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T G Cooke

Publications and source records attributed to T G Cooke.

At least 37 records · Page 2Linked to original sources
PubMed1997

Prospective study of circulating T-lymphocyte subpopulations and disease progression in colorectal cancer.

PURPOSE: It has recently been reported that CD4+ T-lymphocytes are reduced in advanced colorectal cancer patients. However, it is not clear whether such changes in T-lymphocyte subsets are an early or late event in such patients. The aim of this study was to examine the relationship between these subsets and disease progression in colorectal cancer. METHODS: Flow cytometric analysis of T-lymphocyte subsets was performed in 39 patients who, approximately 12 months previously, had undergone surgery for colorectal cancer. These patients were grouped according to whether they developed a recurrence in the following two years. A group of healthy subjects was studied as controls. RESULTS: There was a significant increase in the median neutrophil count (4.3 vs. 3.7 10(6)/ml) and the median numbers of platelets (282 vs. 216 10(6)/ml) of the recurrence group compared with the control group, respectively (P < 0.05). The median numbers (0.28 vs. 0.73 10(6)/ml) and percentage (29 vs. 38 percent) of CD4+ T-lymphocytes of the recurrence group were significantly reduced compared with that of the control group (P < 0.05). There were also reductions in the median percentage of CD3+ cells (67 vs. 74 percent) and the median numbers of CD4+ T-lymphocytes (0.28 vs. 0.46 10(6)/ml) of the recurrence group compared with the no recurrence group (P < 0.05). CONCLUSIONS: Reduction of CD4+ T-lymphocytes occurs before detectable recurrence of colorectal cancer. Results of the present study are consistent with impaired immunity, as measured by such lymphocyte subset populations, being important in tumor recurrence in colorectal cancer.

Adult↗
PubMed1997

Doppler index perfusion in the detection of hepatic metastases secondary to gastric carcinoma.

BACKGROUND: The early detection of liver metastases in patients with gastric carcinoma is important for determining the appropriate therapy; however conventional imaging techniques are limited for detecting "occult" liver metastases. Previous studies have shown that the measurement of the Doppler perfusion index (DPI)-ratio of hepatic arterial to total liver blood flow-can detect the presence of even small hepatic tumors. In this study, we compared the measurement of DPI with computed tomography (CT) for detecting gastric liver metastases. METHODS: At presentation, 43 patients with gastric carcinoma underwent CT scanning of the liver and after 12 hours of fasting, DPI measurement was carried out using Doppler sonography. RESULTS: Both techniques detected overt liver metastases in 9 of the 43 patients. Of the 34 remaining patients with an apparently disease-free liver on the basis of CT, laparotomy, or laparoscopy, 14 subsequently develop liver metastases over a follow-up period of 4 years, 13 of which had been predicted by DPI at the time of presentation. CONCLUSION: The data suggest that the measurement of the DPI is more sensitive than a CT scan for detecting liver metastases secondary to gastric carcinoma.

Aged↗
PubMed1996

Quantitative estimation of epidermal growth factor receptor and c-erbB-2 in human breast cancer.

Epidermal growth factor receptor (EGFR) expression by human breast cancer has been shown to predict poor patient outcome, as has amplification of the c-erbB-2 proto-oncogene. We have developed a quantitative immunohistochemical method for measuring protein levels of both receptors and have applied this to a series of 123 breast primaries. We find EGFR expression is substantially lower than normal in nearly all breast cancers (97%). Quantification of p185erbB-2 indicates overexpression in 91% of the tumors. Two separate tumor populations are apparent with levels of c-erbB-2 expression ranging from 0.33 to 19 and 45 to 480 times normal, respectively. Within the lower population, p185erbB-2 expression is inversely related to EGFR expression (rank correlation, P < 0.0005). Using fluorescent in situ hybridization we show that tumors in the latter population have c-erbB-2 amplification and that amplification is restricted to this group. Our findings indicate that significant overexpression of p185erbB-2 occurs in the absence of amplification; these lower levels of expression may have functional significance. Fifty-three patients underwent in vivo bromodeoxyuridine labeling, allowing flow cytometric analysis of tumor cell cycle kinetics. EGFR expression correlates directly to the labeling index (P = 0.011) and indirectly to potential doubling time (P = 0.010), but not to the duration of the S-phase (P = 0.502). Conversely, p185erbB-2 expression does not relate to indices of proliferation. Our results have important implications for the use of both receptor types as therapeutic targets.

Adolescent↗
PubMed1996

Cell kinetics in vivo of human breast cancer.

