Voriconazole Antifungal Prophylaxis in Children With Malignancies: A Nationwide Study.

BACKGROUND: Antifungal prophylaxis (AFP) is recommended in at-risk hematology-oncology patients. We evaluated the safety of AFP with voriconazole (VRC) in pediatric hematology/oncology patients. MATERIALS AND METHODS: A retrospective study of VRC AFP in children with malignancies hospitalized in all 7 Greek pediatric hematology/oncology centers during 2008 to 2012 was conducted. Patients' demographics, outcome, and adverse event (AE) data were recorded. RESULTS: Four hundred twenty-nine VRC AFP courses in 249 patients (median age 6 y, 55% boys) were studied. The most common underlying diseases were acute lymphoblastic leukemia (51%), non Hodgkin lymphoma (8.6%), and acute myeloid leukemia (7.7%). The median number of VRC courses per patient was 1.7, whereas the median VRC dose was 7 mg/kg (range, 5 to 7 mg/kg) every 12 hours. During the last 2 weeks before AFP, 51% of the patients had received corticosteroids, 43% suffered from severe neutropenia, and 17.3% from mucositis. The median duration of VRC AFP was 17 days (range, 1 to 31 d). A single breakthrough fungemia due to Candida glabrata was recorded. Only 1 patient died due to the underlying disease. The most common AEs reported in 70/429 (16.3%) courses with ≥1 AE were elevated liver enzymes (50%), hypokalemia (24.3%), and ophthalmological disorders (14.3%). The median time of AE onset was 5 days (range, 1 to 21 d). Among 70 AEs reported, 38.5%, 48.4%, and 12.8% were of grade I, II, and III, respectively. CONCLUSIONS: VRC prophylaxis in pediatric hematology/oncology patients appears to be well tolerated.

Use of Tigecycline in Pediatric Patients With Infections Predominantly Due to Extensively Drug-Resistant Gram-Negative Bacteria.

BACKGROUND.: Emergence of extensively drug-resistant (XDR) bacteria has forced clinicians to use off-label antimicrobial agents such as tigecycline. We present our experience on salvage use of tigecycline for the treatment of infections caused by XDR Gram-negative bacteria in critically ill children and review published cases. METHODS.: We conducted a retrospective chart review in pediatric departments of a tertiary level hospital from January 2009 to May 2014. Patients were identified using pharmacy database. For the literature review, relevant articles were identified from PubMed. RESULTS.: In our case series, 13 children (7 males) with a median age of 8 years (range, 2.5 months-14 years) received tigecycline for ≥2 days as treatment for healthcare-associated infections including 5 bacteremias, 6 lower respiratory tract infections, and 3 other infections. Isolated pathogens were XDR Gram-negative bacteria except 1. A loading dose (range, 1.8-6.5 mg/kg) was given in all except 2 cases. Maintenance dose was given at 1-3.2 mg/kg q12 h. Other antimicrobials including colistin and aminoglycosides (85% and 62%, respectively) were coadministered to all patients. No serious adverse events were detected in these very ill children. Twenty cases of children treated with tigecycline were previously published, mostly for multidrug-resistant/XDR bacteria. An episode of acute pancreatitis and neutrophil engraftment delay in 2 cases were reported during tigecycline treatment. Analyzing reported and all our cases together, mortality in bloodstream infections was 86%, whereas in nonbacteremic cases it was 24% (P = .009). CONCLUSIONS.: Tigecycline, given at the range of administered doses as salvage therapy and in combination with other antimicrobial agents, seemed to be well tolerated in a series of mainly critically ill pediatric patients and demonstrated relatively good clinical response in nonbacteremic patients.

Ewing's Sarcoma of Mandible: An Impressive Case of Spontaneous Mandible Regeneration.

