Trends in mortality of childhood-onset insulin-dependent diabetes mellitus in Leicestershire: 1940-1991

The relative risk of death by calendar date of diagnosis was investigated in a population-based incident cohort of 845 (463 males:382 females) IDDM diagnosed in Leicestershire before the age of 17 years between 1940 and 1989. The mortality status of 844 (99.9%) patients was determined as of the 31 December 1991, representing 14,346 person-years of risk. Trends in relative risk of death were investigated using Cox proportional hazards modelling for within cohort comparisons and age/sex and calendar time adjusted standardized mortality ratios (SMR) using generalized linear modelling for external comparisons. Median age at diagnosis was 10 years (range 3 months to 16 years); median duration of diabetes 15 years (range 1-51 years). Forty-four patients had died (5.2%; median age at death 31 years, range 11-51 years). A further four patients died at presentation (within 24 h) from ketoacidosis and are excluded from all analyses. Calendar date of diagnosis was found to be an important predictor of mortality. Adjusting for attained age there was evidence of a decline in relative risk of death with calendar date of diagnosis of 3.4% (95% CI, 0.005-6.9%) per annum, equivalent to a 32% fall per decade (95% CI, 5-51%), or 84% (95% CI, 21-97) from 1940 to 1989. The data are consistent with a large fall in mortality between the 1940s and 1950s representing over 50% of the total reduction in mortality between 1940 and 1991. Neither sex nor age at diagnosis were significant predictors of mortality. Over the study period 1940-89 the SMR (male and female combined) fell from 981 (541-1556) to 238 (60-953) relative to the general population. This population-based study shows that the prognosis for Type 1 (insulin-dependent) diabetes mellitus has improved markedly over the period 1940-1991.     

FPSUND: a pan-Canadian evaluation of a clinical classification of urinary incontinence

To obtain quantitative information on the risk of invasive cancers following a diagnosis of basal cell carcinoma (BCC) of the skin, patients with incident BCC cases listed in the cancer registries of the Swiss cantons of Vaud and Neuchatel between 1974 and 1994 were actively followed up through December 31, 1994, for the occurrence of subsequent invasive neoplasms. Among 11,878 persons with incident BCC who were followed for a total of 76,510 person-years at risk, 1,543 metachronous cancers were observed versus 1,397.9 expected, corresponding to a standardized incidence ratio (SIR) of 1.1 (95% confidence interval (CI) 1.0-1.2). However, after exclusion of skin cancers (mostly squamous cell carcinoma and melanoma), 975 second primary cancers were observed versus 1,059 expected (SIR = 0.9, 95% CI 0.8-1.0). Significant excesses were registered for cancer of the lip (SIR = 2.2), for squamous cell skin cancer (SIR = 4.5) and melanoma of the skin (SIR = 2.5), and for non-Hodgkin's lymphoma (SIR = 1.9). The SIRs were also above unity, though not significantly, for cancers of the salivary glands (SIR = 2.8) and the small intestine (SIR = 2.1) and for soft-tissue sarcomas (SIR = 1.7). The SIR for lung cancer was 0.9. The SIRs for salivary gland and skin cancer were appreciably greater below age 70 years. For most sites, particularly for squamous cell cancer and melanoma of the skin, the SIRs remained elevated 5 or more years after BCC diagnosis. The cumulative incidence of squamous cell skin cancer was 13% at 19 years; this stresses the importance of carefully monitoring skin lesions among persons previously diagnosed with BCC.     

Field studies and cost-effectiveness analysis of vaccination with Gavac against the cattle tick Boophilus microplus

This study presents findings from an updated retrospective cohort mortality study of male police officers from January 1, 1950 to December 31, 1990 (n = 2,593; 58,474 person-years; 98% follow-up). Significantly higher than expected mortality rates were found for all cause mortality (Standardized mortality ratio [SMR] = 110; 95% confidence interval [95% CI] = 1.04-1.17), all malignant neoplasms (SMR = 125; 95% CI = 1.10-1.41), cancer of the esophagus (SMR = 213; 95% CI = 1.01-3.91), cancer of the colon (SMR = 187; 95% CI = 1.29-2.59), cancer of the kidney (SMR = 2.08, 95% CI = 100-3.82), Hodgkin's disease (SMR = 313; 95% CI = 1.01-7.29), cirrhosis of the liver (SMR = 150; 95% CI = 1.00-2.16), and suicide (SMR = 153; 95% CI = 1.00-2.24). All accidents were significantly lower (SMR = 53; 95% CI = 0.34-0.79). Mortality by years of police service showed higher than expected rates for (1) all malignant neoplasms in the 1- to 9-years-of-service group; (2) all causes, bladder cancer, leukemia, and arteriosclerotic heart disease in the 10 to 19-year group; and (3) colon cancer and cirrhosis of the liver in the over 30 years of service group. Hypotheses for findings are discussed.     

