Colon adenocarcinoma and B-16 melanoma grow larger following laparotomy vs. pneumoperitoneum in a murine model

BACKGROUND: The purpose of our study was to find out whether bleeding symptoms are predictive factors of subsequent gynecological or urinary cancers among women screened negative. METHODS: The data stemmed from the Finnish Mass Screening Registry, and were linked to the National Cancer Registry: 37,596 screening negative women in the nationwide population-based mass screening program for cervical cancer were classified by their bleeding symptom (bloody discharge, coital bleeding, irregular bleeding, postmenopausal bleeding) at the time of screening (1985-1990) and followed up (1985-1994) in order to assess the subsequent risk of cancer. RESULTS: Bleeding symptoms with prevalence of 5.9% were more likely to be signs of preinvasive than invasive cervical cancer with the exception of coital bleeding, nevertheless relative risk of cervical cancer (SIR 1.1, 95% CI 0.8-1.4) was not significantly increased during the total follow-up of maximum 10 years. Women with any bleeding symptom had increased risk of cancer of the corpus uteri (SIR 2.1, 95% CI 1.6-2.6), postmenopausal bleeding was the strongest symptom (RR 3.6, 95% CI 2.0-6.0). None of the bleeding symptoms increased subsequent risk of ovarian, vaginal or vulvar carcinoma. The risk of kidney cancer was increased (SIR 1.7, 95% CI 1.0-2.6). CONCLUSIONS: The prevalence of bleeding symptoms was small and relative risks for cancers were low for them to be suitable as predictive factors of cancer neither in clinical practice nor for public health purposes, e.g. in developing selective screening based on this high risk group. Only 34 gynecological cancers during 220,000 person-years in women with bleeding symptoms were attributable to bleeding. Relative risks remained increased only for a short time after screening. Therefore, short term surveillance is important, but due to the fact that relative risks approached unity during the follow-up, reassurance of a woman that she is cancer-free should be emphasized more in the long term after the bleeding symptoms.     

Endovaginal ultrasound to exclude endometrial cancer and other endometrial abnormalities

CONTEXT: Postmenopausal vaginal bleeding is a common clinical problem. Endovaginal ultrasound (EVUS) is a noninvasive diagnostic test that may help determine which women should undergo endometrial biopsy. OBJECTIVE: To determine the accuracy of EVUS in detecting endometrial disease in postmenopausal women with vaginal bleeding according to hormone replacement use. DATA SOURCES: Literature search of English-language and non-English-language articles published from 1966 through November 1996 using MEDLINE and by a manual search of bibliographies of published articles. STUDY SELECTION: Studies were included if they prospectively collected EVUS measurements of endometrial thickness prior to obtaining endometrial tissue for histologic evaluation in postmenopausal women with vaginal bleeding. Of 85 studies that included data on EVUS and endometrial histology, 35 were included in the meta-analysis and included 5892 women. DATA EXTRACTION: Articles were reviewed and independently selected and abstracted by 2 reviewers. Disagreement was resolved by consensus. DATA SYNTHESIS: The overall summary mean weighted estimates of sensitivity and specificity were calculated for thresholds of endometrial thickness from 3 to 10 mm. Using a 5-mm threshold to define abnormal endometrial thickening, 96% (95% confidence interval [CI], 94%-98%) of women with cancer had an abnormal EVUS result, whereas 92% (95% CI, 90%-93%) of women with endometrial disease (cancer, polyp, or atypical hyperplasia) had an abnormal result. This did not vary by hormone replacement use. However, the number of women with normal histology who had an abnormal EVUS result did vary by hormone replacement use. In women who were not using hormone replacement therapy, 593 (8%) with normal histological findings had an abnormal EVUS result (specificity, 92%; 95% CI, 90%-94%), whereas 1544 (23%) using hormone replacement therapy had an abnormal EVUS result (specificity, 77%; 95% CI, 75%-79%). For a postmenopausal woman with vaginal bleeding with a 10% pretest probability of endometrial cancer, her probability of cancer is 1% following a normal EVUS result. CONCLUSION: Endovaginal ultrasound has a high sensitivity for detecting endometrial cancer and other endometrial disease and can reliably identify postmenopausal women with vaginal bleeding who are highly unlikely to have significant endometrial disease so that endometrial sampling may be unnecessary.     

Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium

The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.     

Cancer incidence in a cohort of infertile women

Among 2,496 infertile Israeli women treated between 1964 and 1974, 143 cancer cases were observed as compared with 116.1 expected (standardized incidence ratio (SIR) = 1.2, 95% confidence interval (CI) 1.0-1.5) through 1991. Site-specific analysis revealed 12 ovarian cancers versus 7.2 expected (SIR = 1.6, 95% CI 0.8-2.9), 21 endometrial cancers versus 4.3 expected (SIR = 4.85, 95% CI 3.0-7.4), and 59 breast cancers versus 46.6 expected (SIR = 1.3, 95% CI 0.96-1.6). Sensitivity analysis revealed that confounding was unlikely to explain the raised risk of endometrial cancer, but nulliparity might explain the increased risk of ovarian cancer. The excess of endometrial cancer was prominent among patients with normal estrogen production but progesterone deficiency (SIR = 9.4, 95% CI 5.0-16.0). The risk for ovarian cancer was similar among the total groups of treated and untreated patients (SIR = 1.7 vs. 1.6). The standardized incidence ratio for endometrial cancer was higher among the treated group than the untreated group, although not significantly. Treatment with ovulation-inducing drugs does not appear to increase the risk for ovarian cancer, but its role cannot be completely excluded.     

Relation between the incidence of invasive cervical cancer and the screening interval: is a five year interval too long?

OBJECTIVE: To examine the incidence of invasive cervical cancer per 100,000 women years at risk and relative risk according to screening history among eligible women aged 25-69 in Southampton and South West Hampshire during the three years after completion of the first round of comprehensive screening. RESULTS: There was a significantly higher incidence of invasive cervical cancer in women who had not been screened during the preceding 0.5-5.5 years than in those who had been screened (relative risk (RR) 2.6; 95% confidence interval (CI) 1.6 to 4.3). Among the latter group of women (with interval cancers) there was a significantly higher incidence in those with a long interval of 3.5-5.5 years since their most recent smear than in those with a short interval of 0.5-3.5 years (RR 2.2; 95% CI 1.3 to 3.8). Among women with non-interval cancers, there was a significantly higher incidence among those who had no cytology record than among those who had been screened but were overdue for a smear (RR 3.0; 95% CI 1.2 to 7.3). When screen detected cancers were excluded from the figures the relative risks for all the comparative groups described above were greater, though the 95% confidence limits were wider because the numbers were smaller. The most pronounced difference in incidence was between symptomatic cancers in women with a short screening interval (5.8 per 100,000 women years at risk) and in women with no cytology record (71.3 per 100,000 years at risk). Most cancers were interval cancers (76%) because of the high screening coverage: 89.2% of eligible women aged 25-69 had been screened during the preceding 0.5-5.5 years. The overall incidence per 100000 women years at risk approached that of interval cancers, and was nearer to that observed in the short than the long interval because 74.7% of women had been screened within 3.5 years. CONCLUSION: The results confirm the effectiveness of screening but suggest that a five year screening interval may be too long, at least during the early rounds of screening.     

Digital archival and exchange of events in a simple format for polygraphic recordings with application in event related potential studies

The relationship between sequential mammographic parenchymal patterns and breast cancer was estimated and the results were applied to selective screening. In a pilot screening program 4163 Finnish women aged 40-47 years at entry were invited to be screened every second year from 1982 to 1990. Mammographic parenchymal patterns (Wolfe's classification) were recorded at each screening round. The follow-up ended in 1993 and up until that time 68 new breast cancers were diagnosed. The age-adjusted relative risk of breast cancer was 2.5 (95% CI 1.5-4.0) among women with high-risk mammographic parenchymal patterns (P2,DY) at the screenings preceding cancer diagnosis compared with those with low-risk patterns (N1,P1). After further adjustment for body mass index, number of pregnancies and size of the breast, the relative risk increased to 2.8 (95% CI 1.7-4.9). The mammographic parenchymal pattern is an independent risk factor of breast cancer but not strong enough to be used as a criterion for selective screening.     

