaneal BMD and total lower-limb BMC. However, no correlations were noted between bone mineral loss and decreased VPA.

Maintenance steroid use at 30 days post-transplant and outcomes of pediatric heart transplantation: A propensity matched analysis of the Pediatric Heart Transplant Study database.

PubMed

Auerbach, Scott R; Kukreja, Manisha; Gilbert, Deborah; Bastardi, Heather; Feingold, Brian; Knecht, Kenneth; Kaufman, Beth D; Brown, Robert N; Miyamoto, Shelley D

2015-08-01

Maintenance steroid (MS) use in pediatric heart transplantation is variable. The purpose of this study was to evaluate the impact of MS use on graft outcomes. All patients <18 years old in the Pediatric Heart Transplant Study database at the time of first heart transplant between 1993 and 2011 who survived ≥30 days post-transplant and were from centers with a protocolized approach to MS use were included (N = 2,178). Patients were grouped by MS use at 30 days post-transplant as MS+ or MS- (no MS use). Propensity score analysis was used to generate matched groups of MS+ and MS- patients based on pre-transplant and peri-transplant factors. Kaplan-Meier survival analysis was used to compare freedom from graft loss, graft loss secondary to rejection, rejection, rejection with severe hemodynamic compromise (RSHC), malignancy, and infection between groups. Of patients, 1,393 (64%) were MS+ and 785 (36%) were MS-. There were 315 MS- patients who had propensity matched MS+ controls. Kaplan-Meier estimates showed no difference in graft loss (p = 0.9) or graft loss secondary to rejection (p = 0.09). At 1 year post-transplant, there was no difference in freedom from rejection (p = 0.15) or malignancy (p = 0.07), but there was lower freedom from RSHC and infection in the MS- group (p = 0.05 and p = 0.02, respectively). MS use at 30 days post-transplant was not associated with enhanced graft survival after pediatric heart transplant. MS- patients had a higher incidence of RSHC and infection. These risks should be taken into consideration when determining MS use for pediatric recipients of heart transplants. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Metabolic Bone Disease in the Context of Metastatic Neuroendocrine Tumor: Differentiation from Skeletal Metastasis, the Molecular PET-CT Imaging Features, and Exploring the Possible Etiopathologies Including Parathyroid Adenoma (MEN1) and Paraneoplastic Humoral Hypercalcemia of Malignancy Due to PTHrP Hypersecretion.

PubMed

Ranade, Rohit; Basu, Sandip

2017-01-01

Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan. Similar picture of metabolic bone disease [18-sodium fluoride (18NaF)/68Ga-DOTATATE mismatch] was documented in the other two patients, while fluorodeoxyglucose (FDG)-PET-CT was variably positive, primarily showing tracer uptake in the metabolic skeletal lesions of the patient with hypersecretion of parathyroid hormone-related protein (PTHrP) by the underlying tumor. Discordance between 18NaF PET-CT and 68Ga-DOTATATE PET-CT serves as a good marker for identification of metabolic bone disease and diagnosing such a clinical entity. In a patient of NET with metabolic bone disease and hypercalcemia, thus, two causes need to be considered: (i) Coexisting parathyroid adenoma in multiple endocrine neoplasia type I (MEN-I) syndrome and (ii) humoral hypercalcemia of malignancy (HHM) related to hypersecretion of PTHrP by the tumor. The correct diagnosis of metabolic bone disease in metastatic NET can alter the management substantially. Interestingly, peptide receptor radionuclide therapy (PRRT) can emerge as a very promising treatment modality in patients of metabolic bone disease caused by HHM in the setting of NET.

Conditional survival of pediatric, adolescent, and young adult soft tissue sarcoma and bone tumor patients.

PubMed

Ou, Judy Y; Spraker-Perlman, Holly; Dietz, Andrew C; Smits-Seemann, Rochelle R; Kaul, Sapna; Kirchhoff, Anne C

2017-10-01

Survival estimates for soft tissue sarcomas (STS) and malignant bone tumors (BT) diagnosed in pediatric, adolescent, and young adult patients are not easily available. We present survival estimates based on a patient having survived a defined period of time (conditional survival). Conditional survival estimates for the short-term were calculated for patients from diagnosis to the first five years after diagnosis and for patients surviving in the long-term (up to 20 years after diagnosis). We identified 703 patients who were diagnosed with a STS or BT at age ≤25 years from January 1, 1986 to December 31, 2012 at a large pediatric oncology center in Salt Lake City, Utah, United States. We obtained cancer type, age at diagnosis, primary site, and demographic data from medical records, and vital status through the National Death Index. Cancer stage was available for a subset of the cohort through the Utah Cancer Registry. Cox proportional hazards models, adjusted for age and sex, calculated survival estimates for all analyses. Short-term survival improves over time for both sarcomas. Short-term survival for STS from diagnosis (Year 0) did not differ by sex, but short-term survival starting from 1-year post diagnosis was significantly worse for male patients (Survival probability 1-year post-diagnosis [SP1]:77% [95% CI:71-83]) than female patients (SP1:86% [81-92]). Survival for patients who were diagnosed at age ≤10 years (Survival probability at diagnosis [SP0]:85% [79-91]) compared to diagnosis at ages 16-25 years (SP0:67% [59-75]) was significantly better at all time-points from diagnosis to 5-years post-diagnosis. Survival for axial sites (SP0:69% [63-75]) compared to extremities (SP0:84% [79-90]) was significantly worse from diagnosis to 1-year post-diagnosis. Survival for axial BT (SP0: 64% [54-74] was significantly worse than BT in the extremities (SP0:73% [68-79]) from diagnosis to 3-years post diagnosis. Relapsed patients of both sarcoma types had significantly worse short-term survival than non-relapsed patients. Long-term survival for STS in this cohort is 65% at diagnosis, and improves to 86% 5-years post-diagnosis. BT survival improves from 51% at diagnosis to 78% at 5-years post-diagnosis. Conditional survival for short- and long-term STS and BT improve as time from diagnosis increases. Short-term survival was significantly affected by patients' sex, age at diagnosis, cancer site, and relapse status. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Human Figure Drawing with Donor and Nondonor Siblings of Pediatric Bone Marrow Transplant Patients.

ERIC Educational Resources Information Center

Packman, Wendy L.; Beck, Vanessa L.; VanZutphen, Kelly H.; Long, Janet K.; Spengler, Gisele

2003-01-01

There is little research on the psychological impact of bone marrow transplantation (BMT) on family members. This study uses the Human Figure Drawing (HFD) to measure siblings' emotional distress toward BMT. Among the siblings, feelings of isolation, anger, depression, anxiety, and low self-esteem emerged as major themes. Findings indicate the…

Vincristine-induced peripheral neuropathy in pediatric cancer patients

PubMed Central

Mora, Erika; Smith, Ellen M Lavoie; Donohoe, Clare; Hertz, Daniel L

2016-01-01

Vincristine is a chemotherapeutic agent that is a component of many combination regimens for a variety of malignancies, including several common pediatric tumors. Vincristine treatment is limited by a progressive sensorimotor peripheral neuropathy. Vincristine-induced peripheral neuropathy (VIPN) is particularly challenging to detect and monitor in pediatric patients, in whom the side effect can diminish long term quality of life. This review summarizes the current state of knowledge regarding VIPN, focusing on its description, assessment, prediction, prevention, and treatment. Significant progress has been made in our knowledge about VIPN incidence and progression, and tools have been developed that enable clinicians to reliably measure VIPN in pediatric patients. Despite these successes, little progress has been made in identifying clinically useful predictors of VIPN or in developing effective approaches for VIPN prevention or treatment in either pediatric or adult patients. Further research is needed to predict, prevent, and treat VIPN to maximize therapeutic benefit and avoid unnecessary toxicity from vincristine treatment. PMID:27904761

Temporal bone dissection simulator for training pediatric otolaryngology surgeons

NASA Astrophysics Data System (ADS)

Tabrizi, Pooneh R.; Sang, Hongqiang; Talari, Hadi F.; Preciado, Diego; Monfaredi, Reza; Reilly, Brian; Arikatla, Sreekanth; Enquobahrie, Andinet; Cleary, Kevin

2017-03-01

Cochlear implantation is the standard of care for infants born with severe hearing loss. Current guidelines approve the surgical placement of implants as early as 12 months of age. Implantation at a younger age poses a greater surgical challenge since the underdeveloped mastoid tip, along with thin calvarial bone, creates less room for surgical navigation and can result in increased surgical risk. We have been developing a temporal bone dissection simulator based on actual clinical cases for training otolaryngology fellows in this delicate procedure. The simulator system is based on pre-procedure CT (Computed Tomography) images from pediatric infant cases (<12 months old) at our hospital. The simulator includes: (1) simulation engine to provide the virtual reality of the temporal bone surgery environment, (2) a newly developed haptic interface for holding the surgical drill, (3) an Oculus Rift to provide a microscopic-like view of the temporal bone surgery, and (4) user interface to interact with the simulator through the Oculus Rift and the haptic device. To evaluate the system, we have collected 10 representative CT data sets and segmented the key structures: cochlea, round window, facial nerve, and ossicles. The simulator will present these key structures to the user and warn the user if needed by continuously calculating the distances between the tip of surgical drill and the key structures.

SPECT imaging in evaluating extent of malignant external otitis: case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

English, R.J.; Tu'Meh, S.S.; Piwnica-Worms, D.

1987-03-01

Otitis externa, a benign inflammatory process of the external auditory canal, is general responsive to local therapy. Some patients however, develop a less controllable disease leading to chondritis and osteomyelitis of the base of the skull. The direct invasive characteristic of the disease has led to the descriptive term malignant external otitis (MEO), more appropriately called necrotizing or invasive external otitis. Malignant external otitis is caused by an aggressive pseudomonas or proteus infection that almost exclusively occurs in elderly diabetic patients. The primary imaging modalities previously used in the diagnosis and evaluation of MEO were standard planar scintigraphic techniques withmore » technetium-99M (/sup 99m/Tc) bone agents and gallium-67 (/sup 67/Ga), and pluridirectional tomography. The advent of high resolution computed tomography (CT) effectively allowed demonstration of the soft tissue extension and bone destruction associated with MEO, but still suffered from the low sensitivity constraints of all radiographic techniques in determining early inflammatory bone involvement. Recent work suggests that scintigraphic detection of MEO with /sup 99m/Tc-MDP and /sup 67/Ga, combined with the cross-sectional resolution of single photon emission computed tomography (SPECT) may be of value in planning treatment of this inflammatory condition.« less

Quality of harvest and role of cell dose in unrelated bone marrow transplantation: an Italian Bone Marrow Donor Registry-Gruppo Italiano Trapianto di Midollo Osseo Study.

PubMed

Fagioli, Franca; Quarello, Paola; Pollichieni, Simona; Lamparelli, Teresa; Berger, Massimo; Benedetti, Fabio; Barat, Veronica; Marciano, Renato; Rambaldi, Alessandro; Bacigalupo, Andrea; Sacchi, Nicoletta

2014-01-01

In this study, we investigated the factors affecting cell dose harvest and the role of cell dose on outcome. We analysed data from a cohort of 703 patients who underwent unrelated bone marrow transplantation facilitated by IBMDR in GITMO centers between 2002 and 2008. The median-infused cell doses is 3.7 × 10(8)/kg, the correlation between the nucleated cells requested from transplant centers and those harvested by collection centers was adequate. A harvested/requested cells ratio lower than 0.5 was observed only in 3% of harvests. A volume of harvested marrow higher than the median value of 1270 ml was related to a significant lower infused cell dose (χ(2): 44.4; P < 0.001). No patient- or donor-related variables significantly influenced the cell dose except for the recipient younger age (χ(2): 95.7; P < 0.001) and non-malignant diseases (χ(2): 33.8; P < 0.001). The cell dose resulted an independent predictor factor for a better outcome in patients affected by non-malignant disease (P = 0.05) while early disease malignant patients receiving a lower cell dose showed a higher risk of relapse (P = 0.05).

Inverse association between brown adipose tissue activation and white adipose tissue accumulation in successfully treated pediatric malignancy1234

PubMed Central

Chalfant, James S; Smith, Michelle L; Hu, Houchun H; Dorey, Fred J; Goodarzian, Fariba; Fu, Cecilia H

2012-01-01

Background: Although the accumulation of white adipose tissue (WAT) is a risk factor for disease, brown adipose tissue (BAT) has been suggested to have a protective role against obesity. Objective: We studied whether changes in BAT were related to changes in the amounts of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in children treated for malignancy. Design: We examined the effect of BAT activity on weight, SAT, and VAT in 32 pediatric patients with cancer whose positron emission tomography–computed tomography (PET-CT) scans at diagnosis showed no BAT activity. Changes in weight, SAT, and VAT from diagnosis to remission for children with metabolically active BAT at disease-free follow-up (BAT+) were compared with those in children without visualized BAT when free of disease (BAT−). Results: Follow-up PET-CT studies (4.7 ± 2.4 mo later) after successful treatment of the cancer showed BAT+ in 19 patients but no active BAT (BAT−) in 13 patients. BAT+ patients, in comparison with BAT− patients, gained significantly less weight (3.3 ± 6.6% compared with 11.0 ± 11.6%; P = 0.02) and had significantly less SAT (18.2 ± 26.5% compared with 67.4 ± 71.7%; P = 0.01) and VAT (22.6 ± 33.5% compared with 131.6 ± 171.8%; P = 0.01) during treatment. Multiple regression analysis indicated that the inverse relations between BAT activation and measures of weight, SAT, and VAT persisted even after age, glucocorticoid treatment, and the season when the PET-CT scans were obtained were accounted for. Conclusion: The activation of BAT in pediatric patients undergoing treatment of malignancy is associated with significantly less adipose accumulation. This trial was registered at clinicaltrials.gov as NCT01517581. PMID:22456659

Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy—A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee

PubMed Central

Grimberg, Adda; Waguespack, Steven G.; Miller, Bradley S.; Sklar, Charles A.; Meacham, Lillian R.; Patterson, Briana C.

2015-01-01

Context: GH and IGF-1 have been shown to affect tumor growth in vitro and in some animal models. This report summarizes the available evidence on whether GH therapy in childhood is associated with an increased risk of neoplasia during treatment or after treatment is completed. Evidence Acquisition: A PubMed search conducted through February 2014 retrieved original articles written in English addressing GH therapy and neoplasia risk. Subsequent searches were done to include additional relevant publications. Evidence Synthesis: In children without prior cancer or known risk factors for developing cancer, the clinical evidence does not affirm an association between GH therapy during childhood and neoplasia. GH therapy has not been reported to increase the risk for neoplasia in this population, although most of these data are derived from postmarketing surveillance studies lacking rigorous controls. In patients who are at higher risk for developing cancer, current evidence is insufficient to conclude whether or not GH further increases cancer risk. GH treatment of pediatric cancer survivors does not appear to increase the risk of recurrence but may increase their risk for subsequent primary neoplasms. Conclusions: In children without known risk factors for malignancy, GH therapy can be safely administered without concerns about an increased risk for neoplasia. GH use in children with medical diagnoses predisposing them to the development of malignancies should be critically analyzed on an individual basis, and if chosen, appropriate surveillance for malignancies should be undertaken. GH can be used to treat GH-deficient childhood cancer survivors who are in remission with the understanding that GH therapy may increase their risk for second neoplasms. PMID:25839904

Epidemiology of pediatric primary malignant central nervous system tumors in Iran: a 10 year report of National Cancer Registry.

PubMed

Beygi, Sara; Saadat, Soheil; Jazayeri, Seyed Behzad; Rahimi-Movaghar, Vafa

2013-08-01

CNS tumors are the leading cause of cancer related deaths among children and adolescents. Nonetheless, the incidence of pediatric CNS tumors in developing countries is poorly understood. We aimed to provide epidemiologic features of primary malignant CNS tumors in Iranian children 0-19 years of age using National Cancer Registry (NCR) data bank. The data recorded by NCR over a 10 year period (2000-2010) were reviewed. Of 1948 tumor cases, 93.3% were located in brain, 5.1% were found in the spinal cord & cauda equina, and 1.6% affected cranial nerves and other parts of the nervous system. The overall average annual age specific incidence rate was 1.43 per 100,000. Males were more likely to develop CNS tumors (1.65 per 100,000) compared to females (1.21 per 100,000, p<0.01). Children under 5 years of age had the highest age specific incidence rate (1.86 per 100,000). Astrocytic tumors with the incidence rate of 0.61 per 100,000 were the most frequent specific histology followed by embryonal (0.38 per 100,000), and ependymal tumors (0.10 per 100,000). With regard to the histological distribution of tumors, some unique features including the high proportion of unspecified malignant neoplasms (7.6%) were noted. The overall incidence rate was markedly lower than western findings. Major differences were also observed in incidence rates of specific histologies. Although the discrepancies may be attributable to diversity in classification schemes and registration practices, a real ethnic and geographical variation in predisposition to development of pediatric CNS cancers is strongly suggested. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sun Exposure and Protection Habits in Pediatric Patients with a History of Malignancy

PubMed Central

Levy-Shraga, Yael; Cohen, Rinat; Ben Ami, Michal; Yeshayahu, Yonatan; Temam, Vered; Modan-Moses, Dalit

2015-01-01

Background Survivors of childhood cancer are at high risk for developing non-melanoma skin cancer and therefore are firmly advised to avoid or minimize sun exposure and adopt skin protection measures. We aimed to compare sun exposure and protection habits in a cohort of pediatric patients with a history of malignancy to those of healthy controls. Methods Case-control study of 143 pediatric patients with a history of malignancy (aged 11.2±4.6y, Male = 68, mean interval from diagnosis 4.4±3.8y) and 150 healthy controls (aged 10.4±4.8y, Male = 67). Sun exposure and protection habits were assessed using validated questionnaires. Results Patients and controls reported similar sun exposure time during weekdays (94±82minutes/day vs. 81±65minutes/day; p = 0.83), while during weekends patients spent significantly less time outside compared to controls (103±85minutes/day vs. 124±87minutes/day; p = 0.02). Time elapsed from diagnosis positively correlated with time spent outside both during weekdays (r = 0.194, p = 0.02) and weekends (r = 0.217, p = 0.01), and there was a step-up in sun exposure starting three years after diagnosis. There was no significant difference regarding composite sun protection score between patients and controls. Age was positively correlated with number of sunburns per year and sun exposure for the purpose of tanning, and was negatively correlated with the use of sun protection measures. Conclusions Although childhood cancer survivors are firmly instructed to adopt sun protection habits, the adherence to these instructions is incomplete, and more attention should be paid to improve these habits throughout their lives. Since sunlight avoidance may results in vitamin D deficiency, dietary supplementation will likely be needed. PMID:26348212

Demographic and clinicopathologic distribution of head and neck malignant tumors in pediatric patients from a Brazilian population: A retrospective study.

PubMed

Arboleda, Lady Paola Aristizabal; Hoffmann, Iva Loureiro; Cardinalli, Izilda Aparecida; Santos-Silva, Alan Roger; de Mendonça, Regina Maria Holanda

2018-05-04

The incidence of pediatric head and neck cancer (PHNC) is increasing worldwide, especially when compared with childhood cancer in general. However, there is still a lack of knowledge about the demographic profile of such patients across the globe. Therefore, the aim of this study was to describe demographic, topographic, and histopathological features of PHNC patients from a single Brazilian institution. Medical records were retrospectively reviewed for all cancer cases diagnosed from 1986 to 2016 affecting patients aged 19 years and younger. The demographic variables (age, gender, race), topographic aspects of primary tumors, and histopathological diagnoses were collected and analyzed by descriptive statistics. Three hundred and sixty-seven (5.11%) head and neck malignant tumors were found among 7181 pediatric cancers diagnosed in this period. Mean age at diagnosis was 9.35 years with male (65.67%) predominance. Patients between the age group of 10-14 years presented the higher prevalence of malignant tumors. In terms of race, 73.02% of the patients were white and 9.54% were black. The main affected anatomic site was the neck and lymph nodes (41.42%), followed by nasopharynx (22.89%) and thyroid gland (6.54%). The most common cancer type was lymphoma (52.86%), followed by carcinoma (22.89%), and sarcoma (19.07%). Burkitt lymphoma, nodular sclerosis Hodgkin lymphoma, nasopharyngeal carcinoma, and rhabdomyosarcoma were the most common histopathological diagnoses (16.62%, 13.08%, 12.81%, and 12.81%, respectively). This study originally demonstrated that lymphomas may be more frequent than carcinomas and sarcomas in Brazilian PHNC patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy--A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee.

PubMed

Raman, Sripriya; Grimberg, Adda; Waguespack, Steven G; Miller, Bradley S; Sklar, Charles A; Meacham, Lillian R; Patterson, Briana C

2015-06-01

GH and IGF-1 have been shown to affect tumor growth in vitro and in some animal models. This report summarizes the available evidence on whether GH therapy in childhood is associated with an increased risk of neoplasia during treatment or after treatment is completed. A PubMed search conducted through February 2014 retrieved original articles written in English addressing GH therapy and neoplasia risk. Subsequent searches were done to include additional relevant publications. In children without prior cancer or known risk factors for developing cancer, the clinical evidence does not affirm an association between GH therapy during childhood and neoplasia. GH therapy has not been reported to increase the risk for neoplasia in this population, although most of these data are derived from postmarketing surveillance studies lacking rigorous controls. In patients who are at higher risk for developing cancer, current evidence is insufficient to conclude whether or not GH further increases cancer risk. GH treatment of pediatric cancer survivors does not appear to increase the risk of recurrence but may increase their risk for subsequent primary neoplasms. In children without known risk factors for malignancy, GH therapy can be safely administered without concerns about an increased risk for neoplasia. GH use in children with medical diagnoses predisposing them to the development of malignancies should be critically analyzed on an individual basis, and if chosen, appropriate surveillance for malignancies should be undertaken. GH can be used to treat GH-deficient childhood cancer survivors who are in remission with the understanding that GH therapy may increase their risk for second neoplasms.

Can a Modified Bosniak Classification System Risk Stratify Pediatric Cystic Renal Masses?