The risk of subsequent primary carcinoma of the pancreas in patients with cutaneous malignant melanoma

BACKGROUND: Carcinoma of the pancreas is the fifth leading cancer in the U.S. and has the poorest survival rate of the major malignancies. Recent studies have reported an increased risk of carcinoma of the pancreas in malignant melanoma-prone kindreds and have suggested a link between malignant melanoma and pancreas carcinoma and mutations in the p16INK4 gene. This study evaluates the risk of carcinoma of the pancreas in a population-based cohort of patients with malignant melanoma. METHODS: The malignant melanoma patients were identified from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The cohort was followed within the SEER system to ascertain the occurrence of subsequent microscopically confirmed primary carcinoma of the pancreas from January 1973 through December 1993. The time of follow-up was expressed as person-years of observation. Standardized incidence ratios (SIR) and 95% confidence intervals (95% CI) were calculated. RESULTS: There were 43,781 malignant melanoma patients providing 263,528 person-years of follow-up. A nearly 2-fold increased risk of subsequent carcinoma of the pancreas in patients diagnosed with malignant melanoma before age 50 years was observed (SIR = 1.76; 95% CI = 0.80-3.34) and the greatest estimated risk occurred in young white females (SIR = 2.27; 95% CI = 0.73-5.30). CONCLUSIONS: These results provide some evidence in support of observations in recent studies that not only a family history of malignant melanoma but also malignant melanoma diagnosed at an early age may be associated with the subsequent development of carcinoma of the pancreas. Further research with larger numbers of melanoma patients is necessary to explore these potential associations.     

Rheumatoid arthritis and the risk of malignancy

OBJECTIVE: To determine the relative risks of malignancy and of site-specific malignancies in patients with rheumatoid arthritis (RA). METHODS: In a prospective cohort study, 862 patients with RA (96% white) were enrolled from 1966 to 1974 and were followed up for up to 35 years (mean 17.4 years) at the University of Saskatchewan Rheumatic Disease Unit. All diagnoses of cancer were cross-referenced with the Provincial Cancer Registry. Expected cancer incidence rates were determined based on province of Saskatchewan population statistics matched to each study patient for age, sex, and calendar year. Standardized incidence ratios (SIRs) of the observed-to-expected cancer incidence and 95% confidence intervals (95% CI) were then calculated. RESULTS: A total of 136 cases of cancer were observed compared with 168 expected (SIR 0.80, P = 0.011 [95% CI 0.67-0.95]). The relative risk of colorectal malignancy was significantly reduced in the RA study population (SIR 0.52, P = 0.037 [95% CI 0.25-0.96]). A significant excess of leukemia was found (SIR 2.47, P = 0.026 [95% CI 1.12-4.69]), whereas the incidence rates for Hodgkin's disease and non-Hodgkin's lymphoma and all other site-specific malignancies were not found to be significantly different from general population rates. CONCLUSION: In our cohort of RA patients, colorectal cancer was detected in only half the expected number of patients. This risk reduction may be related to long-term nonsteroidal antiinflammatory drug (NSAID) use in RA, as has been suggested in several other studies of long-term NSAID use. An increased risk of leukemia was confirmed. This may be due to the persistent immune stimulation associated with RA itself, since other potential explanatory factors for increased leukemia were not apparent. Despite the excess of hemopoietic malignancy and despite treatment of RA with potentially oncogenic agents, the overall risk of malignancy was reduced in this RA cohort.     

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.     

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.     

Increased mortality after successful treatment for Hodgkin's disease

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.     

