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Several vaccine strategies have been tested for the treatment of follicular lymphoma; however, none have proven successful. In a phase I dose-escalation protocol, we developed a vaccine consisting of lethally irradiated whole lymphoma cells admixed with K562 cells that constitutively secreted granulocyte-macrophage colony-stimulating factor (GM-K562)(ClinicalTrials.gov identifier: NCT00487305). Patients with grade 1, 2, or 3 A follicular lymphoma were divided into 2 study tiers based on prior treatment and received a maximum of 6 vaccines. Vaccines contained dose levels of 5 × 106 or 1 × 107 GM-K562 cells admixed with autologous tumor cells at doses ranging from 1 × 105 to 5 × 107.Correlative studies did not demonstrate a significant immune response as assessed by delayed-type hypersensitivity reactions, B and T cell subsets, and natural killer cell subsets. Future vaccine studies should focus on identifying lymphoma-specific immunogenic proteins and modifying the vaccine immune adjuvant.
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Central nervous system (CNS) cancers account for approximately one quarter of all pediatric tumors and are the leading cause of cancer-related death in children. More than 4,000 brain and CNS tumors are diagnosed each year in children and teens, and the incidence rate has remained stagnant in recent years. The most common malignant pediatric CNS tumors are gliomas, embryonal tumors consisting of predominately medulloblastomas, and germ cell tumors. The inaugural version of the NCCN Guidelines for Pediatric Central Nervous System Cancers focuses on the diagnosis and management of patients with pediatric diffuse high-grade gliomas. The information contained in the NCCN Guidelines is designed to help clinicians navigate the complex management of pediatric patients with diffuse high-grade gliomas. The prognosis for these highly aggressive tumors is generally poor, with 5-year survival rates of <20% despite the use of combined modality therapies of surgery, radiation therapy and systemic therapy. Recent advances in molecular profiling has expanded the use of targeted therapies in patients whose tumors harbor certain alterations. However, enrollment in a clinical trial is the preferred treatment for eligible patients.
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Neoplasias del Sistema Nervioso Central , Glioma , Neoplasias de Células Germinales y Embrionarias , Adolescente , Niño , Humanos , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/epidemiología , Neoplasias del Sistema Nervioso Central/terapia , Glioma/diagnóstico , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/terapia , Pronóstico , Encéfalo/patologíaRESUMEN
Background: The mechanism of tumorigenicity potentially evolved in mesenchymal stem cells (MSCs) remains elusive, resulting in inconsistent clinical application efficacy. We hypothesized that subclones in MSCs contribute to their tumorgenicity, and we approached MSC-subclones at the single-cell level. Methods: MSCs were cultured in an osteogenic differentiation medium and harvested on days 12, 19, and 25 for cell differentiation analysis using Alizarin Red and followed with the single-cell transcriptome. Results: Single-cell RNA-seq analysis reveals a discrete cluster of MSCs during osteogenesis, including differentiation-resistant MSCs (DR-MSCs), differentiated osteoblasts (DO), and precursor osteoblasts (PO). The DR-MSCs population resembled cancer initiation cells and were subjected to further analysis of the yes associated protein 1 (YAP1) network. Verteporfin was also used for YAP1 inhibition in cancer cell lines to confirm the role of YAP1 in MSC--involved tumorigenicity. Clinical data from various cancer types were analyzed to reveal relationships among YAP1, OCT4, and CDH6 in MSC--involved tumorigenicity. The expression of cadherin 6 (CDH6), octamer-binding transcription factor 4 (OCT4), and YAP1 expression was significantly upregulated in DR-MSCs compared to PO and DO. YAP1 inhibition by Verteporfin accelerated the differentiation of MSCs and suppressed the expression of YAP1, CDH6, and OCT4. A survey of 56 clinical cohorts revealed a high degree of co-expression among CDH6, YAP1, and OCT4 in various solid tumors. YAP1 inhibition also down-regulated HeLa cell viability and gradually inhibited YAP1 nuclear localization while reducing the transcription of CDH6 and OCT4. Conclusions: We used single-cell sequencing to analyze undifferentiated MSCs and to discover a carcinogenic pathway in single-cell MSCs of differentiated resistance subclones.