PubMed

Saltzman, Amanda F; Carrasco, Alonso; Colvin, Alexandra N; Meyers, Mariana L; Cost, Nicholas G

2018-03-20

We characterize and apply the modified Bosniak classification system to a cohort of children with cystic renal lesions and known surgical pathology. We identified all patients at our institution with cystic renal masses who also underwent surgery for these lesions. Patients without available preoperative imaging or pathology were excluded. All radiological imaging was independently reviewed by a pediatric radiologist blinded to pathological findings. Imaging characteristics (size, border, septations, calcifications, solid components, vascularity) were recorded from the most recent preoperative ultrasounds and computerized tomograms. The modified Bosniak classification system was applied to these scans and then correlated with final pathology. A total of 22 patients met study criteria. Median age at surgery was 6.1 years (range 11 months to 16.8 years). Of the patients 12 (54.5%) underwent open nephrectomy, 6 (27.3%) open partial nephrectomy, 2 (9.1%) laparoscopic cyst decortication, 1 (4.5%) open renal biopsy and 1 (4.5%) laparoscopic partial nephrectomy. Final pathology was benign in 9 cases (41%), intermediate in 6 (27%) and malignant in 7 (32%). All malignant lesions were modified Bosniak class 4, all intermediate lesions were modified class 3 or 4 and 8 of 9 benign lesions (89%) were modified class 1 or 2. Cystic renal lesions in children with a modified Bosniak class of 1 or 2 were most often benign, while class 3 or 4 lesions warranted surgical excision since more than 90% of masses harbored intermediate or malignant pathology. The modified Bosniak classification system appears to allow for a reasonable clinical risk stratification of pediatric cystic renal masses. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Patterns of Care in Proton Radiation Therapy for Pediatric Central Nervous System Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Odei, Bismarck; Frandsen, Jonathan E.; Boothe, Dustin

Purpose: Proton beam therapy (PBT) potentially allows for improved sparing of normal tissues, hopefully leading to decreased late side effects in children. Using a national registry, we sought to perform a patterns-of-care analysis for children receiving PBT for primary malignancies of the central nervous system (CNS). Methods and Materials: Using the National Cancer Data Base, we identified pediatric patients with primary CNS malignancies that were diagnosed between 2004 and 2012. We used a standard t test for comparison of means and χ{sup 2} testing to identify differences in demographic and clinical characteristics. Univariate and multivariate logistical regression was applied tomore » identify predictors of PBT use. Results: We identified 4637 pediatric patients receiving radiation therapy from 2004 to 2012, including a subset of 267 patients treated with PBT. We found that PBT use increased with time from <1% in 2004 to 15% in 2012. In multivariate logistical regression, we found the following to be predictors of receipt of PBT: private insurance, the highest income bracket, younger age, living in a metropolitan area, and residing >200 miles from a radiation treatment facility (P<.05). Conclusions: We noted the proportion of children receiving PBT to be significantly increasing over time from <1% to 15% from 2004 to 2012. We also observed important disparities in receipt of PBT based on socioeconomic status. Children from higher-income households and with private insurance were more likely to use this expensive technology. As we continue to demonstrate the potential benefits of PBT in children, efforts are needed to expand the accessibility of PBT for children of all socioeconomic backgrounds and regions of the country.« less

Preclinical Evaluation of Engineered Oncolytic Herpes Simplex Virus for the Treatment of Pediatric Solid Tumors

PubMed Central

Megison, Michael L.; Gillory, Lauren A.; Stewart, Jerry E.; Nabers, Hugh C.; Mroczek-Musulman, Elizabeth; Waters, Alicia M.; Coleman, Jennifer M.; Kelly, Virginia; Markert, James M.; Gillespie, G. Yancey; Friedman, Gregory K.; Beierle, Elizabeth A.

2014-01-01

Recently, investigators showed that mice with syngeneic murine gliomas that were treated with a neuroattenuated oncolytic herpes simplex virus-1 (oHSV), M002, had a significant increase in survival. M002 has deletions in both copies of the γ134.5 gene, enabling replication in tumor cells but precluding infection of normal cells. Previous studies have shown antitumor effects of other oHSV against a number of adult tumors including hepatocellular carcinoma and renal cell carcinoma. The purpose of the current study was to investigate the oncolytic potential of M002 against difficult to treat pediatric liver and kidney tumors. We showed that the oHSV, M002, infected, replicated, and decreased cell survival in hepatoblastoma, malignant rhabdoid kidney tumor, and renal sarcoma cell lines. In addition, we showed that in murine xenografts, treatment with M002 significantly increased survival and decreased tumor growth. Finally, these studies showed that the primary entry protein for oHSV, CD111 (nectin-1) was present in human hepatoblastoma and malignant rhabdoid kidney tumor specimens. We concluded that M002 effectively targeted these rare aggressive tumor types and that M002 may have potential for use in children with unresponsive or relapsed pediatric solid tumors. PMID:24497984

Pediatric cancer gone viral. Part I: strategies for utilizing oncolytic herpes simplex virus-1 in children

PubMed Central

Cripe, Timothy P; Chen, Chun-Yu; Denton, Nicholas L; Haworth, Kellie B; Hutzen, Brian; Leddon, Jennifer L; Streby, Keri A; Wang, Pin-Yi; Markert, James M; Waters, Alicia M; Gillespie, George Yancey; Beierle, Elizabeth A; Friedman, Gregory K

2015-01-01

Progress for improving outcomes in pediatric patients with solid tumors remains slow. In addition, currently available therapies are fraught with numerous side effects, often causing significant life-long morbidity for long-term survivors. The use of viruses to kill tumor cells based on their increased vulnerability to infection is gaining traction, with several viruses moving through early and advanced phase clinical testing. The prospect of increased efficacy and decreased toxicity with these agents is thus attractive for pediatric cancer. In part I of this two-part review, we focus on strategies for utilizing oncolytic engineered herpes simplex virus (HSV) to target pediatric malignancies. We discuss mechanisms of action, routes of delivery, and the role of preexisting immunity on antitumor efficacy. Challenges to maximizing oncolytic HSV in children are examined, and we highlight how these may be overcome through various arming strategies. We review the preclinical and clinical evidence demonstrating safety of a variety of oncolytic HSVs. In Part II, we focus on the antitumor efficacy of oncolytic HSV in pediatric tumor types, pediatric clinical advances made to date, and future prospects for utilizing HSV in pediatric patients with solid tumors. PMID:26436135

High-dose etoposide (VP-16)-containing preparatory regimens in allogeneic and autologous bone marrow transplantation for hematologic malignancies.

PubMed

Blume, K G; Forman, S J

1992-12-01

High-dose etoposide has been added to total body irradiation, cyclophosphamide, carmustine, or busulfan in preparatory regimens for allogeneic or autologous bone marrow transplantation for patients with leukemia, Hodgkin's disease, lymphoma, or multiple myeloma. The treatment results are encouraging, indicating that etoposide may be a valuable addition to the previously established regimens. Etoposide should be incorporated into collaborative, prospective trials to define its ultimate role in bone marrow transplantation.

Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

ClinicalTrials.gov

2016-05-16

Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

A Rare Case of Malignant Melanoma of the Mandible: 
CT and MRI Findings.

PubMed

Ogura, Ichiro; Sasaki, Yoshihiko; Kameta, Ayako; Sue, Mikiko; Oda, Takaaki

Malignant melanoma of the mandibular gingiva is extremely rare. It is a malignant tumour of melanocytes or their precursor cells, and often misinterpreted as a benign pigmented process. A few reports have described computed tomography (CT) and magnetic resonance imaging (MRI) findings of malignant melanoma in the oral cavity. We report a rare case of malignant melanoma of the mandible and the related CT and MRI findings. Soft tissue algorithm contrast-enhanced CT showed an expansile mass and irregular destruction of alveolar bone in the right side of the mandibular molar area. MR images showed an enhancing mass and the tumour had a low to intermediate signal intensity and a high-signal intensity. Soft tissue algorithm contrast-enhanced CT and MR images showed lymphadenopathy involving the submandibular lymph nodes. Histopathological examination confirmed the diagnosis of malignant melanoma.

Evaluation of neoadjuvant chemotherapy effects on liver parenchyma in resected pediatric malignancies.

PubMed

Scuderi, Maria Grazia; Magro, Gaetano; Di Cataldo, Andrea; Pesce, Antonino; Scalora, Luisa; Vecchio, Giada Maria; Portale, Rosanna; Di Benedetto, Vincenzo; Puleo, Stefano

2013-08-01

Neoadjuvant chemotherapy for colorectal liver metastases in adults is responsible for chemotherapy-associated liver injury (CALI), characterized by steatosis, steatohepatitis, and sinusoidal obstruction syndrome. These alterations cause delayed operation to reduce the risk of hemorrhage, portal hypertension, and hepatic failure. Children with hepatic malignancies usually receive neoadjuvant chemotherapy prior to surgery. The aim of this study was to evaluate retrospectively whether the CALI occurs in this pediatric population. This study evaluated patients referred since 1996 for hepatic malignancies who received hepatectomy after chemotherapy. Liver resection material was reviewed, in order to investigate the presence of morphological changes compatible with the CALI in the peritumoral hepatic tissue. Twelve patients were recruited. All patients satisfied the inclusion criteria except one who did not receive neoadjuvant chemotherapy. Eleven children underwent surgery 1 month after the last chemotherapy cycle. All are alive disease-free. Histological examination of specimen revealed only mild changes such as diffuse swelling of hepatocytes and focal, mild portal inflammation. Severe hepatic changes such as steatosis, necrosis, or fibrosis were not identified. CALI-related morphological changes were not found in our patients. The absence of the CALI could be attributed to the younger age of patients (possible different response to stress) and/or to the different chemotherapy schedules compared to those in use for adults patients.

Oropharyngeal candidiasis in children with lymphohematopoietic malignancies in Mashhad, Iran

PubMed Central

Berenji, F; Zabolinejad, N; Badiei, Z; Kakhi, S; Andalib Aliabadi, Z; Ganjbakhsh, M

2015-01-01

Background and Purpose: Over the past years, the role of fungi as a cause of nosocomial infections in hospitalized patients has been accentuated. Candida species constitute an important group of fungi causing diseases in immunocompromised patients. Oropharyngeal candidiasis continues to be a prevalent infection in immunodeficient patients. In this study, we aimed to determine the incidence of oropharyngeal candidiasis in children with lymphohematopoietic malignancies. Materials and Methods: In total, 102 patients with lymphohematopoietic malignancies and 50 healthy controls were examined in terms of Candida infections via direct sampling of the oropharyngeal cavity. Fresh smears were prepared with 10% potassium hydroxide and Gram staining was carried out. Subsequently, the obtained specimens were cultured on Sabouraud dextrose agar for further analysis. Results: The most common Candida species were Candida albicans (31%), other non-C. albicans species (14.7%), C. glabrata (6.8%), and C. krusei (0.98%) in the case group, while in the control group, other non-C. albicans species (10%) and C. albicans (8%) were the most common species. Conclusion: In the present study, Candida species were the most common fungal pathogens in pediatric cancer patients; therefore, efforts should be made to prevent fungemia and fungal pneumonia. Also, non-C. albicans species must be considered as a new risk factor for pediatric cancer patients. PMID:28681002

Oropharyngeal candidiasis in children with lymphohematopoietic malignancies in Mashhad, Iran.

PubMed

Berenji, F; Zabolinejad, N; Badiei, Z; Kakhi, S; Andalib Aliabadi, Z; Ganjbakhsh, M

2015-12-01

Over the past years, the role of fungi as a cause of nosocomial infections in hospitalized patients has been accentuated. Candida species constitute an important group of fungi causing diseases in immunocompromised patients. Oropharyngeal candidiasis continues to be a prevalent infection in immunodeficient patients. In this study, we aimed to determine the incidence of oropharyngeal candidiasis in children with lymphohematopoietic malignancies. In total, 102 patients with lymphohematopoietic malignancies and 50 healthy controls were examined in terms of Candida infections via direct sampling of the oropharyngeal cavity. Fresh smears were prepared with 10% potassium hydroxide and Gram staining was carried out. Subsequently, the obtained specimens were cultured on Sabouraud dextrose agar for further analysis. The most common Candida species were Candida albicans (31%), other non- C. albicans species (14.7%), C. glabrata (6.8%), and C. krusei (0.98%) in the case group, while in the control group, other non- C. albicans species (10%) and C. albicans (8%) were the most common species. In the present study, Candida species were the most common fungal pathogens in pediatric cancer patients; therefore, efforts should be made to prevent fungemia and fungal pneumonia. Also, non -C. albicans species must be considered as a new risk factor for pediatric cancer patients.

Metastatic mediastinal mature teratoma with malignant transformation in a young man with an adenocarcinoma in a Klinefelter's syndrome: Case report and review of the literature.

PubMed

Le Fèvre, C; Vigneron, C; Schuster, H; Walter, A; Marcellin, L; Massard, G; Lutz, P; Noël, G

2018-05-01

Malignant transformation of mediastinal mature teratoma is extremely rare and worsens the prognosis of the disease. Transformation can appear synchronously to or several years after the initial diagnosis. Clinical and radiological signs can orientate the clinician but the definitive diagnosis is obtained thanks to histology. An 11 year-old boy presented with a mediastinal mature teratoma and bone and pulmonary metastases. He received six cycles of chemotherapy combining etoposide, ifosfamide, cisplatin, followed by resection of a 16×14×9cm mediastinal mass. Karyotype analysis revealed the presence of an additional sex chromosome X (47 XXY) pathognomonic of Klinefelter's syndrome. Ten years later, sciatalgia revealed malignant transformation of a pre-existing sacral bone metastasis into gastrointestinal adenocarcinoma. The patient received four cycles of chemotherapy combining oxaliplatin, 5-fluorouracil and cetuximab. This treatment was followed by a complete resection of the sacral metastasis and completed with adjuvant irradiation of 54Gy in 30 daily fractions. Twelve months after the diagnosis of relapse, the patient remained alive without disease. To our knowledge, this is the first case of adenocarcinoma developed in bone metastases of a mediastinal mature teratoma in a boy with a Klinefelter's syndrome. We propose a review of the literature and an analysis of 20 others published cases of mediastinal teratoma with malignant transformation into adenocarcinoma. Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

A Histologically Diagnosed Case with Infantile Osteopetrosis Complicated by Hypopituitarism

PubMed Central

Calkavur, Sebnem; Buyukinan, Muammer; Altay, Canan

2015-01-01

Malignant infantile osteopetrosis is a rarely seen severe disorder which appears early in life with general sclerosis of the skeleton. It is caused by functionally defective osteoclasts which fail to resorb bone. Affected infants can exhibit a wide spectrum of clinical manifestations including impaired hematopoiesis, hepatosplenomegaly, visual impairment, and hypocalcemia. With the exception of secondary hyperparathyroidism, involvement of the endocrine system seems to be quite rare. Hypopituitarism is defined as underproduction of the growth hormone in combination with deficiencies of other pituitary hormones. Any lesion that damages hypothalamus, pituitary stalk, or anterior pituitary can cause secondary hypopituitarism. In this report, we presented a rare combination of malignant infantile osteopetrosis and secondary hypopituitarism in a newborn who presented predominantly with endocrinological symptoms. This is the first case report of malignant infantile osteopetrosis accompanied by hypopituitarism secondary to sclerosis of the sella turcica. On the other hand, this is a very interesting case which was diagnosed based on histological examination of bone marrow biopsy specimens despite lack of any clinical suspicion. PMID:26576309

Severe pediatric Graves orbitopathy in adolescents of African origin.

PubMed

Papp, Andrea; Vasserot-Merle, Clemence; Dorner, Guido; Paridaens, Dion

2016-12-01

This article reports on two cases of severe pediatric Graves orbitopathy (GO) in two adolescents of African origin. Two black male adolescents presented with highly active GO and signs of beginning compressive optic neuropathy. Neither of them were smokers nor had a family history of GO. Besides urgent referral to pediatric endocrinologists, intravenous methylprednisolon pulse therapy was initiated. In spite of the fluctuating thyroid hormone levels in the initial phase of antithyroid therapy, intravenous steroid administration stopped the progression of malignant GO rapidly in both of our patients without any considerable side effects. Although the course of GO during childhood is considered to be mild, severe, sight threatening GO-requiring immunosuppression-may occur at young age, as in the reported adolescent patients of African descent.

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment.

PubMed

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas.

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

PubMed Central

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas. PMID:26448930

Creation of a pediatric mature B-cell non-Hodgkin lymphoma cohort within the Pediatric Health Information System Database.

PubMed

Citrin, Rebecca; Horowitz, Joseph P; Reilly, Anne F; Li, Yimei; Huang, Yuan-Shung; Getz, Kelly D; Seif, Alix E; Fisher, Brian T; Aplenc, Richard

2017-01-01

Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a collection of relatively rare pediatric malignancies. In order to utilize administrative data to perform large-scale epidemiologic studies within this population, a two-step process was used to assemble a 12-year cohort of B-NHL patients treated between 2004 and 2015 within the Pediatric Health Information System database. Patients were identified by ICD-9 codes, and their chemotherapy data were then manually reviewed against standard B-NHL treatment regimens. A total of 1,409 patients were eligible for cohort inclusion. This process was validated at a single center, utilizing both an institutional tumor registry and medical record review as the gold standards. The validation demonstrated appropriate sensitivity (91.5%) and positive predictive value (95.1%) to allow for the future use of this cohort for epidemiologic and comparative effectiveness research.

Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells.

PubMed

Yong, Pierre L; Orange, Jordan S; Sullivan, Kathleen E

2010-08-01

Recent studies suggest that patients with common variable immunodeficiency (CVID) and low numbers of switched memory B cells have lower IgG levels and higher rates of autoimmune disease, splenomegaly, and granulomatous disease; however, no prior literature has focused exclusively on pediatric cases. We examined the relationship between switched memory B cells and clinical and immunologic manifestations of CVID in a pediatric population. Forty-five patients were evaluated. Patients were categorized as Group I (<5 switched memory B cells/ml, n = 24) or Group II (> or =5 switched memory B cells/mL, n = 21). CD3(+) T-cell counts and CD19(+) B-cell levels were lower among Group I patients. Only those in Group I had meningitis, sepsis, bronchiectasis, granulomatous lung disease, autoimmune cytopenias, or hematologic malignancies. Segregation of pediatric patients into high risk (Group I) and average risk (Group II) may assist in targeting surveillance appropriately.

Development of a Novel Synthetic Drug for Osteoporosis and Fracture Healing

DTIC Science & Technology

2012-09-01

application to chondrosarcoma , and preparation for bone fracture study. Body Aim 1: Development of salubrinal formulations and determination of...development of bone marrow derived cells, osteoclasts, osteoblasts, and chondrocytes. Application to chondrosarcoma : Besides osteoporosis and...osteoarthritis, we considered a potential application of salubrinal to skeletal malignancies. Approximately one-third of skeletal cancers form chondrosarcoma

An Alu-like RNA promotes cell differentiation and reduces malignancy of human neuroblastoma cells.

PubMed

Castelnuovo, Manuele; Massone, Sara; Tasso, Roberta; Fiorino, Gloria; Gatti, Monica; Robello, Mauro; Gatta, Elena; Berger, Audrey; Strub, Katharina; Florio, Tullio; Dieci, Giorgio; Cancedda, Ranieri; Pagano, Aldo

2010-10-01

Neuroblastoma (NB) is a pediatric cancer characterized by remarkable cell heterogeneity within the tumor nodules. Here, we demonstrate that the synthesis of a pol III-transcribed noncoding (nc) RNA (NDM29) strongly restricts NB development by promoting cell differentiation, a drop of malignancy processes, and a dramatic reduction of the tumor initiating cell (TIC) fraction in the NB cell population. Notably, the overexpression of NDM29 also confers to malignant NB cells an unpredicted susceptibility to the effects of antiblastic drugs used in NB therapy. Altogether, these results suggest the induction of NDM29 expression as possible treatment to increase cancer cells vulnerability to therapeutics and the measure of its synthesis in NB explants as prognostic factor of this cancer type.

Trichosporon asahii sepsis in a patient with pediatric malignancy.

PubMed

Ozkaya-Parlakay, Aslinur; Karadag-Oncel, Eda; Cengiz, Ali Bulent; Kara, Ates; Yigit, Atilla; Gucer, Safak; Gur, Deniz

2016-02-01

Trichosporon asahii is a rare opportunistic infection, especially in children, causing a life-threatening fungal infection underlying hematologic malignancies. Predisposing factors for infection with this pathogen are immunodeficiency including underlying malignancy, organ transplantation, extensive burns, human immunodeficiency virus infection, corticosteroid therapy, prosthetic valve surgery, and peritoneal dialysis. In the literature, a breakthrough under caspofungin, micafungin therapy is reported. In this article we report on a 16-year-old patient with Ewing sarcoma who had T. asahii sepsis. The patient died although he had been receiving caspofungin for less than 3 months and amphotericin B therapy for 3 days. A postmortem study of conchal tissues revealed T. asahii and mucormycosis histopathologically, and blood culture grew T. asahii. Copyright © 2013. Published by Elsevier B.V.

Laparoscopic Treatment of Mixed Malignant Ovarian Germ Cell Tumor in a 16-Year-Old Female Adolescent.

PubMed

Friedman, Caroline; Fenster, Tamatha

2016-12-01

Malignant ovarian germ cell tumors are rare entities, although they account for a large proportion of ovarian masses in young women. These tumors have traditionally been removed via laparotomy, because of their large size and solid nature. The use of laparoscopy for treatment of adnexal masses in adolescents has been heavily debated and poorly studied to date. A 16-year-old female patient presented with abdominal pain and an 11-cm adnexal mass on ultrasound. An emergent laparoscopic salpingo-oophorectomy was performed without complication. Pathology revealed a mixed malignant ovarian germ cell tumor. Laparoscopic fertility-sparing surgery offers many benefits over laparotomy, and should be considered in cases of young women with large adnexal masses, even if potential for malignancy exists. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Examination of life-threatening injuries in 431 pediatric facial fractures at a level 1 trauma center.