High risk of breast carcinoma after irradiation of young women with Hodgkin's disease

BACKGROUND: Treatment-associated second neoplasms have emerged as a major threat to the continued survival of patients cured of Hodgkin's disease. In this study, the authors investigated the risk of breast carcinoma in an irradiated Hodgkin's disease population. METHODS: One hundred and eleven women younger than 60 years presenting between 1964 and 1984 with Stage I and II Hodgkin's disease who received mantle irradiation were retrospectively analyzed and compared with an age specific population. Median follow-up was 18 years (range, 10-30 years), and the median age at initiation of therapy was 24 years. Kaplan-Meier actuarial risks, relative risks (RRs) (the ratio of the observed to the expected cases) with 95% confidence intervals (CIs), and the log rank test for trends were calculated. RESULTS: Fourteen women developed breast carcinoma: 8 of 33 patients younger than 20 years at the time of irradiation, 5 of 48 patients age 20 to 29 years, and 1 of 30 patients age 30 years or older. Actuarial calculation predicted a 34.0% (CI, 14.2-53.8) risk of breast carcinoma at 25 years after therapy for the youngest group, 22.3% (CI, 4.1-40.5) for the group of intermediate age, and 3.5% (CI, 0-10.1) for the oldest group. The RR of breast carcinoma was 56 (CI, 23.3-107) for those 19 years or younger at the time of treatment, 7.0 (CI, 2.3-16.4) for those age 20-29 years, and 0.9 (CI, 0-5.3) for those 30 years and older. Excluding 1 patient who was age 38 years at the time of irradiation, the remaining 13 breast carcinomas were tightly clustered in women irradiated between the ages of 14 through 25, and were detected in years 11 through 25 after treatment, with 7 occurring in years 15 through 18. CONCLUSIONS: Women younger than 30 years, particularly those younger than 20 years, who have received mantle irradiation for Hodgkin's disease require meticulous follow-up for breast carcinoma. The high incidence of breast carcinoma in this patient population should be considered when making treatment decisions in young women with early stage Hodgkin's disease.     

Microbiological evaluation of glycerolized cadaveric donor skin

Record linkage was carried out between the national Registry of AIDS and 13 Cancer Registries (CRs) covering, in 1991, about 15% of the Italian population. Observed and expected numbers of cancers and standardized incidence ratios (SIRs) were assessed in 6067 persons with AIDS, for a total of 25,759 person-years. Significantly increased SIRs were found for Hodgkin's disease [8.9, 95% confidence interval (CI) 4.4-16.0], in which seven of 11 cases were of mixed cellularity type; invasive carcinoma of the cervix uteri (15.5; 95% CI 4.0-40.1); and non-melanomatous skin cancer (3.0, 95% CI 1.3-5.9), in which five of eight cases were basal cell carcinoma. An excess was also seen for brain tumours, but this may be partly due to misdiagnosis of brain non-Hodgkin's lymphoma or other brain diseases occurring near the time of the AIDS diagnosis. The risk for all cancer types, after exclusion of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), was approximately twice the general population risk. An increased SIR for Hodgkin's disease in persons with AIDS is thus confirmed, though it is many times smaller than that for NHL. An association with invasive carcinoma of the cervix is also shown at a population level. The excess of non-melanomatous skin cancer seems to be lower than in transplant recipients.     

Early prognostic indicators in primary perinatal human immunodeficiency virus type 1 infection: importance of viral RNA and the timing of transmission on long-term outcome

The time of perinatal human immunodeficiency virus type 1 (HIV-1) transmission and the pattern of early plasma viremia as predictors of disease progression were evaluated in infected infants followed from birth. Cox proportional hazards modeling demonstrated that a 1-log higher HIV-1 RNA copy number at birth was associated with a 40% increase in the relative hazard (RH) of developing CDC class A or B symptoms (P = .004), a 60% increase in developing AIDS (P = .01), and an 80% increase in the of risk death (P = .023) over the follow-up period of up to 8 years. The peak HIV-1 RNA copy number for infants during primary viremia was also predictive of progression to AIDS (RH, 9.9; 95% confidence interval [95% CI], 1.8-54.1; P = .008) and death (RH, 6.9; 95% CI, 1.1-43.8; P = .04). The results indicate that high levels of HIV-1 RNA at birth and during primary viremia are associated with early onset of symptoms and rapid disease progression to AIDS and death in perinatally infected children.     

