Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial.

PURPOSE: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, increases survival when combined with irinotecan-based chemotherapy in first-line treatment of metastatic colorectal cancer (CRC). This randomized, phase II trial compared bevacizumab plus fluorouracil and leucovorin (FU/LV) versus placebo plus FU/LV as first-line therapy in patients considered nonoptimal candidates for first-line irinotecan. PATIENTS AND METHODS: Patients had metastatic CRC and one of the following characteristics: age > or = 65 years, Eastern Cooperative Oncology Group performance status 1 or 2, serum albumin < or = 3.5 g/dL, or prior abdominal/pelvic radiotherapy. Patients were randomly assigned to FU/LV/placebo (n = 105) or FU/LV/bevacizumab (n = 104). The primary end point was overall survival. Secondary end points were progression-free survival, response rate, response duration, and quality of life. Safety was also assessed. RESULTS: Median survival was 16.6 months for the FU/LV/bevacizumab group and 12.9 months for the FU/LV/placebo group (hazard ratio, 0.79; P = .16). Median progression-free survival was 9.2 months (FU/LV/bevacizumab) and 5.5 months (FU/LV/placebo); hazard ratio was 0.50; P = .0002. Response rates were 26.0% (FU/LV/bevacizumab) and 15.2% (FU/LV/placebo) (P = .055); duration of response was 9.2 months (FU/LV/bevacizumab) and 6.8 months (FU/LV/placebo); hazard ratio was 0.42; P = .088. Grade 3 hypertension was more common with bevacizumab treatment (16% v 3%) but was controlled with oral medication and did not cause study drug discontinuation. CONCLUSION: Addition of bevacizumab to FU/LV as first-line therapy in CRC patients who were not considered optimal candidates for first-line irinotecan treatment provided clinically significant patient benefit, including statistically significant improvement in progression-free survival.     

Role of delayed enhancement MRI in patients with acute coronary syndrome and unobstructed coronary arteries: reply

We thank Coceani and L'Abbate for their comments on our paper.We concur that ‘pathophysiology cannot be inferred fromcoronary lumenography alone’, and this was one of thekey motivations in conducting the present study.     

Genetics of epilepsy: epilepsy research foundation workshop report.

The Sixth Epilepsy Research Foundation workshop, held in Oxford in March 2006, brought together basic scientists, geneticists, epidemiologists, statisticians, pharmacologists and clinicians to consider progress, issues and strategies for harnessing genetics to improve the understanding and treatment of the epilepsies. General principles were considered, including the fundamental importance of clear study design, adequate patient numbers, defi ned phenotypes, robust statistical data handling, and follow-up of genetic discoveries. Topics where some progress had been made were considered including chromosomal abnormalities, neurodevelopment, hippocampal sclerosis, juvenile myoclonic epilepsy, focal cortical dysplasia and pharmacogenetics. The ethical aspects of epilepsy genetics were reviewed. Principles and limitations of collaboration were discussed. Presentations and their matched discussions are produced here. There was optimism that further genetic research in epilepsy was not only feasible, but might lead to improvements in the lives of people with epilepsy.     

Deep vein thrombosis and pulmonary embolus associated with a ruptured popliteal aneurysm – a cautionary note

Popliteal artery aneurysms representing 80% of peripheral artery aneurysms rarely rupture (a reported incidence of 0.1–2.8 %) and second commonest in frequency after aorto-iliac aneurysms. They usually present with pain, swelling, occlusion or distal embolisation and can cause diagnostic difficulties. We report a 78 year old man who was previously admitted to hospital with a pulmonary embolus secondary to deep venous thrombosis. He was heparinized then warfarinised and was readmitted with a ruptured popliteal aneurysm leading to a large pseudo aneurysm formation. The pulmonary embolus had been due to popliteal vein thrombosis and propagation of the clot. A thorough review of literature identified only one previously reported case of ruptured popliteal artery aneurysm and subsequent large pseudo aneurysm formation. We feel it is important to exclude a popliteal aneurysm in a patient with DVT. This may be more common than the published literature suggests.     

Primary mesenteric venous thrombosis: a study from western India.

INTRODUCTION: The prevalence and clinical spectrum of mesenteric venous thrombosis (MVT) in India is largely unknown. METHODS: We retrospectively re-viewed the case records of patients with primary mesenteric venous thrombosis seen over a 10-year period and retrieved information on clinical picture, underlying hypercoagulable states and outcome. RESULTS: The 28 cases (mean age 41.2 [SD 10.2] years; 19 male) included 13 with acute MVT, 10 with subacute MVT and 5 with chronic MVT. Ten patients had past thromboembolic events (multiple events in five); four patients had isolated superior mesenteric vein involvement and 14 had multiple vessel involvement. Hypercoagulable state was identified in 17 patients, with multiple etiologies in 7 patients. Pre-operative diagnosis was made in all patients. Ten patients needed surgical management; the rest were managed medically initially, but 2 required surgery on follow up. Seven patients died during a follow up of up to 10 years, with in-hospital mortality during index admission in six. CONCLUSIONS: Most of the patients with MVT have multiple intra-abdominal vessel involvement and underlying hypercoagulable state. The policy of early treatment with anticoagulation in all and surgical treatment as per need, achieves low mortality.