Compression ultrasonography in hospitalized patients with suspected deep venous thrombosis.

Compression ultrasonography was compared with contrast venography in 215 hospitalized patients (218 limbs) with suspected deep venous thrombosis. All scans were performed using a 5-MHz linear-array scanner. The calf veins were not assessed owing to their small caliber. Distribution of deep venous thrombosis was proximal in 113 of 215 patients (number of limbs with deep venous thrombosis being the same as the number of patients) and limited to the calf veins (distal) in 29 patients. Deep venous thrombosis was detected by compression ultrasonography in 101 of 113 patients (sensitivity, 89%) and falsely diagnosed in two of 76 limbs (73 patients) with negative venographic results (specificity, 97%). The method was less sensitive below the knee, where deep venous thrombosis of the distal popliteal vein was not detected in five of 10 patients as compared with seven of 103 patients with thrombus extension above the knee. Pelvic vein deep venous thrombosis (n = 34) was detected by compression ultrasonography in 71% of the patients. The results of this study indicate that venography may be omitted in patients where compression ultrasonography demonstrates proximal deep venous thrombosis. In patients with negative compression ultrasonographic results, however, venographic verification is needed since venography has a considerably higher sensitivity than compression ultrasonography in detecting isolated iliac and calf vein deep venous thrombosis.

Predictive value of tumour cell proliferation in locally advanced breast cancer treated with neoadjuvant chemotherapy.

We previously reported that defects in apoptotic pathways (mutations in the TP53 gene) predicted resistance to doxorubicin monotherapy. The aim of this study was to evaluate whether cell proliferation, as assessed by mitotic frequency and Ki-67 levels, may provide additional predictive information in the same tumours and to assess any potential correlations between these markers and mutations in the TP53 gene and erbB-2 overexpression. Surgical specimens were obtained from ninety locally advanced breast cancers before commencing primary chemotherapy consisting of weekly doxorubicin (14 mg/m2) for 16 weeks. 38% of the patients had a partial response (PR) to therapy, 52% had stable disease (SD) while 10% had progressive disease (PD). Univariate analysis showed a significant association between a high cell proliferation rate (expressed as a high mitotic frequency) and resistance to doxorubicin (P = 0.001). Further analyses revealed this association to be limited to the subgroup of tumour expressing wild-type TP53 (P = 0.016), and TP53 mutation status was the only factor predicting drug resistance in the multivariate analyses. The finding that a high mitotic frequency, as well as a high Ki-67 staining, correlated to TP53 mutations (P = 0.001 for both), suggests TP53 mutations are the key predictor of drug resistance, although cell proliferation may play an additional role in tumours harbouring wild-type TP53. Regarding overall (OS) and relapse-free survival (RFS), multivariate analyses (Cox' proportional hazards regression) revealed a high histological grade and negative oestrogen receptor (ER) status to be the variables that were most strongly related to breast cancer death (P = 0.001 and P = 0.001, respectively). A key reason for this difference with respect to the factors predicting chemotherapy resistance could be due to the adjuvant use of tamoxifen in all patients harbouring ER-positive tumours.