In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatinbased chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB -IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P ¼ 0.005) or the only (in FIGO IIIC, P ¼ 0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(À) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P ¼ 0.047) and by BCL2 expression in the TP53(À) group (P ¼ 0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P ¼ 0.049); its loss was found with advancing FIGO stage (P ¼ 0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

A total of 700 patients who had carotid endarterectomy (CEA) in the UK and Ireland during a 6-month interval between March and August 1994 were studied prospectively. Some 108 patients (15.4 per cent) had a contralateral internal carotid artery occlusion. Previous reports have shown an associated stroke rate of about 10 per cent in these patients. This study assessed complications and outcome for patients undergoing CEA with contralateral internal carotid artery occlusion compared with those without. The indications for surgery were comparable between the two groups although the patients with occlusion had a slightly higher incidence of arrhythmia and stroke. Intraoperative shunts were used in a significantly higher proportion of those with occlusion (83.3 versus 64.7 per cent, P = 0.0001). The combined death and stroke rate for patients with occlusion was 5.6 per cent compared with 2.4 per cent for the remainder (P not significant). On the basis of the present data, CEA with a contralateral carotid artery occlusion carries only a slight increase in the rate of postoperative stroke and death. This increase was not statistically significant and is lower than that reported previously.

Patients with acute leg ischaemia are generally treated by vascular specialists, with modern methods and acceptable results. This is being achieved despite insufficient vascular surgeons and radiologists for formal emergency rotas in most hospitals.

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long-term oral anticoagulation was associated with reduced risk of recurrent limb ischaemia and amputation, but more research is needed to define the benefits and risks, especially for thrombosisin situ. Clinicians should give clear advice about anticoagulation when patients are discharged from hospital.

Changes in cell survival contribute to tumour development, influence tumour biology and its response to chemotherapy. p53 gene alterations should negatively affect apoptosis by impaired p53-dependent apoptotic response. We looked for associations between spontaneous apoptosis, p53 gene mutation, p53 protein accumulation, growth fraction, bcl-2 expression and histological parameters in 64 ovarian, four tubal and three peritoneal carcinomas. Apoptotic cells were detected with the TUNEL method. p53 gene variants were detected by the single-strand conformation polymorphism and were sequenced directly. P53, Ki-67 and bcl-2 protein expressions were detected immunohistochemically. A weighed multiple logistic regression model was applied. Apoptotic index (Al) ranged 0.02–0.18 (mean 0.11); proliferation index (PI) ranged 3–90% (mean 54%). p53 gene mutations were present in 51, p53 protein accumulation in 46, and diffuse bcl-2 expression in 29 of 71 tumours. The AI was positively associated with the presence of p53 gene mutation ( P = 0.011). However, the PI included into the analysis did positively influence the AI ( P = 0.02) and diminished the association with p53 gene mutation ( P = 0.082). The AI was negatively associated with good histological differentiation ( P = 0.0006), the serous tumour type ( P = 0.002), and diffuse bcl-2 expression ( P = 0.025). Strong bcl-2 expression was associated with endometrioid tumour type ( P = 0.002). FIGO stage and p53 protein accumulation were the only parameters that influenced overall survival time. Thus, our results suggest that histological tumour type and grade are major determinants of spontaneous apoptosis in ovarian carcinomas; p53 alterations do not adversely but rather positively affect spontaneous apoptosis by increasing growth fraction. This, in turn, suggests p53-independency of spontaneous apoptosis in ovarian carcinomas. © 2000 Cancer Research Campaign

BACKGROUND: The Vascular Surgical Society carried out an audit of follow-up after acute thromboembolic lower limb ischaemia. METHODS: The audit of acute lower limb ischaemia was done between 1 January and 31 March 1996 and included 474 patients. This report describes a 2-year follow-up of patients with a diagnosis of thrombosis or embolism who survived 30 days. Details were obtained for 214 (75 per cent) of 287 patients: half (107) were men, and the age range was 21-96 (mean 74) years. RESULTS: Amputation of the leg affected initially had been required (after 30 days) in 12 per cent. Further acute leg ischaemia had occurred in 11 per cent, and 9 per cent had undergone arterial reconstruction (11), angioplasty (seven) or thrombolysis (two). Major medical events were reported in 31 per cent and 35 per cent had died during the 2-year period. After the episode of acute ischaemia, warfarin was started in 57 per cent of patients, but was continued in only 43 per cent. Reasons for stopping were seldom known, nor was duration of treatment (range 1-22 (median 6) months in reported cases). Significantly more patients who were not on warfarin suffered recurrent acute limb ischaemia (19 versus 3 per cent; P < 0.01). No significant association was found between recurrent acute ischaemia and initial diagnosis of embolism, thrombosis or atrial fibrillation (but numbers of recurrences in each group were small). CONCLUSION: The incidence of recurrent acute thromboembolic limb ischaemia up to 2 years was significantly lower in patients treated with warfarin. Warfarin treatment is often stopped for no clear reason, especially in the elderly. Explicit advice about long-term warfarin therapy should be given when these patients are discharged from hospital.