Perioperative external ventricular drainage vs. no-EVD strategy in pediatric posterior fossa tumors-pilot study results.

INTRODUCTION: Pediatric brain tumors of the posterior fossa often present with occlusive hydrocephalus. Endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunting (VPS) has been established for definite hydrocephalus treatment. The aim of the study was to analyze the impact and safety of perioperative temporary external ventricular CSF drainage (EVD) placement on postoperative hydrocephalus outcome compared to a no-EVD strategy. PATIENTS AND METHODS: In a prospective database, 36 posterior fossa tumor patients of 2-18 years were included with a follow-up of 1 year. Fifty-eight percent presented with preoperative hydrocephalus. Patients were assigned to non-hydrocephalus group: group I (n = 15) and to preoperative hydrocephalus, group IIa with EVD placement (n = 9), and group IIb without EVD (n = 12). RESULTS: Median age of patients was 8.1 years (range 3.17 to 16.58 years). One-third of 21 hydrocephalus patients required ETV or VPS (n = 7). Occurrence of de novo hydrocephalus in group I after surgery was not observed in our cohort. Age and histology were no confounding factor for EVD placement between group IIa and IIb (p = 0.34). The use of EVD did not result in better control of hydrocephalus compared to no-EVD patients considering pre- and postoperative MRI ventricular indices (p = 0.4). Perioperative placement of an EVD resulted in a threefold risk for subsequent VPS or ETV (group IIa 55.5% vs group IIb 16.6%): relative risk for EVD patients compared to no-EVD patients with hydrocephalus was 3.3 (CI = 1.06-13.43, p = 0.09). CONCLUSION: Perioperative EVD placement appears to harbor a threefold relative risk of requiring subsequent permanent CSF diversion in children above 2 years. EVD was not more effective to control ventricular enlargement compared to tumor removal alone. The no-EVD strategy was safe and did not result in postoperative complications. Thus, to evaluate potential adverse effects on hydrocephalus outcome by EVD placement, a prospective study is warranted to falsify the results.

Pediatric Colorectal Carcinoma is Associated With Excellent Outcome in the Context of Cancer Predisposition Syndromes.

INTRODUCTION: Colorectal carcinoma (CRC) is the second most common adult cancer in Germany, however, it is extremely rare in children and adolescents. In these patients, previous literature describes aggressive behavior and diagnosis at advanced stage. METHOD: Thirty-one patients with CRC age ≤ 18 years and treated between 1990 and 2012 have been identified through the structures and registries of the German Society for Pediatric Oncology and Hematology. RESULTS: The age range was 9-18 years (median 13.5 years); the median follow-up time was 43.9 months (range 1-124 months). Twenty-six patients (84%) were tested for a genetic tumor syndrome (GTS); of these, 11 patients (35% of all patients) tested positive (eight cases of Lynch syndrome, one patient with familial adenomatous polyposis, two patients with constitutional mismatch repair deficiency). An unfavorable histology was reported in 55% of the records (n = 17), a poor differentiation (grade III) in 68% of carcinoma (n = 21). Overall survival (OS) and event-free survival at 5 years was 52.0% and 65.6%, respectively. Five-year survival according to stage was 100% in stage II (n = 2), 100% in stage III (n = 13), and 12.9% in stage IV (n = 15; P < 0.001). Five-year OS in patients with and without a defined GTS was 100% and 36.5% (P = 0.019), respectively. CONCLUSION: Children and adolescents with CRC are frequently diagnosed in advanced stages and have an unfavorable prognosis. In this study, a high percentage of pediatric CRC patients presented with a tumor predisposition syndrome and showed an especially favorable OS.

Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group 87.

