Hirntumoren bei Kindern und Jugendlichen

Every year, around 380 children younger than 16 years are diagnosed in Germany with a brain tumor. Different types of brain tumors are found in children compared to adults. Diagnosis is often delayed in spite of presentation with characteristic symptoms. Thus, unspecific, persistent symptoms should be followed up with further diagnostics. Since the 1980s, multimodal therapeutic regimens have been developed systematically by the Society for Pediatric Oncology and Hematology in the context of treatment optimization trials. Neurosurgery, chemotherapy and radiation are applied according to the histology, stage of metastasis, and age of the children. Currently, 80–90% of children diagnosed with a brain tumor in Germany are treated within the framework of the ‘treatment network HIT’. The principle aims are improved survival and quality of life, the reduction of therapy-associated toxicity and late effects, and better diagnostic and therapeutic standards. In this article, typical clinical symptoms, diagnostic recommendations and treatment strategies are described.     

A randomized phase II trial of the matrix metalloproteinase inhibitor BMS-275291 in hormone-refractory prostate cancer patients with bone metastases.

BACKGROUND: BMS-275291 is a selective matrix metalloproteinase inhibitor (MMPI) that does not inhibit sheddases implicated in the dose-limiting arthritis of older MMPIs. We conducted a randomized phase II trial of two doses of BMS-275291 (1,200 versus 2,400 mg) in hormone-refractory prostate cancer (HRPC) patients with bone metastases to probe for a dose-response relationship and to assess differential toxicities. Serial serum and urine specimens were collected to assess for markers of bone metabolism. METHODS: The primary end point was 4-month progression-free survival (PFS). Eligibility criteria included documentation of androgen-independent disease (including anti-androgen withdrawal), skeletal metastasis, adequate end-organ function and performance status, and no more than one prior chemotherapy regimen. Patients were randomized to 1,200 mg orally once daily (arm A) or 1,200 mg orally twice daily (arm B). Response was assessed every 56 days. RESULTS: Eighty patients were enrolled: 39 in arm A and 41 in arm B. There were no responders by prostate-specific antigen or measurable disease to treatment. Stable disease was noted at 8 weeks in 39% of patients in arm A and in 17% of patients in arm B. Progression of disease at 8 weeks was seen in 61% of patients in arm A versus 83% of patients in arm B. Median survival time was 21.6 months (95% confidence interval, 17.5; not reached), whereas median PFS time was 1.8 months (95% confidence interval 1.74; 2) for all patients. Patients in arm A had a median survival time that was not reached, whereas patients on arm B has a median survival time of 21 months (P = 0.2). PFS at 4 months favored arm A: 22% versus 10% (log-rank, P = 0.008). Grade 3 toxicities occurred in 5 (13%) patients in arm A and in 9 (22%) patients in arm B. Grade 4 toxicities were uncommon (only 4% of patients): one each of thrombosis, fatigue, and motor neuropathy was seen in the arm B. Bone marker studies showed that baseline serum levels of N-telopeptide, osteocalcin, procollagen I NH2-terminal propeptide, and PICP had prognostic significance for PFS and/or overall survival. CONCLUSIONS: Regardless of dose schedule, BMS-275291 was well tolerated in HRPC patients and had no dose-limiting arthritis. Toxicities differed modestly according to the dose schedule employed. As overall survival and PFS favored the once daily schedule, this dose schedule is recommended for future studies. Baseline markers of bone metabolism may have prognostic value in HRPC patients with bone metastases.     

Nerve injury proximal or distal to the DRG induces similar spinal glial activation and selective cytokine expression but differential behavioral responses to pharmacologic treatment

The specific mechanisms by which nervous system injury becomes a chronic pain state remain undetermined. Historically, it has been believed that injuries proximal or distal to the dorsal root ganglion (DRG) produce distinct pathologies that manifest in different severity of symptoms. This study investigated the role of injury site relative to the DRG in (1) eliciting behavioral responses, (2) inducing spinal neuroimmune activation, and (3) responding to pharmacologic interventions. Rats received either an L5 spinal nerve transection distal to the DRG or an L5 nerve root injury proximal to the DRG. Comparative studies assessed behavioral nociceptive responses, spinal cytokine mRNA and protein expression, and glial activation after injury. In separate studies, intrathecal pharmacologic interventions by using selective cytokine antagonists (interleukin-1 [IL-1] receptor antagonist and soluble tumor necrosis factor [TNF] receptor) and a global immunosuppressant (leflunomide) were performed to determine their relative effectiveness in these injury paradigms. Behavioral responses assessed by mechanical allodynia and thermal hyperalgesia were almost identical in the two models of persistent pain, suggesting that behavioral testing may not be a sensitive measure of injury. Spinal IL-1beta, IL-6, IL-10, and TNF mRNA and IL-6 protein were significantly elevated in both injuries. The overall magnitude of expression and temporal patterns were similar in both models of injury. The degree of microglial and astrocytic activation in the L5 spinal cord was also similar for both injuries. In contrast, the pharmacologic treatments were more effective in alleviating mechanical allodynia for peripheral nerve injury than nerve root injury, suggesting that nerve root injury elicits a more robust, centrally mediated response than peripheral nerve injury. Overall, these data implicate alternate nociceptive mechanisms in these anatomically different injuries that are not distinguished by behavioral testing or the neuroimmune markers used in this study.     