Rates of cell proliferation within tumours may provide prognostic information and help in the rational administration of chemotherapy and radiotherapy. In vivo labelling with 5-bromo-2'-deoxyuridine (BrdU) was used in 89 women with breast cancer to determine the labelling index for BrdU (BLI), the length of S phase (TS) and the potential doubling time of the tumour (Tpot). Kinetic data were obtained in 84 patients. The median BLI was 3.2 per cent, TS 12 h, and Tpot 12.5 days. There was no systematic difference in the labelling index determined by flow cytometry and by manual counting on sections. Labelling indices were significantly higher in aneuploid tumours, and in tumours not expressing oestrogen receptors, but were not correlated with tumour size, nodal status, or expression of c-erbB2. In vivo measurement of tumour cell kinetics can be made rapidly and reliably in the majority of human breast cancers, and may have a role to play in planning therapy.

Breast Neoplasms↗
PubMed1996

Response to regional chemotherapy in patients with variant hepatic arterial anatomy.

Regional chemotherapy for colorectal liver metastases is conventionally delivered by a catheter inserted into the gastroduodenal artery. However, up to 40 per cent of patients have 'unconventional' hepatic arterial anatomy. The response rate to regional chemotherapy was examined in 28 patients with normal and in 17 with variant hepatic arterial anatomy. There was no significant difference in response rates between the two groups.

Antimetabolites, Antineoplastic↗
PubMed1996

Anatomical basis of intra-arterial chemotherapy for patients with locally advanced breast cancer.

Twenty-eight patients with locally advanced breast cancer received four doses of regional chemotherapy via angiographically placed percutaneous catheters into the internal mammary artery (IMA) and lateral thoracic artery. Patent blue dye was injected to outline the relative contribution to perfusion of each of these vessels. The IMA was found to perfuse 67 (range 20-95) per cent of the breast and the lateral thoracic artery 15 (range 0-35) per cent. In 33 per cent of patients the lateral thoracic artery did not contribute to breast perfusion and a large area of the lateral aspect of the breast was perfused from a further branch of the subclavian or axillary artery. The blood supply to the breast is extremely variable and must be determined in each patient before delivering regional chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Intraoperative ultrasound in colorectal cancer patients undergoing apparently curative surgery: correlation with two year follow-up.

Conventional ultrasound (US) and computerized tomography (CT) are well recognized to be limited in the detection of small liver metastases. In this study, we assessed the use of intraoperative ultrasound (IOUS) in the detection of 'occult' liver metastases in colorectal cancer patients undergoing apparently curative surgery of the primary colonic carcinoma. Ninety three colorectal cancer patients undergoing apparently curative surgery on the basis of preoperative US, CT and laparotomy were studied. All patients underwent IOUS examination of the liver. After two year follow-up, 27 of these 93 patients developed overt liver metastases and of these 27, only five had been detected by IOUS examinations at the time of laparotomy. The results suggest that IOUS is relatively insensitive in the detection of occult colorectal liver metastases. Its routine use as a screening tool during primary surgery is therefore not recommended.

Colorectal Neoplasms↗
PubMed1996

Prediction of radiotherapy response of cervical carcinoma through measurement of proliferation rate.

Estimation of tumour proliferation may allow the design of individualised radiotherapy schedules to optimise response. This prospective study correlates the tumour proliferation rate of cervical carcinoma with response to conventional radiotherapy. The potential tumour cell doubling rate (Tpot) was estimated following flash labelling of the tumours in vivo using the DNA precursor, bromodeoxyuridine (BrdUrd); samples were analysed by flow cytometry. Tumour ploidy, DNA index and mitotic count were also assessed as was histological grade and type. Multiple biopsies from each tumour were obtained from 121 women. The median Tpot was 4.0 days, median S-phase duration 12.8 h and median adjusted labelling index 9.8%. Higher BrdUrd labelling was seen in patients who developed pelvic tumour recurrence following radiotherapy. This was the only biological/histological parameter with univariate and multivariate significance in relation to locoregional recurrence (P = 0.006 and P = 0.034 respectively). This study represents the first assessment of Tpot in relation to long-term response of cervical tumours treated by radiotherapy treatment. The association of high BrdUrd labelling and poor pelvic disease-free survival indicates the need for further research into the potential of radiotherapy schedule alteration to reflect tumour proliferation. The predictive value may be enhanced by combination with other biological parameters.

Aged↗
PubMed1996

Overexpression of p53 protein and its significance for recurrent progressive bladder tumours.

