Cerebellar pilocytic astrocytoma in adults: a management paradigm for a rare tumour

Background

Pilocytic astrocytoma is one of the commonest subtypes of glioma to affect children. However, they are rarely diagnosed in patients over the age of 18 years. In adults, these tumours appear more frequently supra-tentorially than in the cerebellum and some reports suggest a different clinical course in adults. We reviewed ten patients aged 18 or over who had been operated on for cerebellar pilocytic astrocytoma to assess the impact of tumour biology and extent of resection on outcome in adults.

Method

Patients were identified from a neuropathology database and a retrospective chart review of ten patients was performed. Recorded data included patient demographics, tumour location, presenting features, radiological appearance, extent of surgical resection, tumour recurrence and Ki-67 proliferation index.

Results

Nine patients were men and one patient was a woman. Median follow up is 41.5 months (range 15–334 months). Complete surgical resection was achieved in nine of the patients operated in our institution. One patient had prior subtotal resection elsewhere. Tumour recurrence was seen only in the two patients with subtotal resection, at 7 and 25 years. Ki-67 ranged from <1 to 10 % and appears to have no correlation to recurrence. No patients in this series had adjuvant treatment.

Conclusions

Cerebellar pilocytic astrocytomas in adults should be treated with macroscopic complete surgical resection whenever possible. If this is achieved, long-term survival rates are excellent, whereas subtotal resection carries a high risk of tumour recurrence. Ki-67 is less important prognostically than the extent of initial resection.     

An update of the role of nutritional therapy in the management of Crohn’s disease

Crohn's disease is an increasingly global health concern. Currently without a cure, it significantly alters the quality of life of Crohn's disease sufferers and places a heavy financial burden on the community. Recent reports show that the rising prevalence of Crohn's disease is no longer confined to Western countries, with considerable increases seen particularly in Asia. Nutritional problems are often associated with Crohn's disease, most notably in the paediatric population, with underweight and stunting commonly seen at presentation. In addition, linear growth retardation and pubertal delay can also manifest in these younger patients. Therefore, exclusive enteral nutrition has been used as a therapeutic option to treat Crohn's disease, in part to address the nutritional complications of the disease. Exclusive enteral nutrition can improve nutrition as well as induce remission at a rate equivalent to corticosteroids. It is safe particularly with long-term use and can induce mucosal healing, considered the gold standard for therapy, at a rate superior to corticosteroids. Exclusive enteral nutrition has thus become the preferred therapeutic option in many centres for the treatment of paediatric Crohn's disease. This review discusses the role of exclusive enteral nutrition as a therapeutic option for the treatment of Crohn's disease, as well as the latest findings into its mechanisms of action.     

Vagal nerve stimulation in children under 12 years old with medically intractable epilepsy

Objective

This study aims to assess the efficacy and safety of vagal nerve stimulation (VNS) in children less than 12 years old operated on at the University Hospital Wales.

Method

Retrospective review of patients undergoing VNS insertion, over a 3-year period, was undertaken. All children had a minimum follow-up period of 2 years. Sixteen patients were identified via the paediatric epilepsy surgery database. A case note review and telephone evaluation was conducted. Seizure frequency using the McHugh classification was the primary outcome measure, with anti-epileptic drug (AED) use as a secondary outcome measure.

Results

There were 10 males and 6 females. The mean time with epilepsy prior to surgery was 5.7 years and the mean age at the time of surgery was 7.6 years. Overall, nine (56 %) children experienced a reduction in their seizure frequency of 50 % or more. Of these, four (25 %) had a reduction of more than 80 %. Seven children (44 %) had no reduction in their seizure frequency, although two of these patients reported benefit regarding seizure control and post-ictal recovery. The VNS system was removed in two patients due to infection and no benefit, respectively. Half of the cohort (50 %) reduced the number of anti-epileptic drugs post-surgery, and there was an overall mean reduction of AED of 0.5.

Conclusion

This study suggests that VNS is a safe and effective adjuvant therapy in children under 12 years old, with over half reporting significant benefit. Further studies are needed to enable preoperative selection of patients in order to maximise the potential benefit.     

Anterior cervical discectomy plus intervertebral polyetheretherketone cage fusion over three and four levels without plating is safe and effective long-term

Anterior cervical discectomy and fusion (ACDF) is an established treatment for single-level cervical spondylotic myelopathy and radiculopathy, yet its stand-alone use for multi-level disease of the subaxial cervical spine remains controversial. We report a prospectively studied case series of 30 patients receiving polyetheretherketone (PEEK) cage fusion over three and four cervical levels without anterior plating. Seven (23.3%) four-level procedures (all C3 to C7) were performed, the other 23 (76.7%) being three-level, with 19 (64.4%) at C4 to C7 and four (12.3%) at C3 to C6. Long-term follow-up of more than 2 years was available in 67% of patients. This cohort showed statistically significant improvements in visual analogue score for neck pain (p = 0.0006), arm pain (p = 0.0003) and Japanese Orthopaedic Association myelopathy score (p = 0.002). Fused segment heights increased by 0.6–1.1%. Adjacent segment disease requiring ACDF at C3–4 was seen in 6.7% of patients (one after trauma) at a mean follow-up of 62 months. Same segment recurrence requiring posterior decompression with instrumented fusion was found in 10% of patients at a mean follow-up of 49 months, only one of whom had radiological evidence of cage subsidence. The results suggest the procedure is safe and effective with potentially less morbidity than anterior plating, shorter inpatient stays than posterior approaches, acceptable same segment recurrence and lower than predicted adjacent segment disease rates.     

