The histologic grade is a main prognostic factor for patients with intracranial ependymomas treated in the microneurosurgical era: an analysis of 258 patients

BACKGROUND: Ependymomas account for 3-5% of all intracranial malignancies and occur most often in children and young adults. These neoplasms continue to generate considerable controversy with regard to their rational clinical management. It has been shown that the histologic classification of ependymoma is a significant predictor of clinical outcome in patients with ependymoma. METHODS: Ependymomas from 258 patients who underwent microsurgery at a single institution were evaluated histologically to elucidate the prognostic utility of a recently proposed grading scheme. Pathologic and clinical data then were compared using univariate and multivariate analyses. RESULTS: Increasing grade of ependymoma malignancy was found to be associated strongly and independently with worse clinical outcomes in terms of both event-free survival and overall survival. The effect of radiotherapy also was found to be related to histologic grade and was more beneficial for patients who had anaplastic ependymomas and had undergone complete tumor removal. CONCLUSIONS: The application of a uniform diagnostic criteria for grading ependymomas highlighted the key role of tumor histology in clinical outcome in a cohort of patients who were treated in the microsurgical era. The recently proposed grading scheme is likely to be practically useful, reproducible, and clinically applicable.     

Consequences of a short pulse of pesticide exposure for survival and reproduction of Gammarus pulex

The aim of the present study was to examine the effects of a short and environmentally realistic pulse exposure of different life stages of the freshwater amphipod, Gammarus pulex, to the pyrethroid insecticide, esfenvalerate. We were particularly interested in determining the extent to which detectable effects on key life-history traits persisted following cessation of a brief exposure to this pesticide. Our results indicate that environmentally realistic exposure concentrations of this widely used insecticide can have a significant effect on the survival and reproduction of Gammarus pulex. Comparison of LC(50) values indicates that G. pulex has a similar sensitivity to esfenvalerate as the standard test invertebrate, Daphnia magna and is more sensitive than other common stream invertebrates. Despite 100% survival during pulses of up to 2 microg l(-1), mortality increased, in some cases markedly, following transfer to clean conditions. Pulse exposure to esfenvalerate at concentrations in the range 0.1-0.6 microg l(-1) for as little as 1h can have effects on G. pulex survival, pairing behaviour, and reproductive output that can still be detected at least 2 weeks following the pulse. Reproductive traits were very sensitive to esfenvalerate, and exposure to 0.05 microg l(-1) for 1h led to immediate disruption of reproducing pairs, release of eggs or offspring from the brood pouch, and substantial delays in pair formation and subsequent reproduction following transfer to clean water. The kinds of effects on reproductive behaviour observed in this study could potentially impact the population dynamics of G. pulex in the field. Whether such effects occur will depend on the frequency, duration, timing, and spatial extent of pesticide exposure in freshwater stream ecosystems, about which relatively little is known. Such information is essential if effects on non-target aquatic species are to be more accurately assessed.     

Modified radical vaginal hysterectomy with or without laparoscopic nerve-sparing dissection: a comparative study

OBJECTIVE: Nerve-sparing dissection of the lateral portion of the cardinal ligament (paracervical lymphadenectomy) has been recently developed with the goal of reducing the late urinary adverse effects of radical hysterectomy without impairing the outcome. This work has been carried out in order to investigate the influence of additional paracervical lymph node dissection at the time of laparoscopically assisted modified radical hysterectomy on outcome and urinary sequelae. METHODS: A total of 95 patients underwent a modified radical hysterectomy using a combined laparoscopic and vaginal approach since 1991. In 47 of these patients treated since 1996 an additional laparoscopic paracervical lymphadenectomy was performed. The operative, postoperative, and survival outcomes were assessed. In 60 patients, 32 and 28 in the groups of patients with or without paracervical dissection, respectively, a careful interview on urinary symptoms was conducted by an independent investigator. RESULTS: Paracervical dissection involves no operative complication and lenghthens the postoperative urinary retention, but has no adverse influence on long-term urinary discomfort. The yield of paracervical dissection is negligible for small tumors: no positive node was found in 38 patients with tumors less than 2 cm in diameter. The outcome of patients after minimal access surgery for tumors less than 2 cm is excellent whether or not a paracervical dissection has been performed. CONCLUSION: Paracervical dissection does not worsen the late urinary symptoms after vaginal radical hysterectomy. It has a limited value in the surgical management of small-size (less than 2 cm) cervical cancers, although it may prevent long-term lateropelvic recurrences.     

DNA methylation as an etiologic factor in carcinogenesis

The paper presents current data on theepigenetic regulation of gene expression in malignant tumors. Methylation of CpG islands in the gene promoter regions not accompanied by DNA structural changes leads to gene inactivation. The analytical methods of DNA methylation are described in detail. Methylation of certain genes in different tumor types are examplified. Since methylation is an early marker of carcinogenesis, there is an opportunity of elaborating of prospective diagnostic protocols.     

