Radiotherapy as an adjuvant in the management of intracranial meningiomas: are we practising evidence-based medicine?

Although increasingly used, the precise role of radiotherapy in the management of meningiomas is still disputed. The objective of this study, therefore, was to appraise the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, and to compare and contrast it with the current opinion and practice of neurosurgeons in the United Kingdom and the Republic of Ireland. The use of radiotherapy as a primary treatment strategy or its use in the treatment of recurrence was not considered. We performed a systematic review of the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, surveyed current opinion amongst neurosurgeons involved in such cases and ascertained local practice using data from the regional cancer registry. Overall, 10 cohorts were identified that fulfilled our eligibility criteria. Four studies showed significantly improved local control in patients receiving adjuvant radiotherapy for incompletely resected grade I meningiomas. Our survey demonstrated that the vast majority (98%) of neurosurgeons would not recommend adjuvant radiotherapy in grade I meningioma. In grade II meningioma, most (80%) would not advocate adjuvant radiotherapy if completely excised, but the majority (59%) would recommend radiotherapy in cases of subtotal resection. Significant variation in opinion between centres exists, however, particularly in cases of completely resected atypical meningiomas (p = 0.02). Data from the Eastern Cancer Registration and Information Centre appears to be in line with these findings: less than 10% of patients with grade I meningiomas, but almost 30% of patients with grade II meningiomas received adjuvant radiotherapy in the Eastern region. In conclusion, our study has highlighted significant variation in opinion and practice, reflecting a lack of class 1 evidence to support the use of adjuvant radiotherapy in the treatment of meningiomas. Efforts are underway to address this with a randomized multicentre trial comparing a policy of watchful waiting versus adjuvant irradiation.

The surgical management of metastatic spinal disease: prospective assessment and long-term follow-up.

The last decade has witnessed a resurgence of interest in the surgical treatment of metastatic spinal disease to compliment radiotherapy. A recent randomized controlled trial looking directly at this issue concluded strongly in favour of a combination of surgical decompression and radiotherapy, and there is now growing enthusiasm for surgery to play a role in the management of these patients. We present a prospective cohort study of 62 patients who presented with metastatic cord or cauda equina compression, and were treated with surgical decompression and fixation where necessary. Patients were treated by one surgeon working in a single unit. They were followed-up long term and were assessed objectively, by clinical assessment and prospective questionnaires that included SF36, visual analogue pain scores and Roland Morris back pain scores. Sixty-two patients with a median age of 62 (22-79 years, 27 male) were included in the study. The commonest primary tumours were breast (26%) and lymphoma (13%). The majority of patients had involvement of thoracic vertebrae (58%). 56% of patients were alive at 1 year and 28% at 3 years, with significant improvements observed in both walking and continence. Similarly, significant improvements were seen in SF36 quality of life scores as well as pain. With careful patient selection, long-term survival and good quality of life can be achieved. However, not every patient is suitable or appropriate for surgery, and the discussion focuses on where the surgical threshold should be set.

Laminectomy for lumbar canal stenosis: a safe and effective treatment.

Lumbar canal stenosis (LCS) is a common condition affecting elderly patients for which a significant number undergo surgery. The validity and safety of simple laminectomy in this condition is not fully understood. Furthermore, the presence of pre-existing spondylolisthesis is controversial with respect to the need for additional spinal stabilization. We prospectively studied a consecutive cohort of 100 patients with clinical and radiological LCS under the care of a single spinal surgeon. Outcome measures (SF-36, visual analogue scores for back and leg symptoms, and the Roland/Morris back pain scores) were assessed preoperatively, 3 months postsurgery and at long-term (median 2 years) follow-up. We have shown a significant improvement in outcome sustained in the long-term with minimal morbidity. Patients with pre-existing spondylolisthesis accounted for 23% of the cohort and, having received identical treatment, showed no significant difference in outcome compared with patients with normal alignment.

Improving the health profile: decreasing risk for cancer through primary prevention.

Cancer is the second leading cause of death among adults in the United States. Trends indicate that the incidence of all cancers has increased since 1973. It is currently estimated that 1 in 3 Americans now living will develop the disease. Cancer accounts for 11% of all health care costs, and its devastating physical and emotional consequences are far reaching. Despite these grim statistics, there is hope for decreasing this huge burden. Nearly two thirds of all cancers are related to life style choices, such as tobacco use, dietary factors, and exercise; therefore, the opportunity exists to reduce cancer risk greatly. The article presents an overview of major cancers and strategies for primary prevention of those cancers that are most amenable to risk reduction.

NMR structure determination of tick anticoagulant peptide (TAP).

Tick anticoagulant peptide (TAP) is a potent and selective 60-amino acid inhibitor of the serine protease Factor Xa (fXa), the penultimate enzyme in the blood coagulation cascade. The structural features of TAP responsible for its remarkable specificity for fXa are unknown, but the binding to its target appears to be unique. The elucidation of the TAP structure may facilitate our understanding of this new mode of serine protease inhibition and could provide a basis for the design of novel fXa inhibitors. Analyses of homo- and heteronuclear two-dimensional NMR spectra (total correlation spectroscopy, nuclear Overhauser effect spectroscopy [NOESY], constant time heteronuclear single quantum correlation spectroscopy [CT-HSQC], and HSQC-NOESY; 600 MHz; 1.5 mM TAP; pH 2.5) of unlabeled, 13C-labeled, and 15N-labeled TAP provided nearly complete 1H sequence-specific resonance assignments. Secondary structural elements were identified by characteristic NOE patterns and D2O amide proton-exchange experiments. A three-dimensional structure of TAP was generated from 412 NOESY-derived distance and 47 dihedral angle constraints. The structural elements of TAP are similar in some respects to those of the Kunitz serine protease inhibitor family, with which TAP shares weak sequence homology. This structure, coupled with previous kinetic and biochemical information, confirms previous suggestions that TAP has a unique mode of binding to fXa.