Shapes of early change in psychotherapy under routine outpatient conditions

Although improvement of clients' state is a central concern for psychotherapy, relatively little is known about how change in outcome variables unfolds during psychotherapy. Client progress may follow highly variable temporal courses, and this variation in treatment courses may have important clinical implications. By analyzing treatment progress using growth mixture modeling up to the 6th session in a sample of 192 outpatients treated under routine clinic conditions, the authors identified 5 client groups based on similar progress on the short form versions of the Clinical Outcomes in Routine Evaluation-Outcome Measure. The shapes of early change typical for these client groups were characterized by (a) high initial impairment, (b) low initial impairment, (c) early improvement, (d) medium impairment with continuous treatment progress, or (e) medium impairment with discontinuous treatment progress. Moreover, the shapes of early change were associated with different treatment outcomes and durations, and several intake variables (depression, anxiety, and age) enabled prediction of the shape of early change and/or prediction of individual treatment progress within client groups with similar shapes of change.     

Administration of an antagonist of neurokinin receptors 1, 2, and 3 results in reproductive tract changes in beagle dogs, but not rats

SCH 206272, an antagonist of neurokinin receptors 1, 2, and 3, was administered orally by gavage for 1 month to 8- to 10-month-old dogs at doses of 0, 15, 30, or 60 mg/kg, and to 6-week-old rats at doses of 0, 30, 100, or 300 mg/kg. The most important changes occurred in the reproductive tract of the dogs at all doses. Absolute and relative group mean organ weights for the testes, prostate gland, epididymides, ovaries, and uterus were 33-86% lower than concurrent controls in groups receiving SCH 206272. Organ weight changes were not dose-related. Microscopic changes that correlated with the organ weight changes occurred in all groups receiving SCH 206272. For males, they included minimal to severe atrophy of the testes, epididymides, and prostate gland. In addition, the epididymides exhibited severe oligospermia or aspermia, minimal epithelial apoptosis and mild epithelial vacuolation. In female dogs, the ovaries and uteri appeared immature. Microscopic changes were similar in incidence and severity in dogs receiving 30 or 60 mg/kg, but were slightly less in dogs receiving 15 mg/kg. In contrast, similar findings were not observed in the reproductive tract of male or female rats, despite overlapping systemic, hypothalamic, and pituitary gland concentrations of SCH 206272.     

A histological survey of green fluorescent protein expression in 'green' mice: implications for stem cell research

AIMS: The transgenic enhanced green fluorescent protein (EGFP) expressing 'green' mouse (C57BL/6-TgN(ACTbEGFP)1Osb) is a widely used tool in stem cell research, where the ubiquitous nature of EGFP expression is critical to track the fate of single or small groups of transplanted haematopoietic stem cells (HSC). Our aim was to investigate this assumed ubiquitous expression by performing a detailed histological survey of EGFP expression in these mice. METHODS: Fluorescent microscopy of frozen tissue sections was used to perform a detailed histological survey of the pattern of EGFP expression in these mice. Flow cytometry was also used to determine the expression pattern in blood and bone marrow. RESULTS: Three patterns of EGFP expression were noted. In most tissues there was an apparently stochastic variegation of the transgene, with individual cell types demonstrating highly variable rates of EGFP expression. Certain specific cell types such as pancreatic ductal epithelium, cerebral cortical neurones and glial cells and glomerular mesangial cells consistently lacked EGFP expression, while others, including pancreatic islet cells, expressed EGFP only at extremely low levels, barely distinguishable from background. Lastly, in the colon and stomach the pattern of EGFP expression was suggestive of clonal inactivation. Only cardiac and skeletal muscle showed near ubiquitous expression. CONCLUSIONS: These findings raise questions regarding the 'ubiquitous' expression of EGFP in these transgenic mice and suggest caution in relying overly on EGFP alone as an infallible marker of donor cell origin.     

Reproducibility of reference tissue quantification of dynamic contrast-enhanced data: comparison with a fixed vascular input function

Reference tissues are currently used to analyse dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data. The assessment of tumour response to treatment with anti-cancer drugs is a particularly important application of this type of analysis and requires a measure of reproducibility to define a level above which a significant change due to therapy can be inferred. This study compares the reproducibility of such quantification strategies with that found using a published, group-averaged uptake curve. It is shown that reference tissue quantification gives poorer reproducibility for most parameters than that found using a group-averaged plasma curve (a change in K(trans) of greater than 41.8% and 16.4% would be considered significant in the two approaches, respectively), but successfully incorporates some of the variability observed in plasma kinetics between visits and provides vascular input functions that, across the group, are comparable with the group-averaged curve. This study therefore provides an indirect validation of the methodology.