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Over the past decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumours. It has become evident that paediatric high-grade gliomas differ from those in adults with respect to multiple defining aspects including: DNA copy number, gene expression profiles, tumour locations within the CNS and genetic alterations such as somatic histone mutations. Despite these advances, clinical trials for children with gliomas have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences between the two. Additionally, although our knowledge of the intrinsic cellular mechanisms driving tumour progression has considerably expanded, little is known about the dynamic tumour immune microenvironment in paediatric high-grade gliomas. In this review, we explore the genetic and epigenetic landscape of these gliomas and how this drives the creation of specific tumour subgroups with meaningful survival outcomes. Further, we provide a comprehensive analysis of the paediatric high-grade glioma tumour immune microenvironment and discuss emerging therapeutic efforts aimed at exploiting the immune functions of these tumours.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/inmunología , Glioma/diagnóstico , Glioma/inmunología , Microambiente Tumoral/inmunología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Niño , Epigénesis Genética/efectos de los fármacos , Epigénesis Genética/genética , Epigénesis Genética/inmunología , Glioma/genética , Glioma/terapia , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inmunoterapia/métodos , Clasificación del Tumor/métodos , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/genéticaRESUMEN
Importance: Pediatric cancers are epigenetic diseases; therefore, considering tumor gene expression information is necessary for a complete understanding of the tumorigenic processes. Objective: To evaluate the feasibility and utility of incorporating comparative gene expression information into the precision medicine framework for difficult-to-treat pediatric and young adult patients with cancer. Design, Setting, and Participants: This cohort study was conducted as a consortium between the University of California, Santa Cruz (UCSC) Treehouse Childhood Cancer Initiative and clinical genomic trials. RNA sequencing (RNA-Seq) data were obtained from the following 4 clinical sites and analyzed at UCSC: British Columbia Children's Hospital (n = 31), Lucile Packard Children's Hospital at Stanford University (n = 80), CHOC Children's Hospital and Hyundai Cancer Institute (n = 46), and the Pacific Pediatric Neuro-Oncology Consortium (n = 24). The study dates were January 1, 2016, to March 22, 2017. Exposures: Participants underwent tumor RNA-Seq profiling as part of 4 separate clinical trials at partner hospitals. The UCSC either downloaded RNA-Seq data from a partner institution for analysis in the cloud or provided a Docker pipeline that performed the same analysis at a partner institution. The UCSC then compared each participant's tumor RNA-Seq profile with more than 11â¯000 uniformly analyzed tumor profiles from pediatric and young adult patients with cancer, downloaded from public data repositories. These comparisons were used to identify genes and pathways that are significantly overexpressed in each patient's tumor. Results of the UCSC analysis were presented to clinical partners. Main Outcomes and Measures: Feasibility of a third-party institution (UCSC Treehouse Childhood Cancer Initiative) to obtain tumor RNA-Seq data from patients, conduct comparative analysis, and present analysis results to clinicians; and proportion of patients for whom comparative tumor gene expression analysis provided useful clinical and biological information. Results: Among 144 samples from children and young adults (median age at diagnosis, 9 years; range, 0-26 years; 72 of 118 [61.0%] male [26 patients sex unknown]) with a relapsed, refractory, or rare cancer treated on precision medicine protocols, RNA-Seq-derived gene expression was potentially useful for 99 of 144 samples (68.8%) compared with DNA mutation information that was potentially useful for only 34 of 74 samples (45.9%). Conclusions and Relevance: This study's findings suggest that tumor RNA-Seq comparisons may be feasible and highlight the potential clinical utility of incorporating such comparisons into the clinical genomic interpretation framework for difficult-to-treat pediatric and young adult patients with cancer. The study also highlights for the first time to date the potential clinical utility of harmonized publicly available genomic data sets.
