Kanta Bhambhani

B-type natriuretic peptide as a marker for cardiac dysfunction in anthracycline-treated children.

Anthracyclines (AC) are useful antineoplastic agents, whose utility is limited by progressive cardiotoxicity. Our purpose was to evaluate plasma B‐type natriuretic peptide (BNP), as a screening test for detecting late cardiac dysfunction in AC‐treated children and to determine the prevalence of late cardiac dysfunction at low cumulative AC doses.

Medulloblastoma with adverse reaction to radiation therapy in nijmegen breakage syndrome.

A 3-year-old child with microcephaly, facial dysmorphism, growth retardation, and developmental delay was diagnosed with medulloblastoma. Craniospinal irradiation resulted in severe radiation-induced dermatitis and gastroesophagitis, unresponsive to further medical therapy. Colony survival assay on the patients transformed lymphocytes revealed a high degree of radiosensitivity ex vivo. The presence of radiation sensitivity, both clinically and ex vivo, in association with microcephaly and growth retardation, prompted a diagnostic workup for Nijmegen breakage syndrome. The patient was confirmed to have a compound heterozygote genotype for the common founder mutation of NBS1 675del5 in exon 6, and 1142delC in exon 10. Because irradiation is an important component of therapy for brain tumors, caution should be exercised in cancer patients with associated microcephaly and growth retardation, as they may turn out to have the rare diagnosis of Nijmegen breakage syndrome.

Second malignant neoplasms after primary central nervous system malignancies of childhood and adolescence.

The standardized incidence ratios (SIR) and cumulative incidence rates were determined for developing second malignant neoplasms (SMNs) after primary central nervous system (CNS) malignancies occurring during childhood using registry data. A total of 4553 cases of primary CNS malignancies were identified. Forty-six cases developed SMNs, 19 occurring in a previously radiated field. The SIRs of developing second malignant neoplasms were 6.3 and 3.1 for those cases receiving and not receiving radiation therapy, respectively. The 20-year cumulative incidences for developing SMNs were 3.3 and 1.2% for cases receiving and not receiving radiation therapy, respectively. Children surviving CNS malignancies have an increased susceptibility for SMNs.

Permanent I-125 brain stem implants in children

Abstract Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gy×4 fractions. After 4–6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7–9 months from diagnosis) and four patients remain alive (5–38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.

Early deaths in childhood cancer

BACKGROUND Deaths prior to or shortly after the diagnosis of childhood cancer may reflect inadequacies in detection and appropriate referral for care. This study was performed to determine the extent of and factors associated with early death in childhood cancer. PROCEDURE Patients with of primary cancer, aged <20 years at diagnosis, were identified from the SEER data (n = 23,470) from 1973 to 1995. Early deaths were defined as cases identified by 1) death certificate, 2) autopsy report, or 3) death within 1 month of initial diagnoses (n = 481). Cause of death was determined by ICD-8 and -9 codes. Age at diagnosis, year of diagnosis, morphology, site of disease, race, and gender were evaluated for association with early death. RESULTS Age <1 year at diagnosis (6.2% early deaths), being diagnosed earlier in the observation period, and a diagnosis of a brain tumor, neuroblastoma, leukemia, or liver tumor were associated with increased early death. Gender and race were not associated with early death. Among the cases for whom the malignant diagnosis was made at the time of death (n = 119), the cause of death was nonmalignant for 36. For 22 of these cases the malignancy was an incidental finding and appeared not to contribute directly to the cause of death. Among these patients, 11 had neuroblastoma, 9 being <1 year of age. CONCLUSIONS A decrease in the proportion of early deaths associated with childhood cancer has occurred during the past 2 decades. This decrease may reflect earlier diagnosis or improved imaging capabilities, surgical techniques, medical therapy, and supportive care. Awareness among pediatricians, general practitioners, and emergency physicians is warranted, with a focus on high-risk groups for early detection among childhood cancer patients.

Acute otitis media in children: Are decongestants or antihistamines necessary?

