Self-sampling for analysis of respiratory viruses in a large-scale epidemiological study in Sweden.

Viral diagnosis of respiratory tract infections has so far required sampling by health professionals,hampering large-scale epidemiological studies of virus-specific disease outcomes. As part of a population-based, prospective study of work-related risk factors for transmission of viral infections (SWEDE-I), we developed a scheme for self-sampling with nasal swabs. Random selection from the gainfully employed population of a medium-sized town in central Sweden resulted in a study cohort of 2,237 men and women aged 25 to 63 years. From September 2011 through May 2012, the cohort reported all instances of respiratory tract infection or gastroenteritis and participants concomitantly sent self-sampled nasal swabs for analysis using regular mail. Diagnosis of 14 viruses was performed. A total of 1,843 samples were received. The week-wise average delay between disease on set and arrival of the specimens at the laboratory varied between four and six days, and the corresponding median delay was between 3.5 and six days. In line with previous community-based studies, picorna- and coronaviruses dominated in specimens obtained from the self-sampling scheme. The results of self-sampling were contrasted to those from contemporaneous routine clinical sampling, on the same age group, in the adjacent Stockholm county. Although higher proportions of positive samples for respiratory syncytial virus and influenza were observed in the clinical sampling scheme, estimations of seasonality for influenza A and picornaviruses derived from both schemes were similar. Our findings show that nasal self-sampling is feasible in large-scale surveillance of respiratory infections and opens new prospects for population based,virologically verified research on virus spread,burden of disease, and effects of environmental factors or interventions.

Dietary quercetin intake and risk of gastric cancer: results from a population-based study in Sweden.

BACKGROUND: To study the impact of the dietary antioxidant quercetin on risk of gastric adenocarcinoma. PATIENTS AND METHODS: Using data from a large Swedish population-based case-control study of gastric cancer (505 cases and 1116 controls), we studied the association between quercetin and risk of anatomic (cardia/noncardia) and histological (intestinal and diffuse) subtypes of gastric cancer. RESULTS: We found strong inverse associations between quercetin and the risk of noncardia gastric adenocarcinoma, with an adjusted odds ratio (OR) of 0.57 (95% confidence interval 0.40-0.83) for the highest quintile (≥11.9 mg) of daily quercetin intake relative to the lowest quintile of intake (<4 mg quercetin/day), supported by a significant decreasing linear trend (P value < 0.001). Similar findings were observed for the intestinal and diffuse subtype. For cardia cancer, we found a less evident and nonsignificant inverse relationship. The protection of quercetin appeared to be stronger among female smokers, with the OR leveled of at values <0.2 in quintiles 3-5 (>6 mg quercetin/day). CONCLUSIONS: High dietary quercetin intake is inversely related to the risk of noncardia gastric adenocarcinoma, and the protection appears to be particularly strong for women exposed to oxidative stress, such as tobacco smoking.

No survival benefit from early-start dialysis in a population-based, inception cohort study of Swedish patients with chronic kidney disease.

OBJECTIVE: To investigate how the timing of dialysis initiation is associated with mortality. DESIGN: Population-based, prospective, observational cohort study. SETTING: Clinical laboratories (n = 69) provided information on all patients in Sweden whose serum creatinine level for the first time and exceeded 3.4 mg dL(-1) (men) or 2.8 mg dL(-1) (women) between 20 May 1996 and 31 May 1998. SUBJECTS: All patients (n = 901), aged 18-74 years, in whom the cause of serum creatinine elevation was chronic kidney disease, were included in the study; participants were interviewed and followed for 5-7 years. MAIN OUTCOME MEASURES: Information on date of death was obtained from a national Swedish population register. Early-start dialysis [estimated glomerular filtration rate from serum creatinine (eGFR) ≥7.5 mL min(-1) per 1.73 m(2)] was compared to late start of dialysis (eGFR <7.5 mL min(-1) per 1.73 m(2)), and no dialysis. Relative risk [hazard ratio (HR)] of death was modelled with time-dependent multivariate Cox proportional hazards regression. RESULTS: Mean eGFR was 16.1 mL min(-1) per 1.73 m(2) at inclusion and 7.6 mL min(-1) per 1.73 m(2) at the start of dialysis. Among the 385 patients who started dialysis late, 36% died during follow-up compared to 52% of 323 who started early. The adjusted HR for death was 0.84 [95% confidence interval (CI) 0.64, 1.10] among late versus early starters. The mortality among nondialysed patients increased significantly at eGFR below 7.5 mL min(-1) per 1.73 m(2) (HR 4.65; 95% CI 2.28, 9.49; compared to eGFR 7.5-10 mL min(-1) per 1.73 m(2)). After the start of dialysis, the mortality rate further increased. Compared to nondialysed patients with eGFR ≤15 mL min(-1) per 1.73 m(2), adjusted HR was 2.65 (95% CI 1.80, 3.89) for patients receiving dialysis. CONCLUSION: We found no survival benefit from early initiation of dialysis.