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Neoplasias/genética , ARN Neoplásico/análisis , Análisis de Secuencia de ARN , Canadá , Niño , Preescolar , Femenino , Expresión Génica , Humanos , Lactante , Recién Nacido , Masculino , Medicina de Precisión , Estados Unidos , Adulto JovenRESUMEN
The clinical benefits of the MammaPrint® signature for breast cancer is well documented; however, how these genes are related to cell cycle perturbation have not been well determined. Our single-cell transcriptome mapping (algorithm) provides details into the fine perturbation of all individual genes during a cell cycle, providing a view of the cell-cycle-phase specific landscape of any given human genes. Specifically, we identified that 38 out of the 70 (54%) MammaPrint® signature genes are perturbated to a specific phase of the cell cycle. The MammaPrint® signature panel derived its clinical prognosis power from measuring the cell cycle activity of specific breast cancer samples. Such cell cycle phase index of the MammaPrint® signature suggested that measurement of the cell cycle index from tumors could be developed into a prognosis tool for various types of cancer beyond breast cancer, potentially improving therapy through targeting a specific phase of the cell cycle of cancer cells.
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Síndromes de Inmunodeficiencia/genética , Quinasas Janus/antagonistas & inhibidores , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT3/genética , Adolescente , Adulto , Niño , Femenino , Mutación con Ganancia de Función , Humanos , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Masculino , Nitrilos , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , Resultado del TratamientoRESUMEN
There is little known regarding the immune infiltrate present in pediatric brain tumors and how this compares to what is known about histologically similar adult tumors and its correlation with survival. Here, we provide a descriptive analysis of the immune infiltrate of 22 fresh pediatric brain tumor tissue samples of mixed diagnoses and 40 peripheral blood samples. Samples were analyzed using a flow cytometry panel containing markers for immune cell subtypes, costimulatory markers, inhibitory signals, and markers of activation. This was compared to the standard method of immunohistochemistry (IHC) for immune markers for 89 primary pediatric brain tumors. Both flow cytometry and IHC data did not correlate with the grade of tumor or mutational load and IHC data was not significantly associated with survival for either low grade or high grade gliomas. There is a trend towards a more immunosuppressive phenotype in higher grade tumors with more regulatory T cells present in these tumor types. Both PD1 and PDL1 were present in only a small percentage of the tumor infiltrate. T cell receptor sequencing revealed up to 10% clonality of T cells in tumor infiltrates and no significant difference in clonality between low and high grade gliomas. We have shown the immune infiltrate of pediatric brain tumors does not appear to correlate with grade or survival for a small sample of patients. Further research and larger studies are needed to fully understand the interaction of pediatric brain tumors and the immune system.
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Neoplasias Encefálicas/inmunología , Adolescente , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Encéfalo/inmunología , Encéfalo/patología , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Niño , Preescolar , Humanos , Inmunofenotipificación , Lactante , Mutación , Clasificación del Tumor , Receptor de Muerte Celular Programada 1/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T Reguladores/patologíaRESUMEN
Central nervous system tumors are the leading cause of cancer related death in children. Despite much progress in the field of pediatric neurooncology, modern combination treatment regimens often result in significant late effects, such as neurocognitive deficits, endocrine dysfunction, secondary malignancies, and a host of other chronic health problems. Precision medicine strategies applied to pediatric neurooncology target specific characteristics of individual patients' tumors to achieve maximal killing of neoplastic cells while minimizing unwanted adverse effects. Here, we review emerging trends and the current literature that have guided the development of new molecularly based classification schemas, promising diagnostic techniques, targeted therapies, and delivery platforms for the treatment of pediatric central nervous system tumors.
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Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/terapia , Medicina de Precisión , Animales , Neoplasias del Sistema Nervioso Central/clasificación , Niño , HumanosRESUMEN
BACKGROUND: Gain-of-function (GOF) mutations in the human signal transducer and activator of transcription 1 (STAT1) manifest in immunodeficiency and autoimmunity with impaired TH17 cell differentiation and exaggerated responsiveness to type I and II interferons. Allogeneic bone marrow transplantation has been attempted in severely affected patients, but outcomes have been poor. OBJECTIVE: We sought to define the effect of increased STAT1 activity on T helper cell polarization and to investigate the therapeutic potential of ruxolitinib in treating autoimmunity secondary to STAT1 GOF mutations. METHODS: We used in vitro polarization assays, as well as phenotypic and functional analysis of STAT1-mutated patient cells. RESULTS: We report a child with a novel mutation in the linker domain of STAT1 who had life-threatening autoimmune cytopenias and chronic mucocutaneous candidiasis. Naive lymphocytes from the affected patient displayed increased TH1 and follicular T helper cell and suppressed TH17 cell responses. The mutation augmented cytokine-induced STAT1 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reduced hyperresponsiveness to type I and II interferons, normalized TH1 and follicular T helper cell responses, improved TH17 differentiation, cured mucocutaneous candidiasis, and maintained remission of immune-mediated cytopenias. CONCLUSIONS: Autoimmunity and infection caused by STAT1 GOF mutations are the result of dysregulated T helper cell responses. Janus kinase inhibitor therapy could represent an effective targeted treatment for long-term disease control in severely affected patients for whom hematopoietic stem cell transplantation is not available.