OBJECTIVE: To determine the prognostic value of the overexpression of p53 protein as determined by immunohistochemistry in recurrent progressive transitional cell carcinomas of the bladder. PATIENTS AND METHODS: A total of 222 tumours from 86 patients with recurrent disease, 20 from patients with no evidence of recurrence after resection of initial tumour and 11 normal bladder (controls) were investigated. Using a microwave technique to expose antigens, formalin-fixed sections were immunohistochemically stained for p53 using a polyclonal antiserum. Two independent observers scored the sections for evidence of overexpression of p53. RESULTS: Of 86 patients with recurrent disease, 51 demonstrated overexpression of p53 protein, as did six of 20 patients with non-recurrent disease. Overexpression was not linked to recurrence (P = 0.5) but was related to worsening histological stage (P < 0.01) and increasing grade (P < 0.01). Regression analysis showed that overexpression of p53 for the primary tumour was not of predictive prognostic value for death from bladder cancer, time to progression or time to recurrence. Tumour grade was the only variable of prognostic value in all the statistical models. Patients with overexpression of p53 showed no reduction in overall survival. CONCLUSION: These findings suggest that overexpression of p53, as determined immunohistochemically, appears to have no predictive prognostic value over stage and grade in bladder tumours.

Aged↗
PubMed1996

Prognostic power of Doppler perfusion index in colorectal cancer. Correlation with survival.

OBJECTIVE: The authors assessed the relative value of Dukes' staging and Doppler perfusion index (DPI) as prognostic indices of early death in patients with colorectal cancer who have had apparently curative surgery. SUMMARY BACKGROUND DATA: Dukes' classification is recognized as the gold standard against which other prognostic factors should be compared; however, its discriminatory power is limited. No established method exists for accurately identifying patients who, despite having undergone an apparently curative resection for colorectal carcinoma, are at high risk. METHODS: Eighty consecutive patients undergoing apparently curative surgery for colorectal cancer were staged using Dukes' classification. In addition, DPI (ratio of hepatic arterial to total liver blood flow) was measured before surgery by means of a duplex/color Doppler sonography. RESULTS: On the basis of 2-year follow-up data, Dukes' classification failed to define clearly those patients who died or who developed recurrent disease. In contrast, DPI clearly identified two groups of patients: 78% of patients with an abnormally elevated DPI value developed recurrent disease or died, whereas 97% of patients with a normal DPI value survived. CONCLUSION: This technique can identify patients at high risk for colorectal cancer, after having undergone apparently curative resection, who would be suitable for adjuvant therapy.

Colorectal Neoplasms↗
PubMed1996

Therapeutic potential of octreotide in the treatment of liver metastases.

Octreotide is a synthetic analogue of somatostatin that has clear inhibitory effects on the growth of many animal and human cell lines, including colorectal cell lines both in vitro and in vivo. Colorectal cancer metastatic to the liver is clinically important, both in terms of the number of patients affected and the lack of any effective treatment for the majority of patients. Octreotide inhibits the growth of colorectal liver tumour in a number of experimental models and, in at least three tumour types, inhibits the growth of established micro-metastases. The precise mechanism of action is not known. However, the drug is likely to be most beneficial in the treatment of liver metastases when the tumour burden is relatively small. The available evidence, although experimental, suggests that octreotide may also have a beneficial effect on the development of liver metastases when used as an adjuvant to surgery in colorectal cancer and this area warrants urgent clinical investigation. The cytotoxics which are currently used as an adjuvant to surgery for colorectal cancer have unpleasant side effects which can be life-threatening. There will also be a proportion of patients who have undergone a truly curative resection of their tumour and will thus be treated unnecessarily. The potential benefits of octreotide in the adjuvant setting, although promising, remain speculative, but octreotide has an acceptably low incidence of side effects and can be administered safely for a prolonged period of time.

Animals↗
PubMed1996

Quantitative radioimmunohistochemical measurements of p185(erbB-2) in frozen tissue sections.

