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T Cooke

Publications and source records attributed to T Cooke.

At least 73 records · Page 4Linked to original sources

A randomized controlled trial of adjuvant portal vein cytotoxic perfusion in colorectal cancer.

In this randomized trial adjuvant cytotoxic portal vein perfusion in patients undergoing surgery for colorectal cancer without liver metastases was assessed to determine whether the incidence of metachronous liver metastases could be reduced and survival thereby improved. There were 127 control patients and 117 patients who received adjuvant perfusion. A further 13 patients were excluded following randomization because of cirrhosis in 1, liver metastases at laparotomy in 3 and technical problems with cannulation in 9. Dukes' staging and degree of differentiation were similar in the two groups. There were fewer liver metastases in the perfusion patients and overall survival was improved. However, the benefit appears to be greatest in patients with Dukes' B colon cancer.

Aged↗

Effect of warfarin on cell kinetics, epithelial morphology and tumour incidence in induced colorectal cancer in the rat.

The effect of low dose warfarin and high dose warfarin on epithelial cell kinetics (as determined by stathmokinetic techniques), and preneoplastic morphological changes was studied during azoxymethane induced carcinogenesis in the rat. Warfarin, at either low or high dose, had no effect on crypt cell production rate (CCPR) at any time interval whereas tumour incidence in both low dose warfarin and high dose warfarin groups was significantly reduced. Morphological changes were observed using scanning electron microscopy, which by conventional histology were shown to be adenoma precursors. In the control group the number of microadenomas increased with time after starting azoxymethane. In warfarin treated animals, the number of microadenomas also increased with time, but the actual incidence was reduced when compared with controls. These results suggest that the effects of warfarin on tumour development is unrelated to its anticoagulant effect, because increased dose did not result in greater tumour reduction. Furthermore, there was no overall change in CCPR when warfarin was administered. Warfarin may exert a specific effect, by preventing neoplastic change in cells which have undergone morphologically undetectable changes associated with early carcinogenesis.

Adenoma↗

Detection of early neoplastic changes in experimentally induced colorectal cancer using scanning electron microscopy and cell kinetic studies.

Colonic tumours were induced in Wistar rats using 12 consecutive subcutaneous injections of azoxymethane at a dose of 10 mg/kg/week. Pairs of rats were killed at five weekly intervals after initial injection until 25 weeks. Colonic mucosa was sampled from five standard areas along the length of the colon and examined by both scanning electron microscopy and conventional light microscopy. The crypt cell production rate was measured by stathmokinetic techniques. Scanning electron microscopy showed microadenomas as early as five weeks and consistently after 15 weeks. They were found predominantly in the distal colon and increased in size with time. The lesions showed a progressive increase in the number of crypts per adenoma and increasingly disorganised slit shaped crypt orifices. The presence of epithelial dysplasia in the microadenomas and of invasion of the colonic wall by carcinoma was confirmed histologically, although fewer lesions were identified in tissue sections than by scanning electron microscopy. Crypt cell production rate increased with time, particularly in the distal colon. This increase was significant between five and 25 weeks. The results of these observations suggest that there is an adenoma-carcinoma sequence in this animal model. The value of scanning electron microscopy in identifying and quantifying the mucosal changes during carcinogenesis is emphasised.

Adenoma↗

Assessment of a scoring scheme for the preoperative diagnosis of breast lumps.

The value and accuracy of a scoring system applied to clinical examination, aspiration cytology and mammography has been assessed in the diagnosis of 224 consecutive 'new' patients attending a breast clinic with a breast lump. In 72 of 99 patients with breast cancer (80%) the scores were high enough to allow definitive surgery without formal histology; all were subsequently confirmed as breast carcinomas. Cytology proved the most accurate investigation with no false positives and a correct diagnosis in 146 of 148 adequate specimens (98.6%). This system reduced the frozen section rate by 74% and allowed for a more appropriate counselling of patients prior to mastectomy.

Adult↗

Bile acid receptors in colorectal cancer.