Ewing's sarcoma (ES) is an uncommon aggressive bone malignancy that mainly affects children and adolescents. Mandible involvement is quite rare and usually represents metastasis from another skeletal site. Combined therapy including wide surgical resection and preoperative and postoperative chemotherapy has been demonstrated as the mainstay of therapeutic approach. As improved therapeutic modalities have significantly increased survival over the last decades, functional and esthetic reconstruction of the postmandibulectomy defect is usually necessary for patient's total rehabilitation. We report a case of ES of the mandible with special consideration to the postresection spontaneous structural and functional regeneration of the mandible. HOW TO CITE THIS ARTICLE: Chatzistefanou I, Kabesi S, Paraskevopoulos K, Koliouskas D, Antoniades K. Ewing's Sarcoma of Mandible: An Impressive Case of Spontaneous Mandible Regeneration. Int J Clin Pediatr Dent 2016;9(3):273-277.

Glucose Levels Before the Onset of Asparaginase Predicts Transient Hyperglycemia in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Transient hyperglycemia (TH) represents an acknowledged adverse event that occurs during treatment in children with acute lymphoblastic leukemia (ALL) and has recently been associated with an increased risk for developing metabolic disturbances in future life. Our aim was to estimate the incidence of TH and to identify risk factors, thus serving as markers for identifying candidates for prevention interventions. PROCEDURE: All patients treated with induction treatment for ALL in our department from January 2004 to April 2015 had their data retrieved from medical files and retrospectively analyzed. RESULTS: One hundred and two children with ALL treated at our department were identified (49 females and 53 males) with a mean age of 6.03 ± 3.78 years at the time of diagnosis. Sixteen patients developed TH (15.68%). Age at diagnosis >10 years is associated with an 11-fold increase in the risk of developing TH. Additionally, fasting glucose on the eighth day of treatment is an important prognostic factor as fasting glucose >100 mg/dl at that time point is associated with a threefold increase in developing TH during residual treatment period. CONCLUSIONS: Fasting glucose levels >110 mg/dl on the eighth day of treatment could serve as a trigger for intervention strategies that will prevent the development of TH in pediatric patients treated for ALL. Additional studies are needed to confirm and further extend this preliminary observation.

Acute visual loss as the initial presentation in a child with systemic Burkitt lymphoma.

Non-Hodgkin lymphoma (NHL) accounts for 10% of pediatric malignancies and is the third most common malignancy in childhood. We report a previous healthy 3-year-old boy with stage IV Burkitt lymphoma presenting with acute visual loss. In funduscopy his pupils were fixed at 6 mm in diameter without light perception. He started therapy according to the UKCCSG 9003 protocol. The boy didn't show any visual improvement but some slight light perception despite his partial remission after CYVE II. He died of neutropenic septicemia before his scheduled radiotherapy. In conclusion, loss of vision is a rare presenting sign in NHL. Differential diagnosis is crucial as early diagnosis and effective treatment are important for survival as well as for visual restoration.

Polyclonal outbreak of vancomycin-resistant Enterococcus faecium in a pediatric oncology department.

We present a polyclonal outbreak of vancomycin-resistant enterococci (VRE) colonization in a pediatric oncology department and the role of a bundle of actions. After the occurrence of VRE bloodstream infections in 2 patients, an active surveillance of VRE colonization was started. Enhanced infection control measures and closure of the department to new admissions for the first 3 months were implemented. Among 32 patients screened for VRE, 21 were found colonized. Daily prevalence of VRE colonization among hospitalized patients ranged from 40% to 75%, but no new VRE infections occurred. Monthly incidence of VRE colonization decreased from 2.5 to 0.6 cases per 100 occupied bed-days at the end of this outbreak by the implementation of the above-mentioned measures. All VRE isolates tested were Enterococcus faecium carrying VanA gene. Pulsed field gel electrophoresis showed a polyclonal outbreak. A case-control study did not show any particular risk factors for colonization. High use of glycopeptide was noted before study outbreak that was drastically decreased during the study but only temporarily. Control of VRE in pediatric oncology departments with high colonization rates is challenging and requires a multifaceted strategy. Polyclonal spread of VRE found in this study suggests a possible effect of prior antimicrobial overuse and the critical need for antimicrobial stewardship especially in the era of multidrug-resistant bacteria.