Schwann cell-conditioned medium inhibits angiogenesis in vitro and in vivo

BACKGROUND: Neuroblastomas are biologically heterogeneous tumors that consist of two main cell populations: neuroblastic/ganglionic cells and Schwann cells. The amount of Schwannian stroma strongly impacts prognosis. Low tumor vascularity, localized stage, and favorable outcome are associated with tumors that are Schwannian stroma-rich/stroma-dominant. PROCEDURE: To investigate if Schwann cells play a role in inhibiting angiogenesis in neuroblastoma tumors, we examined the ability of human Schwann cell-conditioned medium to affect bFGF- and VEGF-induced endothelial cell proliferation and migration, and in vivo angiogenesis. RESULTS: Schwann cell-conditioned medium significantly inhibited bFGF- and VEGF-induced endothelial cell proliferation and migration. This effect appears to be specific for endothelial cells as smooth muscle cell and fibroblast proliferation were not inhibited by this medium. Schwann cell-conditioned medium also inhibited in vivo angiogenesis in rat corneal assays. CONCLUSIONS: Schwann cells produce a potent inhibitor(s) of angiogenesis that may be responsible for the low level of vascularity and more benign clinical behavior of Schwannian stroma-rich/stroma-dominant neuroblastoma tumors. Studies to identify the inhibitor(s) are ongoing.     

Hirntumoren bei Kindern und Jugendlichen

Every year in Germany, around 380 children younger than 16 years of age are diagnosed with a brain tumor. Compared with adults, different types of brain tumors are found in children. The diagnosis is often delayed despite presentation with characteristic symptoms. Nonspecific persistent symptoms must be followed with further diagnostics. Since the 1980s, multimodal therapeutic regimens have been developed systematically by the Society for Pediatric Oncology and Hematology (GPOH) in the context of treatment optimization trials. Neurosurgery, chemotherapy, and irradiation are applied according to the histology, stage of metastasis, and age of the child. Currently, 80–90% of the children diagnosed with brain tumors in Germany are treated according to the respective trial in the context of the treatment network HIT. The principle aims are improved survival and quality of life, reduction of therapy-associated toxicity and late effects, and better diagnostic and therapeutic standards. In this article, typical clinical symptoms and diagnostic recommendations are described, and the structure of the HIT treatment network is illustrated.     

Sinus venosus atrial septal defect associated with vein of Galen malformations: Report of two cases

Summary Two unique cases are presented of infants with signs of vein of Galen malformations, whose unsuspected associated sinus venosus atrial septal defects were detected during routine echocardiography. A conservative approach to cardiac treatment is advocated.     

Total parenteral nutrition in cancer patients

One hundred and twenty-one cancer patients received 134 courses of total parenteral nutrition (TPN); almost all were treated with chemotherapy and/or radiotherapy. The average weight loss prior to TPN was 6.7 kg and albumin 3.1 g%/patient; 25% glucose solution with 4.25 g% amino acids was used as a calorie and nitrogen source. The average weight gain was 2.6 kg for those who received TPN less than 2 wk and 4.5 kg if TPN was given for greater than 2 wk. Complications were low; 3% had proven TPN-related septicemia. Mild to moderate reversible metabolic complications were common, although severe complications were rare; no one died because of TPN. Our experience confirms the previous reports that TPN can be given safely to malnourished compromised cancer patients.     

Responses to the purr call in three areas of the guinea pig auditory cortex

Single electrodes were used to record from anaesthetized animals stimulated with a closed sound system. Neural responses to the purr call were very different in the dorsocaudal core field and in two long-latency belt areas, the ventrorostral belt and the dorsocaudal belt. Responses in the dorsocaudal core field were accurately timed to the start of the nine rhythmic pulses within the purr while the ventrorostral belt responses were more sustained and less temporally precise and most dorsocaudal belt units did not respond. These results are consistent with the separate processing of narrow-band tonal stimuli such as the purr by a ventrorostral pathway involving the primary auditory area and the ventrorostral belt but not by a dorsocaudal pathway from the dorsocaudal core field to the dorsocaudal belt area.