PubMed

Hoppe, Ian C; Kordahi, Anthony M; Paik, Angie M; Lee, Edward S; Granick, Mark S

2014-09-01

Pediatric facial fractures represent a challenge in management due to the unique nature of the growing facial skeleton. Oftentimes, more conservative measures are favored to avoid rigid internal fixation and disruption of blood supply to the bone and soft tissues. In addition, the great force required to fracture bones of the facial skeleton often produces concomitant injuries that present a management priority. The purpose of this study was to examine a level 1 trauma center's experience with pediatric facial trauma resulting in fractures of the underlying skeleton with regards to epidemiology and concomitant injuries. A retrospective review of all facial fractures at a level 1 trauma center in an urban environment was performed for the years 2000 to 2012. Patients aged 18 years or younger were included. Patient demographics were collected, as well as location of fractures, concomitant injuries, and surgical management strategies. A significance value of 5% was used. During this period, there were 3147 facial fractures treated at our institution, 353 of which were pediatric patients. Upon further review, 68 patients were excluded because of insufficient data for analysis, leaving 285 patients for review. The mean age of patients was 14.2 years with a male predominance (77.9%). The mechanism of injury was assault in 108 (37.9%), motor vehicle accident in 68 (23.9%), pedestrian struck in 41 (14.4%), fall in 26 (9.1%), sporting accident in 20 (7.0%), and gunshot injury in 16 (5.6%). The mean Glasgow Coma Scale (GCS) on arrival to the emergency department was 13.7. The most common fractures were those of the mandible (29.0%), orbit (26.5%), nasal bone (14.4%), zygoma (7.7%), and frontal bone/frontal sinus (7.5%). Intracranial hemorrhage was present in 70 patients (24.6%). A skull fracture was present in 50 patients (17.5%). A long bone fracture was present in 36 patients (12.6%). A pelvic or thoracic fracture was present in 30 patients (10.5%). A cervical spine fracture was present in 10 patients (3.5%), and a lumbar spine fracture was present in 11 patients (3.9%). Fractures of the zygoma, orbit, nasal bone, and frontal sinus/bone were significantly associated with intracranial hemorrhage (P < 0.05). Fractures of the zygoma and orbit were significantly associated with cervical spine injury (P < 0.05). The mean GCS for patients with and without intracranial hemorrhages was 11.0 and 14.6, respectively (P < 0.05). The mean GCS for patients with and without cervical spine fractures was 11.2 and 13.8, respectively (P < 0.05). Pediatric facial fractures in our center are often caused by interpersonal violence and are frequently accompanied by other more life-threatening injuries. The distribution of fractures parallels previous literature. Midface fractures and a depressed GCS showed a strong correlation with intracranial hemorrhage and cervical spine fracture. A misdiagnosed cervical spine injury or intracranial hemorrhage has disastrous consequences. On the basis of this study, it is the authors' recommendation that any patient sustaining a midface fracture with an abnormal GCS be evaluated for the aforementioned diagnoses.

The Kinetic Family Drawing with Donor and Nondonor Siblings of Pediatric Bone Marrow Transplant Patients.

ERIC Educational Resources Information Center

Packman, Wendy L.; Crittenden, Mary R.; Fischer, Jodie B. Rieger; Cowan, Morton J.; Long, Janet K.; Gruenert, Carol; Schaeffer, Evonne; Bongar, Bruce

1998-01-01

Utilizes the Kinetic Family Drawings-Revised (KFD-R) to measure siblings' (N=44) feelings and attitudes toward bone marrow transplants. Data from drawings and discussions with siblings underscore that not all children are affected by stress in the same way. How a particular child responds depends on factors such as life history, personality,…

Trial of Dasatinib in Advanced Sarcomas

ClinicalTrials.gov

2017-03-20

Rhabdomyosarcoma; Malignant Peripheral Nerve Sheath Tumors; Chondrosarcoma; Sarcoma, Ewing's; Sarcoma, Alveolar Soft Part; Chordoma; Epithelioid Sarcoma; Giant Cell Tumor of Bone; Hemangiopericytoma; Gastrointestinal Stromal Tumor (GIST)

Multiple myeloma

MedlinePlus

Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... Multiple myeloma most commonly causes: Low red blood cell count ( anemia ), which can lead to fatigue and ...

Primary Neoplasms of Bones in Mice: Retrospective Study and Review of Literature

PubMed Central

Kavirayani, A. M.; Sundberg, J. P.; Foreman, O.

2011-01-01

To compare and summarize the mechanisms, frequencies of occurrence, and classification schemes of spontaneous, experimental, and genetically engineered, mouse skeletal neoplasms, the literature was reviewed and archived case material at The Jackson Laboratory examined. The frequency of occurrence of spontaneous bone neoplasms was less than 1% for most strains, with the exceptions of osteomas in CF-1 (5.5% and 10% in two studies) and OF-1 outbred strains (35%), and osteosarcomas in NOD/ShiLtJ (11.5%) and NOD derived (7.1%) mice. The frequency was 100% for osteochondromas induced by conditional inactivation of exostoses (multiple) 1 (Ext1) in chondrocytes, osteosarcomas induced by tibial intramedullary inoculation of Moloney’s murine sarcoma virus, and osteosarcomas induced by conditional inactivation of Trp53-with or without inactivation of Rb1-in osteoblast precursors. Spontaneous osteogenic neoplasms were more frequent than spontaneous cartilaginous and vascular types. Malignant neoplasms were more frequent than benign ones. The age of occurrence for spontaneous neoplasms ranged from 37 to 720 (Mean 316.35) days for benign, and 35 to 990 (Mean 299.28) days for malignant neoplasms. In genetically engineered mice, the average age of occurrence ranged from 28 to 70 days for benign, and from 35 to 690 days for malignant neoplasms. Histologically, non-osteogenic neoplasms were similar across strains and mutant stocks; osteogenic neoplasms exhibited greater diversity. This comparison and summarization of mouse bone neoplasms provides valuable information for the selection of strains to create, compare, and validate models of bone neoplasms. PMID:21343597

Self-perception and quality of life in adolescents during treatment for a primary malignant bone tumour.

PubMed

van Riel, Christel A H P; Meijer-van den Bergh, Esther E M; Kemps, Hennie L M; Feuth, Ton; Schreuder, Hendrik W B; Hoogerbrugge, Peter M; De Groot, Imelda J M; Mavinkurve-Groothuis, Annelies M C

2014-06-01

Adolescents experience physical and psychosocial changes as part of their normal development. It can be hypothesized that they have lower scores on Quality of Life (QoL) and self-perception when additional changes occur due to cancer treatment. The purpose of our study was to assess self-perception and QoL of adolescents during or up to three months after adjuvant treatment for a primary malignant bone tumour. Ten adolescent patients (median age of 15 years) were included. Every patient was matched with two healthy peers. Participants completed the dutch version of the Self Perception Profile of Adolescents (SPPA) to measure self-perception and the KIDSCREEN-52 questionnaire for QoL. For both instruments, normative data were available. Adolescents with a bone tumour had consistently lower scores on QoL as compared to healthy peers. Significantly on domains: physical well-being (P < 0.002), autonomy (P = 0.02), social support (P = 0.04) and school environment (P = 0.02). Scores on self-perception in this group were similar in both the study and control group. Adolescents with a primary malignant bone tumour during or up to three months after adjuvant treatment had lower scores on QoL (KIDSCREEN-52), significantly on domains of physical well-being and social functioning. Unlike most other quality of life instruments, the KIDSCREEN-52 contains different areas of social functioning and has shown to be a useful instrument in our patient group. Scores on self-perception in this group were similar in both study and control group. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nodular Fasciitis with Cortical Erosion of the Hand

PubMed Central

Park, Jin Sung; Lee, Jong-Sil; Na, Jae-Boem

2012-01-01

Nodular fasciitis is a benign, reactive myofibroblastic tumor that is often mistaken for a sarcoma because of its histological appearance and rapid growth. Involvement of a finger is extremely rare. We report a case of nodular fasciitis of the thumb, accompanied by bone erosion. Magnetic resonance findings suggested the possibility of a malignancy, which could have led to misdiagnosis as a malignant soft tissue sarcoma. Instead, the lesion was treated by excisional biopsy, which confirmed nodular fasciitis. There has been no evidence of local recurrence at recent follow-up, 1 year after surgery. This case illustrates that, to avoid unnecessarily aggressive surgery, nodular fasciitis must be included in the differential diagnosis for any finger lesion that resembles a sarcoma, even if bone erosion is present. PMID:22379562

Atlas of computerized blood flow analysis in bone disease.

PubMed

Gandsman, E J; Deutsch, S D; Tyson, I B

1983-11-01

The role of computerized blood flow analysis in routine bone scanning is reviewed. Cases illustrating the technique include proven diagnoses of toxic synovitis, Legg-Perthes disease, arthritis, avascular necrosis of the hip, fractures, benign and malignant tumors, Paget's disease, cellulitis, osteomyelitis, and shin splints. Several examples also show the use of the technique in monitoring treatment. The use of quantitative data from the blood flow, bone uptake phase, and static images suggests specific diagnostic patterns for each of the diseases presented in this atlas. Thus, this technique enables increased accuracy in the interpretation of the radionuclide bone scan.

Excess comorbidities associated with malignant hyperthermia diagnosis in pediatric hospital discharge records.

PubMed

Li, Guohua; Brady, Joanne E; Rosenberg, Henry; Sun, Lena S

2011-09-01

Case reports have linked malignant hyperthermia (MH) to several genetic diseases. The objective of this study was to quantitatively assess excess comorbidities associated with MH diagnosis in pediatric hospital discharge records. Data for this study came from the Kids' Inpatient Database (KID) for the years 2000, 2003, and 2006. The KID contains an 80% random sample of patients under the age of 21 discharged from short-term, non-Federal hospitals in the United States, with up to 19 diagnoses recorded for each patient. Using all pediatric inpatients as the reference, we calculated the standardized morbidity ratios (SMRs) and 95% confidence intervals (CIs) for children with MH diagnosis according to major disease groups and specific medical conditions. Of the 5,916,989 nonbirth-related hospital discharges studied, 175 had a recorded diagnosis of MH. Compared with the general pediatric inpatient population, children with MH diagnosis were significantly more likely to be diagnosed with diseases of the musculoskeletal system and connective tissue (SMR 5.7; 95% CI: 3.9-7.9), diseases of the circulatory system (SMR 3.3; 95% CI: 2.1-4.8), and congenital anomalies (SMR 3.2; 95% CI: 2.3-4.4). The specific diagnosis that was most strongly associated with MH was muscular dystrophies (SMR 31.3; 95% CI 12.6-64.6). Diseases of the musculoskeletal system and connective tissue are significantly associated with MH diagnosis in children. Further research is warranted to determine the clinical utility of these comorbidities in assessing MH susceptibility in children. © 2011 Blackwell Publishing Ltd.

Literature Review of Periclitoral Cysts in the Prepubertal Population.

PubMed

Nelson, Kayla L; McQuillan, Sarah K; Brain, Philippa

2016-12-01

Clitoral cysts in the pediatric population are rare conditions that require careful evaluation. In this review of the literature we discuss the evaluation of clitoral abnormalities in the pediatric population, the development of clitoral cysts, and how to differentiate benign from malignant tumors. In addition, a summary of relevant cases of clitoral tumors in the literature are discussed. Literature review. A MedLine and advanced PubMed search was conducted of all English language articles published using the search terms "clitoris" and "cyst" until February 2015. Reference tracing was completed for all articles for completeness. Literature review of clitoral cysts in the prepubertal population. In total, we found 15 cases of benign, spontaneously forming clitoral cysts reported. Eleven of those cases document symptom onset before puberty. Reports of other benign clitoral lesions in the pediatric population include 1 angiokeratoma, 1 hemangiopericytoma, 1 granular cell tumor, 6 hemangiomas, and approximately 30 neurofibromas. Clitoral malignancies in the pediatric population are even more rare with only 3 cases of clitoral schwannomas, 2 rhabdomyosarcomas, 1 lymphoma, and 1 endodermal sinus tumor documented in the literature. Clitoral cysts must be considered as a possible cause of clitoral enlargement in the prepubertal population. Clitoral tumors are distinguished clinically from hormonal abnormalities and intersex disorders by their hormonal profile, and the presence of an underlying mass. Ultrasound and magnetic resonance imaging might be useful imaging modalities to further characterize the clitoral enlargement. When confirmed as the most likely diagnosis, surgical resection is the mainstay of treatment for clitoral cysts. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Malignancy in Pediatric-onset Systemic Lupus Erythematosus.

PubMed

Bernatsky, Sasha; Clarke, Ann E; Zahedi Niaki, Omid; Labrecque, Jeremy; Schanberg, Laura E; Silverman, Earl D; Hayward, Kristen; Imundo, Lisa; Brunner, Hermine I; Haines, Kathleen A; Cron, Randy Q; Oen, Kiem; Wagner-Weiner, Linda; Rosenberg, Alan M; O'Neil, Kathleen M; Duffy, Ciarán M; von Scheven, Emily; Joseph, Lawrence; Lee, Jennifer L; Ramsey-Goldman, Rosalind

2017-10-01

To determine cancer incidence in a large pediatric-onset systemic lupus erythematosus (SLE) population. Data were examined from 12 pediatric SLE registries in North America. Patients were linked to their regional cancer registries to detect cancers observed after cohort entry, defined as date first seen in the clinic. The expected number of malignancies was obtained by multiplying the person-years in the cohort (defined from cohort entry to end of followup) by the geographically matched age-, sex-, and calendar year-specific cancer rates. The standardized incidence ratio (SIR; ratio of cancers observed to expected) was generated, with 95% CI. A total of 1168 patients were identified from the registries. The mean age at cohort entry was 13 years (SD 3.3), and 83.7% of the subjects were female. The mean duration of followup was 7.6 years, resulting in a total observation period of 8839 years spanning the calendar period 1974-2009. During followup, fourteen invasive cancers occurred (1.6 cancers per 1000 person-yrs, SIR 4.13, 95% CI 2.26-6.93). Three of these were hematologic (all lymphomas), resulting in an SIR for hematologic cancers of 4.68 (95% CI 0.96-13.67). SIR were increased for both male and female patients, and across age groups. Although cancer remains a relatively rare outcome in pediatric-onset SLE, our data do suggest an increase in cancer for patients followed an average of 7.6 years. About one-fifth of the cancers were hematologic. Longer followup, and study of drug effects and disease activity, is warranted.

Comparison of temporal bone fractures in children and adults.

PubMed

Kang, Ho Min; Kim, Myung Gu; Hong, Seok Min; Lee, Ho Yun; Kim, Tae Hyun; Yeo, Seung Geun

2013-05-01

Contrary to our expectation, that the clinical characteristics of temporal bone fracture would differ in children and adults, we found that the two groups were similar. Most studies of temporal bone fractures have been performed in adults. To our knowledge, no study has investigated differences in temporal bone fractures in children and adults. We therefore investigated differences in temporal bone fractures in adults and children by examining the manifestations and clinical symptoms of temporal bone fractures in pediatric patients. The demographic and clinical characteristics were assessed in 32 children and 186 adults with temporal bone fractures. All patients underwent computed tomography of the temporal bone. Causes of fracture, gender distribution, manifestations of temporal bone fracture, and clinical symptoms were similar in adults and children (p > 0.05 each). Petrous fracture, ear fullness, dizziness, and tinnitus were significantly more frequent in adults than in children (p < 0.05 each).

Inner ear anomalies and conductive hearing loss in children with Apert syndrome: an overlooked otologic aspect.

PubMed

Zhou, Guangwei; Schwartz, Lynn Thomas; Gopen, Quinton

2009-02-01

To identify the occurrence of inner ear structural anomalies and conductive hearing loss (CHL) in children with Apert syndrome. Retrospective review. Pediatric tertiary referral center. Twenty pediatric patients with Apert syndrome were found; all patients (38/40 ears) had inner ear anomalies. Computerized tomography of the head/temporal bone, pure-tone (including air and bone conduction) audiometry, and tympanometry. Imaging demonstrating inner ear anomalies, including malformations of the cochlea, dilated vestibule, and/or semicircular canal; audiologic findings of air-bone gap(s). Hearing loss was found in 90% of the patients with Apert syndrome, and 80% of them had CHL. Air-bone gaps were found at all frequencies, with larger gaps at low frequencies. Fifty percent (20/40) of the ears had better than 0 dB hearing level bone conduction thresholds at 250 and/or 500 Hz. Normal middle ear pressure and mobility were found in all ears with intact eardrum. Inner ear anomalies were found in all patients, and 90% of them had bilateral involvement. Most frequently observed inner ear anomalies were dilated vestibule, malformed lateral semicircular canal, and cochlear dysplasia. Children with Apert syndrome may present with significant CHL that cannot be explained by minor middle ear pathologies alone. This conductive loss may be, at least partially, attributed to the inner ear anomalies; however, these structural anomalies are usually not recognized in these patients. Failure to close air-bone gap after surgical intervention may raise the suspicion of inner ear anomalies, and computed tomographic scan of the temporal bone can provide definitive proof.

Gene stage-specific expression in the microenvironment of pediatric myelodysplastic syndromes.

PubMed

Roela, Rosimeire A; Carraro, Dirce M; Brentani, Helena P; Kaiano, Jane H L; Simão, Daniel F; Guarnieiro, Roberto; Lopes, Luiz Fernando; Borojevic, Radovan; Brentani, M Mitzi

2007-05-01

Using cDNA microarray assays we have observed a clear difference in the gene expression pattern between bone marrow stromal cells obtained from healthy children (CT) and from pediatric patients with either myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) associated with MDS (MDS-AML). The global gene function profiling analysis indicated that in the pediatric MDS microenvironment the disease stages may be characterized mainly by underexpression of genes associated with biological processes such as transport. Furthermore, a subset of downregulated genes related to endocytosis and protein secretion was able to discriminate MDS from MDS-AML.

Comparison of circummandibular wiring with resorbable bone plates in pediatric mandibular fractures.

PubMed

Saikrishna, D; Gupta, Nimish

2010-06-01

Pediatric patients present a unique challenge to maxillofacial surgeons in terms of their treatment planning as well as in their functional and nutritional needs which are different from that of adult patients. Early literature has advocated conservative closed management of pediatric fractures to prevent complications. However recent advances in maxillofacial surgery has enabled us to use biodegradable plates and screws, which overcomes the limitations of metallic plates. We present a comparison of two cases of parasymphysis fracture treated with circum-mandibular wiring and biodegradable plate fixation their outcome in terms of fracture healing and functional stability.

NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: endocrine challenges-thyroid dysfunction, growth impairment, bone health, & reproductive risks.

PubMed

Dvorak, Christopher C; Gracia, Clarisa R; Sanders, Jean E; Cheng, Edward Y; Baker, K Scott; Pulsipher, Michael A; Petryk, Anna

2011-12-01

The endocrine system is highly susceptible to damage by high-dose chemotherapy and/or irradiation before hematopoietic cell transplantation (HCT) during childhood. The specific endocrine organs most affected by HCT include the thyroid gland, the pituitary, and the gonads. In addition, hormones that support development and stability of the skeletal system are also affected. Insufficiency of thyroid hormone is 1 of the most common late sequelae of HCT, and occurs more often in young children. Deficiency in the pituitary's production of growth hormone is a problem of unique concern to the pediatric population. The reproductive risks of HCT depend on the patient's gender and pubertal status at the time of HCT. Pubertal or gonadal failure frequently occurs, especially in females. Infertility risks for both genders remain high, whereas methods of fertility preservation are limited in all but postpubertal males. Bone health post-HCT can be compromised by low bone mineral density as well as avascular necrosis, but the data on both problems in the pediatric HCT population are limited. In this paper, the current state of knowledge, gaps in that knowledge, and recommendations for future research are addressed in detail for each of these systems. Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Pediatric Chiari malformation type I: long-term outcomes following small-bone-window posterior fossa decompression with autologous-fascia duraplasty

PubMed Central

Liu, Hai; Yang, Chenlong; Yang, Jun; Xu, Yulun

2017-01-01

Chiari malformation type I (CM-I) is a common hindbrain disorder that is associated with deformity and elongation of the cerebellar tonsils. Although CM-I occurs in both pediatric and adult patients, its prevalence, clinical features and management in the pediatric population are not well defined. The current study evaluated a consecutive case series of 92 children (38 females and 54 males) who were diagnosed with congenital CM-I. All patients underwent small-bone-window posterior fossa decompression with autologous-fascia duraplasty. Clinical and radiological features were analyzed and long-term follow-up data were recorded. Risk factors associated with clinical outcomes were investigated using comprehensive statistical methods. Out of the 92 children, 11 (12.0%) were asymptomatic. Associated ventricular dilation was observed in 24 children (26.1%) and concomitant syringomyelia was observed in 72 children (78.3%). A total of 44 children (47.8%) showed scoliosis on plain films. Follow-up data (mean duration, 88.6 months) were available for all patients. Syringomyelia was absent or markedly reduced in 56 patients (77.8%). Symptoms were alleviated in 66 patients, remained unchanged in 12 patients and progressed in 3 patients. Statistical analysis indicated that the cerebellar tonsillar descent (CTD) grade, basilar invagination and platybasia influenced the clinical outcome (P<0.05). In conclusion, early recognition and surgical treatment of CM-I in pediatric patients can lead to good outcomes. The current results suggested that small-bone-window posterior fossa decompression with autologous-fascia duraplasty was an effective safe treatment option with a low complication rate. High CTD grade, basilar invagination and platybasia were indicated to be predictors of poor clinical prognosis. PMID:29285106

The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

PubMed Central

Greim, Helmut; Kaden, Debra A.; Larson, Richard A.; Palermo, Christine M.; Rice, Jerry M.; Ross, David; Snyder, Robert

2014-01-01

Hematopoietic stem cells (HSCs) are a unique population of somatic stem cells that can both self-renew for long-term reconstitution of HSCs and differentiate into hematopoietic progenitor cells, which in turn give rise, in a hierarchical manner, to the entire myeloid and lymphoid lineages. The differentiation and maturation of these lineages occurs in the bone marrow niche, a microenvironment that regulates self-renewal, survival, differentiation, and proliferation, with interactions among signaling pathways in the HSCs and the niche required to establish and maintain homeostasis. The accumulation of genetic mutations and cytogenetic abnormalities within cells of the partially differentiated myeloid lineage, particularly as a result of exposure to benzene or cytotoxic anticancer drugs, can give rise to malignancies like acute myeloid leukemia and myelodysplastic syndrome. Better understanding of the mechanisms driving these malignancies and susceptibility factors, both within hematopoietic progenitor cells and cells within the bone marrow niche, may lead to the development of strategies for prevention of occupational and cancer therapy–induced disease. PMID:24495159

Transition of Care from Childhood to Adulthood: Congenital Adrenal Hyperplasia.

