Obituary: Yehuda Matoth (1913-1986)

Like pediatricians elsewhere, Austrian pediatricians have always dealt with hematological and oncological problems. However, up to the 1970s in Austria only case reports and a few single institutional reviews with generally unsatisfactory therapy results have been published.^1-3 With the issue of the first cooperative and prospective treatment protocol for acute lymphoblastic leukemia (ALL) in 1974, a fruitful nationwide cooperation in the field of hematology/oncology began.⁴ This date is considered the birthday of the Austrian Leukemia Study Group. In 1978, the Austrian Pediatric Oncology Group was established as a result of the group's intention to encompass all pediatric malignancies in its collective work. The main objective of the group was the development of standardized therapy protocols with the aim of improving the results nationwide. The achievement of this goal has to be largely attributed to the work of Paul Krepler, MD, the former head of the St. Anna Children's Hospital in Vienna. Since 1974, six consecutive national ALL studies have been performed. Three of them were essentially derived from the Memphis protocols, the latter from modifications of the Berlin-Frankfurt-Münster (BFM) strategy.^5,6 Furthermore, national cooperations in the treatment of Wilms’ tumor,⁷ neuroblastoma,⁸ non-Hodgkin's lymphoma,⁹ soft-tissue sarcoma,¹⁰ acute myeloid leukemia,¹¹ and histiocytosis syndromes were initiated, in part with international cooperation.     

Carboplatin in childhood Medulloblastoma/PNET: Feasibility of an in vivo sensitivity test in an “up-front” study

Sixteen patients with high risk MB/PNET at diagnosis were included in a pilot study employing carboplatin (CBDCA) as a single drug prior to conventional therapy. The main goal of the study was to identify in a short-term trial a significant response that would predict further response to CBDCA in the single patient. Exploration of CBDCA activity was focused on response after the first course as compared to the response following the second course. A course consisted of CBDCA 600 mg/m² on days 1 and 2 administered in a 1 h infusion to be repeated 3–4 weeks later. After two cycles we observed 1 CR and 9 PR, that is a 62% response rate. The first course resulted in 5 PR, 5 MR, 5 SD, and 1 PD; after the subsequent course in all responding patients, response persisted or improved whereas in no patient with SD any improvement was observed. The correlation of response to the first course with response to the second course was statistically significant (P = 0.0009). The main toxicity of the single course was hematologic and consisted of rapidly reversible grade 3–4 neutropenia and thrombocytopenia in 94% of patients. Pharmacokinetic studies showed a very limited interpatient variability of both Cmax (57.6 ± 9.9 μg/ml) and AUC (15.3 ± 1.5 mg/ml · min) of free CBDCA, which eliminates an important variable in the evaluation of response. In conclusion, this “in vivo test” appears effective, reasonably safe, and reproducible in identifying patients likely to benefit from CBCDA: after a period of time as short as 3–4 weeks following the first course, multidrug chemotherapy including CBDCA may be employed in the responding patients, whereas an alternative regimen would be indicated in the non-responding patients. © 1995 Wi1ey-Liss Inc.     

“Nasal Gliomas” and Related Brain Heterotopias: A Pathologist's Perspective

Brain heterotopias arc rare congenital malformations embryologically related to encephaloceles. They present as a mass in or about the nose (nasal glioma) or in the nasopharynx. We present the clinical and pathological features of 5 cases of heterotopic brain tissue. Four nasal gliomas consisted of mature neuroglial tissue, including neurons in 2 cases, embedded in a fibrovascular stroma. A nasopharyngeal brain heterotopia showed histologic features of mature neuroglial tissue including neurons and ependymal-lined cystic structures. The finding of mature neuroglial tissue in a mass from the head and neck region raises three differential diagnostic possibilities: teratoma, encephalocele, or heterotopic tissue. A teratoma can be ruled out by examination of the entire specimen. Encephaloceles and brain heterolopias can be distinguished only after correlation with the patient's clinical and radiologic findings.     

Multifactorial analysis of opsoclonus‐myoclonus syndrome etiology (“Tumor” vs. “No tumor”) in a cohort of 356 US children

1 Background

Pediatric opsoclonus‐myoclonus syndrome (OMS) presents a paradox of etiopathogenesis: A neuroblastic tumor (NB) is found in only one half of the cases, the others are ascribed to infections or designated as idiopathic.

2 Method

From an IRB‐approved observational study of 356 US children with OMS, secondary analysis of “etiology” and related factors was performed on a well‐characterized cohort. The “Tumor” (n = 173) and “No Tumor” groups (n = 183), as defined radiologically, were compared according to multiple factors considered potentially differentiating. Data were analyzed retrospectively using parametric and nonparametric tests as indicated.

3 Results

Patients with NB were not distinguishable by prodromal symptoms, OMS onset age, gender, race/ethnicity, OMS severity, rank order of neurological sign appearance, or geographic distribution. Various CSF immunologic biomarker abnormalities of OMS did not vary in the presence or absence of a detectable tumor: frequency of six lymphocyte subsets, or concentrations of 18 cytokines/chemokines, cytokine antagonists, chemokine receptors, cell adhesion molecules, or neuronal/glial markers. Prior responsiveness to conventional immunotherapy was not contingent on tumor/no tumor designation.

4 Conclusions

Multiple convergent factors provide compelling empirical evidence and rationalize the concept that OMS is one neurological disorder, regardless of apparent etiology. Limitations to the current clinical etiologic classifications as paraneoplastic, parainfectious/post‐infectious, and idiopathic etiology require antigen‐based biological solutions to tease out the molecular pathophysiology of viral/tumoral mechanisms. Systematic studies, regardless of presumed etiology, will be necessary to find the highest‐yield combination of imaging approaches, screening for infectious agents, and new biomarkers. Two testable hypotheses for future research are presented.     

Direct provider feedback to decrease chemotherapy ordering errors: The “gray envelope” initiative

Chemotherapy errors are the second leading cause of mortality related to medication errors. Most medication errors occur in the provider ordering process. We evaluated the rate of chemotherapy ordering errors in our center and designed an intervention to decrease the rate of ordering errors. The intervention focused on direct confidential written feedback to the providers. Our intervention resulted in a significant decrease in ordering errors from 7% pre‐intervention to 3.9% post intervention (P < 0.001). We conclude that direct written provider feedback can result in a significant decrease in chemotherapy ordering errors. Pediatr Blood Cancer 2012; 59: 1330–1331. © 2012 Wiley Periodicals, Inc.     

Fatal pneumothorax in “BCNU lung”

A patient with recurrent glioma treated with BCNU developed pneumothorax and interstitial pulmonary fibrosis. She died from “BCNU lung” and its complications, although she was free of her initial disease.