The relationship between expression of the c-erbB-2 proto-oncogene and the biology of breast cancer has been investigated widely, most studies using immunohistochemistry in formalin-fixed, paraffin-embedded tissues. This technique is at best semiquantitative and there is a high degree of interstudy variability because of its subjective nature and poor methodological standardization. The relationship between the levels of expression and biology can be examined thoroughly only with an accurately quantitative technique. We have developed a radioimmunohistochemical assay to measure p185(erbB-2) in tissue biopsy specimens. The method involves incubating frozen sections with 125I-labeled monoclonal antibody, microautoradiograpy, and grain counting with image analysis. Sections of cell pellets with known c-erbB-2 levels are processed with each batch of samples as internal calibration standards. We have quantified c-erbB-2 expression in 60 breast carcinomas and compared the results with conventional immunohistochemistry. Radioimmunohistochemistry measured receptor levels throughout the range of expression in breast carcinomas, whereas conventional immunohistochemistry detected the protein only in the highest expressing tumors. The quantitative, objective data produced by radioimmunohistochemistry allow a more thorough evaluation of the relationship between c-erbB-2 expression and tumor biology. This technique may have applications in other fields where quantitative data is required and relevant monoclonal antibodies are available.

Breast Neoplasms↗
PubMed1996

A prospective study of six methods for detection of hepatic colorectal metastases.

Many techniques are available for the identification of patients with hepatic colorectal metastases. The accuracy and clinical relevance of transabdominal ultrasound (US), computed tomography (CT), static scintigraphy, dynamic scintigraphy (HPI), intraoperative ultrasound (IOUS) and manual palpation, in the detection of intrahepatic colorectal metastases were assessed in 73 consecutive patients presenting with colorectal carcinoma; 39 were male and 34 female with a mean age of 68 years (range 43-90 years). In 33 patients either intraoperative ultrasound or palpation were omitted owing to emergency presentation (n = 14) or subsequent non-operative management (n = 19). All six investigations were completed in 40 patients. Computed tomography and hepatic perfusion scintigraphy (HPI) were the most sensitive, detecting over 90% of lesions, the others identifying approximately 80% of lesions, Specificity in all methods, apart from dynamic scintigraphy, was over 80%. Contrast-enhanced CT would appear to remain the most accurate method available. However, if the prognostic ability of HPI is confirmed on subsequent follow-up, the accuracy of HPI will rise with time, whereas that of CT will fall. Intraoperative ultrasonography took time to perform and did not alter the management of any patient within the study. We suggest that its use is limited to those patients in whom resection is contemplated, where the vascular anatomical detail provided may be invaluable.

Adult↗
PubMed1995

A prospective study of tumor recurrence and the acute-phase response after apparently curative colorectal cancer surgery.

BACKGROUND: Approximately 70% of patients who are going to develop tumor recurrence following curative colorectal surgery do so within 24 months of surgery. PATIENTS AND METHODS: The relationship was prospectively examined between an ongoing acute-phase response and subsequent clinical relapse in 36 colorectal cancer patients who had undergone a curative resection. Approximately 4 months after their operation, patients were grouped according to the presence (n = 15) or absence (n = 21) of an acute-phase response (C-reactive protein > 5 mg/L) and were followed-up for a minimum of 24 months. RESULTS: Age, tumor site, and serum carcinoembryonic antigen concentrations were similar in both groups. There was a significantly higher recurrence rate in patients with an acute-phase response (11 of 15) compared to those with no acute-phase response (2 of 21, P < 0.01). CONCLUSIONS: These results are consistent with the presence of an acute-phase response being an important predictive factor in the early stages of tumor recurrence in patients who have had apparently curative colorectal surgery.

Acute-Phase Reaction↗
PubMed1995

Effect of extended ibuprofen administration on the acute phase protein response in colorectal cancer patients.

The regulation of acute phase protein production and the relationship of the acute phase protein response to tumour growth was examined in colorectal cancer patients (n = 9). Ibuprofen (1200 mg/d) was administered for 8-11 days. Following ibuprofen administration there were reductions in circulating concentrations of C-reactive protein (P = 0.01), interleukin-6 (P = 0.06), cortisol (P = 0.04) and also in the platelet count (P = 0.01). There was no significant change in albumin, insulin and carcinoembryonic antigen. These results indicate that ibuprofen administered over a prolonged period substantially reduces acute protein production via its effect on interleukin-6 and cortisol. It remains to be determined whether ibuprofen is useful in moderating tumour growth in colorectal cancer patients.

Acute-Phase Proteins↗
PubMed1995

Dynamic hepatic scintigraphy in colorectal cancer.

The clinical usefulness of the hepatic perfusion index (HPI) at the time of presentation has been evaluated in patients with colorectal cancer. In 83 consecutive patients, the HPI was abnormally elevated in 34 of 37 (93%) patients with overt metastases. This study confirms that the HPI is elevated in most patients with overt hepatic metastases. Long-term follow-up of patients with abnormal HPI and no obvious liver metastases is continuing.

Carcinoma↗