PubMed

Bachelot, Anne

2018-01-01

Deficiency of the 21-hydroxylase enzyme is the most common form of congenital adrenal hyperplasia (CAH), accounting for more than 95% of the cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, impaired bone mineral density, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and practitioners. In adulthood, the aims of the medical treatment are to substitute cortisol and, when necessary, aldosterone deficiency, to ensure normal fertility, and to avoid the long-term consequences of glucocorticoid use on bone, metabolism, and cardiovascular risk. Recent data suggest that poor health status is likely to begin in adolescence and persist into adulthood, highlighting the importance of this time period in a patient's endocrine care. During transition from pediatric to adult specific care, a shift in treatment goals is thus needed. Successful transition from pediatric to adult health care requires a regular follow-up of patients by a multidisciplinary team including pediatric endocrinologists, urologists, gynecologists, psychiatrists, and adult endocrinologists. All of this could be included in a specific therapeutic education program regarding transition and/or CAH. © 2018 S. Karger AG, Basel.

Dose assessment of digital tomosynthesis in pediatric imaging

NASA Astrophysics Data System (ADS)

Gislason, Amber; Elbakri, Idris A.; Reed, Martin

2009-02-01

We investigated the potential for digital tomosynthesis (DT) to reduce pediatric x-ray dose while maintaining image quality. We utilized the DT feature (VolumeRadTM) on the GE DefiniumTM 8000 flat panel system installed in the Winnipeg Children's Hospital. Facial bones, cervical spine, thoracic spine, and knee of children aged 5, 10, and 15 years were represented by acrylic phantoms for DT dose measurements. Effective dose was estimated for DT and for corresponding digital radiography (DR) and computed tomography (CT) patient image sets. Anthropomorphic phantoms of selected body parts were imaged by DR, DT, and CT. Pediatric radiologists rated visualization of selected anatomic features in these images. Dose and image quality comparisons between DR, DT, and CT determined the usefulness of tomosynthesis for pediatric imaging. CT effective dose was highest; total DR effective dose was not always lowest - depending how many projections were in the DR image set. For the cervical spine, DT dose was close to and occasionally lower than DR dose. Expert radiologists rated visibility of the central facial complex in a skull phantom as better than DR and comparable to CT. Digital tomosynthesis has a significantly lower dose than CT. This study has demonstrated DT shows promise to replace CT for some facial bones and spinal diagnoses. Other clinical applications will be evaluated in the future.

Searching the optimal PTH target range in children undergoing peritoneal dialysis: new insights from international cohort studies.

PubMed

Haffner, Dieter; Schaefer, Franz

2013-04-01

The treatment of the mineral and bone disorder associated with chronic kidney disease (CKD-MBD) remains a major challenge in pediatric patients. The principal aims of therapeutic measures are not only to prevent the debilitating skeletal complications and to achieve normal growth but also to preserve long-term cardiovascular health. Serum parathyroid hormone (PTH) levels are used as a surrogate parameter of bone turnover. Whereas it is generally accepted that serum calcium and phosphate levels should be kept within the range for age, current pediatric consensus guidelines differ markedly with respect to the optimal PTH target range and operate on a limited evidence base. Recently, the International Pediatric Dialysis Network (IPPN) established a global registry collecting detailed clinical and biochemical information, including data relevant to CKD-MBD in children on chronic peritoneal dialysis (PD). This review highlights the current evidence basis regarding the optimal PTH target range in pediatric CKD patients, and re-assesses the current guidelines in view of the outcome data collected by the IPPN registry. Based on a comprehensive evaluation of CKD-MBD outcome measures in this global patient cohort, a PTH target range of 1.7-3 times the upper limit of normal (i.e. 100-200 pg/ml) appears reasonable in children undergoing chronic PD.

Estimating differences in volumetric flat bone growth in pediatric patients by radiation treatment method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hua Chiaho; Shukla, Hemant I.; Merchant, Thomas E.

2007-02-01

Purpose: To estimate potential differences in volumetric bone growth in children with sarcoma treated with intensity-modulated (IMRT) and conformal (CRT) radiation therapy using an empiric dose-effect model. Methods and Materials: A random coefficient model was used to estimate potential volumetric bone growth of 36 pelvic bones (ischiopubis and ilium) from 11 patients 4 years after radiotherapy. The model incorporated patient age, pretreatment bone volume, integral dose >35 Gy, and time since completion of radiation therapy. Three dosimetry plans were entered into the model: the actual CRT/IMRT plan, a nontreated comparable IMRT/CRT plan, and an idealized plan in which dose wasmore » delivered only to the planning target volume. The results were compared with modeled normal bone growth. Results: The model predicted that by using the idealized, IMRT, and CRT approaches, patients would maintain 93%, 87%, and 84%, respectively (p = 0.06), of their expected normal growth. Patients older than 10 years would maintain 98% of normal growth, regardless of treatment method. Those younger than 10 years would maintain 87% (idealized), 76% (IMRT), or 70% (CRT) of their expected growth (p = 0.015). Post hoc testing (Tukey) revealed that the CRT and IMRT approaches differed significantly from the idealized one but not from each other. Conclusions: Dose-effect models facilitate the comparison of treatment methods and potential interventions. Although treatment methods do not alter the growth of flat bones in older pediatric patients, they may significantly impact bone growth in children younger than age 10 years, especially as we move toward techniques with high conformity and sharper dose gradient.« less

Selective embolization of the internal iliac arteries for the treatment of intractable hemorrhage in children with malignancies.

PubMed

Bae, Sul Hee; Han, Dong Kyun; Baek, Hee Jo; Park, Sun Ju; Chang, Nam Kyu; Kook, Hoon; Hwang, Tai Ju

2011-04-01

Acute internal hemorrhage is an occasionally life-threatening complication in pediatric cancer patients. Many therapeutic approaches have been used to control bleeding with various degrees of success. In this study, we evaluated the efficacy of selective internal iliac artery embolization for controlling acute intractable bleeding in children with malignancies. We retrospectively evaluated the cases of 6 children with various malignancies (acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, T-cell prolymphocytic leukemia, Langerhans cell histiocytosis, and rhabdomyosarcoma), who had undergone selective arterial embolization (SAE) of the internal iliac artery at the Chonnam National University Hwasun Hospital between January 2004 and December 2009. SAE was performed by an interventional radiologist using Gelfoam® and/or Tornado® coils. The patients were 5 boys and 1 girl with median age of 6.9 years (range, 0.7-14.8 years) at the time of SAE. SAE was performed once in 4 patients and twice in 2, and the procedure was unilateral in 2 and bilateral in 4. The causes of hemorrhage were as follows: hemorrhagic cystitis (HC) in 3 patients, procedure-related internal iliac artery injuries in 2 patients, and tumor rupture in 1 patient. Initial attempt at conservative management was unsuccessful. Of the 6 patients, 5 (83.3%) showed improvement after SAE without complications. SAE may be a safe and effective procedure for controlling acute intractable hemorrhage in pediatric malignancy patients. This procedure may obviate the need for surgery, which carries an attendant risk of morbidity and mortality in cancer patients with critical conditions.

Secondary Chondrosarcoma of the Upper Thoracic Costovertebral Junction with Neural Foraminal Extension and Compressing the Spinal Cord.

PubMed

Bouali, Sofiene; Bouhoula, Asma; Maatar, Nidhal; Abderrahmen, Khansa; Boubaker, Adnen; Kallel, Jalel; Jemel, Hafedh

2016-08-01

Chondrosarcoma is a rare malignant tumor of bone. This family of tumors can be primary malignant tumors or a secondary malignant transformation of an underlying benign cartilage tumor. Secondary chondrosarcoma arising from a benign solitary costal osteochondroma is extremely rare. Data show that the reported incidence of costal osteochondroma is very low and they are usually found in the anterior region at the costochondral junction. To our knowledge, however, there have been no previous reports, in English literature, describing osteochondroma malignant transformation located in the thoracic costovertebral junction. We report the case of a man with chondrosarcoma arising from the malignant degeneration of an osteochondroma at the right first thoracic costovertebral junction with neural foraminal extension and compressing the spinal cord. Although it is rare in solitary osteochondromas of rib, malignant transformation must always be considered. Copyright © 2016 Elsevier Inc. All rights reserved.

Cold lesions on bone imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sy, W.M.; Westring, D.W.; Weinberger, G.

1975-11-01

Photon-deficient foci or cold lesions were demonstrated on /sup 99m/Tc- polyphosphate bone imaging in eight individuals with various malignancies and one in sickle cell crisis. The bone radiographs of five of these persons failed to show corresponding bony changes at the time of the imaging. Most of the cold lesions observed on bone imaging were located in the denser and tubular bones. A postulate has been advanced regarding the factors that might influence the different gamma-imaging manifestations of radiographically demonstrable lytic lesions. The cases presented herein further emphasize the importance of recognizing the existence of cold areas in the imagesmore » of bones and the need to place these in proper perspective when interpreting scans. (auth)« less

Still's Disease in a Pediatric Patient after Liver Transplantation.

PubMed

Meza, Juan-Carlos; Muñoz-Buitrón, Evelyn; Bonilla-Abadía, Fabio; Cañas, Carlos Alberto; Tobón, Gabriel J

2013-01-01

Still's disease (SD) is a multisystemic inflammatory disease characterized by persistent arthritis and in many cases with fever of unknown origin. Diagnosis of SD is challenging because of nonspecific characteristics and especially in the case of a patient with solid organ transplantation and immunosuppressive therapy where multiple causes of fever are possible. There is no diagnostic test for SD, even though some useful diagnostic criteria or laboratory findings, such as serum ferritin levels, have been proposed, and useful imaging studies for the diagnosis or followup of SD have not been developed. We report the case of a 9-year-old child who presented with high grade fever associated with joint pain after a history of liver transplantation and immunosuppressive therapy. Laboratory tests showed increased acute phase reactants, elevated ferritin, and leukocytosis. An 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed identifying abnormal hypermetabolic areas localized in spleen, transplanted liver, and bone marrow secondary to inflammatory process. All infectious, autoimmune, and malignant causes were ruled out. A diagnosis of SD was performed and a steroid-based regimen was initiated with adequate response and no evidence of recurrence. To our knowledge this is the first case of SD following a solid organ transplant.

Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced In Vivo Imaging

PubMed Central

Batey, Michael A.; Almeida, Gilberto S.; Wilson, Ian; Dildey, Petra; Sharma, Abhishek; Blair, Helen; Hide, I. Geoff; Heidenreich, Olaf; Vormoor, Josef; Maxwell, Ross J.; Bacon, Chris M.

2014-01-01

Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2−/−/γc−/− mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000–5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised “malignant” bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which resemble the human disease. We have shown the utility of small animal bioimaging for tracking disease progression, making this model a useful assay for preclinical drug testing. PMID:24409320

Multiple Myeloma, Version 2.2016

PubMed Central

Anderson, Kenneth C.; Alsina, Melissa; Atanackovic, Djordje; Biermann, J. Sybil; Chandler, Jason C.; Costello, Caitlin; Djulbegovic, Benjamin; Fung, Henry C.; Gasparetto, Cristina; Godby, Kelly; Hofmeister, Craig; Holmberg, Leona; Holstein, Sarah; Huff, Carol Ann; Kassim, Adetola; Krishnan, Amrita Y.; Kumar, Shaji K.; Liedtke, Michaela; Lunning, Matthew; Raje, Noopur; Singhal, Seema; Smith, Clayton; Somlo, George; Stockerl-Goldstein, Keith; Treon, Steven P.; Weber, Donna; Yahalom, Joachim; Shead, Dorothy A.; Kumar, Rashmi

2016-01-01

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Recent statistics from the American Cancer Society indicate that the incidence of MM is increasing. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) included in this issue address management of patients with solitary plasmacytoma and newly diagnosed MM. PMID:26553768

Utility of the immature platelet fraction in pediatric immune thrombocytopenia: Differentiating from bone marrow failure and predicting bleeding risk.

PubMed

McDonnell, Alicia; Bride, Karen L; Lim, Derick; Paessler, Michele; Witmer, Char M; Lambert, Michele P

2018-02-01

Differentiating childhood immune thrombocytopenia (ITP) from other cause of thrombocytopenia remains a diagnosis of exclusion. Additionally factors that predict bleeding risk for those patients with ITP are currently not well understood. Previous small studies have suggested that immature platelet fraction (IPF) may differentiate ITP from other causes of thrombocytopenia and in combination with other factors may predict bleeding risk. We performed a retrospective chart review of thrombocytopenic patients with an IPF measured between November 1, 2013 and July 1, 2015. Patients were between 2 months and 21 years of age with a platelet count <50 × 10 9 /l. Each patient chart was reviewed for final diagnosis and bleeding symptoms. A bleeding severity score was retrospectively assigned. Two hundred seventy two patients met inclusion criteria, 97 with ITP, 11 with bone marrow failure (BMF), 126 with malignancy, and 38 with other causes of thrombocytopenia. An IPF > 5.2% differentiated ITP from BMF with 93% sensitivity and 91% specificity. Absolute immature platelet number (AIPN) was significantly lower in ITP patients with severe to life-threatening hemorrhage than those without, despite similar platelet counts. On multivariate analysis, an IPF < 10.4% was confirmed as an independent predictor of bleeding risk at platelet counts <10 × 10 9 /l in patients with ITP. IPF measurement alone has utility in both the diagnosis of ITP and identifying patients at increased risk of hemorrhage. Further study is required to understand the pathophysiological differences of ITP patients with lower IPF/AIPN. © 2017 Wiley Periodicals, Inc.

Does microtia predict severity of temporal bone CT abnormalities in children with persistent conductive hearing loss?

PubMed

Tekes, Aylin; Ishman, Stacey L; Baugher, Katherine M; Brown, David J; Lin, Sandra Y; Tunkel, David E; Unalp-Arida, Aynur; Huisman, Thierry A G M

2013-07-01

This study aimed to determine the spectrum of temporal bone computed tomography (CT) abnormalities in children with conductive hearing loss (CHL) with and without microtia. From 1993 to 2008, a total of 3396 pediatric records including CHL were reviewed at our institution and revealed 180 cases of persistent CHL, 46 of whom had diagnostic temporal bone CT examinations. All of these examinations were systematically reviewed by two pediatric neuroradiologists, working in consensus, who had 5 and 18 years, respectively, of dedicated pediatric neuroradiology experience. Of the 46 children, 16 were boys and 30 were girls (age: 0.2-16 years; mean: 5 years). Also, 21 (46%) children had microtia and 25 (54%) children did not, as determined by clinical evaluation. External auditory canal atresia/stenosis (EAC-A/S) was the most common anomaly in both microtia and non-microtia groups. Two or more anomalies were observed in 18/21 children with microtia. The frequency of EAC-A/S was greater in children with microtia versus those without it (86% versus 32%, respectively; P = 0.0003). Syndromic diagnoses were also significantly more frequently made in children with microtia versus those without microtia (76% versus 20%, respectively; P = 0.0001). Temporal bone CT scans were normal in 10 children (22%) with persistent CHL. Microtia is an important finding in children with CHL. EAC and middle ear/ossicle anomalies were significantly more frequently seen in children with microtia, and multiple anomalies and bilateral microtia were more common in children with syndromic associations. These findings highlight the importance of understanding the embryological development of the temporal bone. The presence of one anomaly should raise suspicion of the possibility of other anomalies, especially in the setting of microtia. Bilateral microtia and multiple anomalies should also raise suspicion of genetic syndromes. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Pathological Calcification and Ossification in Relation to Leriche and Policard's Theory.

PubMed

Jones, W; Roberts, R E

1933-05-01

(1) Pathology of calcification and ossification.-The Leriche-Policard theories. Hyperaemia of bone causes decalcification. Reduced blood supply causes sclerosis. Diminution of vascularity of fibrous tissue causes calcification. Excess of calcium, adequate blood supply and fibroblasts give rise to bone anywhere. Subperiosteal ossification. "Myositis ossificans."(2) Radiological significance of density of bone shadows.-Decalcification of disuse, of infections, of neoplasms. Traumatic and infective scquestra. Evidence that a fragment of bone is avascular.(3) Hyperaemic decalcification of bone.-Delayed and non-union of fractures. Kummel's disease. Spontaneous hyperaemic dislocation of the atlas. Hyperaemic decalcification and nephrolithiasis.(4) Anaemic sclerosis of bone.-Syphilitic bone disease. Malignant bone disease. Fragility of sclerosed bone-Paget's, Kienboch's, Kohler's and Panner's, Albers-Schönberg's diseases.(5) Pathological calcification.-Calcification of supraspinatus tendon. Calcification of tumours-angioma, haematoma, and thrombosed vessels, lipoma, cysts, etc. Calcification of semilunar cartilages and intervertebral discs.(6) Pathological ossification.-Ossification of tendons. Ossification of semilunar cartilages.

Comparing catheter-related bloodstream infections in pediatric and adult cancer patients.

PubMed

Zakhour, Ramia; Hachem, Ray; Alawami, Hussain M; Jiang, Ying; Michael, Majd; Chaftari, Anne-Marie; Raad, Issam

2017-10-01

Central venous catheters (CVCs) are essential to treatment of children with cancer. There are no studies comparing catheter-related bloodstream infections (CRBSIs) in pediatric cancer patients to those in adults, although current guidelines for management of CRBSI do not give separate guidelines for the pediatric population. In this study, we compared CRBSIs in both the pediatric and adult cancer population. We retrospectively reviewed the electronic medical records of 92 pediatric and 156 adult patients with CRBSI cared for at MD Anderson Cancer Center between September 2005 and March 2014. We evaluated 248 patients with CRBSI. There was a significant difference in etiology of CRBSI between pediatric and adult patients (P = 0.002), with the former having less Gram-negative organisms (27 vs. 46%) and more polymicrobial infections (10 vs. 1%, P = 0.003). Pediatric patients had less hematologic malignancies (58 vs. 74%) and less neutropenia at presentation (40 vs. 54%) when compared with adult patients. Peripheral blood cultures were available in only 43% of pediatric cases. CVC was removed in 64% of pediatric cases versus 88% of adult cases (P < 0.0001). We found higher rates of Gram-negative organisms in adults and higher rates of polymicrobial in children. Because of the low rates of peripheral blood cultures and the low rates of CVC removal, CRBSI diagnosis could be challenging in pediatrics. A modified CRBSI definition relying more on clinical criteria may be warranted. © 2017 Wiley Periodicals, Inc.

Interventional Endoscopy Database for Pancreatico-biliary, Gastrointestinal and Esophageal Disorders

ClinicalTrials.gov

2017-02-16

Ampullary Cancer; Duodenal Cancer; Bile Duct Cancer; Bile Duct Disorders; Gallstones; Obstructive Jaundice; Pancreatic Disorders (Noncancerous); Colorectal Cancer; Esophageal Cancer; Barrett's Esophagus; Gastric Malignancies; Pancreatic Cancer; Pediatric Gastroenterology; Cholangiocarcinoma; Pancreatic Pseudocysts; Acute and Chronic Pancreatitis; Recurrent Pancreatitis; Cholangitis; Bile Leak; Biliary Strictures; Pancreatic Divisum; Biliary and Pancreatic Stones; Choledocholithiasis

Chronic Diseases in the Pediatric Age Group. Matrix No. 7.

ERIC Educational Resources Information Center

Katz, Michael

This paper briefly outlines current problems associated with chronic diseases in children and youth and provides indications for the types of future research and analysis needed to facilitate the development of solutions. In general, these problems are associated with the following: malignancies, hereditary anemias, cystic fibrosis, other chronic…

Childhood Soft Tissue Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Pediatric soft tissue sarcomas are a heterogenous group of malignant tumors that originate from primitive mesenchymal tissue and account for 7% of all childhood tumors. Get detailed information about clinical presentation, diagnosis, prognosis, and treatment of newly diagnosed and recurrent soft tissue sarcoma in this summary for clinicians.

Interventions to Improve Neuropsychological Functioning in Childhood Cancer Survivors

ERIC Educational Resources Information Center

Butler, Robert W.; Sahler, Olle Jane Z.; Askins, Martha A.; Alderfer, Melissa A.; Katz, Ernest R.; Phipps, Sean; Noll, Robert B.

2008-01-01

A very brief historical review on the identification of neurocognitive deficits in patients treated for a pediatric malignancy that involved CNS disease, treatment, or a combination is provided. This review is particularly directed toward providing a foundation upon which the introduction of specific brain injury rehabilitation efforts and…

Understanding deregulated cellular and molecular dynamics in the haematopoietic stem cell niche to develop novel therapeutics for bone marrow fibrosis.