Effect of BRCA1 and BRCA2 on the association between breast cancer risk and family history

BACKGROUND: The discovery of BRCA1 and BRCA2 has led to a reassessment of the association between family history of breast/ovarian cancer and breast cancer risk after controlling for carrier status for mutations in the BRCA1 and BRCA2 genes. We examined whether family history of breast cancer remains a predictive risk factor for this disease after carrier status for BRCA1 and/or BRCA2 mutations is taken into consideration. METHODS: The data are from 4730 case subjects with breast cancer and 4688 control subjects enrolled in the Cancer and Steroid Hormone Study. The probability of being a BRCA1 and/or BRCA2 gene carrier was calculated for each woman. Among predicted noncarriers, logistic regression was used to assess the relationship (odds ratios and 95% confidence intervals [CIs]) between case or control status and family history of breast or ovarian cancer. Estimates of age-specific breast cancer risk are presented by predicted carrier status. RESULTS: Among predicted noncarriers, case subjects were 2.06 times (95% CI = 1.69-2.50) and 1.24 times (95% CI = 1.17-1.32) more likely to report a first-degree or second-degree family history of breast cancer, respectively, than were control subjects. Case subjects were 1.99 times (95% CI = 1.63-2.44), 1.66 times (95% CI = 1.18-2.38), and 2.23 times (95% CI = 0.21-24.65) more likely to report an affected mother, sister, or both, respectively, than were control subjects. A family history of ovarian cancer was not statistically significantly associated with breast cancer risk. Noncarriers were predicted to have a lifetime risk of 9% of developing breast cancer compared with a 63% risk for carriers. CONCLUSIONS: Among women with a moderate family history of breast cancer, i.e., predicted noncarriers of BRCA1 and/or BRCA2 mutations, family history remains a factor in predicting breast cancer risk. In families with breast and ovarian cancers, the aggregation of these two cancers appears to be explained by BRCA1/BRCA2 mutation-carrier probability.     

Features of the spike activity of globus pallidus neurons and pallido-thalamic functional interactions during targeted verbally cued movements in humans

OBJECTIVE: To estimate the relative risk and lifetime risk of ovarian cancer in women with various categories of family history. DESIGN: A meta-analysis of all published case-control and cohort studies. METHODS: Pooled relative risk estimates were calculated for the case control studies, using the Mantel-Haenzel method. These estimates were combined with the relative risks from the cohort studies. The pooled estimates of relative risk were used to estimate lifetime risks of ovarian cancer from age 15 up to age 75, for various categories of family history. MAIN OUTCOME MEASURES: Relative risks and lifetime risks of developing ovarian cancer were calculated for the categories of women with 1. an affected first degree relative; 2. an affected mother; 3. an affected sister; and 4. women with more than one affected relative. RESULTS: The relative risk to first degree relatives is 3.1 (95% CI 2.6-3.7). There is some evidence that this relative risk declines with age. The relative risk to mothers of cases 1.1 (95% CI 0.8-1.6) was lower than the relative risks to sisters: 3.8 (95% CI 2.9-5.1), and daughters: 6.0 (95% CI 3.0-11.9); the explanation of this difference is unclear. CONCLUSIONS: Women with a family history of ovarian cancer have a substantially higher risk of developing ovarian cancer compared with women without such a history. However the risk is small for most categories of family history, except for the small number of individuals who have more than one affected relative.     