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Anemia Hemolítica Autoinmune/genética , Inhibidores de Proteínas Quinasas/farmacología , Púrpura Trombocitopénica Idiopática/genética , Pirazoles/farmacología , Factor de Transcripción STAT1/genética , Células TH1/efectos de los fármacos , Células Th17/efectos de los fármacos , Anemia Hemolítica Autoinmune/inmunología , Autoinmunidad/efectos de los fármacos , Candidiasis Mucocutánea Crónica/genética , Candidiasis Mucocutánea Crónica/inmunología , Niño , Citocinas/inmunología , Femenino , Humanos , Quinasas Janus/antagonistas & inhibidores , Mutación , Nitrilos , Púrpura Trombocitopénica Idiopática/inmunología , Pirimidinas , Factor de Transcripción STAT1/inmunología , Células TH1/inmunología , Células Th17/inmunologíaRESUMEN
BACKGROUND: Clinical genomics platforms are needed to identify targetable alterations, but implementation of these technologies and best practices in routine clinical pediatric oncology practice are not yet well established. METHODS: Profile is an institution-wide prospective clinical research initiative that uses targeted sequencing to identify targetable alterations in tumors. OncoPanel, a multiplexed targeted exome-sequencing platform that includes 300 cancer-causing genes, was used to assess single nucleotide variants and rearrangements/indels. Alterations were annotated (Tiers 1-4) based on clinical significance, with Tier 1 alterations having well-established clinical utility. OncoCopy, a clinical genome-wide array comparative genomic hybridization (aCGH) assay, was also performed to evaluate copy number alterations and better define rearrangement breakpoints. RESULTS: Cancer genomes of 203 pediatric brain tumors were profiled across histological subtypes, including 117 samples analyzed by OncoPanel, 146 by OncoCopy, and 60 tumors subjected to both methodologies. OncoPanel revealed clinically relevant alterations in 56% of patients (44 cancer mutations and 20 rearrangements), including BRAF alterations that directed the use of targeted inhibitors. Rearrangements in MYB-QKI, MYBL1, BRAF, and FGFR1 were also detected. Furthermore, while copy number profiles differed across histologies, the combined use of OncoPanel and OncoCopy identified subgroup-specific alterations in 89% (17/19) of medulloblastomas. CONCLUSION: The combination of OncoPanel and OncoCopy multiplex genomic assays can identify critical diagnostic, prognostic, and treatment-relevant alterations and represents an effective precision medicine approach for clinical evaluation of pediatric brain tumors.
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Neoplasias Encefálicas/genética , Variaciones en el Número de Copia de ADN , Exoma , Genómica/métodos , Medicina de Precisión/métodos , Neoplasias Encefálicas/diagnóstico , Niño , Hibridación Genómica Comparativa , Dosificación de Gen , Humanos , Mutación , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
Malignant germ cell tumors (GCT) arise from abnormal migration of primordial germ cells and are histologically identical whether they occur inside or outside the central nervous system (CNS). However, the treatment strategy for GCTs varies greatly depending on the location of the tumor. These differences are in part due to the increased morbidity of surgery in the CNS but may also reflect differential sensitivity of the tumors to chemotherapy and radiation therapy (RT) or not-yet-understood biologic differences between these tumors. Historically, specialists caring for extracranial and intracranial GCT in the United States have practiced separately without much cross communication. The focus of this review is a discussion of differences between the management of CNS and extra-CNS GCTs and opportunities for collaboration and future research.