PubMed

Gleitz, Hélène Fe; Kramann, Rafael; Schneider, Rebekka K

2018-06-01

Bone marrow fibrosis is the continuous replacement of blood-forming cells in the bone marrow with excessive scar tissue, leading to failure of the body to produce blood cells and ultimately to death. Myofibroblasts are fibrosis-driving cells and are well characterized in solid organ fibrosis, but their role and cellular origin in bone marrow fibrosis have remained obscure. Recent work has demonstrated that Gli1 + and leptin receptor + mesenchymal stromal cells are progenitors of fibrosis-causing myofibroblasts in the bone marrow. Genetic ablation or pharmacological inhibition of Gli1 + mesenchymal stromal cells ameliorated fibrosis in mouse models of myelofibrosis. Conditional deletion of the platelet-derived growth factor (PDGF) receptor-α (PDGFRA) gene (Pdgfra) and inhibition of PDGFRA by imatinib in leptin receptor + stromal cells suppressed their expansion and ameliorated bone marrow fibrosis. Understanding the cellular and molecular mechanisms in the haematopoietic stem cell niche that govern the mesenchymal stromal cell-to-myofibroblast transition and myofibroblast expansion will be critical to understand the pathogenesis of bone marrow fibrosis in both malignant and non-malignant conditions, and will guide the development of novel therapeutics. In this review, we summarize recent discoveries of mesenchymal stromal cells as part of the haematopoietic niche and as myofibroblast precursors, and discuss potential therapeutic strategies in the specific targeting of fibrotic transformation in bone marrow fibrosis. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Acute haematogenous community-acquired methicillin-resistant Staphylococcus aureus osteomyelitis in an adult: Case report and review of literature

PubMed Central

2012-01-01

Background Methicillin-resistant Staphylococcus aureus (MRSA) has of late emerged as a cause of community-acquired infections among immunocompetent adults without risk factors. Skin and soft tissue infections represent the majority of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clinical presentations, whilst invasive and life-threatening illness like necrotizing pneumonia, necrotizing fasciitis, pyomyositis, osteomyelitis and sepsis syndrome are less common. Although more widely described in the pediatric age group, the occurrence of CA-MRSA osteomyelitis in adults is an uncommonly reported entity. Case presentation We describe an invasive CA-MRSA infection in a 28 year-old previously healthy male, manifesting with bacteraemia, osteomyelitis of femur, pyomyositis and septic arthritis of the knee. Initially a preliminary diagnosis of osteosarcoma was suggested by imaging studies and patient underwent a bone biopsy. MRSA was subsequently isolated from blood cultures taken on day of admission, bone, tissue and pus cultures. Incision and drainage of abscess was performed and patient was treated with vancomycin, with fusidic acid added later. It took 6 months for the inflammatory markers to normalize, warranting 6-months of anti-MRSA therapy. Patient was a fervent deer hunter and we speculate that he acquired this infection from extensive direct contact with deer. Molecular characterization of this isolate showed that it belonged to multilocus sequence type (MLST) ST30 and exhibited the staphylococcal chromosome cassette mec (SCCmec) type IV, staphylococcus protein A (spa) type t019, accessory gene regulator (agr) type III and dru type dt10m. This strain harbored Panton-Valentine leukocidin (pvl) genes together with 3 other virulent genes; sei (enterotoxin), hlg (hemolysin) and fnbA (fibronectin binding protein). Conclusion This case study alerts physicians that beyond the most commonly encountered skin and soft tissue infections, pvl positive CA-MRSA can lead to invasive life-threatening disease especially in an immunocompetent adult. Heightened alertness is needed for osteomyelitis of long bones in adults, as it is not uncommon for this disease to mimic primary bone malignancy. Cure is achievable with early appropriate antibiotics guided by inflammatory markers. PMID:23098162

Acute haematogenous community-acquired methicillin-resistant Staphylococcus aureus osteomyelitis in an adult: case report and review of literature.

PubMed

Dhanoa, Amreeta; Singh, Vivek Ajit; Mansor, Azura; Yusof, Mohd Yasim; Lim, King-Ting; Thong, Kwai-Lin

2012-10-25

Methicillin-resistant Staphylococcus aureus (MRSA) has of late emerged as a cause of community-acquired infections among immunocompetent adults without risk factors. Skin and soft tissue infections represent the majority of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clinical presentations, whilst invasive and life-threatening illness like necrotizing pneumonia, necrotizing fasciitis, pyomyositis, osteomyelitis and sepsis syndrome are less common. Although more widely described in the pediatric age group, the occurrence of CA-MRSA osteomyelitis in adults is an uncommonly reported entity. We describe an invasive CA-MRSA infection in a 28 year-old previously healthy male, manifesting with bacteraemia, osteomyelitis of femur, pyomyositis and septic arthritis of the knee. Initially a preliminary diagnosis of osteosarcoma was suggested by imaging studies and patient underwent a bone biopsy. MRSA was subsequently isolated from blood cultures taken on day of admission, bone, tissue and pus cultures. Incision and drainage of abscess was performed and patient was treated with vancomycin, with fusidic acid added later. It took 6 months for the inflammatory markers to normalize, warranting 6-months of anti-MRSA therapy. Patient was a fervent deer hunter and we speculate that he acquired this infection from extensive direct contact with deer.Molecular characterization of this isolate showed that it belonged to multilocus sequence type (MLST) ST30 and exhibited the staphylococcal chromosome cassette mec (SCCmec) type IV, staphylococcus protein A (spa) type t019, accessory gene regulator (agr) type III and dru type dt10m. This strain harbored Panton-Valentine leukocidin (pvl) genes together with 3 other virulent genes; sei (enterotoxin), hlg (hemolysin) and fnbA (fibronectin binding protein). This case study alerts physicians that beyond the most commonly encountered skin and soft tissue infections, pvl positive CA-MRSA can lead to invasive life-threatening disease especially in an immunocompetent adult. Heightened alertness is needed for osteomyelitis of long bones in adults, as it is not uncommon for this disease to mimic primary bone malignancy. Cure is achievable with early appropriate antibiotics guided by inflammatory markers.

Treatment of unicameral bone cysts in pediatric patients with an injectable regenerative graft: a preliminary report.

PubMed

Gentile, John V; Weinert, Carl R; Schlechter, John A

2013-01-01

Multiple treatment modalities exist for unicameral bone cysts (UBC), including steroid injection, autologous bone marrow injection, mechanical decompression, intramedullary fixation, curettage, and bone grafting. All have their own potential limitations such as high recurrence rates, cyst persistence, need for multiple procedures, and prolonged immobilization. A minimally invasive regimen consisting of curettage, decompression, and injection of a calcium sulfate-calcium phosphate (CaSO4-CaPO4) composite has been utilized at our institution in an attempt to obtain optimal results for the treatment of UBCs in the pediatric population. We retrospectively evaluated 16 patients with pathologically confirmed UBC who were treated with curettage, decompression, and injection of a calcium sulfate-calcium phosphate composite between April 2006 and August 2010 at a single institution. The average age of the patients at time of surgical intervention was 9.4 years of age (range, 3 to 16 y). Average follow-up was 16 months (range, 6 to 36 mo). Radiographic healing, clinical outcomes, and complications were evaluated. Final follow-up radiographs demonstrated healing in 93.7% (15 of 16) of patients after a single procedure. Complete healing was observed in 14 of 16 patients and partially healed with a defect in 1 of 16 patients. One patient had a persistent cyst but did not wish to receive further treatment. All patients returned to full activities including sports on average at 3.1 months (range, 1 to 6 mo) and were asymptomatic on most recent follow-up. No postoperative complications, including refracture, were observed. Curettage, decompression, and injection of a calcium sulfate-calcium phosphate composite for UBC in the pediatric population demonstrates encouraging results with low recurrence rates and complications compared with conventional methods. Case series, Level of Evidence IV.

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).

PubMed

Joeris, Alexander; Lutz, Nicolas; Blumenthal, Andrea; Slongo, Theddy; Audigé, Laurent

2017-04-01

Background and purpose - To achieve a common understanding when dealing with long bone fractures in children, the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation, we present the most relevant fracture patterns in the upper extremities of a representative population of children classified according to the PCCF. Patients and methods - We included children and adolescents (0-17 years old) diagnosed with 1 or more long bone fractures between January 2009 and December 2011 at the university hospitals in Bern and Lausanne (Switzerland). Patient charts were retrospectively reviewed and fractures were classified from standard radiographs. Results - Of 2,292 upper extremity fractures in 2,203 children and adolescents, 26% involved the humerus and 74% involved the forearm. In the humerus, 61%, and in the forearm, 80% of single distal fractures involved the metaphysis. In adolescents, single humerus fractures were more often epiphyseal and diaphyseal fractures, and among adolescents radius fractures were more often epiphyseal fractures than in other age groups. 47% of combined forearm fractures were distal metaphyseal fractures. Only 0.7% of fractures could not be classified within 1 of the child-specific fracture patterns. Of the single epiphyseal fractures, 49% were Salter-Harris type-II (SH II) fractures; of these, 94% occurred in schoolchildren and adolescents. Of the metaphyseal fractures, 58% showed an incomplete fracture pattern. 89% of incomplete fractures affected the distal radius. Of the diaphyseal fractures, 32% were greenstick fractures. 24 Monteggia fractures occurred in pre-school children and schoolchildren, and 2 occurred in adolescents. Interpretation - The pattern of pediatric fractures in the upper extremity can be comprehensively described according to the PCCF. Prospective clinical studies are needed to determine its clinical relevance for treatment decisions and prognostication of outcome.

Computed tomography demonstrates abnormalities of contralateral ear in subjects with unilateral sensorineural hearing loss.

PubMed

Marcus, Sonya; Whitlow, Christopher T; Koonce, James; Zapadka, Michael E; Chen, Michael Y; Williams, Daniel W; Lewis, Meagan; Evans, Adele K

2014-02-01

Prior studies have associated gross inner ear abnormalities with pediatric sensorineural hearing loss (SNHL) using computed tomography (CT). No studies to date have specifically investigated morphologic inner ear abnormalities involving the contralateral unaffected ear in patients with unilateral SNHL. The purpose of this study is to evaluate contralateral inner ear structures of subjects with unilateral SNHL but no grossly abnormal findings on CT. IRB-approved retrospective analysis of pediatric temporal bone CT scans. 97 temporal bone CT scans, previously interpreted as "normal" based upon previously accepted guidelines by board certified neuroradiologists, were assessed using 12 measurements of the semicircular canals, cochlea and vestibule. The control-group consisted of 72 "normal" temporal bone CTs with underlying SNHL in the subject excluded. The study-group consisted of 25 normal-hearing contralateral temporal bones in subjects with unilateral SNHL. Multivariate analysis of covariance (MANCOVA) was then conducted to evaluate for differences between the study and control group. Cochlea basal turn lumen width was significantly greater in magnitude and central lucency of the lateral semicircular canal bony island was significantly lower in density for audiometrically normal ears of subjects with unilateral SNHL compared to controls. Abnormalities of the inner ear were present in the contralateral audiometrically normal ears of subjects with unilateral SNHL. These data suggest that patients with unilateral SNHL may have a more pervasive disease process that results in abnormalities of both ears. The findings of a cochlea basal turn lumen width disparity >5% from "normal" and/or a lateral semicircular canal bony island central lucency disparity of >5% from "normal" may indicate inherent risk to the contralateral unaffected ear in pediatric patients with unilateral sensorineural hearing loss. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF)

PubMed Central

Joeris, Alexander; Lutz, Nicolas; Blumenthal, Andrea; Slongo, Theddy; Audigé, Laurent

2017-01-01

Background and purpose To achieve a common understanding when dealing with long bone fractures in children, the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation, we present the most relevant fracture patterns in the upper extremities of a representative population of children classified according to the PCCF. Patients and methods We included children and adolescents (0–17 years old) diagnosed with 1 or more long bone fractures between January 2009 and December 2011 at the university hospitals in Bern and Lausanne (Switzerland). Patient charts were retrospectively reviewed and fractures were classified from standard radiographs. Results Of 2,292 upper extremity fractures in 2,203 children and adolescents, 26% involved the humerus and 74% involved the forearm. In the humerus, 61%, and in the forearm, 80% of single distal fractures involved the metaphysis. In adolescents, single humerus fractures were more often epiphyseal and diaphyseal fractures, and among adolescents radius fractures were more often epiphyseal fractures than in other age groups. 47% of combined forearm fractures were distal metaphyseal fractures. Only 0.7% of fractures could not be classified within 1 of the child-specific fracture patterns. Of the single epiphyseal fractures, 49% were Salter-Harris type-II (SH II) fractures; of these, 94% occurred in schoolchildren and adolescents. Of the metaphyseal fractures, 58% showed an incomplete fracture pattern. 89% of incomplete fractures affected the distal radius. Of the diaphyseal fractures, 32% were greenstick fractures. 24 Monteggia fractures occurred in pre-school children and schoolchildren, and 2 occurred in adolescents. Interpretation The pattern of pediatric fractures in the upper extremity can be comprehensively described according to the PCCF. Prospective clinical studies are needed to determine its clinical relevance for treatment decisions and prognostication of outcome. PMID:27882802

ErbB2 and bone sialoprotein as markers for metastatic osteosarcoma cells

PubMed Central

Valabrega, G; Fagioli, F; Corso, S; Madon, E; Brach del Prever, A; Biasin, E; Linari, A; Aglietta, M; Giordano, S

2003-01-01

Osteosarcoma is the most common malignant bone neoplasia occurring in young patients in the first two decades of life, and represents 20% of all primitive malignant bone tumours. At present, treatment of metastatic osteosarcoma is unsatisfactory. High-dose chemotherapy followed by CD34+ leukapheresis rescue may improve these poor results. Neoplastic cells contaminating the apheresis may, however, contribute to relapse. To identify markers suitable for detecting osteosarcoma cells in aphereses we analysed the expression of bone-specific genes (Bone Sialoprotein (BSP) and Osteocalcin) and oncogenes (Met and ErbB2) in 22 patients with metastatic osteosarcoma and six healthy stem cell donors. The expression of these genes in aphereses of patients affected by metastatic osteosarcoma was assessed by RT–PCR and Southern blot analysis. Met and Osteocalcin proved to be not useful markers since they are positive in aphereses of both patients with metastatic osteosarcoma and healthy stem cell donors. On the contrary, BSP was expressed at significant levels in 85% of patients. Moreover, 18% of patients showed a strong and significantly positive (seven to 16 times higher than healthy stem cell donors) ErbB2 expression. In all positive cases, neoplastic tissue also expressed ErbB2. Our data show that ErbB2 can be a useful marker for tumour contamination in aphereses of patients affected by ErbB2-expressing osteosarcomas and that analysis of Bone Sialoprotein expression can be an alternative useful marker. PMID:12569382

Long-term sequelae of autologous bone marrow or peripheral stem cell transplantation for lymphoid malignancies.

PubMed

Vose, J M; Kennedy, B C; Bierman, P J; Kessinger, A; Armitage, J O

1992-02-01

The study was made to evaluate the long-term physical and psychosocial changes after high-dose therapy and autologous bone marrow or peripheral stem transplantation for recurrent lymphoid malignancies. Patients who had undergone high dose therapy and autologous bone marrow or peripheral stem cell transplantation for recurrent lymphoid malignancies at least 1 year previously were contacted by phone interview regarding their status after the transplant. The patients' comments were confirmed by checking medical records when possible. Fifty patients who had undergone transplantation at the University of Nebraska Medical Center at least 1 year before the interview were available for interview and willing to answer questions. After transplant, many patients noticed temporary changes in their appearance, which usually returned to normal within 1 year. Few patients reported remarkable cardiovascular, gastrointestinal, or pulmonary changes after transplantation. However, up to one-third of the patients reported changes in sexual function or desire. The most common infectious problem after transplant was Herpes zoster, which occurred in 25% of the patients. Overall, the patients had a positive outlook after high-dose therapy and transplantation, with most being able to return to work and enjoy a normal life style. Ninety-six percent of the patients stated that they would be willing to undergo high-dose therapy and transplantation again under the same circumstances.

Candidiasis in pediatric patients with cancer interned in a university hospital

PubMed Central

De Carvalho Parahym, Ana Maria Rabelo; De Melo, Luciana Resende Bandeira; De Morais, Vera Lúcia Lins; Neves, Rejane Pereira

2009-01-01

Fungi are common causes of infection in immunocompromised patients. Candida species are frequently involved in these cases. In order to investigate candidiasis in pediatric patients with cancer, clinical samples were collected from one hundred and twenty two patients interned in the Oswaldo Cruz University Hospital in Recife, Brazil. Yeasts were isolated from thirty-four clinical samples. The species isolated were: Candida albicans (fourteen isolates), C. parapsilosis (nine isolates), C. guilliermondii (two isolates) and C. tropicalis (two isolates). We found that candidemia was most frequent in patients with malignant hematology and that C. parapsilosis infections caused the highest mortality. PMID:24031365

A case of primary osseous malignant immunoblastic B-cell lymphoma with intracytoplasmic mu lambda immunoglobulin inclusions.

PubMed

Fiche, M; Le Tourneau, A; Audouin, J; Touzard, R C; Diebold, J

1990-02-01

Primary malignant lymphoma of bone, so-called Parker-Jackson reticulosarcoma, is a rare form of extranodal lymphoma with a relatively good prognosis. It often corresponds to B-cell lymphoma of high-grade malignancy. We report a case of mu lambda immunoblastic lymphoma showing two distinctive features: an abundant reactive T-lymphocytic population and unusual intra-cytoplasmic inclusions. These inclusions were PAS positive and consisted of monotypic mu lambda immunoglobulin localized in peculiar aggregates of rough endoplasmic reticulum. Their morphological appearances resembled the well-documented inclusions described in some varieties of non-Hodgkin's lymphoma.

Therapeutic radiation and the potential risk of second malignancies.

PubMed

Kamran, Sophia C; Berrington de Gonzalez, Amy; Ng, Andrea; Haas-Kogan, Daphne; Viswanathan, Akila N

2016-06-15

Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. © 2016 American Cancer Society. © 2016 American Cancer Society.

Improving the histopathologic diagnosis of pediatric malignancies in a low-resource setting by combining focused training and telepathology strategies.

PubMed

Santiago, Teresa C; Jenkins, Jesse J; Pedrosa, Francisco; Billups, Catherine; Quintana, Yuri; Ribeiro, Raul C; Qaddoumi, Ibrahim

2012-08-01

Accurate diagnosis is critical for optimal management of pediatric cancer. Pathologists with experience in pediatric oncology are in short supply in the developing world. Telepathology is increasingly used for consultations but its overall contribution to diagnostic accuracy is unknown. We developed a strategy to provide a focused training in pediatric cancer and telepathology support to pathologists in the developing world. After the training period, we compared trainee's diagnoses with those of an experienced pathologist. We next compared the effectiveness of static versus dynamic telepathology review in 127 cases. Results were compared by Fisher's exact test. The diagnoses of the trainee and the expert pathologist differed in only 6.5% of cases (95% CI, 1.2-20.0%). The overall concordance between the telepathology and original diagnoses was 90.6% (115/127; 95% CI, 84.1-94.6%). Brief, focused training in pediatric cancer histopathology can improve diagnostic accuracy. Dynamic and static telepathology analyses are equally effective for diagnostic review. Copyright © 2012 Wiley Periodicals, Inc.

Risk factors for the development of Clostridium difficile infection in hospitalized children.

PubMed

Samady, Waheeda; Pong, Alice; Fisher, Erin

2014-10-01

This article defines the risk factors for Clostridium difficile infection (CDI) in hospitalized children in light of recent studies demonstrating a change in the epidemiology of these infections in both adults and children. Antibiotic exposure within the past 4-12 weeks was noted in a majority of published cases of pediatric CDI, and that remains a key risk factor for infection. Past and/or prolonged hospitalization increase a child's risk for CDI as they increase potential contact with C. difficile spores. Of all CDI, hospital-acquired infection remains more common. Many comorbid conditions have been linked with CDI, with the strongest association existing in children with cancer and inflammatory bowel disease. Severe infections occur infrequently in pediatric patients. Markers established in adults for severe CDI resulting in colectomy or transfer to ICU have not been shown to correlate in pediatric patients. Recent antibiotic exposure and hospitalization remain key risk factors for CDI in the hospitalized pediatric patient. Patients with comorbid conditions such as malignancy and inflammatory bowel disease are at higher risk for CDI. Resistant infections and severe outcomes are not common in the pediatric population.

Central diabetes insipidus: an unusual complication in a child with juvenile myelomonocytic leukemia and monosomy 7.

PubMed

Surapolchai, Pacharapan; Ha, Shau-Yin; Chan, Godfrey Chi-Fung; Lukito, Johannes B; Wan, Thomas S K; So, Chi-Chiu; Chiang, Alan Kwok-Shing

2013-03-01

Central diabetes insipidus (DI) is well-documented as a presenting feature of myelodysplastic syndrome and acute myeloid leukemia in adults. However, DI is unusual in pediatric patients with myeloid malignancies. We report here this rare complication in a child with neurofibromatosis type 1 who developed juvenile myelomonocytic leukemia and monosomy 7. Our case and previously reported cases of DI arising as a complication in myeloid malignancies demonstrate a close association with deletion of chromosome 7. The clinical characteristics and outcomes of these uncommon cases in children are reviewed and discussed.

Daily subcutaneous parecoxib injection for cancer pain: an open label pilot study.

PubMed

Kenner, David J; Bhagat, Sandeep; Fullerton, Sonia L

2015-04-01

Nonsteroidal anti-inflammatory analgesics (NSAIDs) are useful in cancer pain but the specific use of subcutaneous parecoxib has not been previously reported. This pilot study aimed to establish the efficacy and side effect profile of short-term sequential single daily dose subcutaneous parecoxib sodium in patients with severe cancer bone pain. Nineteen hospitalized patients with advanced cancer and uncontrolled malignant bone pain (9 males, 10 females) received 24 courses of one, two, or three days sequential therapy with 'off-label' daily subcutaneous parecoxib. All patients were receiving opioid therapy; the median baseline daily oral equivalent dose (OED) of morphine was 180 mg. Pain was assessed at baseline, 24 hours, 48 hours, and 72 hours. Pain scores as assessed on an 11-point numeric pain rating scale (NPRS), any side effects including subcutaneous site reactions, as well as patient satisfaction rating with analgesia were recorded. A clinically significant decrease in pain scores was defined as a reduction of two or more points on the NPRS. Median pain score of all patient treatments decreased from 7 to 4.5 at 24 hours (p<0.001) and 4.0 at 48 hours. A response was seen in 17 (71%) of the 24 treatments at 24 hours. There was no difference between median negative change in pain scores in 19 (79%) treatments where pain was either strongly movement related, or in 22 (94%) treatments where local bone tenderness was more pronounced. No major side effects were observed during treatment. One patient died from pulmonary embolism after cessation of concurrent prophylactic low molecular weight heparin prior to staging liver biopsy. Subcutaneous site reactions occurred in 2 (8%) treatments and were mild and self limiting. Short-term daily subcutaneous parecoxib injection was effective for malignant bone pain when added to existing analgesic therapy and was well tolerated. Further research is warranted into the short-term use of parecoxib in hospitalized patients with intractable malignant bone pain.