Relationship between number of ovulatory cycles and accumulation of mutant p53 in epithelial ovarian cancer

BACKGROUND: It has been suggested that increased numbers of ovulations might increase the risk of p53 gene (also known as TP53) mutation in the ovarian epithelium, thereby leading to the development of cancer. The data supporting this hypothesis have come from an observation that accumulation of p53 protein in epithelial ovarian cancer was strongly associated with increasing numbers of ovulatory cycles. We have further investigated the association between ovulatory history and p53 gene mutation by use of data from a large case-control study of ovarian cancer in Australia. METHODS: Tissue blocks were available for immunohistochemical analysis of p53 protein from 234 case subjects, aged 18-79 years, who had invasive epithelial ovarian cancer. Epidemiologic data were also available for these women and for 855 control subjects. Case-case comparisons were made by use of prevalence ratios and 95% confidence intervals (CIs), and case-control comparisons were made by use of odds ratios (ORs) and 95% CIs. All statistical tests were two-sided. RESULTS: There was no association between p53 accumulation and years of ovulation. Women with p53-positive cancers had undergone an average of 29.3 years of ovulation compared with 29.0 years of ovulation for women with p53-negative cancers (P=.8). Although the overall risk of ovarian cancer development was significantly increased in women who had undergone more years of ovulation (OR=2.17; 95% CI =1.54-3.05-for > or =35 years versus <23 years of ovulation), there was no difference in the risk associated with p53-positive and p53-negative cancers. CONCLUSIONS: These results confirm the association between increased ovulation and ovarian cancer risk but do not support the hypothesis that this association is due to an increased risk of p53 mutation with a greater number of ovulatory cycles.     

CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution

BACKGROUND: Although increasing rates of breast carcinoma incidence have been observed in Asian countries, appropriate strategies for detecting early stage breast carcinoma in such communities have been difficult to formulate, particularly because no large population screening trial specifically involving Asian women has been reported. The objective of this study was to evaluate the effectiveness and quality of mammography as a screening technique for Singaporean women, who are predominantly Chinese. METHODS: In this prospective study, 166,600 women in Singapore ages 50-64 years were randomized to either 2-view mammography without physical examination (67,656) or observation (97,294, controls) over 2 years. RESULTS: Of these women, 28,231 (41.7%) responded and were screened; they were more likely to be married, have more formal education, be working, be Chinese, and be in a higher socioeconomic group (P < 0.001 for all variables). To assess for response bias that could affect outcome, results were also evaluated for nonrespondents (n = 39,425). The incidence rate of cancers among nonrespondents (1 per 1000 woman-years) was less than the 1.3 in women not invited to have screening (P = 0.03, relative risk [RR], 1.3; 95% confidence interval [CI], 1.0-1.7). However, cancers arising from nonrespondents did not differ significantly in stage distribution when compared with cancers within the control group. For every 1000 women screened, 4.8 cancers were detected. The prevalence ratio (the number of cancers detected per 1000 women at first screening divided by the corresponding incidence rate in controls per year) was 3.6 for screened women and 2.4 for women invited to have screening. The majority of cancers detected through screening were early stage, with 64% as either ductal carcinoma in situ (26%) or Stage I disease (38%) and was significantly more than the corresponding 26% in women not invited to have screening (P < 0.001). When only invasive cancers were considered, screened women still had more early cancers, with 65% having no lymph node involvement, compared with 47% in the group not invited to have screening (P = 0.001; RR, 1.4; 95% CI, 1.2-1.7). Women who were screened had half the risk of having Stage II or later cancers (P < 0.0001; RR, 0.5; 95% CI, 0.4-0.7) when compared with women not invited to have screening. This higher detection rate of early cancers through screening was accomplished with acceptable recall rates of 8% for further mammographic films or physical examination and a biopsy rate of 1.0% (10 per 1000 women screened). The interval cancer rate was 2.1 per 10,000 women screened in the first year of follow-up. CONCLUSIONS: These positive results of intermediate measures suggest that, in Asian communities, screening mammography could be an important modality for detecting early stage breast carcinoma. However, the low compliance rates suggest that health education efforts must focus on issues related to acceptability if such programs are to succeed.     