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Neoplasias de Células Germinales y Embrionarias/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante AutólogoRESUMEN
Post-transplant lymphoproliferative disease (PTLD) is a lymphoproliferative disorder secondary to chronic immunosuppression and is the most common malignancy in transplanted patients [Kamdar et al. Curr Opin Organ Transplant, 2011; 16:274-280]. Although PTLD usually presents as B or T cell lymphoma, plasmacytomas have been reported, mostly in the adult population. Six cases of pediatric plasmacytoma-like PTLD have been reported, all of which were treated with vincristine, adriamycin, and dexamethasone (VAD), high dose dexamethasone alone, or dexamethasone + thalidomide [Tcheng et al. Pediatric Blood Cancer, 2006; 47:218-223; Perry et al. Blood, 2013; 8:1377-1383]. We present two cases of pediatric plasmacytoma-like PTLD in combined liver and small bowel transplant patients both successfully treated with bortezomib and dexamethasone based on multiple myeloma protocols [Kyle and Rajkumar, Clin Lymphoma Myeloma, 2009; 9:278-288; Adams and Kaufmann, Cancer Invest, 2004; 22:304-311].
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Intestino Delgado/trasplante , Trasplante de Hígado/efectos adversos , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/patología , Antiinflamatorios/uso terapéutico , Antineoplásicos/uso terapéutico , Ácidos Borónicos/uso terapéutico , Bortezomib , Niño , Dexametasona/uso terapéutico , Femenino , Humanos , Huésped Inmunocomprometido , Lactante , Trastornos Linfoproliferativos/tratamiento farmacológico , Pirazinas/uso terapéuticoRESUMEN
Immunotherapy has the potential to improve clinical outcomes with little toxicity for pediatric patients with brain tumors. We conducted a pilot feasibility study of tumor lysate-pulsed dendritic cell (DC) vaccination in pediatric patients (1 to 18 years old) with newly diagnosed or recurrent high-grade glioma (HGG). A total of nine DC vaccine doses, each containing 1 × 10(6) cells per dose were administered to three out of the seven originally enrolled patients. Toxicities were limited to mild side-effects, except in one case of elevated alkaline phosphatase, which resolved without clinical consequences. Two patients with primary lesions amongst the three vaccinated were alive at the time of writing, both without evidence of disease. Pre- and post-vaccination tumor samples from a patient with an anaplastic oligoastrocytoma that recurred failed to demonstrate immune cell infiltration by immunohistochemistry. Peripheral cytokine levels were evaluated in one patient following DC vaccination and demonstrated some changes in relation to vaccination. DC vaccine is tolerable and feasible with some limitations for pediatric patients with HGG. Dendritic cell based immunotherapy may provide some clinical benefit in pediatric patients with glioma, especially for patients with minimal residual disease, but further investigation of this modality is required.
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Neoplasias Encefálicas/terapia , Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/inmunología , Glioma/terapia , Inmunoterapia , Recurrencia Local de Neoplasia/terapia , Adolescente , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/inmunología , Vacunas contra el Cáncer/inmunología , Niño , Preescolar , Citocinas/metabolismo , Células Dendríticas/trasplante , Estudios de Factibilidad , Femenino , Glioma/diagnóstico , Glioma/inmunología , Humanos , Técnicas para Inmunoenzimas , Lactante , Leucaféresis , Masculino , Clasificación del Tumor , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/inmunología , Proyectos PilotoRESUMEN
BACKGROUND/INTRODUCTION: Undifferentiated embryonal liver sarcoma (UELS) makes up 9% to 15% of all malignant liver tumors in children. UELS is characteristically diagnosed between the ages of 6 and 10 years and presents with abdominal pain, vomiting, and an abdominal mass. There is currently no standardized treatment for UELS except attempt at complete surgical resection. There have been only about 150 cases of UELS reported in the literature all with historically poor overall survival of <37.5% at 5 years. This report is one of the largest single-institution reports of UELS consisting of 5 patients over 2 decades. The purpose of this study is to characterize presentation and to report treatment success in UELS in children, adolescents, and young adults and the use of liver transplantation and, lastly, to suggest a use of positron emission tomography/computed tomography (PET/CT) in monitoring of this disease process. METHODS: