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Biomedical subjects

Jack Cuzick

Publications and source records attributed to Jack Cuzick.

50 records · Page 3Linked to original sources

Wide variation in adenoma detection rates at screening flexible sigmoidoscopy.

BACKGROUND & AIMS: Wide between-center variation in adenoma detection rates (ADRs) was observed in the U.K. Flexible Sigmoidoscopy Screening Trial (overall, 12.1%; range, 8.6%-15.9%; P < 0.0001). The aim of this study was to determine whether the observed differences could be attributed to varying performance by endoscopists, to examine the effect of experience on performance, and to identify an attainable, standard ADR to which endoscopists could aspire. METHODS: Thirteen medical endoscopists, one per trial center, each performed about 3000 examinations (200 per month) using the same equipment and protocol. Overall and monthly ADRs were compared using multivariable logistic regression. RESULTS: Differences in ADRs were not explained by patient characteristics, incidence of colorectal cancer in the local population, or the endoscopists' medical specialty or previous experience. Average ADRs increased significantly with screening experience (up to 400 examinations). Endoscopists were classified as higher, intermediate, or lower adenoma detectors, and performance levels were maintained over time. Higher detectors had ADRs of 15% overall (men, 20%; women, 10%) and also detected more adenomas per case (higher/lower detectors, 21.7/10.4 adenomas per 100 examinations). CONCLUSIONS: The differences in ADRs were due to variation in performance of the endoscopists. Long-term follow-up will determine whether this variation is clinically important. We suggest that the standards in higher detecting centers should be achievable by all endoscopists screening unscreened populations aged older than 55 years. Endoscopists should aim to stay above the lower 95% confidence interval band for 200 examinations (10% overall; 5% in women, 15% in men).

Adenoma↗

Inherited and acquired risk factors for venous thromboembolic disease among women taking tamoxifen to prevent breast cancer.

PURPOSE: Venous thromboembolism (VTE) is of particular concern in women receiving tamoxifen in a chemopreventive setting. We investigate the association between acquired and inherited risk factors for VTE in the International Breast Cancer Intervention Study (IBIS-I) trial of tamoxifen prophylaxis for women at increased risk of breast cancer. METHODS: We used a nested case-control study design to investigate the role of tamoxifen and acquired risk factors in the risk of developing a VTE. RESULTS: Tamoxifen was associated with a significantly increased risk of developing a major VTE (odds ratio [OR], 2.1; 95% CI, 1.1 to 4.1). Women who had surgery, immobilization, or fracture in the previous month had a greatly increased risk of developing a major VTE (OR, 4.7; 95% CI, 2.2 to 10.1). Prothrombin and factor V Leiden mutations were found exclusively among control women: factor V Leiden in eight of 159 control women (5.0%) and the prothrombin mutation in three control women (1.9%). Thirty-five women with a VTE and a blood sample were negative for these mutations. The upper one-sided 97.5% CI for the OR of having either mutation was 1.87. Being overweight, smoking, or taking hormone replacement therapy was not associated with VTE in this study, but the CIs were wide. CONCLUSION: Tamoxifen and prior surgery, fracture, or immobilization were associated with a significantly increased risk of developing a VTE. Factor V Leiden and prothrombin mutations were not associated with thrombosis in this population.

Adult↗

Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial.

BACKGROUND: As a consequence of mammographic breast screening programmes, ductal carcinoma in situ is diagnosed with increasing frequency. Mastectomy for localised ductal carcinoma in situ is thought to be an over-treatment by many physicians, but there is much controversy as to whether complete local excision alone is sufficient. We aimed to assess the effectiveness of adjuvant radiotherapy and tamoxifen. METHODS: We used a 2x2 factorial design in a randomised controlled trial. Between May, 1990, and August, 1998, 1701 patients recruited from screening programmes were randomised to both treatments in combination or singly, or to none, or to either one (eg, radiotherapy) with an elective decision to give or to withhold the other (ie, in this case tamoxifen). Patients had complete surgical excision of the lesion confirmed by specimen radiography and histology. Patients have been followed up at least once a year. Median follow-up was 52.6 (range 2.4-118.3) months. Our primary endpoint was the incidence of ipsilateral invasive disease. FINDINGS: Ipsilateral invasive disease was not reduced by tamoxifen but recurrence of overall ductal carcinoma in situ was decreased (hazard ratio 0.68 [0.49-0.96]; p=0.03). Radiotherapy reduced the incidence of ipsilateral invasive disease (0.45 [0.24-0.85]; p=0.01) and ipsilateral ductal carcinoma in situ (0.36 [0.19-0.66]; p=0.0004), but there was no effect on the occurrence of contralateral disease. There was no evidence of interaction between radiotherapy and tamoxifen. INTERPRETATION: Radiotherapy can be recommended for patients with ductal carcinoma in situ treated by complete local excision; however, there is little evidence for the use of tamoxifen in these women.