Cancer mortality among electricity utility workers in a the state of Sao Paulo, Brazil

A number of epidemiologic studies have observed an association between exposure to 50-60 Hz electromagnetic fields and the development of specific types of cancer. In Brazil, a preliminary report from a study of electricity facility workers in Rio de Janeiro (RJ) has mentioned relatively similar results. An exploratory analysis of death certificates obtained from a sample of electricity workers in S. Paulo was made. Data was analysed by using the Proportional Mortality Ratio (PMR) and the Proportional Cancer Mortality Ratio (PCMR). A slightly elevated all-sites cancer mortality was observed among these workers (PMR 1.11; 95% CI 0.91-1.35). Site specific analysis has shown a statistically significant higher mortality of laryngeal cancer (PCMR 2.04; 95% CI 1.05-4.20). An excess of deaths was also seen for cancers of the buccal cavity/pharynx, prostate, bladder, brain and Hodgkin's disease, although the results lacked statistical significance. When analysed by categories of estimated exposure to magnetic fields, an excess of deaths from bladder cancer (PCMR 4.17; 95% CI 1.35-9.72), neoplasms of the brain (PCMR 7.7; 95% CI 1.02-9.65) and Hodgkin's disease (PCMR 5.55; 95% CI 1.14-16.21) was observed in the group with probably higher exposure to EMF. A comparison of cancer mortality between these workers and petrochemical employees has shown a higher PCMR for larynx tumours (PCMR 3.51; 95% CI 3.02-15.51) and bladder cancer (PCMR 7.53; 95% CI 3.02-15.51). For brain tumours, however, a PCMR of 0.74 (95% CI 0.27-1.61) was noted. Although restrictions related to sample size in the study and the lack of information about known confounders must be considered, the results of this study do not fully disagree with others previously mentioned in the literature.     

Cancer in the offspring of parents with lung cancer

Despite several studies on the role of passive smoking in the development of childhood cancer, particularly leukaemia, lymphomas and brain cancer, no definitive answer has yet been provided. The aim of the cohort study reported here was to analyse the incidence of cancer in the offspring of young lung cancer patients on the basis of the assumption that all of the offspring were exposed passively to smoke. The files of the Danish Cancer Registry provided 3348 cases of lung cancer patients born after 1935, and their offspring (n = 6417) were identified through the Danish Population Register. The files of the offspring were then linked with the files of the Danish Cancer Registry and the numbers of cancers observed in the offspring were compared with those expected from national age-specific and calendar-time-specific rates. A total of 135,333 person-years was the basis for analysis. Twenty-six cancers were observed, with 30.3 expected, yielding a standardised incidence ratio (SIR) of 0.9 (90% confidence interval (CI), 0.6-1.2). There was no excess of brain tumours, leukaemias or lymphomas. Stratification for sex of the lung cancer patients revealed a non-significantly increased risk for both non-Hodgkin's lymphoma (three cases; SIR = 3.4; 90% CI: 0.9-8.7) and Hodgkin's disease (three cases; SIR = 2.6; 90% CI: 0.7-6.6) in the offspring of female lung cancer patients. These results suggest that there is little evidence of an excess cancer risk in childhood, whether due to passive smoking or to as yet unidentified genetic factors, among the offspring of people who develop lung cancer. However, the results are limited by the fact that exposure was only assessed indirectly, with no measurement of actual cigarette consumption made.     

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.     

A case-control study of reproductive factors and risk of lymphomas and myelomas

The relationship between reproductive factors and risk of lymphoid neoplasms was investigated in a hospital-based case-control study conducted in northern Italy on women with histologically confirmed incident Hodgkin's disease (HD) (n = 68), non-Hodgkin's lymphomas (NHL) (n = 180) and multiple myelomas (MM) (n = 71), and 448 controls admitted to hospitals, for acute, non-neoplastic, non-immunological and non-gynecological conditions. The odds ratios (OR) of HD were 0.6 for > or = 3 pregnancies compared to nulligravidae, and 0.5 for > or = 1 total (spontaneous and induced) abortions compared to women reporting no abortions. Compared to nulliparae, the OR of HD was 0.9 in parae and 0.3 in those with first birth when aged < 20 years. The OR of NHL and MM in relation to number of pregnancies, abortions and births, age at first birth and time since last birth were close to unity. Results were similar for the relation between reproductive factors and HD in women younger than 50 years. The OR of NHL was above unity (OR 2.2, 95% CI 1.0 to 4.9) for women aged < 50 years reporting one or more pregnancies as compared to nulliparae, and for women reporting the last birth since less than 10 years (OR 2.9, 95% CI 1.1 to 7.4). Early events in pregnancy, including changes in immunological status, rather than exposure to female sex hormones are likely mechanisms for the protection of pregnancies and abortions on the risk of HD.     

