Lene Mellemkjær

Prognosis of cancers associated with venous thromboembolism.

BACKGROUND Little is known about the prognosis of cancer discovered during or after an episode of venous thromboembolism. METHODS We linked the Danish National Registry of Patients, the Danish Cancer Registry, and the Danish Mortality Files to obtain data on the survival of patients who received a diagnosis of cancer at the same time as or after an episode of venous thromboembolism. Their survival was compared with that of patients with cancer who did not have venous thromboembolism (control patients), who were matched in terms of type of cancer, age, sex, and year of diagnosis. RESULTS Of 668 patients who had cancer at the time of an episode of deep venous thromboembolism, 44.0 percent of those with data on the spread of disease (563 patients) had distant metastasis, as compared with 35.1 percent of 5371 control patients with data on spread (prevalence ratio, 1.26; 95 percent confidence interval, 1.13 to 1.40). In the group with cancer at the time of venous thromboembolism, the one-year survival rate was 12 percent, as compared with 36 percent in the control group (P<0.001), and the mortality ratio for the entire follow-up period was 2.20 (95 percent confidence interval, 2.05 to 2.40). Patients in whom cancer was diagnosed within one year after an episode of venous thromboembolism had a slightly increased risk of distant metastasis at the time of the diagnosis (prevalence ratio, 1.23 [95 percent confidence interval, 1.08 to 1.40]) and a relatively low rate of survival at one year (38 percent, vs. 47 percent in the control group; P<0.001). CONCLUSIONS Cancer diagnosed at the same time as or within one year after an episode of venous thromboembolism is associated with an advanced stage of cancer and a poor prognosis.

The Risk of a Diagnosis of Cancer after Primary Deep Venous Thrombosis or Pulmonary Embolism

BACKGROUND Several small studies have indicated an association between deep venous thrombosis or pulmonary embolism and a subsequent diagnosis of cancer, but the subject is controversial. METHODS We conducted a nationwide study of a cohort of patients with deep venous thrombosis or pulmonary embolism that was drawn from the Danish National Registry of Patients for the years 1977 through 1992. The occurrence of cancer in the cohort was determined by linkage to the Danish Cancer Registry. The expected number of cancer cases was estimated on the basis of national age-, sex-, and site-specific incidence rates. RESULTS A total of 15,348 patients with deep venous thrombosis and 11,305 patients with pulmonary embolism were identified. We observed 1737 cases of cancer in the cohort with deep venous thrombosis, as compared with 1372 expected cases (standardized incidence ratio, 1.3; 95 percent confidence interval, 1.21 to 1.33). Among the patients with pulmonary embolism, the standardized incidence ratio was 1.3, with a 95 percent confidence interval of 1.22 to 1.41. The risk was substantially elevated only during the first six months of follow-up and declined rapidly thereafter to a constant level slightly above 1.0 one year after the thrombotic event. Forty percent of the patients given a diagnosis of cancer within one year after hospitalization for thromboembolism had distant metastases at the time of the diagnosis of cancer. There were strong associations with several cancers, most pronounced for those of the pancreas, ovary, liver (primary hepatic cancer), and brain. CONCLUSIONS An aggressive search for a hidden cancer in a patient with a primary deep venous thrombosis or pulmonary embolism is not warranted.

Rheumatoid Arthritis and Cancer Risk

The aim of this study was to examine the cancer pattern in a large group of patients with rheumatoid arthritis (RA). A follow-up study of cancer incidence in RA was conducted within a cohort of 20,699 patients recorded in the Danish Hospital Discharge Register during 1977-1987 by linkage with the Danish Cancer Registry through 1991. There were consistent excesses of non-Hodgkins lymphoma and Hodgkins disease in both sexes and during both early and late periods of follow-up. Risks for lung cancer and non-melanoma skin cancer were also increased, with no predilection for any specific histological subtype, while risks for colorectal cancer and female breast cancer were reduced. The cancer pattern seen among Danish RA patients largely supports findings from two earlier Nordic investigations. Thus, there seem to be consistent positive associations between RA and non-Hodgkins lymphoma, Hodgkins disease and lung cancer and a consistent negative association with colorectal cancer.

Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin

OBJECTIVE:Aspirin products are known to cause irritation and injury to the gastric mucosa. We examined the risk of hospitalization for upper gastrointestinal bleeding with use of low-dose aspirin.METHODS:This was a cohort study based on record linkage between a population-based prescription database and a hospital discharge registry in North Jutland County, Denmark, from January 1, 1991, to December 31, 1995. Incidence rates of upper gastrointestinal bleeding in 27,694 users of low-dose aspirin were compared with the incidence rates in the general population in the county.RESULTS:A total of 207 exclusive users of low-dose aspirin experienced a first episode of upper gastrointestinal bleeding with admission to the hospital during the study period. The standardized incidence rate ratio was 2.6 (95% confidence interval, 2.2–2.9), 2.3 in women and 2.8 in men. The standardized incidence rate ratio for combined use of low-dose aspirin and other nonsteroidal anti-inflammatory drugs was 5.6 (95% confidence interval, 4.4–7.0). The risk was similar among users of noncoated low-dose aspirin (standardized incidence rate ratio, 2.6; 95% confidence interval, 1.8–3.5) and coated low-dose aspirin (standardized incidence rate ratio, 2.6; 95% confidence interval, 2.2–3.0).CONCLUSIONS:Use of low-dose aspirin was associated with an increased risk of upper gastrointestinal bleeding, with still higher risks when combined with other nonsteroidal anti-inflammatory drugs. Enteric coating did not seem to reduce the risk. The findings from this observational study raise the possibility that prophylactic use of low-dose aspirin may convey an increased risk of gastrointestinal bleeding, which may offset some of its benefits.

Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study

There is increasing evidence of an inverse association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of colorectal cancer. However, data regarding other cancer sites are limited. Using data from the population-based North Jutland Prescription Database and the Danish Cancer Registry, we compared cancer incidence among 172 057 individuals prescribed nonaspirin NSAIDs with expected incidence (based on county-specific cancer rates) during a 9-year study period. A total of 6081 incident cancer cases were diagnosed among NSAID users vs 5722 expected (standardised incidence ratio (SIR) 1.1, 95% confidence interval (CI)1.0–1.1). The SIRs for colon and rectal cancer among persons who obtained 10 or more prescriptions were 0.7 (95% CI 0.6–0.9) and 0.6 (95% CI 0.4–0.9), respectively. Similarly, reduced risk estimates were found for stomach (SIR 0.7, 95% CI 0.4–1.1) and ovarian cancer (SIR 0.7, 95% CI 0.4–1.0). Standardised incidence ratios for other cancers among those with 10 or more prescriptions tended to be close to 1.0, except for lung, kidney, and prostate cancers with SIRs of 1.3 (95% CI 1.1–1.6), 1.4 (95% CI 0.9–2.1), and 1.6 (95% CI 1.3–2.0), respectively. We found protective associations of NSAIDs against colon, rectal, stomach, and ovarian cancer. Reasons for the increased risk for some cancer sites are not clear.

Familial aggregation of Hodgkin lymphoma and related tumors

The importance of genetic factors in the etiology of Hodgkin lymphoma (HL) has been suggested by family and population studies. However, the spectrum of malignancies associated with common genetic etiology and the effects of gender and age on familial risk have not been established.