FDG-PET response of skeletal (bone marrow and bone) involvement after induction chemotherapy in pediatric Hodgkin lymphoma - Are specific response criteria required?

PubMed

Georgi, Thomas Walter; Kluge, Regine; Kurch, Lars; Chavdarova, Lidia; Hasenclever, Dirk; Stoevesandt, Dietrich; Pelz, Tanja; Landman-Parker, Judith; Wallace, Hamish; Karlen, Jonas; Fernandez-Teijeiro, Ana; Cepelova, Michaela; Fossa, Alexander; Balwierz, Walentyna; Attarbaschi, Andishe; Ammann, Roland A; Pears, Jane; Hraskova, Andrea; Uyttebroeck, Anne; Beishuizen, Auke; Dieckmann, Karin; Leblanc, Thierry; Daw, Stephen; Baumann, Julia; Körholz, Dieter; Sabri, Osama; Mauz-Körholz, Christine

2018-04-13

Purpose: This study focused on skeletal involvement in FDG-PET (PET) in Hodgkin lymphoma (HL). We aimed at a systematic evaluation of the different types of skeletal involvement and their PET response after two cycles of chemotherapy (PET-2), to answer the question whether the current PET response criterion for skeletal involvement is suitable. A secondary objective was to observe the influence of initial uptake intensity and metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: Initial PET scans (PET-0) of 1068 pediatric HL patients from the EuroNet-PHL-C1 (C1) trial were evaluated by central review for skeletal involvement. Three types of skeletal lesions were distinguished: skeletal lesions detected only in PET (PETonly), bone marrow (BM) lesions confirmed by MRI or BM biopsy and bone lesions. Uptake intensity (measured as qPET value) and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response in PET-2 of skeletal and nodal involvement were compared. Results: 139/1068 (13%) C1 patients showed skeletal involvement (44/139 PETonly patients, 32/139 BM patients and 63/139 bone patients). 101/139 (73%) patients became PET-2 negative in the skeleton while lymph node involvement was PET-2 negative in 94/139 (68%) patients. Highest skeletal PET-2 negative rate was seen in 42/44 (95%) PETonly patients, followed by 22/32 (69%) BM patients and 37/63 (59%) bone patients. Skeletal lesions who became PET-2 negative showed lower median values for initial qPET (2.74) and MTV (2ml) than lesions who remained PET-2 positive (3.84; 7ml). Conclusion: In this study with pediatric HL patients, the complete response rate in PET-2 of skeletal and nodal involvement was similar. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion - comparison with the local skeletal background - is well suited. Initial uptake intensity and MTV of skeletal lesions were predictive for the PET-2 result. Higher values for both parameters were associated with a worse PET-2 response. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Precursor B cell lymphoblastic lymphoma presenting as periorbital swelling

PubMed Central

Galway, Niamh; Johnston, Robert; Cairns, Carole; Thompson, Andrew James

2016-01-01

An 11-year-old girl was admitted for further investigation as to the cause of her bilateral papilloedema and periorbital swelling. She had a 2-week history of headache and unilateral eyelid swelling, and a 2-day history of right-sided groin swelling. CT and MRI scans revealed soft tissue adjacent to the lateral orbital walls within the extraconal lateral aspects of both orbits, more on the right than the left. The scans also revealed extensive lymphadenopathy above and below the diaphragm. The patient underwent bone marrow studies and biopsy of the lymph node in her groin. The results revealed normal bone marrow with no evidence of malignancy. The lymph node histology confirmed malignant lymphoma in keeping with B cell lymphoblastic lymphoma. The patient was started on the UKALL 2011 chemotherapy trial. PMID:27166006

Long-term outcome of pediatric renal transplantation: a single center study in Japan.

PubMed

Yamada, Akio; Tashiro, Atsushi; Hiraiwa, Tomoko; Komatsu, Tomonori; Kinukawa, Tsuneo; Ueda, Norishi

2014-08-01

Little is known about the risk factors for long-term poor outcome in pediatric renal transplantation. Between 1973 and 2010, 111 renal transplants (92 living donations) were performed in 104 children (56 males, mean age, 12.5 yr) at the Social Insurance Chukyo Hospital, and followed-up for a mean period of 13.6 yr. The patient survival at 1, 5, 10, 15, 20 (living- and deceased-donor transplants), and 30 yr (living-donor transplants only) was 98.1%, 92.8%, 87.8%, 84.9%, 82.6%, and 79.3%. The graft survival at 1, 5, 10, 15, 20, and 30 yr was 92.0%, 77.3%, 58.4%, 50.8%, 38.5%, and 33.3%. The most common cause of graft loss was CAI, AR, death with functioning, recurrent primary disease, ATN, and malignancy. Donor gender, ATN, malignancy/cardiovascular events, and eras affected patient survival. AR and CAI were the risk factors for graft loss. The evolved immunosuppression protocols improved the outcome by reducing AR episodes and ATN but not CAI, suggesting CAI as the major risk factor for graft loss. CAI was correlated with AR episodes, CMV infection, and post-transplant hypertension. Strategies for preventing the risk factors for malignancy/cardiovascular events and CAI, including hypertension/infection, are crucial for better outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Sooner the Better? How Symptom Interval Correlates With Outcome in Children and Adolescents With Solid Tumors: Regression Tree Analysis of the Findings of a Prospective Study.

PubMed

Ferrari, Andrea; Lo Vullo, Salvatore; Giardiello, Daniele; Veneroni, Laura; Magni, Chiara; Clerici, Carlo Alfredo; Chiaravalli, Stefano; Casanova, Michela; Luksch, Roberto; Terenziani, Monica; Spreafico, Filippo; Meazza, Cristina; Catania, Serena; Schiavello, Elisabetta; Biassoni, Veronica; Podda, Marta; Bergamaschi, Luca; Puma, Nadia; Massimino, Maura; Mariani, Luigi

2016-03-01

The potential impact of diagnostic delays on patients' outcomes is a debated issue in pediatric oncology and discordant results have been published so far. We attempted to tackle this issue by analyzing a prospective series of 351 consecutive children and adolescents with solid malignancies using innovative statistical tools. To address the nonlinear complexity of the association between symptom interval and overall survival (OS), a regression tree algorithm was constructed with sequential binary splitting rules and used to identify homogeneous patient groups vis-à-vis functional relationship between diagnostic delay and OS. Three different groups were identified: group A, with localized disease and good prognosis (5-year OS 85.4%); group B, with locally or regionally advanced, or metastatic disease and intermediate prognosis (5-year OS 72.9%), including neuroblastoma, Wilms tumor, non-rhabdomyosarcoma soft tissue sarcoma, and germ cell tumor; and group C, with locally or regionally advanced, or metastatic disease and poor prognosis (5-year OS 45%), including brain tumors, rhabdomyosarcoma, and bone sarcoma. The functional relationship between symptom interval and mortality risk differed between the three subgroups, there being no association in group A (hazard ratio [HR]: 0.96), a positive linear association in group B (HR: 1.48), and a negative linear association in group C (HR: 0.61). Our analysis suggests that at least a subset of patients can benefit from an earlier diagnosis in terms of survival. For others, intrinsic aggressiveness may mask the potential effect of diagnostic delays. Based on these findings, early diagnosis should remain a goal for pediatric cancer patients. © 2015 Wiley Periodicals, Inc.

Psoralen inhibits bone metastasis of breast cancer in mice.

PubMed

Wu, Chunyu; Sun, Zhenping; Ye, Yiyi; Han, Xianghui; Song, Xiaoyun; Liu, Sheng

2013-12-01

Breast cancer is the most common female malignancy and it frequently metastasizes to bone. Metastatic breast cancer continues to be the primary cause of death for women in East and Southeast Asia. Psoralen is a furocoumarin that can be isolated from the seeds of Psoralea corylifolia L. Psoralen exhibits a wide range of biological properties and has been demonstrated as an antioxidant, antidepressant, anticancer, antibacterial, and antiviral agent. Additionally, it is involved in the formation and regulation of bone. This study investigated whether psoralen can inhibit metastasis of breast cancer to bone in vivo. Histological, molecular biological, and imaging analyses revealed that psoralen inhibits bone metastases in mice. Psoralen may function to inhibit breast cancer cell growth in the bone microenvironment and regulate the function of osteoblasts and osteoclasts in tumor-bearing mice. The results of this study suggest that psoralen is a bone-modifying agent and a potential therapeutic to treat patients with bone metastases. © 2013.

Denosumab for bone diseases: translating bone biology into targeted therapy.

PubMed

Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

2011-12-01

Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

Bone scintiscanning updated.

PubMed

Lentle, B C; Russell, A S; Percy, J S; Scott, J R; Jackson, F I

1976-03-01

Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.

Cancer-targeted therapies and radiopharmaceuticals

PubMed Central

Rachner, Tilman D; Jakob, Franz; Hofbauer, Lorenz C

2015-01-01

The treatment of bone metastases remains a clinical challenge. Although a number of well-established agents, namely bisphosphonates and denosumab, are available to reduce the occurrence of skeletal-related events, additional cancer-targeted therapies are required to improve patients' prognosis and quality of life. This review focuses on novel targets and agents that are under clinical evaluation for the treatment of malignant bone diseases such as activin A, src and endothelin-1 inhibition or agents that are clinically approved and may positively influence bone, such as the mTOR inhibitor everolimus. In addition, the potential of alpharadin, a novel radiopharmaceutical approved for the treatment of prostatic bone disease, is discussed. PMID:26131359

Prevalence and aetiology of anaemia in lymphoid malignancies.

PubMed

Ghosh, J; Singh, R K Bikramjit; Saxena, R; Gupta, R; Vivekanandan, S; Sreenivas, V; Raina, V; Sharma, A; Kumar, L

2013-01-01

We prospectively studied the prevalence, type and causes of anaemia in newly diagnosed patients with lymphoid malignancies. Between January 2007 and June 2008, a total of 316 newly diagnosed, consecutive patients (aged 15 years or above) of Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia with anaemia (haemoglobin <11 g/dl), were analysed to determine the prevalence and a subgroup of 46 patients was analysed for the cause of anaemia. Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia were the diagnoses in 81 (25.8%), 203 (64.7%) and 30 (9.6%) patients, respectively. Anaemia was present in 134 patients (42.4%). Anaemia of chronic disease was present in 33/46 (71.7%) and iron deficiency in 18/46 (39.1%) patients. Vitamin B12 and/or folate deficiency was detected in 10/46 (21.7%) patients (B12 deficiency alone in 7, folate deficiency alone in 1 and combined B12 and folate deficiency in 2). Autoimmune haemolytic anaemia was detected in 5/46 (10.9%) although direct Coombs test was positive in 17/46 (37%) patients. Among patients with Hodgkin lymphoma and non-Hodgkin lymphoma, anaemia due to bone marrow involvement was present in 16/40 (40%). In most patients with bone marrow involvement, anaemia was due to other causes. In only 3 patients, anaemia was attributable to bone marrow involvement alone. Anaemia was multifactorial in 18/46 (39.1%) patients. Nutritional deficiency alone or in combination was present in 22/46 (47.8%) patients. Anaemia is common in lymphoid malignancies at initial presentation. Besides managing anaemia of chronic disease and bone marrow involvement, nutritional and autoimmune causes should be ruled out. Copyright 2013, NMJI.

Reinforced cementoplasty using dedicated spindles in the management of unstable malignant lesions of the cervicotrochanteric region.

PubMed

Premat, Kévin; Clarençon, Frédéric; Bonaccorsi, Raphael; Degos, Vincent; Cormier, Évelyne; Chiras, Jacques

2017-09-01

In long bones, cementoplasty alone does not provide sufficient stability, which may cause secondary fractures. This study reviewed the safety and efficacy of reinforced cementoplasty (RC) (percutaneous internal fixation using dedicated spindles combined with cementoplasty) for unstable malignant lesions of the cervicotrochanteric region (CTR) of the proximal femur. Eighteen consecutive patients (nine women [50%] and nine men [50%]; mean age 55.1 ± 16.2 years; range 22-85) underwent RC for 19 unstable lesions of the CTR (16/19 [84.2%] bone metastases, 3/19 [15.8%] multiple myeloma lesions). All the patients were considered unsuitable for surgery. Clinical outcome was judged with a mean follow-up of 8.8 ± 7.2 months (range 1-27). The primary endpoints were occurrence of secondary fractures during the follow-up period and local pain relief measured by a visual analogue scale (VAS). No secondary fracture occurred. Mean VAS improved from 5.9 ± 3.1 (range 0-10) to 2.3 ± 2.4 (range 0-7) at 1 month (p = 0.001) to 1.6 ± 1.7 (range 0-5) at final follow-up (p = 0.0002). One symptomatic cement pulmonary embolism was recorded. RC is an original minimally invasive technique providing pain relief and effective bone stability for unstable malignant lesions of the cervicotrochanteric region in patients unsuitable for open surgery. • Reinforced cementoplasty (RC) combines intralesional spindling with cementoplasty. • RC provides effective bone stability and pain relief. • RC is a suitable minimally invasive option for patients in poor general condition.

[Microsurgical transplantation of bone tumors of uncertain prognosis in athymic nude mice].

PubMed

Duprez, A; Féry, A; Sommelet, J

1986-01-01

Eight cases of human bone or soft tissue tumours were transplanted to nude mice. After such transplants to nude mice which are immunologically deficient, the malignant tumors developed like benign tumours, but maintaining malignant cytological characteristics. The transplants of normal human tissues or of benign tumours decreased in size or remained stable. The technique allowed a change of an original diagnosis of osteosarcoma to a final diagnosis of chondrosarcoma. It made it possible to diagnose a benign osteoblastoma, the diagnosis of which was doubtful before the transplant between osteosarcoma and chondroblastoma. It was possible to diagnose the malignancy of a haemangiopericytoma of muscle. Two aggressive tumours--a non-ossifying fibroma and a giant-cell tumour--were rated as benign after transplantation. This technique also allowed a more precise diagnosis of the grade of one chondrosarcoma and one osteosarcoma. Finally, transplantation also made it possible to test the efficacy of chemotherapy. In a patient so treated, the extreme cell proliferation after transplantation to the nude mouse led to a change in the drugs administered.

Radiotherapeutic management of medulloblastoma in a pediatric patient with ataxia telangiectasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hart, R.M.; Kimler, B.F.; Evans, R.G.

1987-08-01

Ataxia telangiectasia (AT) is a genetic disorder with a predisposition to malignancy. Cells from patients with AT demonstrate an increased sensitivity to ionizing radiation which creates a problem when these patients require treatment for their malignant disease. An eleven-year-old boy with a previous diagnosis of AT was seen in consultation following partial resection of medulloblastoma in the posterior fossa. To estimate how much the conventional radiation dose might have to be reduced, we compared the radiosensitivity of bone marrow myeloid progenitor cells from this patient to that of cells from the marrow of normal individuals, using colony formation in anmore » agar culture assay system as the endpoint (CFU-Cs). Neither radiation dose-survival curve exhibited a shoulder--each displayed an extrapolation number of 0.99. The survival curve of normal cells displayed a steep slope with a D0 of 0.98 Gy (0.83-1.19 Gy, 95% confidence limits); the slope for the AT cells was considerably steeper with a value for D0 of 0.32 Gy (0.29-0.35 Gy). The ratio of D0's indicated that these AT cells were approximately 3X more radiosensitive than normal cells. Based on this, the daily dose was reduced from 1.8 to 0.6 Gy and the radiation was restricted to 25 treatments to the posterior fossa rather than the conventional cranio-spinal treatment. An additional 5 treatments at 1.0 Gy per day were given to the whole brain. The patient's skin responded to these reduced fraction sizes and doses to a similar degree as normal patients' skin following a standard schedule and the patient is doing well nine months after initiation of treatment.« less

21 CFR 864.7660 - Leukocyte alkaline phosphatase test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... differentiate chronic granulocytic leukemia (a malignant disease characterized by excessive overgrowth of granulocytes in the bone marrow) and reactions that resemble true leukemia, such as those occuring in severe...

21 CFR 864.7660 - Leukocyte alkaline phosphatase test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... differentiate chronic granulocytic leukemia (a malignant disease characterized by excessive overgrowth of granulocytes in the bone marrow) and reactions that resemble true leukemia, such as those occuring in severe...

The Role of the EGF Receptor and Vitamins A and D in Development and Progression of Breast Cancer to More Malignant Hormones Independent Phenotypes

DTIC Science & Technology

1999-09-01

parathyroid hormone (46) and rat bone sialoprotein (47) genes are perhaps the most frequently cited examples of negative transcriptional regulation...specific to BT549 cells. A similar mechanism has been postulated to explain the vitamin D mediated suppression of the rat bone sialoprotein gene through a...Yamauchi M, Freedman LP, Sodek J 1996 Identification of a vitamin D3-response element that overlaps a unique inverted TATA box in the rat bone sialoprotein

Spinal bone marrow necrosis with vertebral compression fracture: differentiation of BMN from AVN.

PubMed

Nix, J S; Fitzgerald, R T; Samant, R S; Harrison, M; Angtuaco, E J

2014-09-01

Bone marrow necrosis (BMN) is a rare malignancy-associated hematologic disorder characterized by necrosis of myeloid and stromal marrow elements with preservation of cortical bone. Overlap between the imaging appearances of BMN and avascular necrosis (AVN) raises the potential for diagnostic confusion. We report a case of BMN presenting with a traumatic multi-level vertebral body collapse, and finding that may potentially confound distinction between the two entities. We discuss important pathophysiologic, clinical, and radiologic differences between BMN and AVN with emphasis on features important in the differential diagnosis.

Synchronous occurrence of prostate carcinoma and multiple myeloma: a case report.

PubMed

Sehgal, Tushar; Sharma, Sudha; Naseem, Shano; Varma, Neelam; Das, Ashim; Sharma, S C

2014-09-01

We describe a rare case of metastatic prostate cancer to bone marrow and synchronous multiple myeloma as the second malignant disease. Various diagnostic procedures, including cytomorphology and immunohistochemistry analyses together contributed to the detection of metastasis of prostate cancer and synchronous plasma cell proliferation in the bone marrow. The association between these two disorders is poorly understood however, some studies show that bone marrow microenvironment may play a crucial role. The need for further research in this regard is required to unfold this fascinating association.

The impact of the written request process on drug development in childhood cancer.

PubMed

Snyder, Kristen M; Reaman, Gregory; Avant, Debbie; Pazdur, Richard

2013-04-01

The Food and Drug Administration (FDA) Modernization Act, enacted in 1997, created a pediatric exclusivity incentive allowing sponsors to qualify for an additional 6 months of marketing exclusivity after satisfying the requirements outlined in the Written Request (WR). This review evaluates the impact of the WR mechanism on the development of oncology drugs in children. A search of the FDA document archiving, reporting, and regulatory tracking system was performed for January 1, 2000 to December 31, 2010. Drugs were identified and pediatric-specific labeling information was obtained from Drugs@fda.gov and FDA Pediatric Labeling Changes Table. Fifty WRs have been issued for oncology drugs. Pediatric studies have been submitted for 14 drugs. Thirteen received pediatric exclusivity. As of December 31, 2010, labeling changes have been made for 11 drugs. Three drugs were approved for pediatric use. WRs have provided a mechanism to promote the study of drugs in pediatric malignancies. Information from studies resulting from the WRs regarding safety, pharmacokinetics, and tolerability of oncology drugs has been incorporated into pediatric labeling for 11/14 of the drugs. Earlier communication and collaboration between the FDA, National Cancer Institute, clinical investigators, and commercial sponsors are envisioned to facilitate the identification and prioritization of emerging new drugs of interest for WR consideration. Since this is the only regulatory mechanism, resulting from specific legislative initiatives relevant to cancer drug development for children, efforts to enhance its impact on increasing drug approval for pediatric cancer indications are warranted. Copyright © 2013 Wiley Periodicals, Inc.

ADC as a useful diagnostic tool for differentiating benign and malignant vertebral bone marrow lesions and compression fractures: a systematic review and meta-analysis.

PubMed

Suh, Chong Hyun; Yun, Seong Jong; Jin, Wook; Lee, Sun Hwa; Park, So Young; Ryu, Chang-Woo

2018-07-01

To assess the sensitivity and specificity of quantitative assessment of the apparent diffusion coefficient (ADC) for differentiating benign and malignant vertebral bone marrow lesions (BMLs) and compression fractures (CFs) METHODS: An electronic literature search of MEDLINE and EMBASE was conducted. Bivariate modelling and hierarchical summary receiver operating characteristic modelling were performed to evaluate the diagnostic performance of ADC for differentiating vertebral BMLs. Subgroup analysis was performed for differentiating benign and malignant vertebral CFs. Meta-regression analyses according to subject, study and diffusion-weighted imaging (DWI) characteristics were performed. Twelve eligible studies (748 lesions, 661 patients) were included. The ADC exhibited a pooled sensitivity of 0.89 (95% confidence interval [CI] 0.80-0.94) and a pooled specificity of 0.87 (95% CI 0.78-0.93) for differentiating benign and malignant vertebral BMLs. In addition, the pooled sensitivity and specificity for differentiating benign and malignant CFs were 0.92 (95% CI 0.82-0.97) and 0.91 (95% CI 0.87-0.94), respectively. In the meta-regression analysis, the DWI slice thickness was a significant factor affecting heterogeneity (p < 0.01); thinner slice thickness (< 5 mm) showed higher specificity (95%) than thicker slice thickness (81%). Quantitative assessment of ADC is a useful diagnostic tool for differentiating benign and malignant vertebral BMLs and CFs. • Quantitative assessment of ADC is useful in differentiating vertebral BMLs. • Quantitative ADC assessment for BMLs had sensitivity of 89%, specificity of 87%. • Quantitative ADC assessment for CFs had sensitivity of 92%, specificity of 91%. • The specificity is highest (95%) with thinner (< 5 mm) DWI slice thickness.

Impact of long-term exposure to the tyrosine kinase inhibitor imatinib on the skeleton of growing rats.

