Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children's Cancer Group study.

PURPOSE: To investigate the intellectual outcomes of children with medulloblastomas/primitive neuroectodermal tumors (MB/PNET) treated with reduced-dose craniospinal radiotherapy (RT) plus adjuvant chemotherapy. PATIENTS AND METHODS: Forty-three children with average-risk posterior fossa MB/PNETs underwent longitudinal intelligence testing. All had been treated with a reduced-dose craniospinal RT regimen (23.4 Gy to the neuraxis, 32.4-Gy boost to the posterior fossa) and adjuvant chemotherapy. RESULTS: The estimated rate of change from baseline was significant for Full Scale Intelligence Quotient (FSIQ), Verbal IQ (VIQ), and Nonverbal IQ (NVIQ) (P <.001 for all three outcomes). The rate of change was estimated to be -4.3 FSIQ points per year, -4.2 VIQ points per year, and -4.0 NVIQ points per year. Females were more subject to VIQ decline than were males (P =.008), and young children (< 7 years of age) were more negatively affected than were older children, with a significant decline in NVIQ (P =.016). Finally, patients with higher baseline evaluations suffered greater declines in IQ than did those with lower baseline scores. CONCLUSION: This study represents the largest series of patients with average-risk MB/PNETs treated with a combination of reduced-dose RT and adjuvant chemotherapy whose intellectual development has been followed prospectively. Intellectual loss was substantial but suggestive of some degree of intellectual preservation compared with effects associated with conventional RT doses. However, this conclusion remains provisional, pending further research.     

Sexological Competence of Different Rehabilitation Disciplines and Effects of a Discipline-specific Sexological Training

Dealing with sexual problems due to disease or disability is part of medical rehabilitation, but both patients and professionals experience barriers to discuss sexual issues. A brief discipline-specific sexological training for rehabilitation professionals was therefore developed and evaluated in two rehabilitation centers in The Netherlands. Among the 283 participants were physicians (42), physical therapists (38), occupational therapists (40), psychologists and social workers (26), nurses (101), and other disciplines (36). Measurements before training, after training, and at 3–4 months follow-up showed increase of self-rated sexological competence and of scores on the Knowledge, Comfort, Approach, and Attitudes towards Sexuality Scale (KCAASS) during the training that were maintained at follow-up. Disciplines differed in sexual competence before training and in increase of sexual competence after training. Implementation of the training in other rehabilitation centers is recommended.     

Sub-cellular pathology of scrapie: coated pits are increased in PrP codon 136 alanine homozygous scrapie-affected sheep

Sub-cellular studies of transmissible spongiform encephalopathies (TSEs) have been carried out on several animal species and human beings. However, studies of optimal perfusion-fixed tissues have largely been confined to examination of rodents. Using a recently developed technique, heads of scrapie-affected sheep and controls were perfusion fixed with mixed aldehydes. The obexes were immunohistochemically labelled with PrP antibodies, and the dorsal motor nucleus of the vagal nerve was examined by electron microscopy. Irregular neuritic profiles with highly invaginated membranes, associated with coated pits were found in all scrapie-affected sheep, but not in controls. Interestingly, they were consistently more frequent in the homozygous A(136) sheep. This is the first report describing sub-cellular differences in pathology associated with different PrP genotypes. Rarely, amorphous material, or sparse fibrillar structures, were present in the extracellular space. The changes were often associated with irregular plasmalemma and frequent coated pits. Vacuolation typical of TSEs, dystrophic neurites and variable gliosis were present. Herniation of membranes and organelles from apparently healthy processes into adjacent vacuoles and dendrites was also observed. We suggest that the increase in coated pits and plasmalemma invagination is related to an attempted internalisation of aggregated disease-specific PrP, or protofilaments, from the extracellular space.     

Prior ibuprofen exposure does not augment opioid drug potency or modify opioid requirements for pain inhibition in total hip surgery

PURPOSE: In previous animal studies, a prior exposure to non-steroidal anti-inflammatory drugs (NSAID) augmented opioid drug potency. This study was designed to answer the question whether a similar effect can be attained in man. The objective was to use NSAID for preoperative pain reduction and at the same time use the NSAID exposure to reduce opioid requirements for pain inhibition in major orthopedic surgery. METHODS: In this double-blind, randomized study, 50 patients scheduled for total hip surgery were included. Patients of Group I received a placebo drug three times a day two weeks before surgery, and those allocated to Group II received ibuprofen (600 mg) three times a day. For surgical anesthesia, all patients received intrathecal bupivacaine 20 mg plus 0.1 mg morphine in a total volume of 4 mL. RESULTS: The preoperative or postoperative visual analogue scale pain scores or the amount of iv morphine showed no differences between the two groups in the first 24 hr after surgery. The median total blood loss in the ibuprofen group was 1161 mL vs 796 mL in the placebo group (P < 0.01). CONCLUSION: Pretreatment with ibuprofen before major hip surgery does not improve the pain scores or reduce morphine requirement but significantly increases blood loss. Considering the presence of relevant adverse effects, pretreatment with a non-selective NSAID is not recommended.     

Video-assisted mediastinal lymph node dissection assessed in an experimental setting

Background: Feasibility, completeness, and morbidity of videoscopic-assisted mediastinal lymph node dissection (VATS MLND) were compared to the standard surgical technique in an experimental study. Methods: Right upper MLND—together with upper lobectomy in half of the cases—was performed in ten large white pigs. Six animals were operated using VATS (group 1), four using conventional open techniques (group 2). After 1 week, the animals were sacrificed and the mediastinum was assessed for remaining lymph nodes. Results: All animals survived without intra- or post-operative complications. There was no significant difference in the operation time between the two groups (3.2±0.8 vs 3.2±0.2 h). The number of mediastinal lymph nodes harvested was 9.5±2.7 in group 1 and 11.5±0.5 in group 2 (n.s.). The post-mortem assessment of the mediastinum showed in two animals of group 1 and in two animals of group 2 that one lymph node was left behind. In addition, in one animal of group 1 four small retrotracheal lymph nodes were found. Conclusions: VATS MLND can be accomplished without morbidity and is as radical as that achieved with conventional surgery in the paratracheal and peribronchial areas in this experimental setting. However, retrotracheal lymph node dissection might not be as complete as achieved by conventional surgery.     

Early detection of breast cancer based on gene-expression patterns in peripheral blood cells

Introduction

Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells.

Methods

Using macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach.

Results

We identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients.

Conclusion

The results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding.     

An improved methodology for modeling neurobehavioral late-effects of radiotherapy in pediatric brain tumors

BACKGROUND: Technical advances in radiation oncology provide new opportunities to study neurobehavioral outcomes of radiation therapy (RT) in children treated for brain tumors. METHODS: In this study, we describe an approach to modeling late-effects using integral biologically effective dose (IBED) combined with improved measurement of critical neuropsychological functions. RESULTS: IBED was found to provide more differentiated information about dose distribution than prescribed dose in five subjects treated for brain tumors. Furthermore, IBED was more closely related than was prescribed dose to specific changes in Attention 2-3 years post-RT. CONCLUSIONS: Results support the feasibility of this methodology as well as promising preliminary evidence of the relationship of IBED to the construct of Attention. Improved modeling could lead to more refined radiation therapy protocols that preserve critical neuropsychological functions and also provide new insights into the treatment of neurobehavioral sequelae.