No childhood cancer survivor left behind

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Early career mentoring through the American Society of Pediatric Hematology/Oncology: Lessons learned from a pilot program

Abstract

Background

Effective networking and mentorship are critical determinants of career satisfaction and success in academic medicine. The American Society of Pediatric Hematology/Oncology (ASPHO) mentoring program was developed to support Early Career (EC) members. Herein, the authors report on the initial 2-year outcomes of this novel program.

Procedure

Mentees selected mentors with expertise in different subspecialties within the field from mentor profiles at the ASPHO Web site. Of 23 enrolled pairs, 19 mentors and 16 mentees completed electronic program feedback evaluations. The authors analyzed data collected between February 2013 and December 2014. The authors used descriptive statistics for categorical data and thematic analysis for qualitative data.

Results

The overall response rate was 76% (35/46). At the initiation of the relationship, career development and research planning were the most commonly identified goals for both mentors and mentees. Participants communicated by phone, e-mail, or met in-person at ASPHO annual meetings. Most mentor–mentee pairs were satisfied with the mentoring relationship, considered it a rewarding experience that justified their time and effort, achieved their goals in a timely manner with objective work products, and planned to continue the relationship. However, time constraints and infrequent communications remained a challenge.

Conclusions

Participation in the ASPHO mentoring program suggests a clear benefit to a broad spectrum of ASPHO EC members with diverse personal and professional development needs. Efforts to expand the mentoring program are ongoing and focused on increasing enrollment of mentors to cover a wider diversity of career tracks/subspecialties and evaluating career and academic outcomes more objectively.

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Risk factors for bacteremia and central line–associated blood stream infections in children with acute myelogenous leukemia: A single-institution report

Abstract

Background

Central line–associated blood stream infections (CLABSIs) are a source of high morbidity and mortality in children with acute myelogenous leukemia (AML).

Procedure

To understand the epidemiology and risk factors associated with the development of CLABSI in children with AML.

Methods

We retrospectively reviewed all patients with AML over a 5-year period between 2007 and 2011 at the Children's Hospital Colorado. Cases and controls were classified on the basis of the presence of a CLABSI as defined by the National Healthcare Safety Network.

Results

Of 40 patients in the study, 25 (62.5%) developed at least one CLABSI during therapy. The majority of CLABSIs were due to oral or gastrointestinal organisms (83.0%). Skin organisms accounted for 8.5%. In a multivariable analysis, the strongest risk factors associated with CLABSI were diarrhea (odds ratio [OR] 6.7, 95% confidence interval [CI] 1.6–28.7), receipt of blood products in the preceding 4–7 days (OR 10.0, 95%CI 3.2–31.0), not receiving antibiotics (OR 8.3, 95%CI 2.8–25.0), and chemotherapy cycle (OR 3.5, 95%CI 1.4–8.9). CLABSIs led to increased morbidity, with 13 cases (32.5%) versus two controls (1.9%) requiring transfer to the pediatric intensive care unit (P < 0.001). Three (7.5%) of 40 CLABSI events resulted in or contributed to death.

Conclusions

Intensified line care efforts cannot eliminate all CLABSIs in the patients with AML. Exploring the role of mucosal barrier breakdown and/or the use of antibiotic prophylaxis may be effective strategies for further prevention of CLABSIs, supporting ongoing trials in this patient population.

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Multiple unusual lung etiologies in a child with acute lymphocytic leukemia

Abstract

Granulomatous lung disease is a rare and perplexing differential in pediatrics. Pulmonary Cryptococcus falls into the differential but is not high on the list, particularly in a non-AIDS patient. Methotrexate (MTX) is a commonly used agent for chemotherapy in oncology and has been documented to cause lung injury in both patients with rheumatologic and oncologic diseases. Our patient had chronic cough and then developed an opportunistic infection resulting in respiratory failure. Lung biopsy showed two underlying unusual diagnoses: MTX lung injury and cryptococcal pneumonia. His case is presented with particular attention to his prolonged road to diagnosis.