This study was designed to investigate the efficacy of a decongestant-antihistamine preparation in combination with antibiotic treatment of acute otitis media. The effectiveness of a new Dimetapp (DIM) preparation was assessed in comparison with each of its components (brompheniramine maleate [BPM] and phenylephrine hydrochloride [PEH] as well as a placebo (PL) vehicle in the treatment of acute otitis media. In a randomized double blind study, 98 children were treated in the emergency department or outpatient medical clinics at Childrens Hospital of Michigan with amoxicillin and either DIM, BPM, PEH, or PL. They were evaluated at two weeks by clinical examination, pneumatoscopy, and tympanometry. Fifty-eight patients (59%) continued to have evidence of fluid in the middle ear. These patients were continued on the test medications for another two weeks and then reevaluated. There were significant differences between the treatment groups (DIM, BPM, and PEH) and the control PL group; the patients receiving Dimetapp or placebo fared better than those receiving BPM or PEH. However, there was no difference in the overall response between Dimetapp and placebo. Antihistamine-decongestant therapy does not appear to be necessary in the treatment of acute otitis media in children.

Diffuse intrinsic pontine glioma biopsy: A single institution experience

Tumor biopsy is rarely performed in diffuse intrinsic pontine glioma (DIPG) due to the presumed risk of surgical complications, although data on the surgery related morbidity of DIPG biopsy is sparse. We performed a retrospective review on 22 consecutive cases of DIPG diagnosed from 2002 to 2012 at Childrens Hospital of Michigan, 15 of which underwent biopsy. Transient new or worsening neurological deficits were observed in three of 15 cases following surgery. No surgery related mortality or permanent deficit was observed, and the mean overall survival was 10.4 ± 3.8 months. Undergoing biopsy did not adversely affect the outcome. Pediatr Blood Cancer 2015;62:163–165.

Herpes simplex virus pneumonia in a patient with ependymoma.

The authors report a fatal outcome in a 4-year-old boy with herpes simplex virus (HSV) pneumonia and ependymoma. The patient had respiratory distress that worsened despite antibiotic treatment. Bronchoalveolar lavage showed intranuclear viral inclusions, and culture was positive for HSV type 1. His T-cell count was significantly decreased. Although acyclovir and foscarnet were given, the patient died. Postmortem examination showed HSV pneumonitis with severe alveolar damage and severe involutional changes of the thymus with absence of Hassalls corpuscles. HSV must be considered in the differential diagnosis of patients with interstitial pneumonia and T-cell deficiency, especially after craniospinal irradiation.

Vacuolated neuroblastoma cells mimicking FAB L3 lymphoblasts in bone marrow aspirates

Abundant cytoplasmic vacuolation of neuroblasts has been noted on bone marrow aspirate (BMA) smears of two patients with metastatic neuroblastoma. Occasional tumor cells were dispersed as individual cells as well as in clumps. These cells had basophilic cytoplasm and several nucleoli, reminiscent of L3 lymphoblast morphology. Flow cytometric analysis of the bone marrow mononuclear cells and neuron‐specific enolase staining of the bone marrow biopsy samples further distinguished the cells as neuroblasts. Cytoplasmic vacuolations of neuroblasts may be a feature of metastatic neuroblastoma cells in BMA smears. Pediatr Blood Cancer 2007;48:227–229.

Novel mutations in the von Hippel–Lindau gene associated with congenital polycythemia

To the editor: Polycythemia is a rare disorder in children and the vast majority of cases are secondary to causes such as cyanotic congenital heart disease, congenital lung diseases, liver and kidney disease, and masses producing erythropoietin. Mutations in exon 3 of the VHL gene are the most common cause of congenital erythrocytosis [1–3]. Several reports have shown evidence of heterozygous and homozygousmutations in exon 2 of theVHL gene as a cause of congenital polycythemia [4–6]. We report on a 9-month-old female who was referred to the hematology clinic for evaluation by her pediatrician with plethora and erythrocytosis (RBC count 7.67million/mm, hemoglobin 21.5 g/dL, hematocrit 66.2%, MCV 86.3 fL). The erythropoietin level was 48 IU/L (normal 4–27), in the face of marked erythrocytosis. The patient was started on phlebotomy treatments of 5ml/kg of blood which has progressed to 10ml/kg of blood with normal saline replacement every 4weeks with good results. Shewas