PubMed

Tauer, Josephine T; Hofbauer, Lorenz C; Jung, Roland; Gerdes, Sebastian; Glauche, Ingmar; Erben, Reinhold G; Suttorp, Meinolf

2015-01-01

The tyrosine kinase (TK) inhibitor imatinib provides a highly effective therapy for chronic myeloid leukemia (CML) via inhibition of the oncogenic TK BCR-ABL1. However, off-target TKs like platelet-derived growth factor receptors (PDGF-R) and colony-stimulating factor-1 receptor (c-fms), involved in bone remodeling, are also inhibited. Thus, pediatric patients with CML on imatinib exhibit altered bone metabolism, leading to linear growth failure. As TKI treatment might be necessary for a lifetime, long-term effects exerted on bone in children are of major concern. Therefore, we studied the skeletal long-term effects of continuous and intermittent imatinib exposure in a juvenile rat model. Four-weeks-old male Wistar rats were chronically exposed to imatinib via drinking water over a period of 10 weeks. Animals were exposed to a standard and high imatinib dosage continuously and to the high imatinib dose intermittently. Bone mass and strength were assessed using pQCT, micro-computed tomography (μCT), and biomechanical testing at the prepubertal, pubertal, and postpubertal age. Bone length and vertebral height as well as biochemical markers of bone turnover were analyzed. Femoral and tibial bone length were dose-dependently reduced by up to 24% (p<0.0001), femoral and tibial trabecular bone mass density (BMD) were reduced by up to 25% (p<0.01), and femoral breaking strength was lowered by up to 20% (p<0.05). Intermittent exposure mitigated these skeletal effects. Long-term exposure resulted in reduced vertebral height by 15% and lower trabecular BMD by 5%. Skeletal changes were associated with suppressed serum osteocalcin (p<0.01) and non-significantly elevated serum CTX-I and PINP levels. In conclusion, imatinib mainly impaired longitudinal growth of long bones rather than the vertebrae of growing rats. Interestingly, intermittent imatinib exposure has less skeletal side effects, which may be beneficial in pediatric patients taking imatinib.

Management of aggressive B cell NHLs in the AYA population: an adult versus pediatric perspective.

PubMed

Dunleavy, Kieron; Gross, Thomas G

2018-06-12

The adolescents and young adult (AYA) population represent a group where mature B-cell lymphomas constitute a significant proportion of the overall malignancies that occur. Among these are aggressive B-cell non-Hodgkin lymphomas (NHLs) which are predominantly diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL). For the most part, there is remarkable divide in how pediatric/adolescent patients (under the age of 18 years) with lymphoma are treated versus their young adult counterparts and molecular data are lacking, especially in pediatric and AYA series. The outcome for AYA patients with cancers has historically been inferior to that of children or older adults, highlighting the necessity to focus on this population. This review discusses the pediatric versus adult perspective in terms of how these diseases are understood and approached and emphasizes the importance of collaborative efforts in both developing consensus for treatment of this population and planning future research endeavors. Copyright © 2018 American Society of Hematology.

A-Frame free Vascularized Fibular Graft and Femoral Lengthening for Osteosarcoma Pediatric Patients.

PubMed

Cashin, Megan; Coombs, Christopher; Torode, Ian

2018-02-01

Pediatric limb reconstruction after resection of a malignant tumor presents specific challenges. Multiple surgical techniques have been used to treat these patients. This paper describes a staged surgical technique for the reconstruction of large distal femoral defects due to tumor resection in skeletally immature patients. Three pediatric patients with osteosarcoma of the distal femur underwent staged reconstruction. Neoadjuvant chemotherapy was followed by en bloc tumor resection and immediate reconstruction of the distal femoral defect with a vascularized free fibular autograft utilizing a unique A-frame construct combined with intramedullary nail fixation. The second stage was a planned gradual lengthening of the healed construct, over a custom-made magnetically driven expandable intramedullary nail. All patients achieved bony union and satisfactory length with minimal complications. The patients all returned to full, unlimited physical activities. The early results confirm that the described technique is a safe and reliable procedure for the reconstruction of large femoral defects in pediatric patients with osteosarcoma. Level IV-therapeutic.

Peripherally Inserted Central Venous Catheters in Pediatric Hematology/Oncology Patients in Tertiary Care Setting: A Developing Country Experience.

PubMed

Fadoo, Zehra; Nisar, Muhammad I; Iftikhar, Raza; Ali, Sajida; Mushtaq, Naureen; Sayani, Raza

2015-10-01

Peripherally inserted central venous catheters (PICC) have been successfully used to provide central access for chemotherapy and frequent transfusions. The purpose of this study was to assess the feasibility of PICCs and determine PICC-related complications in pediatric hematology/oncology patients in a resource-poor setting. All pediatric patients (age below 16 y) with hematologic and malignant disorders who underwent PICC line insertion at Aga Khan University Hospital from January 2008 to June 2010 were enrolled in the study. Demographic features, primary diagnosis, catheter days, complications, and reasons for removal of device were recorded. Total of 36 PICC lines were inserted in 32 pediatric patients. Complication rate of 5.29/1000 catheter days was recorded. Our study showed comparable complication profile such as infection rate, occlusion, breakage, and dislodgement. The median catheter life was found to be 69 days. We conclude that PICC lines are feasible in a resource-poor setting and recommend its use for chemotherapy administration and prolonged venous access.

Pediatric malignant hyperthermia: risk factors, morbidity, and mortality identified from the Nationwide Inpatient Sample and Kids' Inpatient Database.

PubMed

Salazar, Jose H; Yang, Jingyan; Shen, Liang; Abdullah, Fizan; Kim, Tae W

2014-12-01

Malignant Hyperthermia (MH) is a potentially fatal metabolic disorder. Due to its rarity, limited evidence exists about risk factors, morbidity, and mortality especially in children. Using the Nationwide Inpatient Sample and the Kid's Inpatient Database (KID), admissions with the ICD-9 code for MH (995.86) were extracted for patients 0-17 years of age. Demographic characteristics were analyzed. Logistic regression was performed to identify patient and hospital characteristics associated with mortality. A subset of patients with a surgical ICD-9 code in the KID was studied to calculate the prevalence of MH in the dataset. A total of 310 pediatric admissions were seen in 13 nonoverlapping years of data. Patients had a mortality of 2.9%. Male sex was predominant (64.8%), and 40.5% of the admissions were treated at centers not identified as children's hospitals. The most common associated diagnosis was rhabdomyolysis, which was present in 26 cases. Regression with the outcome of mortality did not yield significant differences between demographic factors, age, sex race, or hospital type, pediatric vs nonpediatric. Within a surgical subset of 530,449 admissions, MH was coded in 55, giving a rate of 1.04 cases per 10,000 cases. This study is the first to combine two large databases to study MH in the pediatric population. The analysis provides an insight into the risk factors, comorbidities, mortality, and prevalence of MH in the United States population. Until more methodologically rigorous, large-scale studies are done, the use of databases will continue to be the optimal method to study rare diseases. © 2014 John Wiley & Sons Ltd.

Aspects and Intensity of Pediatric Palliative Case Management Provided by a Hospital-Based Case Management Team: A Comparative Study Between Children With Malignant and Nonmalignant Disease

PubMed Central

Colenbrander, Derk A.; Bosman, Diederik K.; Grootenhuis, Martha A.; Kars, Marijke C.; Schouten-van Meeteren, Antoinette YN

2017-01-01

Objectives: Anticipating case management is considered crucial in pediatric palliative care. In 2012, our children’s university hospital initiated a specialized pediatric palliative care team (PPCT) to deliver inbound and outbound case management for children with life-shortening disease. The aim of this report is to gain insight in the first 9 months of this PPCT. Methods: Aspects of care during the first 9 months of the PPCT are presented, and comparison is made between patients with malignant disease (MD) and nonmalignant disease (NMD) in a retrospective study design. Insight in the aspects of care of all patients with a life-shortening disease was retrieved from web-based files and the hour registrations from the PPCT. Results: Forty-three children were supported by the PPCT during the first 9 months: 22 with MD with a median of 50 (1-267) days and 29 minutes (4-615) of case management per patient per day and 21 patients with NMD with a median of 79.5 (5-211) days and 16 minutes of case management per day (6-64). Our data show significantly more interprofessional contacts for patients with MD and more in-hospital contacts for patients with NMD. The median number of admission days per patient was 11 (0-22) for MD (44% for anticancer therapy) and 44 (0-303) for NMD (36% for infectious diseases). Significance of Results: This overview of aspects of pediatric palliative case management shows shorter but more intensive case management for MD in comparison with NMD. This insight in palliative case management guides the design of a PPCT. PMID:28273758

Global DNA methylation analysis reveals miR-214-3p contributes to cisplatin resistance in pediatric intracranial nongerminomatous malignant germ cell tumors.

PubMed

Hsieh, Tsung-Han; Liu, Yun-Ru; Chang, Ting-Yu; Liang, Muh-Lii; Chen, Hsin-Hung; Wang, Hsei-Wei; Yen, Yun; Wong, Tai-Tong

2018-03-27

Pediatric central nervous system germ cell tumors (CNSGCTs) are rare and heterogeneous neoplasms, which can be divided into germinomas and nongerminomatous germ cell tumors (NGGCTs). NGGCTs are further subdivided into mature teratomas and nongerminomatous malignant GCTs (NGMGCTs). Clinical outcomes suggest that NGMGCTs have poor prognosis and survival and that they require more extensive radiotherapy and adjuvant chemotherapy. However, the mechanisms underlying this difference are still unclear. DNA methylation alteration is generally acknowledged to cause therapeutic resistance in cancers. We hypothesized that the pediatric NGMGCTs exhibit a different genome-wide DNA methylation pattern, which is involved in the mechanism of its therapeutic resistance. We performed methylation and hydroxymethylation DNA immunoprecipitation sequencing, mRNA expression microarray, and small RNA sequencing (smRNA-seq) to determine methylation-regulated genes, including microRNAs (miRNAs). The expression levels of 97 genes and 8 miRNAs were correlated with promoter DNA methylation and hydroxymethylation status, such as the miR-199/-214 cluster, and treatment with DNA demethylating agent 5-aza-2'-deoxycytidine elevated its expression level. Furthermore, smRNA-seq analysis showed 27 novel miRNA candidates with differential expression between germinomas and NGMGCTs. Overexpresssion of miR-214-3p in NCCIT cells leads to reduced expression of the pro-apoptotic protein BCL2-like 11 and induces cisplatin resistance. We interrogated the differential DNA methylation patterns between germinomas and NGMGCTs and proposed a mechanism for chemoresistance in NGMGCTs. In addition, our sequencing data provide a roadmap for further pediatric CNSGCT research and potential targets for the development of new therapeutic strategies.

Malignant nerve-sheath neoplasms in neurofibromatosis: distinction from benign tumors by using imaging techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levine, E.; Huntrakoon, M.; Wetzel, L.H.

Malignant peripheral nerve-sheath neoplasms frequently complicate neurofibromatosis causing pain, enlarging masses, or neurologic deficits. However, similar findings sometimes also occur with benign nerve neoplasms. Our study was done retrospectively to determine if imaging techniques can differentiate malignant from benign nerve tumors in neurofibromatosis. Eight patients with symptomatic neoplasms (three benign, five malignant) were studied by CT in eight, MR in six, and /sup 67/Ga-citrate scintigraphy in seven. Uptake of /sup 67/Ga occurred in all five malignant lesions but not in two benign neoplasms studied. On CT or MR, all eight lesions, including three benign neoplasms, showed inhomogeneities. Of five lesionsmore » with irregular, infiltrative margins on CT or MR, four were malignant and one was benign. Of three lesions with smooth margins, one was malignant and two were benign. One malignant neoplasm caused irregular bone destruction. Accordingly, CT and MR could not generally distinguish malignant from benign lesions with certainty. However, both CT and MR provided structural delineation to help surgical planning for both types of lesion. /sup 67/Ga scintigraphy appears promising as a screening technique to identify lesions with malignant degeneration in patients with neurofibromatosis. Any area of abnormal radiogallium uptake suggests malignancy warranting further evaluation by CT or MR. Biopsy of any questionable lesion is essential.« less

Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients

PubMed Central

Keel, Siobán B.; Scott, Angela; Sanchez-Bonilla, Marilyn; Ho, Phoenix A.; Gulsuner, Suleyman; Pritchard, Colin C.; Abkowitz, Janis L.; King, Mary-Claire; Walsh, Tom; Shimamura, Akiko

2016-01-01

The clinical and histopathological distinctions between inherited versus acquired bone marrow failure and myelodysplastic syndromes are challenging. The identification of inherited bone marrow failure/myelodysplastic syndromes is critical to inform appropriate clinical management. To investigate whether a subset of pediatric and young adults undergoing transplant for aplastic anemia or myelodysplastic syndrome have germline mutations in bone marrow failure/myelodysplastic syndrome genes, we performed a targeted genetic screen of samples obtained between 1990–2012 from children and young adults with aplastic anemia or myelodysplastic syndrome transplanted at the Fred Hutchinson Cancer Research Center. Mutations in inherited bone marrow failure/myelodysplastic syndrome genes were found in 5.1% (5/98) of aplastic anemia patients and 13.6% (15/110) of myelodysplastic syndrome patients. While the majority of mutations were constitutional, a RUNX1 mutation present in the peripheral blood at a 51% variant allele fraction was confirmed to be somatically acquired in one myelodysplastic syndrome patient. This highlights the importance of distinguishing germline versus somatic mutations by sequencing DNA from a second tissue or from parents. Pathological mutations were present in DKC1, MPL, and TP53 among the aplastic anemia cohort, and in FANCA, GATA2, MPL, RTEL1, RUNX1, SBDS, TERT, TINF2, and TP53 among the myelodysplastic syndrome cohort. Family history or physical examination failed to reliably predict the presence of germline mutations. This study shows that while any single specific bone marrow failure/myelodysplastic syndrome genetic disorder is rare, screening for these disorders in aggregate identifies a significant subset of patients with inherited bone marrow failure/myelodysplastic syndrome. PMID:27418648

Dose and diagnostic image quality in digital tomosynthesis imaging of facial bones in pediatrics

NASA Astrophysics Data System (ADS)

King, J. M.; Hickling, S.; Elbakri, I. A.; Reed, M.; Wrogemann, J.

2011-03-01

The purpose of this study was to evaluate the use of digital tomosynthesis (DT) for pediatric facial bone imaging. We compared the eye lens dose and diagnostic image quality of DT facial bone exams relative to digital radiography (DR) and computed tomography (CT), and investigated whether we could modify our current DT imaging protocol to reduce patient dose while maintaining sufficient diagnostic image quality. We measured the dose to the eye lens for all three modalities using high-sensitivity thermoluminescent dosimeters (TLDs) and an anthropomorphic skull phantom. To assess the diagnostic image quality of DT compared to the corresponding DR and CT images, we performed an observer study where the visibility of anatomical structures in the DT phantom images were rated on a four-point scale. We then acquired DT images at lower doses and had radiologists indicate whether the visibility of each structure was adequate for diagnostic purposes. For typical facial bone exams, we measured eye lens doses of 0.1-0.4 mGy for DR, 0.3-3.7 mGy for DT, and 26 mGy for CT. In general, facial bone structures were visualized better with DT then DR, and the majority of structures were visualized well enough to avoid the need for CT. DT imaging provides high quality diagnostic images of the facial bones while delivering significantly lower doses to the lens of the eye compared to CT. In addition, we found that by adjusting the imaging parameters, the DT effective dose can be reduced by up to 50% while maintaining sufficient image quality.

Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

ClinicalTrials.gov

2017-12-04

Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

What causes bone loss?

MedlinePlus

... Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, PA: Elsevier; 2016:chap 29. ... Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric . 7th ed. Philadelphia, PA: Elsevier ...

Bone Density and Cortical Structure after Pediatric Renal Transplantation

PubMed Central

Terpstra, Anniek M.; Kalkwarf, Heidi J.; Shults, Justine; Zemel, Babette S.; Wetzsteon, Rachel J.; Foster, Bethany J.; Strife, C. Frederic; Foerster, Debbie L.

2012-01-01

The impact of renal transplantation on trabecular and cortical bone mineral density (BMD) and cortical structure is unknown. We obtained quantitative computed tomography scans of the tibia in pediatric renal transplant recipients at transplantation and 3, 6, and 12 months; 58 recipients completed at least two visits. We used more than 700 reference participants to generate Z-scores for trabecular BMD, cortical BMD, section modulus (a summary measure of cortical dimensions and strength), and muscle and fat area. At baseline, compared with reference participants, renal transplant recipients had significantly lower mean section modulus and muscle area; trabecular BMD was significantly greater than reference participants only in transplant recipients younger than 13 years. After transplantation, trabecular BMD decreased significantly in association with greater glucocorticoid exposure. Cortical BMD increased significantly in association with greater glucocorticoid exposure and greater decreases in parathyroid hormone levels. Muscle and fat area both increased significantly, but section modulus did not improve. At 12 months, transplantation associated with significantly lower section modulus and greater fat area compared with reference participants. Muscle area and cortical BMD did not differ significantly between transplant recipients and reference participants. Trabecular BMD was no longer significantly elevated in younger recipients and was low in older recipients. Pediatric renal transplant associated with persistent deficits in section modulus, despite recovery of muscle, and low trabecular BMD in older recipients. Future studies should determine the implications of these data on fracture risk and identify strategies to improve bone density and structure. PMID:22282589

Cancer and Central Nervous System Tumor Surveillance in Pediatric Neurofibromatosis 1.

PubMed

Evans, D Gareth R; Salvador, Hector; Chang, Vivian Y; Erez, Ayelet; Voss, Stephan D; Schneider, Kami Wolfe; Scott, Hamish S; Plon, Sharon E; Tabori, Uri

2017-06-15

Although the neurofibromatoses consist of at least three autosomal dominantly inherited disorders, neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis, NF1 represents a multisystem pleiotropic condition very different from the other two. NF1 is a genetic syndrome first manifesting in childhood; affecting multiple organs, childhood development, and neurocognitive status; and presenting the clinician with often complex management decisions that require a multidisciplinary approach. Molecular genetic testing (see article for detailed discussion) is recommended to confirm NF1, particularly in children fulfilling only pigmentary features of the diagnostic criteria. Although cancer risk is not the major issue facing an individual with NF1 during childhood, the condition causes significantly increased malignancy risks compared with the general population. Specifically, NF1 is associated with highly elevated risks of juvenile myelomonocytic leukemia, rhabdomyosarcoma, and malignant peripheral nerve sheath tumor as well as substantial risks of noninvasive pilocytic astrocytoma, particularly optic pathway glioma (OPG), which represent a major management issue. Until 8 years of age, clinical assessment for OPG is advised every 6 to 12 months, but routine MRI assessment is not currently advised in asymptomatic individuals with NF1 and no signs of clinical visual pathway disturbance. Routine surveillance for other malignancies is not recommended, but clinicians and parents should be aware of the small risks (<1%) of certain specific individual malignancies (e.g., rhabdomyosarcoma). Tumors do contribute to both morbidity and mortality, especially later in life. A single whole-body MRI should be considered at transition to adulthood to assist in determining approaches to long-term follow-up. Clin Cancer Res; 23(12); e46-e53. ©2017 AACR See all articles in the online-only CCR Pediatric Oncology Series . ©2017 American Association for Cancer Research.

Value of 18F-FDG PET and PET/CT for evaluation of pediatric malignancies.

PubMed

Uslu, Lebriz; Donig, Jessica; Link, Michael; Rosenberg, Jarrett; Quon, Andrew; Daldrup-Link, Heike E

2015-02-01

Successful management of solid tumors in children requires imaging tests for accurate disease detection, characterization, and treatment monitoring. Technologic developments aim toward the creation of integrated imaging approaches that provide a comprehensive diagnosis with a single visit. These integrated diagnostic tests not only are convenient for young patients but also save direct and indirect health-care costs by streamlining procedures, minimizing hospitalizations, and minimizing lost school or work time for children and their parents. (18)F-FDG PET/CT is a highly sensitive and specific imaging modality for whole-body evaluation of pediatric malignancies. However, recent concerns about ionizing radiation exposure have led to a search for alternative imaging methods, such as whole-body MR imaging and PET/MR. As we develop new approaches for tumor staging, it is important to understand current benchmarks. This review article will synthesize the current literature on (18)F-FDG PET/CT for tumor staging in children, summarizing questions that have been solved and providing an outlook on unsolved avenues. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Solid variant of aneurysmal bone cyst of the left parietal bone without preceding trauma.

PubMed

Nestler, Ulf; Wagner, Hans-Joachim; Schaenzer, Anne; Preuss, Matthias

2013-12-01

We report the case of a 17-year-old girl with an indolent, smooth swelling of the left cranial vault that had been developing for 2 months. Complete surgical excision was performed and the defect was closed using artificial bone cement. The integrity of the dura mater was conserved and the patient recovered without neurological deficit. Magnetic resonance imaging (MRI) controls 6 and 18 months after the operation did not find signs of recurrence. The lesion consisted of an elastic bone shell containing bony trabeculae with soft brown-greyish tissue and posthemorrhagic dark fluid. Histological assessment found CD68 positive multinucleated giant cells in a highly cellular fibroblastic matrix surrounding bony lamellar structures, without signs of inflammation or malignancy. Hyperparathyroidism was ruled out by normal serum values for parathyroid hormone, calcium, phosphate, and alkaline phosphatase. Histologically, first diagnosis was giant cell reparative granuloma and reference pathology disclosed aneurysmal bone cyst. The solid variant of aneurysmal bone cyst and the giant cell reparative granuloma can be histologically indistinguishable. Both lesions are only rarely encountered in cranial bones and most published cases affected the cranial base or the jaw, mainly in children or young adults. From a clinical point of view, classification into "outward" lesions (osteolysis of external parts of the vault with preservation of internal tabula) and "inward" lesions (intracranial multicystic lesions with raise of intracranial pressure) has been proposed. Three phases of development can be identified, and spontaneous involution has been described. Both entities are benign, but because in several cases an underlying malignant disease has been found, complete resection and regular follow-up by MRI are recommended. Georg Thieme Verlag KG Stuttgart · New York.

Humoral hypercalcemia of malignancy in nude mouse model of a canine adenocarcinoma derived from apocrine glands of the anal sac. Biochemical, histomorphometric, and ultrastructural studies.

