Vascular endothelial growth factor D expression is a potential biomarker of bevacizumab benefit in colorectal cancer.

BACKGROUND: Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and receptors to determine their prognostic and predictive effects. METHODS: We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population. RESULTS: Patients with low expression of VEGF-D (0, 1þ) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CBþCBM), 0.21; 95% CI, 0.08­0.55; overall survival (OS) HR, 0.35; 95% CI, 0.13­0.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2þ PFS HR, 0.67; 95% CI, 0.45­1.00; OS HR, 0.82; 95% CI, 0.52­1.30; VEGF-D 3þ PFS HR, 0.77; 95% CI, 0.50­1.17; OS HR, 1.28; 95% CI, 0.79­2.09) (P interaction o0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression. CONCLUSIONS: The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation.

Docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophagogastric cancer: the AGITG ATTAX2 trial.

BACKGROUND: Cetuximab can reverse chemotherapy resistance in colorectal cancer. This study evaluated the efficacy and safety of the combination of docetaxel and cetuximab as a second-line treatment in docetaxel-refractory oesophagogastric cancer. METHODS: Patients received docetaxel 30 mg m(-2) on days 1 and 8, every 3 weeks and cetuximab 400 mg m(-2) on day 1, then 250 mg m(-2) weekly. Biomarker mutation analysis was performed. RESULTS: A total of 38 patients were enrolled. Response rates were PR 6% (95% CI 2-19%), s.d. 43% (95% CI 28-59%). Main grade 3/4 toxicities were febrile neutropenia, anorexia, nausea, diarrhoea, stomatitis, and acneiform rash. Median progression-free and overall survival were 2.1 and 5.4 months, respectively. A landmark analysis showed a trend to improved survival times with increased grade of acneiform rash. No KRAS, BRAF or PIK3CA mutations were observed. CONCLUSION: Cetuximab and docetaxel achieve modest responses rates, but maintain comparable survival times to other salvage regimens with low rates of toxicity.

Major lower intestinal haemorrhage. Angiographic localisation and current management.

Thirty-four patients with major lower intestinal bleeding underwent emergency selective mesenteric angiography during a 6-year period. Angiography identified a bleeding site in 16 patients (47%). Diverticulosis, found in 22 patients (65%), and angiodysplasia, found in 4 (12%), were the most common causes of major colonic bleeding and originated more frequently from the right colon. Eight patients (24%) bled from less common sources. Radiological control of bleeding was unreliable with a significant complication rate. Fourteen of 16 patients with positive angiograms and 6 of 18 patients with negative angiograms required surgery for persistent major bleeding. Angiographic localisation of colonic bleeding allowed limited resection in 9 of 11 patients with control of haemorrhage in 8 (89%). Fourteen of 34 patients were managed non-operatively; of these 2 had minor recurrent bleeding. The overall mortality rate was 29%, the operative mortality rate 40% and the non-operative mortality rate 14%. A rational diagnostic approach is presented, emphasising the role of selective mesenteric angiography in the management and surgical strategy of major lower intestinal bleeding.

Trends in cardiac surgery at the University of Cape Town, 1971-1981.

A review has been undertaken of the number and types of surgical procedures performed in the Department of Cardiac Surgery of the University of Cape Town during the 11-year period 1971-1981, together with data on associated mortality. A yearly average of 560 operations was carried out, of which 75% were for acquired and 25% for congenital heart disease. The number of patients treated continues to rise, from 434 in 1971 to 690 in 1981. There has been a slight reduction in the overall average yearly mortality, from 6.1% between 1971 and 1975 to 5.0% between 1976 and 1981. There was a significant increase in the number of valve replacements in 1975 and 1976 and a more recent, continuing increase in operations for ischaemic heart disease, which now form 19% of the total operations. In both these groups the average yearly mortality has fallen during the period of study. The number of operations each year for congenital heart disease has remained fairly constant, but, disappointingly, there has been no significant reduction in mortality.