Pancreas cancer as a second primary malignancy. A population-based study

BACKGROUND: The study of second primary malignancies may give clues to the etiology of various cancers. Little is known about risk factors for pancreatic carcinoma; therefore, its occurrence as a second primary malignancy was investigated. METHODS: Data from the Surveillance, Epidemiology, and End-Results (SEER) program were used for the period from January 1, 1973 through December 31, 1990. Person-years of follow-up for various cancer sites were calculated, excluding the initial 6 months after diagnosis, and were multiplied times the age- and sex-specific incidence rates for pancreas cancer to calculate the expected number of second primary pancreas cancer cases. The observed number of cases was divided by the expected number to estimate the relative risk (RR) of pancreas cancer as a second primary cancer, and 95% confidence limits were calculated. RESULTS: The risk of second primary cancer was elevated after lung cancer for men (RR 1.3, 95% CI 1.0-1.6) and women (RR 2.5, 95% CI 1.9-3.2). An elevation in risk also was found after head and neck cancer in women (RR 1.8, 95% CI 1.2-2.5) and bladder cancer in women (RR 1.5, 95% CI 1.1-2.0), but not in men. Other significant elevations were found after prostate cancer (RR 1.2, 95% CI 1.1-1.3), and a decreased risk was found after lymphoma in men (RR 0.2, 95% CI 0.0-0.8). CONCLUSIONS: Second primary pancreas cancer is increased after tobacco-related malignancies, particularly in females, supporting the role of cigarette smoking as a risk factor for pancreas cancer and suggesting a stronger effect of cigarette smoking for women. The elevation in risk after prostate cancer and the decreased risk after lymphoma in males need to be confirmed in other data sets.     

Treatment for infertility and risk of invasive epithelial ovarian cancer

The relationship between the use of fertility drugs and the risk of ovarian cancer was analysed using data from an Italian case-control study. The study comprised 971 women below the age of 75 years with histologically confirmed invasive epithelial ovarian cancer diagnosed within the year before the interview. The controls were 2758 women admitted to the same network of hospitals where the cases of ovarian cancer had been identified. Five cases (0.5%) and 11 controls (0.4%) reported use of fertility drugs. In comparison with women who had never used fertility drugs, the multivariate odds ratio (OR) for women who had taken fertility drugs was 1.1 [95% confidence interval (CI) 0.4-3.3]. The OR were 0.7 (95% CI 0.1-7.9) and 1.0 (95% CI 0.2-3.8) for women who had used fertility drugs for <6 and > or =6 cycles respectively. Considering the 14 cases and 45 controls reporting difficulty in conception, the risk of ovarian cancer was 0.5 (95% CI 0.1-3.6) for women who reported use of fertility drugs. Considering nulliparous women only, the estimated OR of ovarian cancer for any fertility drug use was 0.6 (95% CI 0.1-3.5). Although the present results have limitations in terms of statistical power and available information, they provide reassuring evidence of the absence of a strong association between fertility drugs and subsequent risk of developing epithelial ovarian cancer.     

The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39-49

We carried out a randomized trial of invitation to screening mammography in the city of Gothenburg, Sweden, to estimate the effect of screening on breast cancer mortality in women under age 50 years. A total of 11,724 women aged 39-49 were randomized to the study group, which was invited to mammographic screening every 18 months; 14,217 women in the same age range were randomized to a control group, which was not invited to screening until the fifth screen of the study group. Breast cancers diagnosed in both groups between randomization and immediately after the first screen of the control group were followed up for death from breast cancer to the end of December 1994. There was a significant 44% reduction in mortality from breast cancer in the study group compared to the control group (relative risk [RR] = 0.56, P = 0.042, 95% confidence interval [CI]: 0.32-0.98). A conservative estimate based on removal of the cancers detected at the first screen of the control group gave an RR = 0.59 (P = 0.069, 95% CI: 0.33-1.05). The true answer is likely to lie between the two estimates. These data suggest that mammographic screening can reduce breast cancer mortality in women under age 50, particularly if high-quality mammography is used and a short interscreening interval is adhered to.     