Retroperitoneal leiomyosarcoma and enlarged epididymis associated with a positive pregnancy test

A 57-year-old man presented with a 1-month history of progressive abdominal pain and weight loss. A palpable, nonpulsatile, firm abdominal mass was felt below the xiphisternum down to the pelvis. A pregnancy test performed on a urine sample was positive. Testicular examination and testicular ultrasound were normal. Computerized tomography of the abdomen revealed a retroperitoneal mass measuring 30 x 21 x 13 cm. Serum beta-human chorionic gonadotropin (beta-HCG) was serially increased (19.71-22.71 mIU/mL). Results of histopathology tests confirmed the diagnosis of leiomyosarcoma. The level of serum beta-HCG decreased to < 0.2 mlU/mL after chemotherapy. Beta-HCG is usually increased in germ-cell tumors but few reports in the literature describe beta-HCG-secreting leiomyosarcomas. The incidence of increased levels of beta-HCG in sarcomas in general, and its potential role as a tumor marker, is not known. A simple urine pregnancy test may be done in the work-up of abdominal masses.     

Breast cancer revisited using DNA array-based gene expression profiling

Breast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The resulting clinical heterogeneity makes current diagnostic and therapeutic strategies less than perfectly adapted to each patient. Pathological and clinical factors are insufficient to capture the complex cascade of events that drive the clinical behavior of tumors. High-throughput molecular technologies provide novel tools to tackle this complexity. In particular, DNA arrays allow the simultaneous and quantitative analysis of the mRNA expression levels of thousands of genes in a single assay. Potential applications are multiple in the cancer field and the first research results are promising; comprehensive gene expression profiles of breast tumors are providing insights into mammary oncogenesis and are revealing new tumor subgroups previously indistinguishable. Significant advances will be the identification of new diagnostic, prognostic and predictive biomarkers as well as the discovery of new potential therapeutic targets. This review presents recent applications of DNA arrays in breast cancer research and discusses some issues to address in the near future to allow the technology to reach its full potential.     

Direct Evidence That Polysorbate-80-Coated Poly(Butylcyanoacrylate) Nanoparticles Deliver Drugs to the CNS via Specific Mechanisms Requiring Prior Binding of Drug to the Nanoparticles

Purpose. It has recently been suggested that the poly(butylcyanoacrylate) (PBCA) nanoparticle drug delivery system has a generalized toxic effect on the blood-brain barrier (BBB) (8) and that this effect forms the basis of an apparent enhanced drug delivery to the brain. The purpose of this study is to explore more fully the mechanism by which PBCA nanoparticles can deliver drugs to the brain. Methods. Both in vivo and in vitro methods have been applied to examine the possible toxic effects of PBCA nanoparticles and polysorbate-80 on cerebral endothelial cells. Human, bovine, and rat models have been used in this study. Results. In bovine primary cerebral endothelial cells, nontoxic levels of PBCA particles and polysorbate-80 did not increase paracellular transport of sucrose and inulin in the monolayers. Electron microscopic studies confirm cell viability. In vivo studies using the antinociceptive opioid peptide dalargin showed that both empty PBCA nanoparticles and polysorbate-80 did not allow dalargin to enter the brain in quantities sufficient to cause antinociception. Only dalargin preadsorbed to PBCA nanoparticles was able to induce an antinociceptive effect in the animals. Conclusion. At concentrations of PBCA nanoparticles and polysorbate-80 that achieve significant drug delivery to the brain, there is little in vivo or in vitro evidence to suggest that a generalized toxic effect on the BBB is the primary mechanism for drug delivery to the brain. The fact that dalargin has to be preadsorbed onto nanoparticles before it is effective in inducing antinociception suggests specific mechanisms of delivery to the CNS rather than a simple disruption of the BBB allowing a diffusional drug entry.     

Stroke surveillance: population-based estimates and projections for New Zealand

OBJECTIVE: To estimate the incidence, prevalence and mortality of stroke in New Zealand (NZ) in 2001, projected to 2011. METHODS: Multistate lifetable models were constructed using smoothed rates of first-ever stroke incidence and relative risks of mortality estimated from the most recent Auckland Regional Community Stroke (ARCOS) Study. Estimates of the burden of stroke in NZ were calculated by applying rates output by the model to the 2001 population. Stroke incidence, prevalence and mortality were then projected to 2011, assuming similar trends in stroke incidence and case fatality to those estimated between the 1991/92 and 2002/03 studies. RESULTS: A total of 5,200 first-ever strokes were estimated to have occurred in NZ in 2001. Rates of stroke rose exponentially with increasing age and were 20% higher among males than females at most ages. Nevertheless, the lifetable risk of stroke was lower for males (16%) than females (18%). On average, males survived a year longer than females after a first-ever stroke (9.0 vs. 8.2 years). The incidence rates of first-ever stroke declined by approximately 1% per year between 1991 and 2003. The lifetable risk of stroke remained stable for females but increased for males (from 14% to 16%) over this period. Stroke prevalence also increased by approximately 1% per year, whereas stroke-related mortality fell by 4% per year. If these trends continue, approximately 6,000 first-ever strokes (2% annual increase), 45,000 stroke survivors (2% annual increase) and 2,000 stroke-related deaths (1% annual decline) are expected in 2011. CONCLUSION: Stroke mortality is falling faster than stroke incidence. This, together with population growth and ageing, will lead to a rising burden of stroke-related disability over the next decade.