Pharmacokinetics of recombinant human interferon-alpha 2a combined with 5-fluorouracil in patients with advanced colorectal carcinoma

A cohort study was conducted to estimate the risk of breast cancer recurrence among women diagnosed with ductal carcinoma in situ (DCIS) and to identify tumor or patient characteristics that influence that risk. A population-based cancer registry was used to identify a cohort of 709 female residents of western Washington who were diagnosed with DCIS between January 1980 and June 1992 and were treated with breast-conserving surgery. Information about breast cancer recurrences, treatment, and several patient characteristics and exposures was obtained from postal questionnaires. Recurrences were confirmed using information from the cancer registry or hospital pathology reports. Approximately 15% of women experienced a recurrence within the first 5 years after diagnosis [95% confidence interval (CI), 12-18%]; 31% had a recurrence within 10 years (95% CI, 24-38%). There was a suggestion that risk was slightly elevated for women with larger tumors (> or =1.5 cm) and tumors of comedo subtype. Relative risks (RRs) were elevated for women who were premenopausal at diagnosis of DCIS (RR = 2.3; 95% CI, 1.1-5.0). Women in the upper decile of body mass index were at twice the risk of a recurrence as those women in the lower four deciles (RR = 2.3; 95% CI, 1.1-4.8). There was also a suggestion that women who used menopausal hormones for at least 2 years after their diagnosis of DCIS were at increased risk of recurrence compared to nonusers of menopausal hormones (RR = 1.8; 95% CI, 0.7-5.0). Our results suggest that the risk of recurrence may be related to some tumor characteristics as well as the hormonal milieu of the patient at or after her diagnosis of DCIS. However, larger studies are needed to more clearly document predictors of disease recurrence after DCIS.     

Risk of recurrent biliary tract disease after cholecystectomy in patients with duodenal diverticula

OBJECTIVE: To determine if the presence of duodenal diverticula predisposes to the development of common bile duct stones. DESIGN: Cohort study; median follow-up, 10.0 years (25th and 75th percentiles, 5.2 and 16.1 years, respectively). SETTING: Tertiary care center. PATIENTS: One hundred fifty-seven patients with radiologically diagnosed duodenal diverticula who had undergone cholecystectomy from 1950 through 1987 and were asymptomatic at the initiation of follow-up. MAIN OUTCOME MEASURES: All patients were followed up for evidence of recurrent biliary tract disease to the following end points: (1) evidence of choledocholithiasis demonstrated by radiologic surgical, or biochemical means and (2) clinical or biochemical evidence of biliary pancreatitis. RESULTS: Of the 157 patients in the study cohort, 13 patients were categorized as having had recurrent biliary tract disease. Using the Kaplan-Meier survivorship method, the cumulative probabilities of recurrent biliary tract disease in patients with radiologically diagnosed duodenal diverticula were 3.6% at 5 years (95% confidence interval, 0.5-6.9), 5.5% at 10 years (95% confidence interval, 1.5-9.4), and 10.2% at 15 years (95% confidence interval, 3.8-16.7). Age, common bile duct exploration and choledochotomy, and the presence of common bile duct dilatation were not found to be significantly associated with recurrence based on a univariate analysis of risk factors by means of the log-rank statistic. CONCLUSIONS: For patients with radiologically diagnosed, second-portion duodenal diverticula, the risk of developing recurrent bile duct stones after cholecystectomy is lower than has been suggested in previous studies. In the absence of concurrent choledocholithiasis, sphincterotomy or biliary bypass at the time of cholecystectomy seems unwarranted.     

Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport

Since the 1950s the U.S. military has used intramuscular injections of benzathine penicillin G (BPG) to control outbreaks of respiratory disease. In an effort to find an alternative prophylaxis, a randomized field trial was conducted among 1,016 male U.S. Marine trainee volunteers at high risk for respiratory disease. Participants were evaluated for evidence of acute respiratory infection by serological tests on pretraining and posttraining sera (63 days apart). Oral azithromycin prophylaxis (500 mg/w) outperformed BPG, preventing infection from Streptococcus pyogenes (Efficacy [E] = 84%; 95% confidence interval [CI], 63%-93%), Streptococcus pneumoniae (E = 80%; 95% CI, 50%-92%), Mycoplasma pneumoniae (E = 64%; 95% CI, 25%-83%), and Chlamydia pneumoniae (E = 58%; 95% CI, 15%-79%) in comparison with results in a no-treatment group. Azithromycin group subjects reported few side effects and less respiratory symptoms than the BPG and no-treatment groups. According to serological tests, oral azithromycin is an effective alternative prophylaxis to BPG for military populations.     

Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries

PURPOSE: To compare the risk for fatal myocardial infarction (MI) after adjuvant radiotherapy (RT) for left-sided breast cancer with the risk for MI after adjuvant RT for right-sided breast cancer. METHODS: We studied women with local- and regional-stage breast cancer diagnosed from 1973 to 1992 from the Surveillance, Epidemiology, and End-Results (SEER) cancer registries. We performed life-table analysis, the log-rank test, and Cox proportional hazards regression to compare the time to fatal MI from diagnosis between left-sided and right-sided cases, censoring deaths from other causes. RESULTS: Among irradiated patients, the relative risk (RR) for fatal MI in women with left-sided breast cancer was 1.17 (95% confidence interval [CI], 1.01 to 1.36), controlling for age, compared with those with right-sided breast cancer. The RR for fatal MI among left-sided cases was increased for those under the age of 60 years (RR = 1.98; 95% CI, 1.31 to 2.97) compared with right-sided cases, but not at age 60 years or older. Among women with irradiated regional-stage cancer who were younger than 60 years of age, the risk was significantly increased (RR = 2.24; 95% CI, 1.38 to 3.64) for those with left-sided compared with right-sided breast cancer, but not among patients aged 60 years or older. Among irradiated local-stage cases, the risk for those with left-sided breast cancer was not significantly elevated in either age category. Analysis of 5-year conditional survival cohorts showed an increased risk for irradiated left-sided cases among women younger than 60 years of age in the 10- to 15-year conditional survival cohort (RR = 5.28; 95% CI, 1.82 to 15.3). CONCLUSION: Adjuvant RT for left-sided breast cancer diagnosed in women younger than 60 years of age is associated with a higher risk for fatal MI 10 to 15 years later compared with adjuvant RT for right-sided cases.     

Stroke volume response to cycle ergometry in trained and untrained older men

We evaluated the risk of development of second primary cancers, with particular reference to subsequent hepatocellular carcinoma (HCC), in 592 patients diagnosed as non-Hodgkin's lymphoma (NHL), at Osaka Medical Center for Cancer and Cardiovascular Diseases. During 1978-1994, 2,163 person-years of observation were accrued, and 27 of the patients developed a second primary cancer, yielding an observed-to-expected ratio (O/E) of 1.53 [95% confidence interval (CI) = 1.01-2.23]. Significant excess risk was noted for primary liver cancer (PLC; O/E = 4.36, 95% CI = 1.99-8.28; O = 9) and non-lymphocytic leukemia (O/E = 26.17, 95% CI = 5.26-76.46; O = 3). The excess risk of PLC was relatively constant within the first 10 years after the NHL diagnosis. Patients who received chemotherapy as the NHL treatment had a significantly increased risk of PLC (O/E = 5.91, 95% CI = 2.70-11.23; O = 9). Their clinical reports indicated that all nine patients with PLC were diagnosed as HCC, and eight of them had clinical and/or histologic evidence of cirrhosis at the time of HCC diagnosis. None of the nine patients had a history of blood transfusion between the first NHL treatment and the diagnosis of HCC. These findings suggested that Japanese NHL patients might have an increased risk of developing HCC, and they indicated the importance of medical surveillance for liver malignancies, as well as subsequent leukemias. Possible explanations for the excess risk of subsequent HCC are discussed.