Young children''s understanding of pretense expressions of independent agency

Data from the Cancer Registry of Slovenia were used in a cohort study to determine whether the incidence of second primary cancers in patients with first primary breast cancer differs from the incidence expected in the general population. Special interest was given to long-term survivors. The expected numbers of second primary cancers were calculated by multiplying the number of appropriate person-years at risk by the corresponding age- and calendar-period-specific cancer incidence rates for women in Slovenia. The risk of a second primary cancer was expressed as the standardized incidence ratio (SIR). Of the 8,917 patients newly diagnosed in the period 1961-85 and followed-up to the end of 1994, 547 (6.2 percent) developed second primary cancers, whereas 410 (4.7 percent) were expected (SIR = 1.3, 95 percent confidence interval [CI] = 1.2-1.4). The risk was higher among younger patients. In long-term survivors, the risk was increased significantly for second primary cancer of the breast (SIR = 1.4, CI = 1.1-1.7), lung cancer (SIR = 1.6, CI = 1.1-2.3), melanoma (SIR = 2.7, CI = 1.5-4.4) and non-melanoma skin cancers(SIR = 2.0, CI = 1.6-2.4), corpus uteri cancer(SIR = 1.6, CI = 1.2-2.1), ovarian cancer(SIR = 2.3, CI = 1.7-3.0), and thyroid cancer (SIR = 2.5, CI = 1.2-4.6). Our results confirm the findings of several cohort studies carried out in Europe, the United States, and Japan, indicating that breast cancer patients should be monitored carefully for the occurrence of second primary cancers.     

Cancer in developing countries: Part II--Cancer control: strategies and priorities

In 1992 the first Hereditary Cancer Center in Poland has been organized in Szczecin. DESIGN: One of its goals is application of appropriate management in families with hereditary ovarian cancer. The aims of our program include studies of: incidence, clinical characterization, DNA diagnostic tests and efficiency of screening for early detection of hereditary ovarian tumors in North-West Poland. MATERIAL: Our program includes 234 families with 258 cases of ovarian cancers. RESULTS: Site-specific familial aggregation of ovarian cancer was diagnosed in 16 (6.84%) families, breast-ovarian cancer syndrome in 27 (11.54%), Lynch II syndrome in 5 (2.14%) families, undefined cancer family aggregation in 12 (5.13%) families, sporadic ovarian cancers diagnosed age of 44 in 56 (23.93%) families and other sporadic ovarian cancers in 118 (50.4%). In 17 patients with ovarian cancer from families with breast-ovarian cancer syndrome constitutional BRCA-1 gene mutations were studied by sequencing DNA on automated sequencer of PCR products for all 24 exons. In 1 patient constitutional mutation in exone 11 was detected. We found also multiply polymorphic changes. 124 women-members of 116 families with diagnosed hereditary predisposition for ovarian cancer have been studied for asymptomatic tumors by intravaginal USG and evaluation of CA 125 marker every 6 month beginning from 20-25 years of age. Up to now we found 5 cases of benign serous cystadenomas, 3 cases of cystadenomas of borderline malignancy and 1 cases of serous cystadenocarcinoma. CONCLUSIONS: It seems, that particular surveillance program in women from families with hereditary cancers can be the effective way of detection of early ovarian tumors. Clinical characterization of hereditary ovarian cancers in North-West Poland and other countries is similar.     

Recruitment of women by GPs for pap tests: a meta-analysis

General practitioners (GPs) have a pivotal role to play in recruiting women for Pap tests. In recent times, considerable attention has been paid to the role of reminder systems in encouraging women to have regular Pap tests. Although a number of studies have investigated the effectiveness of reminder systems, there has been no comprehensive review. This paper aims to determine the effectiveness of patient and GP reminders in increasing the proportion of women screened for cervical cancer. Two electronic databases were searched for English-language randomized controlled trials conducted in a general practice or family medicine setting, and examining the effectiveness of GP and patient reminders in increasing the proportion of women screened for cervical cancer. Ten trials were identified, and meta-analytic techniques were employed to analyse the data from these trials. The women whose GPs had been prompted to remind them to have a Pap test were significantly more likely to do so than were control women (typical risk difference (TRD) = 6.6%, 95% CI = 5.2%-8.0%). The typical risk difference for the patient reminder studies was 4.9% (95% CI = 2.6%-7.2%). In both cases, sensitivity analysis revealed that one study stood out as an exceptional result. The omission of this study induced homogeneity among the remaining studies. Once this study was removed, the TRDs for the GP reminder and patient reminder studies were 7.9% (95% CI = 6.5%-9.4%) and 10.8% (95% CI = 8.1%-13.6%), respectively. The results strongly suggest that GPs should make use of GP and patient reminder systems.     

