SummaryBackgroundStents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy.MethodsThe International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470.FindingsThe trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4·0%) events of disabling stroke or death in the stenting group compared with 27 (3·2%) events in the endarterectomy group (hazard ratio [HR] 1·28, 95% CI 0·77–2·11). The incidence of stroke, death, or procedural myocardial infarction was 8·5% in the stenting group compared with 5·2% in the endarterectomy group (72 vs 44 events; HR 1·69, 1·16–2·45, p=0·006). Risks of any stroke (65 vs 35 events; HR 1·92, 1·27–2·89) and all-cause death (19 vs seven events; HR 2·76, 1·16–6·56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0·0197).InterpretationCompletion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.FundingMedical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union.

No abstract

The provision of acute surgical care in the public sector is becoming increasingly difficult because of limitation of resources and the unpredictability of access to theatres during the working day. An acute-care surgical service was developed at the Prince of Wales Hospital to provide acute surgery in a more timely and efficient manner. A roster of eight general surgeons provided on-site service from 08.00 to 18.00 hours Monday to Friday and on-call service in after-hours for a 79-week period. An acute-care ward of four beds and an operating theatre were placed under the control of the rostered acute-care surgeon (ACS). At the end of each ACS roster period all patients whose treatment was undefined or incomplete were handed over to the next rostered ACS. Patient data and theatre utilization data were prospectively collected and compared to the preceding 52-week period. Emergency theatre utilization during the day increased from 57 to 69%. There was a 11% reduction in acute-care operating after hours and 26% fewer emergency cases were handled between midnight and 08.00 hours. There was more efficient use of the entire theatre block, suggesting a significant cultural change. Staff satisfaction was high. On-site consultant-driven surgical leadership has provided significant positive change to the provision of acute surgical care in our institution. The paradigm shift in acute surgical care has improved patient and theatre management and stimulated a cultural change of efficiency.

Imprint cytology is simple and rapid, and has good sensitivity for macrometastases. The significance of poor sensitivity for micrometastases will be determined by trials investigating their natural history.

Hypomagnesemia after total thyroidectomy has not been studied extensively. Our anecdotal experience suggests that it may be important in some patients after thyroid excision. The hypomagnesemic hypocalcemic syndrome has been described in other disease states in which a state of functional hypoparathyroidism exists. This study was designed to determine the incidence of hypomagnesemia after total thyroidectomy and relate it to hypocalcemia and symptoms during the postoperative period. A prospective study of all patients undergoing total thyroidectomy between September 1994 and July 1996 was performed. Patient data, thyroid function, retrosternal extension, initial versus reoperative surgery, operative details, parathyroid resection, and pathology were recorded. Calcium, magnesium, electrolytes, blood count, liver function tests, and albumin were measured prior to surgery and twice daily during the postoperative period. Fifty patients underwent total thyroidectomy: 68% were hypocalcemic, 72% were hypomagnesemic, and 36% were symptomatic during the postoperative period. Hypomagnesemia and gender were associated with hypocalcemia. Volume of fluid and neck dissection were associated with low magnesium levels. Hypomagnesemia and parathyroid resection were risk factors for symptoms after thyroidectomy. No patients developed permanent hypoparathyroidism. Transient hypocalcemia and hypomagnesemia occur frequently after total thyroidectomy. The etiology of this phenomenon is probably multifactorial. Patients are more likely to be symptomatic when both cations are low, and attempting to correct only hypocalcemia may prolong symptoms. It is important to monitor both calcium and magnesium levels after total thyroidectomy and to correct deficiencies to facilitate prompt resolution of symptoms.

Activation of the PI3K/PTEN/Akt/mTOR pathway is implicated both in the pathogenesis of malignancies and development of resistance to anticancer therapies. Therefore, PI3K/Akt/mTOR inhibitors are a promising therapeutic option, in association with systemic cytotoxic and biological therapies, to enable sustained clinical outcomes in cancer treatment. Therapeutic strategies could be tailored according to appropriate biomarkers and patient-specific mutation profiles to maximise benefit of combination therapies.

Purpose: Reactivation of p53 tumor suppressor activity in diseases such as soft-tissue sarcoma is considered an attractive means of targeted therapy. By systematically assessing alterations affecting the p53 pathway, we aimed to (a) classify sarcoma subtypes, (b) define a potential role in malignancy, and (c) identify potential patient biomarkers in this heterogeneous disease.Experimental Design: We have mapped mutational events in a panel of 192 benign or malignant bone and soft-tissue sarcomas. Analyses included TP53 and CDKN2A mutational and SNP status, MDM2 and MDM4 amplification and MDM2 SNP309 status.Results: We found an inverse relationship between MDM2 amplification and TP53 mutations, with a predominantly wild-type CDKN2A background. A high rate of point mutations in TP53 was observed uniquely in leiomyosarcoma, osteosarcoma, and MFH. Both MDM2 and MDM4 were also amplified in a subtype-specific manner, which was frequently seen as a coamplification event. We have also analyzed the risk allele frequencies for MDM2 SNP309, and show that the G allele was strongly associated with both liposarcomas and MDM2 amplification.Conclusions: Our data emphasize the critical role of p53 inactivation in sarcomagenesis, whereby different pathway alterations may be related to the heterogeneity of the disease. Moreover, we observed a strong association of malignancy with TP53 mutation, or MDM2 amplification and the presence of a G allele in SNP309, especially in lipoma versus liposarcoma. We propose, therefore, that MDM2 markers along with TP53 sequencing should be considered as patient biomarkers in clinical trials of sarcomas using MDM2 antagonists. Clin Cancer Res; 17(3); 416-26. Ó2010 AACR.

BackgroundThe aetiological role of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC.MethodsCase-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR).ResultsFrom all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20). Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91).ConclusionsUncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.