We conducted an Institutional Review Board-approved retrospective chart review. Data were collected from UELS patients younger than 21 years seen at the University of California Los Angeles over the past 20 years (January 2001 to September 2011). Descriptive analysis was conducted including multiple parameters of patient demographics, tumor characteristics, treatment modalities, and morbidity and mortality. RESULTS: Five patients with UELS were identified. Patients initially presented with fever, abdominal pain, or nausea. Ages ranged from 10 to 19 years old (median age 13 y old), and there was a 4:1 male-to-female predominance. Tumor size ranged from 6 to 22 cm in largest diameter. One patient presented with metastatic disease to the lungs and heart and 1 patient recurred 2 years from diagnosis with bilateral paraspinal masses. Treatment included local control surgery with neoadjuvant and adjuvant chemotherapy with an anthracycline/alkylating agent combination. One patient with recurrent and refractory disease achieved local control with an orthotopic liver transplantation (OLT). Metastatic disease was controlled with surgery and radiation therapy. 18-Fluorodeoxyglucose PET/CT was a useful imaging tool for judging response to therapy with complete loss of metabolic activity in tumor after neoadjuvant chemotherapy in 2 representative cases. Although follow-up is short for some patients, overall survival in these 5 patients was 100% with follow-up ranging from 21 to 68 months. Disease-free survival ranged from 8 to 46 months with no patients with residual disease. CONCLUSIONS: UELS is an aggressive high-grade primary liver sarcoma with high metastatic potential. This report represents one of the largest single-institution studies of UELS. Using multimodality therapy, patients have achieved 100% overall survival even in the setting of extensive disease, metastases, and recurrence. In cases of unresectable primary tumor or recurrent and refractory disease isolated to the liver, OLT is a potential therapeutic option. We report success with adjuvant chemotherapy and complete surgical resection with OLT as an alternative in unresectable or refractory cases. We also suggest a possible utility of PET/CT in monitoring treatment response in this disease.
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Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Sarcoma/terapia , Adolescente , Antineoplásicos/uso terapéutico , Niño , Terapia Combinada , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Imagen Multimodal , Tomografía de Emisión de Positrones , Radioterapia , Estudios Retrospectivos , Sarcoma/diagnóstico por imagen , Sarcoma/mortalidad , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Vitamin D and holotranscobalamin (HTCII) deficiencies have been seen to demonstrate an association with various types of cancers. The objective of this study is to determine the frequency of vitamin D and HTCII deficiency in cancer patients. Our study investigated vitamin D, total B12, and HTCII levels in 70 cancer patients. Vitamin D status was measured as serum 25-hydroxyvitamin D [25(OH)D, Nichols Advantage assay], and serum B12 was measured as both total B12 and as the metabolically active HTCII (Immulite B12 assay followed by glass adsorption). Insufficiency of serum 25(OH)D levels for this study is defined based on differing literature standards of insufficiency and was selected to be either <50 or <75 nmol/l. When 25(OH)D insufficiency is defined as serum level of <75 nmol/l, 43 of 60 (72%) of cancer patients were found to be insufficient. At the lower definition of insufficiency, <50 nmol/l, 24 of 60 patients (40%) were insufficient. Of 52 patients, only 3 (6%) were found to have insufficient serum levels of total B12 (normal = >300 pg/ml), whereas 17 of 52 (34%) were found to be HTCII insufficient (normal = >69 pg/ml). Of these 17 patients, 14 (84.4%) had normal total B12 levels. Low serum levels of 25(OH)D strongly correlated with low serum HTCII. All 12 HTCII-deficient patients were vitamin D insufficient at the <75-nmol/l standard. Six of 12 HTCII-deficient patients (50%) were vitamin D deficient at the <50-nmol/l cutoff. The standard measurement of total serum B12 alone is inadequate for identifying patients with insufficient levels of metabolically active B12. Deficiency of vitamin D (72%) and HTCII (34%) is prevalent among newly diagnosed patients with cancer and could play a role in cancer development and host response to tumor and therapy. Possible explanations for combined HTCII and 25(OH)D deficiencies include patient age, presence of atrophic gastritis, and lack of sun exposure.