Increased risk for cancer in patients with the Peutz-Jeghers syndrome

BACKGROUND: Some reports describe an increased risk for cancer in patients with the Peutz-Jeghers syndrome. OBJECTIVE: To characterize occurrences of cancer in a large cohort of patients with the Peutz-Jeghers syndrome. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: 34 patients with the Peutz-Jeghers syndrome identified from Mayo Clinic records from 1945 to 1996. MEASUREMENTS: Cases of cancer documented by chart review and telephone follow-up. RESULTS: 26 cases of noncutaneous cancer developed in 18 of the 34 patients: 10 cases of gastrointestinal cancer and 16 cases of extraintestinal cancer. With the use of SEER (Surveillance, Epidemiology, and End Results) data for comparison, the relative risk for cancer was 18.5 (95% CI, 8.5 to 35.2) in women with the Peutz-Jeghers syndrome and 6.2 (CI, 2.5 to 12.8) in men with the syndrome (P = 0.001). In women, the relative risk for breast and gynecologic cancer was 20.3 (CI, 7.4 to 44.2). CONCLUSIONS: The Peutz-Jeghers syndrome is associated with an increased risk for cancer. The relative risk for breast and gynecologic cancers is particularly high.     

Increased cancer mortality following a history of nonmelanoma skin cancer

CONTEXT: Cancer registries have reported an increased incidence of melanoma and certain noncutaneous cancers following nonmelanoma skin cancer (NMSC). Whether these findings were attributable to intensified surveillance, shared risk factors, or increased cancer susceptibility remains unclear. OBJECTIVE: To determine whether a history of NMSC predicts cancer mortality. DESIGN: Prospective cohort with 12-year mortality follow-up adjusted for multiple risk factors. SETTING: Cancer Prevention Study II, United States and Puerto Rico. PARTICIPANTS: Nearly 1.1 million adult volunteers who completed a baseline questionnaire in 1982. MAIN OUTCOME MEASURE: Deaths due to all cancers and common cancers. RESULTS: After adjusting for age, race, education, smoking, obesity, alcohol use, and other conventional risk factors, a baseline history of NMSC was associated with increased total cancer mortality (men's relative risk [RR], 1.30; 95% confidence interval [CI], 1.23-1.36; women's RR, 1.26; 95% CI, 1.17-1.35). Exclusion of deaths due to melanoma reduced these RRs only slightly. Mortality was increased for the following cancers: melanoma (RR, 3.36 in men, 3.52 in women); pharynx (RR, 2.77 in men, 2.81 in women); lung (RR, 1.37 in men, 1.46 in women); non-Hodgkin lymphoma (RR, 1.32 in men, 1.50 in women); in men only, salivary glands (RR, 2.96), prostate (RR, 1.28), testis (RR, 12.7), urinary bladder (RR, 1.41), and leukemia (RR, 1.37); and in women only, breast (RR, 1.34). All-cause mortality was slightly increased (adjusted men's RR, 1.03 [95% CI, 1.00-1.06]; women's RR, 1.04 [95% CI, 1.00-1.09]). CONCLUSIONS: Persons with a history of NMSC are at increased risk of cancer mortality. Although the biological mechanisms are unknown, a history of NMSC should increase the clinician's alertness for certain noncutaneous cancers as well as melanoma.     