Atypical cancer pattern in patients with Parkinson's disease

Among 14 088 patients, with a primary diagnosis of Parkinsons disease during the period 1977–98 identified from the National Register of Patients, 1282 cancers were subsequently recorded in the Danish Cancer Registry, compared with 1464 expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence interval (CI), 0.8–0.9). Significantly reduced risks were found for smoking-related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and urinary bladder (0.52), although moderate reductions in risk were also seen for several nonsmoking-related cancers. In contrast, increased risks were seen for malignant melanoma (SIR, 1.95; 95% CI, 1.4–2.6), nonmelanocytic skin cancer (1.25; 1.1–1.4) and breast cancer (1.24; 1.0–1.5). The observed cancer pattern supports the hypothesis that constituents of tobacco smoke inhibit or delay the development of Parkinsons disease, but a low smoking prevalence appears to be only part of the explanation for the decreased cancer incidence. The increased relative risks of melanoma and nonmelanoma skin cancer are not likely to be artefactual, but further investigations of potential mechanisms are warranted.

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population‐based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943–2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24–1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non‐melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.

Cancer risk following polymyositis and dermatomyositis: a nationwide cohort study in Denmark

Polymyositis and dermatomyositis (PM/DM) have been associated with cancer, although the long-term risks are poorly understood. To evaluate the risk of cancer by time periods subsequent to PM/DM diagnosis, a cohort of 539 patients hospitalized with PM/DM in Denmark between 1977 and 1989 was identified from the Danish Central Hospital Discharge Register. Cancer incidence among cohort members was ascertained by linkage to the Danish Cancer Registry using a unique personal-identification number. The overall cancer risk was elevated significantly among patients with DM (standardized incidence ratio [SIR]=3.8, 95 percent confidence interval [CI]=2.6–5.4) and to a lesser extent PM (SIR=1.7, CI=1.1–2.4). Significant excesses were observed for cancers of lung, ovary, and lymphatic and hematopoietic system. However, the excess cancer incidence declined steadily with increasing years since initial diagnosis of PM/DM. The cancer risk was increased about sixfold (SIR=5.9, CI=3.8–8.7) during the first year, but was lower during the second year (SIR=2.5, CI=1.1–4.8), with no significant excesses in subsequent years of follow-up. These findings confirm that PM/DM may occur as a paraneoplastic syndrome that calls for steps aimed at early cancer detection and treatment. Among long-term survivors of PM/DM, however, there is little evidence to warrant extensive preventive and screening measures beyond those recommended for the general population.

Acromegaly and cancer risk: A cohort study in Sweden and Denmark

Objective: Several studies have suggested that patients with acromegaly have an increased risk of benign and malignant neoplasms, especially of the colon. To further investigate this relationship we evaluated cancer risk in population-based cohorts of acromegaly patients in Sweden and Denmark. Methods: Nationwide registry-based cohorts of patients hospitalized for acromegaly (Denmark 1977–1993; Sweden 1965–1993) were linked to tumor registry data for up to 15–28 years of follow-up, respectively. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were calculated to estimate cancer risk among 1634 patients with acromegaly. Results: The patterns of cancer risk in Sweden and Denmark were similar. After excluding the first year of follow-up, 177 patients with acromegaly had a diagnosis of cancer compared with an expected number of 116.5 (SIR = 1.5, 95% CI = 1.3–1.8). Increased risks were found for digestive system cancers (SIR = 2.1, 95% CI = 1.6–2.7), notably of the small intestine (SIR = 6.0, 95% CI = 1.2–17.4), colon (SIR = 2.6, 95% CI = 1.6–3.8), and rectum (SIR = 2.5, 95% CI = 1.3–4.2). Risks were also elevated for cancers of the brain (SIR = 2.7, 95% CI = 1.2–5.0), thyroid (SIR = 3.7, 95% CI = 1.8–10.9), kidney (SIR = 3.2, 95% CI = 1.6–5.5), and bone (SIR = 13.8, 95% CI = 1.7–50.0). Conclusions: The increased risk for several cancer sites among acromegaly patients may be due to the elevated proliferative and anti-apoptotic activity associated with increased circulating levels of insulin-like growth factor-1 (IGF-1). Pituitary irradiation given to some patients may have contributed to the excess risks of brain tumors and thyroid cancer. Our findings indicate the need for close medical surveillance of patients with acromegaly, and further studies of the IGF-1 system in the etiology of various cancers.