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An 11-year experience of acquired von Willebrand syndrome in children diagnosed with Wilms tumour in a tertiary referral centre

Abstract

Wilms tumour (WT) is the commonest primary malignant renal tumour of childhood. Acquired von Willebrand syndrome (avWS) is a well-described paraneoplastic phenomenon, but it is uncommon and may not be detected until clinically significant bleeding is encountered during interventional procedures. Previous studies on small cohorts of patients have determined an incidence of between 4 and 8%. We have performed a retrospective study on cases of WT presenting over an 11.5-year period to a paediatric haematology/oncology unit in a tertiary referral centre to review the incidence of avWS, bleeding phenotype, management, and response to treatment of the primary pathology.

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Feasibility and applicability of diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging in routine assessments of children with high-grade gliomas

Abstract

Diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) have been used as imaging biomarkers in adults with high-grade gliomas (HGGs). We incorporated free-breathing DW-MRI and DCE-MRI, at a single time point, in the routine follow-up of five children (median age 9 years, range 8–15) with histologically confirmed HGG within a prospective imaging study. It was feasible to incorporate DW-MRI and DCE-MRI in routine assessments of children with HGG. DW and DCE parameters were repeatable in paediatric HGG. Higher median ADC_100-1000 significantly correlated with longer survival in our sample.

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A randomized nutrition counseling intervention in pediatric leukemia patients receiving steroids results in reduced caloric intake

Abstract

Background

Quality of life in survivors of pediatric acute lymphocytic leukemia (ALL) can be compromised by chronic diseases including increased risk of second cancers, cardiovascular disease, and diabetes. Overweight or obesity further increases these risks. Steroids are a component of chemotherapy for ALL, and weight gain is a common side effect. To impact behaviors associated with weight gain, we conducted a randomized nutrition counseling intervention in ALL patients on treatment.

Procedure

ALL patients on a steroid-based treatment regimen at the MD Anderson Children's Cancer Hospital were recruited and randomized into control or intervention groups. The control group received standard care and nutrition education materials. The intervention group received monthly one-on-one nutrition counseling sessions, consisting of a baseline and 12 follow-up visits. Anthropometrics, dietary intake (3-day 24-hr dietary recalls) and oxidative stress measures were collected at baseline, 6 months, and postintervention. Dietary recall data were analyzed using the Nutrition Data System for Research.

Results

Twenty-two patients (median age 11.5 years), all in the maintenance phase of treatment, were recruited. The intervention group (n = 12) reported significantly lower calorie intake from baseline to 12-month follow-up and significant changes in glutamic acid and selenium intake (P < 0.05). Waist circumference was significantly associated with calorie, vitamin E, glutamic acid, and selenium intake.

Conclusions

A year-long dietary intervention was effective at reducing caloric intake in pediatric ALL patients receiving steroid-based chemotherapy, indicating that this is a modality that can be built upon for obesity prevention and management.

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Risk factors and treatment for steroid-related mood and behavior symptoms in preschool children with leukemia: A case series

Abstract

Treatment of pediatric acute lymphoblastic leukemia (ALL) relies on systemic corticosteroids for remission; however, they can cause significant mood and behavior changes that interfere with quality of life and may increase risk for injury. This case series reports on preschool children with preexisting developmental and psychiatric risk factors who presented with behavioral side effects that required intervention. Identification of these vulnerable children may provide opportunities for early intervention, anticipatory guidance, and effective treatment to minimize behavioral side effects and improve quality of life and safety during ALL treatment.

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Selective Activation of Anticancer Chemotherapy by Cancer-Associated Fibroblasts in the Tumor Microenvironment

Background: The tumor microenvironment has recently emerged as a new target of anticancer chemotherapy. Selective activation of anticancer chemotherapy in the tumor microenvironment would further reduce the toxicity of anticancer drugs toward normal tissues. Fibroblast activation protein (FAP) is known to be selectively overexpressed on cancer-associated fibroblasts (CAFs) in the tumor microenvironment. Here, we designed an anticancer chemotherapeutic system based on promelittin, a peptide toxin that is selectively converted from an inactive form to the pore-forming melittin upon cleavage by FAP in the tumor microenvironment.

Methods: We conjugated promelittin-containing FAP-cleavable sequences to pegylated phospholipids and anchored them to reduced graphene oxide (rGO) nanosheets. The resulting nanosheets, PL-rGO, were tested for hemolysis and used for doxorubicin delivery. In vitro cocultures and in vivo tumor growth (n = 5 mice per group) with tissue immunostaining were used to test the selective activation of anticancer chemotherapy by FAP expressed on CAFs.