The diagnostic accuracy of cervico-vaginal fetal fibronectin in predicting preterm delivery: an overview

OBJECTIVE: To determine the accuracy with which cervico-vaginal fetal fibronectin predicts preterm delivery using systematic quantitative overview of the available literature. DESIGN: Online searching of MEDLINE database (1966 to April 1996), scanning of bibliography of known primary and review articles and review of recent journal issues. Study selection, assessment of study quality and data extraction were performed in duplicate under masked conditions. Likelihood ratios were generated in subgroups of symptomatic and asymptomatic pregnant women by pooling data from different studies. An LR of > 10 or < 0.1 indicated conclusive changes in the pretest probability of preterm delivery while an LR of 5-10 or 0.2-0.1 indicated only moderate changes. PARTICIPANTS: Seven hundred and twenty-three symptomatic women with threatened preterm labour included in nine studies and 847 asymptomatic women (635 low risk and 212 high risk) included in six studies selected for meta-analyses. MAIN OUTCOME MEASURES: Likelihood ratios for positive and negative test results using delivery at < 37 and < 34 weeks of gestation, and within one week of testing as outcome measures. RESULTS: In symptomatic women a positive test predicted delivery < 37 weeks of gestation with a pooled likelihood ratio (LR) of 4.6 (95% CI 3.5-6.1) while a negative test had a pooled LR of 0.5 (95% CI 0.4-0.6). For delivery < 34 weeks of gestation, the pooled LR was 2.6 (95% CI 1.8-3.7) for a positive test and 0.2 (95% CI 0.1-0.5) for a negative test. For delivery within one week of testing, the pooled LR was 5.0 (95% CI 3.8-6.4) for a positive test and 0.2 (95% CI 0.1-0.4) for a negative test. In asymptomatic women at low risk of delivery < 37 weeks of gestation the pooled LR was 3.2 (95% CI 2.2-4.8) for a positive test and 0.8 (95% CI 0.7-0.9) for a negative test. In high risk asymptomatic women using delivery < 37 weeks of gestation as an outcome measure the pooled LR was 2.0 (95% CI 1.5-2.6) for a positive test and 0.4 (95% CI 0.2-0.8) for a negative test. For delivery < 34 weeks of gestation in high risk, asymptomatic women the pooled LR was 2.4 (95% CI 1.8-3.2) for a positive test and 0.6 (95% CI 0.4-0.9) for a negative test. CONCLUSION: The presence of fetal fibronectin in cervico-vaginal mucus has limited accuracy in predicting preterm delivery as the likelihood ratios for positive and negative test results generated only minimal to moderate changes in the pretest probability of preterm birth.     

Hormone replacement therapy as a risk factor for epithelial ovarian cancer: results of a case-control study

OBJECTIVE: To evaluate the role of hormone replacement therapy (HRT) as a risk factor for the development of epithelial ovarian cancer. METHODS: A case-control study was performed that used 491 patients with epithelial ovarian cancer frequency matched for age at diagnosis (+/-5 years) with a control population of 741 patients with malignancies of nonestrogen-dependent tissues. The odds ratio (OR) for the development of epithelial ovarian cancer was estimated using logistic regression analysis with adjustment for age at diagnosis, parity, oral contraceptive use, smoking history, family history of epithelial ovarian cancer, age at menarche, menopausal status, income, and education. RESULTS: One hundred of 491 patients (20.4%) in the study population had ever used HRT, and 160 of 741 patients (21.6%) in the control population had ever used HRT (OR 0.85; 95% confidence interval [CI] 0.62, 1.2). A significant association between HRT and specific histologic subtypes of epithelial ovarian cancer was not demonstrable for serous cystadenocarcinoma (OR 1.2, 95% CI 0.8, 1.7), Clear cell carcinoma (OR 1.1, 95% CI 0.4, 3.4), or endometrioid carcinoma (OR 0.4; 95% CI 0.2, 1.2). A significant association between duration of use of HRT and the risk of developing epithelial ovarian cancer was not demonstrable for under 5 years (OR 0.8; 95% CI 0.5, 1.2), 5-9 years (OR 0.6; 95% CI 0.3, 1.1), or 10 or more years (OR 0.6; 95% CI 0.3, 1.4). CONCLUSION: A significant association between the use of HRT and the risk of developing epithelial ovarian cancer, even with prolonged exposure, is not demonstrable.