Bile acids are thought to be involved in both the aetiology and development of colorectal cancer. In this study the existence of specific bile acid receptor proteins has been postulated. A receptor assay which involved labelling with 14C-deoxycholic acid was performed as well as autoradiography using 3H-deoxycholic acid. In an initial study resected colorectal cancer and adjacent histologically normal colorectal mucosa from 39 patients were studied, as were samples of normal gastric mucosa, cancers and benign colorectal tumours. Specific receptors to deoxycholic acid were detected in 12 (30.8 per cent) of the colorectal cancers, but in only 1 (2.6 per cent) of the samples from normal colorectal mucosa (X2 = 11.16, P less than 0.005). No deoxycholic acid receptors were detected in any other tissue studied. Autoradiographs of colorectal cancers showed binding of 3H-deoxycholic acid in receptor-positive tumour tissue. These findings might provide some explanation for the evidence linking bile acids with the disease.

Autoradiography↗

Natural killer (NK) activity in peripheral blood lymphocytes of patients with benign and malignant breast disease.

Previous studies of natural killer (NK) activity in the peripheral blood of breast cancer patients have failed to show a reduction in cytotoxicity, an observation at variance with results obtained in other malignancies. Interpretation of the data however is complicated by the presence of treated and post-mastectomy patients in the groups studied.In this study, lymphocytes from preoperative blood samples of untreated women with benign and malignant breast disease were tested at various effector-to-target ratios for cytotoxicity activity against the NK sensitive erythromyeloid cell line, K562.A significant reduction in NK activity was observed between carcinoma patients and the control group (P=0·02). When the carcinoma group was further divided into pre- and postmenopausal patients, the reduction was found to be a feature only of premenopausal women (P=0·002). The levels of NK activity in patients with benign breast disease were not significantly different from those in controls, irrespective of menstrual status. There was no correlation between NK activity and tumour size, oestrogen-receptor or lymph-node status in the carcinoma patients.A preliminary analysis of NK activities in the control group suggests that women donating blood in the first half of their menstrual cycle show significantly reduced NK activity in comparison with those in the second half (P=0·001). This finding, coupled with the variation in NK activity shown between pre- and postmenopausal breast carcinoma patients, suggests that hormonal effects in conjunction with malignancy determine the level of NK activity in breast cancer.

Adult↗

The clinical application of oestrogen receptor analysis in early cancer of the breast.

The analysis of receptors for oestrogen in early cancer of the breast may be used to predict prognosis. The presence or absence of oestrogen receptors is independent of menstrual status, the stage of the patient's disease, and the histological grade of the tumour. Therefore combination with other prognostic factors gives a more accurate assessment of an individual patient's outlook. In the study described prognostic subgroups were determined from tumour axillary lymph node histology and oestrogen receptor status. The clinical application of these findings is discussed.

Axilla↗

Oestrogen receptors and survival in early breast cancer.

Oestrogen receptor status was related to survival in 414 patients with primary breast cancer. Women with oestrogen receptors in their tumours survived significantly longer than those without receptors; this was true for both premenopausal and postmenopausal women and also when the patients were subdivided into those with and without axillary metastases. Patients with axillary metastases and no oestrogen receptors in their tumours had the worst prognosis, while women with axillary metastases and oestrogen receptors had a death rate similar to that of women with no axillary metastases and no receptors. Patients without oestrogen receptors and with no axillary metastases were identified as a high-risk group, and it would seem appropriate to include such patients in future trials for adjuvant therapy in early breast cancer.

Breast Neoplasms↗

Possible test for selection of adjuvant systemic therapy in early cancer of the breast.

The estrogen receptor content and the thymidine labelling index have been correlated in a series of primary cancers of the breast. Receptor was assayed in tumours of 409 patients with operable breast cancer. Recurrence rates were significantly higher in patients whose tumours did not contain receptors than in those whose tumours did. Women without axillary node involvement whose tumours lacked oestrogen receptors showed the same high rate of recurrence as all women with axillary involvement. The oestrogen receptor status of metatases was similar to that of the primary tumours. The thymidine labelling of 83 tumours was inversely related to their receptor content. Tumours without receptors had the highest indices and therefore the highest potential tumour growth. These results have been discussed in relation to selection of systemic adjuvant therapy.

Breast Neoplasms↗