Intestinal tuberculosis: a diagnostic challenge--case report and review of the literature.

Even though tuberculosis is considered rare in developed countries, its rising incidence, especially in high-risk populations, places intestinal tuberculosis in the differential diagnosis of patients with atypical abdominal symptoms or signs. We, herein, report the case of an immunocompetent woman, from a nonendemic area, who developed intestinal tuberculosis, emphasizing the diagnostic challenges caused due to nonspecific symptoms, inconclusive clinical, laboratory, and imaging findings, which could not rule in or rule out tuberculosis. Antituberculosis treatment was administered based on endoscopic findings and histological features of mucosal biopsies, which were indicative of intestinal tuberculosis, and the patient showed a marked clinical and laboratory improvement. We also review the evidence with regard to the diagnostic accuracy of the different available tests for intestinal tuberculosis.

Thrombomodulin and von Willebrand factor: relation to endothelial dysfunction and disease outcome in children with acute lymphoblastic leukemia.

The severe endothelial dysfunction in children with acute lymphoblastic leukemia (ALL) can result from the disease itself, from treatment, or from other conditions (e.g. sepsis). The aim of this study was to determine the levels of markers of endothelial activation in children with ALL and to assess their potential prognostic value. Fifty-two children with ALL, 19 children with ALL 1-10 years after the completion of therapy, and 28 healthy children were studied. In children with ALL, there was a significant increase in thrombomodulin (TM) and von Willebrand factor (vWF) levels during the acute phase of the disease and during treatment. Children with an unfavorable outcome had higher levels of TM. In conclusion, severe endothelial dysfunction is present during the acute phase of ALL and during treatment and appears to result from the disease itself. Serum TM and vWF levels might represent additional, but not independent, prognostic markers in childhood ALL.

4,4'-Methylenedianiline-induced hepatitis in an industrial worker: case report and review of the literature.

4,4'-Methylenedianiline (MDA) is a chemical used in manufacturing and insulation processes and is a well-known hepatotoxin. We report the case of a 42-year-old construction-site worker who was accidentally exposed to large amounts of MDA and developed acute liver damage. The clinical course is described, with particular emphasis on the timely identification of the underlying cause and prompt management that led to an uneventful recovery. We review the relevant literature and discuss the safety measures necessary to minimize similar occupational hazards in industrial workers.

Carcinoid tumors of the appendix in children: experience from a tertiary center in northern Greece.

BACKGROUND AND OBJECTIVE: Carcinoid tumors of the appendix are rare in childhood and usually have a benign clinical course. Their incidence in appendectomy specimens ranges from 0.1% to 0.9%. The aim of the study was to report the frequency, clinical presentation, tumor characteristics, and outcome of children with appendiceal carcinoid treated in a pediatric oncology department. PATIENTS AND METHODS: All of the cases referred during a 19-year period (1990-2008) were studied retrospectively. Demographics, clinical presentation, tumor characteristics, and follow-up results were recorded. RESULTS: Among 839 admissions, 19 patients (9 boys) with appendiceal carcinoid were identified during the study period. Their median age was 10.5 years (range 4.5-13.2 years). In all of the cases, diagnosis was established after appendectomy. The mean tumor diameter was 4.55 (± 3.45) mm (range 1-15 mm). Concomitant appendicitis was diagnosed in 12 patients. In 18 children tumor size was ≤ 10 mm and did not infiltrate surrounding tissues. In 1 patient the size was 15 mm and a microscopic rupture of the appendix with infiltration of the surrounding fat was present. All of the tumors were located at the tip of the appendix and were of the classic histological type. Staging and follow-up consisted of abdominal ultrasound, chest and abdominal computed tomography scans, Tc bone scan, urine 5-hydroxylindoloacetic acid levels, and 111In octreotide scan. No patient had metastases requiring further therapeutic interventions. No relapses or other neoplasms occurred during a median follow-up period of 45 months (range 6-118 months). CONCLUSIONS: Carcinoid tumors of the appendix in children are rare. Long-term follow-up revealed that a good prognosis is possible provided they are diagnosed and surgically removed at an early stage.