PURPOSE: Approximately 20% of children with acute lymphoblastic leukemia (ALL) suffer a relapse, and their prognosis is unfavorable. Between 1987 and 1990, the multicenter trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 87 was conducted to establish a uniform treatment for these children in Germany and Austria. PATIENTS AND METHODS: Of 207 registered patients, 183 patients were stratified into three groups according to the protocol: A, early bone marrow (BM) relapse (n = 56); B, late BM relapse (n = 101); C, isolated extramedullary relapse (n = 26). Treatment consisted of risk-adapted alternating short-course multiagent systemic and intrathecal chemotherapy, cranial irradiation, if indicated, and conventional maintenance therapy. Additionally, 24 patients with an exceptionally poor prognosis (early BM or any relapse of T-cell ALL) were treated with individual regimens. In 35 patients, stem-cell transplantation was performed. RESULTS: The probability of event-free survival (EFS) and overall survival of all registered patients at 15 years was 0.30 +/- 0.03 and 0.37 +/- 0.03, respectively, with significant differences between the strategic groups (A, 0.18 +/- 0.05 and 0.20 +/- 0.05; B, 0.44 +/- 0.05 and 0.52 +/- 0.05; C, 0.35 +/- 0.09 and 0.42 +/- 0.10). Despite risk-adapted treatment, an early time point of relapse and T-lineage immunophenotype were significant predictors of inferior EFS in uni- and multivariate analyses. CONCLUSION: With the ALL-REZ BFM 87 protocol, more than one-third of patients may be regarded as cured from recurrent ALL with second complete remissions lasting more than 10 years. Immunophenotype and time point of relapse are important prognostic factors that allow us to adapt more precisely treatment intensity to individual prognosis in future trials.

Brief communication: stability and catalytic activity of novel circular DNAzymes.

UNLABELLED: DNAzymes represent a new generation of catalytic nucleic acids for specific RNA targeting in order to inhibit protein translation from the specifically cleaved mRNA. The 10-23 DNAzyme was found to hydrolyze RNA in a sequence-specific manner both in vitro and in vivo. Although single-stranded DNAzymes may represent the most effective nucleic acid drug to date, they are nevertheless sensitive to nuclease degradation and require modifications for in vivo application. However, previously used stabilization of DNAzymes by site-specific phosphorothioate (PT) modifications reduces the catalytic activity, and the PTO displays toxic side effects when applied in vivo. Thus, improving the stability of DNAzymes without reducing their catalytic activity is essential if the potential of these compounds should be realized in vivo. RESULTS: The Circozyme was tested targeting the mRNA of the most common genetic rearrangement in pediatric acute lymphoblastic leukemia TEL/AML1 (ETV6/RUNX1). The Circozyme exhibits a stability comparable to PTO-modified DNAzymes without reduction of catalytic activity and specificity and may represent a promising tool for DNAzyme in vivo applications. CONCLUSION: The inclusion of the catalytic site and the specific mRNA binding sequence of the DNAzyme into a circular loop-stem-loop structure (Circozyme) of approximately 70 bases presented here represents a new effective possibility of DNAzyme stabilization.

Clonal stability of initial leukemia in a child with central nervous system relapse 7.4 years after bone marrow relapse of common acute lymphoblastic leukemic.

Second central nervous system (CNS) relapses represent about 7.3% of subsequent recurrences of childhood acute lymphoblastic leukemia (ALL). In most children these subsequent CNS relapses occur during the first 18 months after diagnosis of the first relapse (mean 1.42 +/- 0.73 years). We present a patient who suffered a second ALL relapse in the CNS more than seven years after diagnosis of his first relapse. The leukemic clone was completely stable over more than ten years as shown by minimal residual disease techniques. Possible reasons for the recurrence of the leukemic clone after this very long period of dormancy (e.g. role of the disease site, immune system dysfunction) are discussed.

Gastric teratoma in a 6-month-old boy.

Gastric teratomas are very rare embryonal neoplasms, accounting for 2.6% of all perinatal diagnosed germ cell tumours. About 85% are well-differentiated mature lesions and about 15% are immature tumours with the potential of malignant transformation. The recommended therapy for gastric teratomas is surgical excision. We present the case of a 6-month-old boy with an incidentally detected epigastric mass. The histological examination revealed a mature gastric teratoma. The diagnostic imaging, therapy and postoperative follow-up are discussed.