Results: FAP-specific hemolytic activity of PL-rGO was observed in cocultures of CAFs and HT29 cells but not in HT29 cells alone. Doxorubicin-loaded PL-rGO (Dox/PL-rGO) showed 3.4-fold greater cell-killing efficacy (compared with free Dox in the CAF/HT29 coculture system, effects that were not observed in HT29 cells alone). Intravenously administered Dox/PL-rGO reduced the growth of HT29 tumors more effectively than other treatments (Dox/PL-rGO: mean = 200.6 mm³, 95% confidence interval [CI] = 148.7 to 252.5 mm³; free Dox: mean = 697.0 mm³, 95% CI = 646.9 to 747.1 mm³, PL: mean = 565.0 mm³, 95% CI = 550.5 to 579.6 mm³; Dox/rGO: mean = 637.6 mm³, 95% CI = 619.5 to 655.7 mm³; PL-rGO: mean = 464.4 mm³, 95% CI = 433.0 to 495.8 mm³). Immunostaining of tumor tissues revealed that survival of CAFs and HT29 cells was lowest in the group treated with Dox/PL-rGO.

Conclusions: The demonstration of selective activation of PL-rGO by FAP on CAFs suggests that PL-rGO may serve as a tumor microenvironment–responsive anticancer chemotherapy system.

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Aberrant DNA methylation of alternative promoter of DLC1 isoform 1 in meningiomas

Abstract

DLC1 encodes GTPase-activating protein with a well-documented tumor suppressor activity. This gene is downregulated in various tumors through aberrant promoter hypermethylation. Five different DLC1 isoforms can be transcribed from alternative promoters. Tumor-related DNA methylation of the DLC1 isoform 1 alternative promoter was identified as being hypermethylated in meningiomas in genome-wide DNA methylation profiling. We determined the methylation pattern of this region in 50 meningioma FFPE samples and sections of 6 normal meninges, with targeted bisulfite sequencing. All histopathological subtypes of meningiomas showed similar and significant increase of DNA methylation levels. High DNA methylation was associated with lack of DLC1 protein expression in meningiomas as determined by immunohistochemistry. mRNA expression levels of 5 isoforms of DLC1 transcript were measured in an additional series of meningiomas and normal meninges. The DLC1 isoform 1 was found as the most expressed in normal control tissue and was significantly downregulated in meningiomas. Transfection of KT21 meningioma cell line with shRNA targeting DLC1 isoform 1 resulted in increased activation of RHO-GTPases assessed with pull-down assay, enhanced cell migration observed in scratch assay as well as slight increase of cell metabolism determind by MTT test. Results indicate that isoform 1 represents the main pool of DLC1 protein in meninges and its downregulation in meningiomas is associated with hypermethylation of CpG dinucleotides within the corresponding promoter region. This isoform is functional GAP protein and tumor suppressor and targeting of its expression results in the increase of DLC1 related cell processes: RHO activation and cell migration.

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Traumatic neuroma of the superficial peroneal nerve in a patient: a case report and review of the literature

Abstract

Background

Traumatic neuromas are rare benign tumors, which are common in trauma or post-operation and accompanied with obvious symptoms of pain. This study will show the superficial peroneal nerve neuroma occurring after resection of hemangioma.

Case presentation

A 44-year-old male had an operation of the right leg cavernous hemangioma resection in 1995. Half a year after the operation, pain around the wound appeared and gradually aggravated. The patient had the lesion exploration resection in 2013, and the pathological result showed traumatic neuroma. Within half a year of the second operation, severe pain showed up again, so neuroma resection proceeded in May 2015. The postoperative pathological and immunohistochemical results showed traumatic neuroma. According to the postoperative follow-up, there were no symptoms of pain appearing again.

Literature review

The pain is obvious, and B ultrasonography is the most efficient way to find neuromas. Both conservative and operative therapy have their advantages and disadvantages.

Conclusions

There remain many unanswered questions in relation to the treatment of traumatic neuromas, and further research is required, although we have already had adequate understanding of traumatic neuromas.

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