Isolated central nervous system recurrence in a child with stage IV neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in children. Survival rates have improved due to advances in treatment with aggressive chemotherapy and autologous bone marrow transplantation. Usual sites of recurrence include the site of primary tumor, residual gross disease, bone, bone narrow, liver, and lungs. The authors describe a 16-month-old boy with stage IV extracerebral primary neuroblastoma who died because of an isolated central nervous system (CNS) relapse. The CNS is a rare site of relapse that is, however, increasingly diagnosed due to prolonged survival. Criteria to identify patients at increased risk of CNS relapse are urgently needed. High-risk patients should be followed-up with brain and spine magnetic resonance imaging (MRI) for timely detection of metastases and appropriate management.

Unusual Epstein-Barr esophageal infection in an immunocompetent patient: a case report.

INTRODUCTION: Epstein-Barr virus esophagitis in an immunocompetent host is a rare entity. It represents either primary infection or reactivation and is usually characterized by acute onset and extensive ulcerative involvement of the upper and middle third of the esophagus. CASE PRESENTATION: A case of Epstein-Barr virus esophagitis in a 27-year-old woman with no immunosuppressive factors, and having gastrointestinal symptoms is reported here. Using real-time polymerase chain reaction, biopsy and blood specimens were tested for candida and herpes viruses. Epstein-Barr virus DNA was detected in tissue samples. The patient was treated with acyclovir with resolution of the symptomatology. CONCLUSIONS: The prevalence of esophagitis remains undefined in both immunodeficient and immunocompetent individuals and should be taken into consideration in a patient presenting with esophageal symptoms. This case report stresses the role of Epstein-Barr virus infection in the pathogenesis of esophagitis, a rare condition in an immunocompetent host. In this setting, active infection may represent a primary infection or reactivation. Histopathological examination alone may miss the diagnosis, while polymerase chain reaction techniques optimize the diagnostic sensitivity, establish a diagnosis, and lead to an appropriate therapy.

Tc-99m HMPAO labeled white blood cell imaging in a child with eosinophilic lung disease.

In radiolabeled leukocyte imaging, Tc-99m HMPAO has a significantly higher selectivity for eosinophils than neutrophils, but this may be clinically meaningful in disorders with eosinophilic infiltration. We present the case of a 2-year-old boy with infection who also developed drug-induced eosinophilic lung disease, as established later by bronchoalveolar lavage and discontinuation of the responsible antistaphylococcal agent. In the investigation of sepsis, diffusely increased pulmonary accumulation of Tc-99m HMPAO labeled leukocytes was observed. These findings were consistent with eosinophilic lung infiltration and underline the importance of clinical and laboratory data in the comprehensive interpretation of Tc-99m HMPAO labeled leukocytes scans.

123I-Metaiodobenzylguanidine accumulation in a urinoma and cortex of an obstructed kidney after surgical resection of an abdominal neuroblastoma.

Surgical ureteric injury is rare and often unsuspected for a long time. We present a child in whom an abdominal neuroblastoma was completely excised, but during surgery the left ureter was transected and anastomosed. One month later, during postoperative disease staging, abnormal (123)I-MIBG accumulation was observed in the left renal cortex and the left side of the abdomen. These findings were consistent with acute total obstruction and urinoma formation and were subsequently confirmed by renography and MRI. Despite treatment efforts, a significant amount of left renal mass and function were lost over the following months. These unusual findings are new additions to the literature regarding potential false-positive interpretations of (123)I-MIBG scans.