Venous thromboembolism in oesophago-gastric carcinoma: incidence of symptomatic and asymptomatic events following chemotherapy and surgery.

Venous thromboembolism (VTE) is a frequent cause of morbidity and mortality in patients with cancer and those having chemotherapy. However, the incidence of VTE during radical treatment for patients with oesophago-gastric cancer is poorly documented. The incidence of VTE was assessed in 200 consecutive patients with oesophago-gastric cancer having surgery with curative intent; 132 (66%) had neo-adjuvant chemotherapy, 37 (18.5%) had adjuvant chemotherapy and 64 (32%) had no chemotherapy. Patients received 40 mg of Enoxaparin subcutaneously daily during the peri-operative hospital stay. Asymptomatic VTE were detected by routine chest computed tomography (CT) pre and post surgery. Symptomatic patients with suspected VTE were investigated and treated as clinically appropriate. Twenty six patients (13%) developed VTE of which 14 (54%) were symptomatic; 12/26 (46%) VTE were detected pre-operatively, all during or after neo-adjuvant chemotherapy, and 14/26 (54%) post-operatively. There were two post-operative deaths caused by pulmonary emboli occurring at days 24 and 56 respectively despite peri-operative VTE prophylaxis. Multivariate analysis demonstrated that neo-adjuvant chemotherapy was the only factor that predicted pre-operative VTE (p = 0.073) and any VTE (p = 0.045). This study found a 13% incidence of VTE in patients undergoing therapy with curative intent for oesophago-gastric cancer and a statistically significant association between neo-adjuvant chemotherapy and VTE. Half of the patients with VTE were asymptomatic but two had fatal PE's. Current VTE prophylaxis regimens for this patient group may be inadequate.

Thrombin generation by apoptotic vascular smooth muscle cells.

Thrombin activation requires assembly of a prothrombinase complex of activated coagulation factors on an anionic phospholipid surface, classically provided by activated platelets. We have previously shown that anionic phosphatidylserine is exposed by rat vascular smooth muscle cells (VSMCs) undergoing apoptosis after serum withdrawal. In this study, using a chromogenic assay, we have shown thrombin generation by apoptotic VSMCs expressing c-myc (VSMC-myc) with an area under the thrombin-generation curve (AUC) of 305 +/- 17 nmol x min/L and a peak thrombin (PT) of 154 +/- 9 nmol/L. The thrombin-generating potential of the apoptotic VSMC-myc cells was greater than that of unactivated platelets (P = .003 for AUC; P = .0002 for PT) and similar to calcium-ionophore activated platelets (AUC of 332 +/- 15 nmol x min/L, P = .3; PT of 172 +/- 8 nmol/L, P = .2). Thrombin activation was also seen with apoptotic human VSMCs (AUC of 211 +/- 8 nmol x min/L; PT of 103 +/- 4 nmol/L) and was inhibited by annexin V (P < .0001 for AUC and PT). VSMC-myc cells maintained in serum generated less thrombin than after serum withdrawal (P = .0002 for AUC and PT). VSMCs derived from human coronary atherosclerotic plaques that apoptose even in serum also generated thrombin (AUC of 260 +/- 2 nmol x min/L; PT of 128 +/- 4 nmol/L). We conclude that apoptotic VSMCs possess a significant thrombin-generating capacity secondary to phosphatidylserine exposure. Apoptotic cells within atherosclerotic plaques may allow local thrombin activation, thereby contributing to disease progression.

Prevention of infection by ciprofloxacin in neutropenia.

Ciprofloxacin with erythromycin, each at a dose of 250 mg 12-hourly, is effective prophylaxis against Gram-negative bacteraemia in neutropenic patients. The erythromycin component may contribute little to prophylaxis and does select for erythromycin-resistant viridans streptococci which then cause bacteraemia. Ciprofloxacin prophylaxis does not prevent coagulase-negative staphylococcal bacteraemia and resistant strains are selected. Initial use of vancomycin with a ureidopenicillin in pyrexial patients is currently justified by the exclusively Gram-positive nature of breakthrough bacteraemia. In patients failing to respond to this regimen, treatment modification to include full-dose amphotericin is frequently effective. Surveillance and containment isolation of patients carrying resistant Gram-negative species is prudent to prevent the spread of such resistant bacteria in oncology/haematology units.