Antineoplastic Agents, Hormonal↗

Human papillomavirus DNA detection in the management of women with twice mildly abnormal cytological smears.

This study was undertaken to investigate the value of HPV testing in women referred with two abnormal smears that were graded as mild dyskaryosis or less who attended for at least three follow-up visits. One hundred forty-nine women were included in the study and a total of 39 high-grade lesions including one cancer were detected. All of these were found to be associated with the persistent presence of one or more of 13 high-risk human papillomavirus types (HPV) as detected by a multiplex type specific PCR technique. Two high-grade lesions were initially missed by cytology. In contrast, no cytological or histological evidence of high-grade lesions was found during a follow-up period of up to 8 years in 62 women with no high-risk HPV infection or in 38 women with only transient high-risk HPV infection. The utility of high-risk HPV detection in the management of women presenting with mild cytological abnormalities is discussed.

Cervix Uteri↗

Aromatase inhibitors in prevention--data from the ATAC (arimidex, tamoxifen alone or in combination) trial and the design of IBIS-II (the second International Breast Cancer Intervention Study).

Current prevention trials have shown that tamoxifen can reduce the incidence of breast cancer by about 30%-40% in high-risk women, but that the risk of thromboembolic disease and endometrial cancer are increased about twofold. An alternative approach for postmenopausal women is to use an aromatase inhibitor to reduce oestrogen to very low levels. Data from the ATAC adjuvant trial indicate that the aromatase inhibitor anastrozole is more effective than tamoxifen in reducing recurrence and preventing new contralateral tumours, and also has a more favourable side-effect profile. This has led us to launch a new prevention trial--IBIS-II--in 6,000 high-risk postmenopausal women comparing anastrozole against placebo. A parallel trial will compare anastrozole against tamoxifen in 4,000 women with locally excised DCIS.

Aged↗

Epidemiology of breast cancer--selected highlights.

The main risk factors for breast cancer can be usefully grouped into four major categories-family history/genetic, reproductive/hormonal, proliferative benign breast pathology, and mammographic density. These factors are briefly reviewed and quantitative estimaters of risk are given. A computer programme for combining them to produce individualized risk profiles is described. The ongoing IBIS-II trial of chemoprevention for high risk postmenopausal women is presented as one approach to managing high risk women.

Breast Neoplasms↗

Psychological impact of colorectal cancer screening.

This article examines the psychological impact of participating in sigmoidoscopy screening for colorectal cancer prevention. The 1st study examined psychological well-being at 3 months, in relation to screening outcome, in 4,153 individuals. The 2nd study used longitudinal data to examine changes in psychological functioning from before to after screening in relation both to screening outcome and baseline indicators of vulnerability. There were few psychological differences between those who had received negative results or had polyps detected. These findings were confirmed in the longitudinal study, which also found no evidence for vulnerability to adverse effects among those who were initially most anxious or who perceived their risk of cancer to be higher. The longitudinal data suggested that screening might produce transient positive effects.

Anxiety↗

Use of human papillomavirus DNA testing to compare equivocal cervical cytologic interpretations in the United States, Scandinavia, and the United Kingdom.

BACKGROUND: Human papillomavirus (HPV) DNA testing may be useful in clarifying equivocal cervical cytologic interpretations. One application might be to standardize the meaning of equivocal interpretations from laboratories in various regions. Because international differences may be particularly marked, international comparisons of emerging data will require clear translations of "equivocal" and similar terms. METHODS: To perform a three-country comparison, the authors selected a morphologically diverse set of 188 conventional Papanicolaou tests initially classified as "squamous atypia" from a study of more than 20,000 women in Portland, Oregon (1989-1990). Previously, five U.S. expert cytopathologists independently interpreted the slides with screening cytotechnologists' marks in place. For this comparison, one British and two Scandinavian reviewers involved in HPV research reviewed the slides after original marks had been removed. The authors compared all eight reviewers' classifications of negative, equivocal, or abnormal in a series of pairwise comparisons using the kappa statistic. They then compared cytologic interpretations with HPV DNA testing. RESULTS: Oncogenic HPV DNA detection was significantly associated with increasingly abnormal interpretations for each reader. The British reader tended to rate tests as more abnormal than the American pathologists did, whereas the Scandinavians tended to rate tests as more normal. Reference to the HPV DNA standard clarified the tendency of readers to render systematically more or less severe interpretations. For example, the Scandinavian cytologists discounted subtle (often HPV-associated) changes in favor of cytologic certainty, making HPV triage of equivocal tests less applicable there. CONCLUSIONS: International research on cytopathology, particularly on the possible uses of HPV DNA testing, will require calibration of local cytologic definitions.

Adolescent↗