PubMed

Rosol, T J; Capen, C C; Weisbrode, S E; Horst, R L

1986-06-01

A serially transplantable tumor line, designated CAC-8, has been developed in nude mice from a spontaneously occurring adenocarcinoma of the anal sac from a hypercalcemic dog. Nude mice with transplanted CAC-8 developed hypercalcemia (mean 16.3 +/- 0.6 mg/dl) and moderate hypophosphatemia without bone metastasis. Urinary excretion of calcium and hydroxyproline were increased 6- and 2.3-fold, respectively. Urinary excretion of cAMP was moderately increased but phosphorus excretion was not significantly altered. Serum 1,25-dihydroxycholecalciferol was increased significantly in tumor-bearing nude mice in proportion to the magnitude of tumor-induced hypercalcemia. Histomorphometric evaluation of lumbar vertebrae from nude mice with CAC-8 revealed decreased total and cortical bone volume, a 3.3-fold increase in bone resorption rate and a 2.5-fold increase in bone formation rate at the tissue level. The transplanted CAC-8 has maintained the histologic pattern of the original carcinoma up to the present sixth passage. Ultrastructural evaluation of transplanted tumor cells revealed 150-250-nm secretory-like granules. The granules did not stain by using an ultrastructural cytochemical (uranaffin) stain specific for neuroendocrine secretory granules. Ultrastructurally, the parathyroid glands of nude mice with CAC-8 appeared inactive with large intracytoplasmic whorl of agranular membranes. These data suggest the transplanted carcinoma secreted a humoral factor which resulted in hypercalcemia. The tumor line (CAC-8) propagated in nude mice represents an animal model of humoral hypercalcemia of malignancy that shares many features with the syndrome described in human patients. Unique features of this transplanted carcinoma associated with hypercalcemia include increased serum dihydroxycholecalciferol, increased rate of bone formation as well as bone resorption, an absence of bone metastases, and evidence of parathyroid gland suppression.

Bone cancer occurrence among beagles given 239Pu as young adults.

PubMed

Lloyd, R D; Taylor, G N; Angus, W; Bruenger, F W; Miller, S C

1993-01-01

The occurrence of skeletal malignancies has been documented among 234 young adult beagles given single intravenous injections of monomeric 239Pu citrate. Occurrence has also been documented among 132 comparable control group animals surviving the minimum latent time period of 2.79 y for radiation-induced bone cancer, who were maintained for lifespan observation. Injected amounts ranged from about 0.02-106 kBq kg-1 body mass with factors of 2 or 3 between dose levels. There were 84 radiographically apparent bone tumors in 76 plutonium-injected dogs and one tumor in a control group dog. Most of these were osteosarcomas except for seven chondrosarcomas, one liposarcoma, and one plasma cell myeloma of bone. The relationship between percent of dogs at any dose level with bone malignancy and average skeletal dose at the presumed time of tumor initiation of 1 y before death appeared to be linear below about 1.3 Gy average skeletal dose. The observed data can be approximated by the expression A = 0.76 + 75 D, where A = percent of dogs with bone cancer at any dose level, D = average skeletal dose in Gy (for doses up to 1.3 Gy) at tumor initiation, and 0.76 represents the percent tumor response in the control animals not given plutonium. Similar analysis of our corresponding data for beagles given 226Ra, excluding the two highest dose levels (approximately 100% occurrence), yielded the expression A = 0.76 + 4.7 D, where D = the average skeletal dose in Gy (for doses up to 20 Gy) at 1 y before death. The ratio of coefficients indicates the effectiveness for bone cancer induction of 239Pu relative to 226Ra, or [(75 +/- 22.5)(4.7 +/- 0.47)-1] = 16 +/- 5 for a single, brief intake of either nuclide into blood.

Model-based segmentation of hand radiographs

NASA Astrophysics Data System (ADS)

Weiler, Frank; Vogelsang, Frank

1998-06-01

An important procedure in pediatrics is to determine the skeletal maturity of a patient from radiographs of the hand. There is great interest in the automation of this tedious and time-consuming task. We present a new method for the segmentation of the bones of the hand, which allows the assessment of the skeletal maturity with an appropriate database of reference bones, similar to the atlas based methods. The proposed algorithm uses an extended active contour model for the segmentation of the hand bones, which incorporates a-priori knowledge of shape and topology of the bones in an additional energy term. This `scene knowledge' is integrated in a complex hierarchical image model, that is used for the image analysis task.

Bone metastases of unknown origin: epidemiology and principles of management.

PubMed

Piccioli, Andrea; Maccauro, Giulio; Spinelli, Maria Silvia; Biagini, Roberto; Rossi, Barbara

2015-06-01

Metastases are the most common malignancies involving bone; breast, prostate, lung and thyroid are the main sites of primary cancer. However, up to 30 % of patients present with bone metastases of unknown origin, where the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination, appropriate laboratory testing and modern imaging technology (CT, MRI, PET). Sometimes only extensive histopathological investigations on bone specimens from biopsy can suggest the primary malignancy. At other times, a bone lesion can have such a highly undifferentiated histological appearance that a precise pathological classification on routine hematoxylin-eosin-stained section is not possible. The authors reviewed the relevant literature in an attempt to investigate the epidemiology of the histological primaries finally identified in patients with bone metastases from occult cancer, and a strategy of management and treatment of bone metastases from occult carcinomas is suggested. Lung, liver, pancreas and gastrointestinal tract are common sites for primary occult tumors. Adenocarcinoma is the main histological type, accounting for 70 % of all cases, while undifferentiated cancer accounts for 20 %. Over the past 30 years, lung cancer is the main causative occult primary for bone metastases and has a poor prognosis with an average survival of 4-8 months. Most relevant literature focuses on the need for standardized diagnostic workup, as surgery for bone lesions should be aggressive only when they are solitary and/or the occult primaries have a good prognosis; in these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Thus, orthopedic surgery has a mainly palliative role in preventing or stabilizing pathological fractures, relieving pain and facilitating the care of the patient in an attempt to provide the most appropriate therapy for the primary tumor as soon as possible. 5.

Malignant otitis externa in a healthy non-diabetic patient.

PubMed

Liu, Xiao-Long; Peng, Hong; Mo, Ting-Ting; Liang, Yong

2016-08-01

A healthy 60-year-old male was initially treated for external otitis, and subsequently received multiple surgeries including abscess drainage, temporal bone debridement, canaloplasty of the external auditory meatus, and fistula excision and was treated with numerous antibiotics at another hospital over a 1-year period. He was seen at our hospital on February 14, 2014 with a complaint of a non-healing wound behind the left ear and drainage of purulent fluid. He had no history of diabetes mellitus or compromised immune function. Computed tomography (CT) and magnetic resonance imaging (MRI) studies at our hospital showed osteomyelitis involving the left temporal, occipital, and sphenoid bones, the mandible, and an epidural abscess. Routine blood testing and tests of immune function were normal, and no evidence of other infectious processes was found. He was diagnosed with malignant otitis externa (MOE). Bone debridement and incision and drainage of the epidural abscess were performed, and vancomycin was administered because culture results revealed Corynebacterium jeikeium, Corynebacterium xerosis, and Enterococcus faecalis. MOE should be considered in healthy patients with external otitis who fail initial treatment.

Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.

PubMed

Hara, Toshiro; Murakami, Yoshinori; Seiki, Motoharu; Sakamoto, Takeharu

2017-08-26

Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetically fluorescent melanoma bone and organ metastasis models.

PubMed

Yang, M; Jiang, P; An, Z; Baranov, E; Li, L; Hasegawa, S; Al-Tuwaijri, M; Chishima, T; Shimada, H; Moossa, A R; Hoffman, R M

1999-11-01

We report here the establishment and metastatic properties of bright, highly stable, green fluorescent protein (GFP) expression transductants of the B16 mouse malignant melanoma cell line and the LOX human melanoma line. The highly fluorescent malignant melanoma cell lines allowed the visualization of skeletal and multiorgan metastases after i.v. injection of B16 cells in C57BL/6 mice and intradermal injection of LOX cells in nude mice. The melanoma cell lines were transduced with the pLEIN expression retroviral vector containing the GFP and neomycin resistance genes. Stable B16F0 and LOX clones expressing high levels of GFP were selected stepwise in vitro in levels of G418 of up to 800 microg/ml. Extensive bone and bone marrow metastases of B16F0 were visualized by GFP expression when the animals were sacrificed 3 weeks after cell implantation. Metastases for both cell lines were visualized in many organs, including the brain, lung, pleural membrane, liver, kidney, adrenal gland, lymph nodes, skeleton, muscle, and skin by GFP fluorescence. This is the first observation of experimental skeletal metastases of melanoma, which was made possible by GFP expression. These models should facilitate future studies of the mechanism and therapy of bone and multiorgan metastasis of melanoma.

The Biology of Bone Metastasis.

PubMed

Esposito, Mark; Guise, Theresa; Kang, Yibin

2018-06-01

Bone metastasis, or the development of secondary tumors within the bone of cancer patients, is a debilitating and incurable disease. Despite its morbidity, the biology of bone metastasis represents one of the most complex and intriguing of all oncogenic processes. This complexity derives from the intricately organized bone microenvironment in which the various stages of hematopoiesis, osteogenesis, and osteolysis are jointly regulated but spatially restricted. Disseminated tumor cells (DTCs) from various common malignancies such as breast, prostate, lung, and kidney cancers or myeloma are uniquely primed to subvert these endogenous bone stromal elements to grow into pathological osteolytic or osteoblastic lesions. This colonization process can be separated into three key steps: seeding, dormancy, and outgrowth. Targeting the processes of dormancy and initial outgrowth offers the most therapeutic promise. Here, we discuss the concepts of the bone metastasis niche, from controlling tumor-cell survival to growth into clinically detectable disease. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Computer-aided resection and endoprosthesis design for the management of malignant bone tumors around the knee: outcomes of 12 cases.

PubMed

Ding, Huan-wen; Yu, Guang-wen; Tu, Qiang; Liu, Bao; Shen, Jian-jian; Wang, Hong; Wang, Ying-jun

2013-11-22

To report the outcomes of computer-aided resection and endoprosthesis design for the management of malignant bone tumors around the knee. Computed tomography (CT) and magnetic resonance imaging (MRI) data were input into computer software to produce three-dimensional (3D) models of the tumor extent. Imaging data was then used to create a template for surgical resection, and development of an individualized combined allogeneic bone/endoprosthesis. Surgical simulations were performed prior to the actual surgery. This study included 9 males and 3 females with a mean age of 25.3 years (range, 13 to 40 years). There were 9 tumors in the distal femur and 3 in the proximal tibia. There were no surgical complications. In all cases pathologically confirmed clear surgical margins were obtained. Postoperative radiographs showed the range of tumor resection was in accordance with the preoperative design, and the morphological reconstruction of the bone defect was satisfactory with complete bilateral symmetry. The mean follow-up time was 26.5 months. Two patients died of their disease and the remaining are alive and well without evidence of recurrence. All patients are able to ambulate freely without restrictions. At the last follow-up, the average International Society of Limb Salvage score was 25.8 (range, 18 to 27), and was excellent in 8 cases and good in 4 cases. Computer-aided design and modeling for the surgical management of bone tumors and subsequent limb reconstruction provides accurate tumor removal with the salvage of a maximal amount of unaffected bone and precise endoprosthesis reconstruction.

Expression of nociceptive ligands in canine osteosarcoma.

PubMed

Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

2015-01-01

Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

The consequences of pediatric renal transplantation on bone metabolism and growth.

PubMed

Bacchetta, Justine; Ranchin, Bruno; Demède, Delphine; Allard, Lise

2013-10-01

During childhood, growth retardation, decreased final height and renal osteodystrophy are common complications of chronic kidney disease (CKD). These problems remain present in patients undergoing renal transplantation, even though steroid-sparing strategies are more widely used. In this context, achieving normal height and growth in children after transplantation is a crucial issue for both quality of life and self-esteem. The aim of this review is to provide an overview of pathophysiology of CKD-mineral bone disorder (MBD) in children undergoing renal transplantation and to propose keypoints for its daily management. In adults, calcimimetics are effective for posttransplant hyperparathyroidism, but data are missing in the pediatric population. Fibroblast growth factor 23 levels are associated with increased risk of rejection, but the underlying mechanisms remain unclear. A recent meta-analysis also demonstrated the effectiveness of rhGH therapy in short transplanted children. In 2013, the daily clinical management of CKD-MBD in transplanted children should still focus on simple objectives: to optimize renal function, to develop and promote steroid-sparing strategies, to provide optimal nutritional support to maximize final height and avoid bone deformations, to equilibrate calcium/phosphate metabolism so as to provide acceptable bone quality and cardiovascular status, to correct all metabolic and clinical abnormalities that can worsen both bone and growth (mainly metabolic acidosis, anemia and malnutrition), promote good lifestyle habits (adequate calcium intake, regular physical activity, no sodas consumption, no tobacco exposure) and eventually to correct native vitamin D deficiency (target of 25-vitamin D >75 nmol/l).

Bone density in the obese child - clinical considerations and diagnostic challenges

PubMed Central

Kelley, Jennifer; Crabtree, Nicola; Zemel, Babette S.

2017-01-01

The prevalence of obesity in children has reached epidemic proportions. Concern about bone health in obese children, in part, derives from the potentially increased fracture risk associated with obesity. Additional risk factors that affect bone mineral accretion, may also contribute to obesity, such as low physical activity and nutritional factors. Consequences of obesity, such as inflammation, insulin resistance and non-alcoholic fatty liver disease, may also affect bone mineral acquisition, especially during the adolescent years when rapid increases in bone contribute to attaining peak bone mass. Further, numerous pediatric health conditions are associated with excess adiposity, altered body composition or endocrine disturbances that can affect bone accretion. Thus, there is a multitude of reasons for considering clinical assessment of bone health in an obese child. Multiple diagnostic challenges affect the measurement of bone density and its interpretation. These include greater precision error, difficulty in positioning, and the effects of increased lean and fat tissue on bone health outcomes. Future research is required to address these issues to improve bone health assessment in obese children. PMID:28105511

Comparison of Survival at Adult versus Pediatric Treatment Centers for Rare Pediatric Tumors in an Adolescent and Young Adult (AYA) Population in the State of Georgia

PubMed Central

Cash, Thomas; Qayed, Muna; Ward, Kevin C.; Mertens, Ann C.; Rapkin, Louis

2014-01-01

Background The type of treatment center where 15-21-year-old adolescent and young adult (AYA) patients with rare pediatric tumors achieve their best clinical outcome is unknown. Procedure We performed a retrospective analysis using the Georgia Cancer Registry (GCR) of 15-21-year-old patients with a malignant, rare pediatric tumor diagnosed during the period from 2000-2009. Patients were identified as being treated at one of five Georgia pediatric cancer centers or at an adult center. Data were analyzed for 10-year overall survival, patient characteristics associated with death, and patient characteristics present at diagnosis associated with choice of treatment center. Results There was a total of 479 patients in our final study population, of which 379 (79.1%) were treated at an adult center and 100 (20.9%) were treated at a pediatric center. Patients treated at an adult center had a 10-year overall survival of 86% compared to 85% for patients treated at a pediatric center (p= 0.31). Race and poverty were not significantly associated with death. Patients with nasopharyngeal carcinoma (OR=7.38; 95% CI=2.30 – 23.75) and ‘other carcinomas’ (OR=2.64; 95% CI=1.25 – 5.60) were more likely to be treated at a pediatric center. Patients with higher-stage disease (OR=4.24; 95% CI=1.71 – 10.52) and higher poverty (OR=2.32; 95% CI=1.23 – 4.37) were also more likely to be treated at a pediatric center. Conclusion Our data suggest that there is no difference in survival for 15-21-year-old patients with rare pediatric tumors when treated at an adult or pediatric center. PMID:25393593

Immunology of malignant diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Byers, V.S.; Baldwin, R.W.

1987-01-01

This book contains 11 chapters. Some of the chapter titles are: Immunoscintigraphy: tumor detection with radiolabelled antitumor monoclonal antibodies; Bone marrow transplantation; Immunomodulating agents; Immunology in bowel cancer; Melanoma; and Immunological features of human bladder cancer.

Interferon Gamma-1b Injection

MedlinePlus

... in people with severe, malignant osteopetrosis (an inherited bone disease). Interferon gamma-1b is in a class of ... you may have flu-like symptoms such as headache, fever, chills, muscle aches, and tiredness after your ...

Localization of m-lodo(/sup 131/I)benzylguanidine in neuroblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hattner, R.S.; Huberty, J.P.; Engelstad, B.L.

1984-08-01

Patient survival and the therapeutic strategy for treatment of neuroblastoma are highly dependent on the stage of the tumor at presentation. For routine staging, the Children's Cancer Study group currently recommends a chest radiograph, abdominal CT scan, radionuclide bone scan, bone marrow biopsy, catecholamine metabolite estimations, and surgical determination of tumor extent. A noninvasive method for detectiton of neuroblastoma that avoids surgery and bone marrow biopsy would be a most welcome addition to the armamentarium of the pediatric oncologist. A case of neuroblastoma demonstrated with m-iodo(/sup 131/I)benzylguanidine (MIBG) scintigraphy is reported.

Non-malignant complications of coeliac disease.

PubMed

Holmes, G K

1996-05-01

Patients with coeliac disease are at increased risk of developing complications which increase morbidity and mortality. Emphasis on malignant complications has often overshadowed the non-malignant risks, which have received relatively little attention, although some of these can be very troublesome and even life-threatening. This article points out that a large population of unidentified or neglected coeliac patients is at potential risk. The challenge is to identify this group by case-finding or screening programmes in selected populations, so that they can be offered a gluten-free diet and other treatments which will not only improve general health but may also prevent or reduce the development of health problems. The non-malignant risks are outlined and bone and neuropsychiatric disturbances considered in more detail because of recent developments in these areas.

Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

ClinicalTrials.gov

2016-06-09

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

[Complete hormonal and metabolic response after iodine-131 metaiodobenzylguanidine treatment in a patient diagnosed of malignant pheochromocytoma].

PubMed

García Alonso, M P; Balsa Bretón, M A; Paniagua Correa, C; Castillejos Rodríguez, L; Rodríguez Pelayo, E; Mendoza Paulini, A; Ortega Valle, A; Penín González, J

2013-01-01

Radiolabeled metaiodobenzylguanidine is an analogue of norepinephrine used to localize tumors that express the neurohormone transporters, specifically those derived from the neural crest having a neuroendocrine origin. It is also used to treat non-surgical metastases derived from them. A review of the literature revealed symptomatic improvements associated to a decrease in hormone levels in a significant percentage of patients after (131)I-MIBG treatment. However, complete tumor remission has been described only in very few cases and hardly ever when bone metastases exist. We present a case of a patient diagnosed of malignant pheochromocytoma who achieved complete hormonal and metabolic response after (131)I-MIBG treatment (600 mCi) in spite of the presence of bone metastases. Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

A disseminated alveolar rhabdomyosarcoma in a 9-year-old boy disclosed by chromosomal translocation (2;13) (q35;q14)

PubMed

Brichard, B; Ninane, J; Gosseye, S; Verellen-Dumoulin, C; Vermylen, C; Rodhain, J; Cornu, G

1991-01-01

A 9-year-old boy presented with a small subcutaneous tumor of the trunk and diffuse bone marrow involvement. The first histological diagnosis given was undifferentiated malignancy possibly of neural crest origin and chemotherapy was started immediately using vincristine, cyclophosphamide, cisplatin, and teniposide (OPEC). Complete response was achieved after four courses of chemotherapy. Histological slides were then reviewed and the final diagnosis of alveolar rhabdomyosarcoma (RMS) was retained. Moreover, chromosome analysis of malignant cells in the bone marrow revealed a translocation involving chromosomes 2 and 13:t(2;13) (q35;q14). This specific karyotype finding has been recently reported in a few cases and could be specific for alveolar RMS. The patient had a relapse 7 months after diagnosis and died 4 months later.

Precursor B cell lymphoblastic lymphoma presenting as periorbital swelling.

PubMed

Galway, Niamh; Johnston, Robert; Cairns, Carole; Thompson, Andrew James

2016-05-10

An 11-year-old girl was admitted for further investigation as to the cause of her bilateral papilloedema and periorbital swelling. She had a 2-week history of headache and unilateral eyelid swelling, and a 2-day history of right-sided groin swelling. CT and MRI scans revealed soft tissue adjacent to the lateral orbital walls within the extraconal lateral aspects of both orbits, more on the right than the left. The scans also revealed extensive lymphadenopathy above and below the diaphragm. The patient underwent bone marrow studies and biopsy of the lymph node in her groin. The results revealed normal bone marrow with no evidence of malignancy. The lymph node histology confirmed malignant lymphoma in keeping with B cell lymphoblastic lymphoma. The patient was started on the UKALL 2011 chemotherapy trial. 2016 BMJ Publishing Group Ltd.

[Bone marrow stromal damage mediated by immune response activity].

PubMed

Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

1994-01-01

The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

The application of 3D printed surgical guides in resection and reconstruction of malignant bone tumor.

PubMed

Wang, Fengping; Zhu, Jun; Peng, Xuejun; Su, Jing

2017-10-01

The clinical value of 3D printed surgical guides in resection and reconstruction of malignant bone tumor around the knee joint were studied. For this purpose, a sample of 66 patients from October 2013 to October 2015 were randomly selected and further divided into control group and observation group, each group consisted of 33 cases. The control group was treated by conventional tumor resection whereas, in the observation group, the tumor was resected with 3D printed surgical guide. However, reconstruction of tumor-type hinge prosthesis was performed in both groups and then the clinical effect was compared. Results show that there was no significant difference in the operation time between the two groups (p>0.05). However, the blood loss, resection length and complication rate were found significantly lower in the observation group than in the control group (p<0.05). The rate of negative margin and the recurrence rate in the 12-month follow-up (p>0.05) between two groups were statistically the same (p>0.05), whereas the Musculoskeletal Tumor Society (MSTS) score of the knee joint in the observation group was significantly better than that of the control group (p<0.05) after 1, 3, 6 and 12 months of the operation. Consequently, the 3D printed surgical guides can significantly improve the postoperative joint function after resection and reconstruction of malignant bone tumor around the knee joint and can reduce the incidence of complications.