National surveillance of surgical-site infection through register-based analysis of antibiotic use after inguinal hernia repair.

BACKGROUND: Systematic surveillance of surgical-site infections is not standard. The aim of this retrospective cohort study was to evaluate the feasibility of using existing national health registers for surveillance of postoperative antibiotic treatment suggestive of surgical-site infection. METHODS: Data from national registers on hospital admissions and drug use were combined. Antibiotic purchases by 8856 patients subject to ambulatory care for inguinal hernia repair in Sweden during 2006 were ascertained during a 30-day interval immediately after surgery (postsurgical period) and in an 11-month control period (6 months before and 5 months after the postsurgical period). RESULTS: The incidence of first purchases of skin and soft tissue antibiotics was 245 per 8697 person-months in the first postoperative month and 180 per 52 612 person-months in the preoperative control period, representing a 1-month risk difference of 2.4 (95 per cent confidence interval (c.i.) 2.0 to 2.7) per cent. Hence, a 1-month risk of 2.4 per cent could be attributed tentatively to the surgery. The rate of episodes with antibiotics used mainly for skin and soft tissue infection was sevenfold higher in the first postoperative month than in the control period (rate ratio 7.01, 95 per cent c.i. 5.94 to 8.27). CONCLUSION: The risk of antibiotic treatment during the postsurgical period was of the same order of magnitude as infection rates reported in the Swedish Hernia Register and review studies. Surveillance of postoperative antibiotic use may be considered as a resource-saving surrogate marker for surgical-site infections or an indicator of inappropriate use.

A foodborne norovirus outbreak at a manufacturing company.

Over 400 office workers from the same unit of a manufacturing company in Stockholm County, Sweden, fell ill with gastroenteritis. A retrospective cohort study of office workers in the affected unit demonstrated that canteen visitors on one day had an increased risk of illness [risk ratio (RR) 27.1, 95% confidence interval (CI) 15.7-46.8] compared to non-visitors. A second study, investigating canteen visitors' consumption of particular food items, showed that both tomatoes from the salad buffet (RR 5.6, 95% CI 3.2-9.6) and hamburgers (RR 4.9, 95% CI 2.4-9.8) were the most likely vehicles of infection. Norovirus GI.3 (Desert Shield) was identified in stool samples from three office workers and from a food handler who prepared the tomatoes for the salad buffet and hamburger ingredients before vomiting at the workplace on 12 November. The outbreak could have been prevented if the food items prepared by the food handler some hours before vomiting had not been served.

Post-transfusion mortality among recipients of ABO-compatible but non-identical plasma.

BACKGROUND AND OBJECTIVES: The consequences of ABO-compatible non-identical plasma for patient outcome have not been studied in randomized clinical trials or large cohort studies and use varies widely in the absence of evidence-based policies. We investigated if transfusion with compatible instead of identical plasma confers any short-term survival disadvantage on the recipients. MATERIALS AND METHODS: The cohort of all 86 082 Swedish patients who received their first plasma transfusion between 1990 and 2002 was followed for 14 days and the risk of death in patients exposed to compatible non-identical plasma compared to recipients of only identical plasma. RESULTS: After adjustment for potential confounding factors, there was an increased mortality associated with exposure to ABO-compatible non-identical plasma, with the excess risk mostly confined to those receiving 5 or more units (relative risk, 1.15; 95% confidence interval, 1.02-1.29). Stratification by blood group indicated higher risks in group O recipients, especially when the compatible plasma was from a group AB donor. CONCLUSIONS: This study suggests that ABO-compatible non-identical plasma is less safe than identical plasma. Subanalyses by blood group suggest a role for circulating immune complexes. Our findings may have policy implications for improving transfusion safety.

Validation of an Inguinal Pain Questionnaire for assessment of chronic pain after groin hernia repair.

BACKGROUND: Long-term pain is an important outcome after inguinal hernia repair. The aim of this study was to test the validity and reliability of a specific Inguinal Pain Questionnaire (IPQ). METHODS: The study recruited patients aged between 15 and 85 years who had undergone primary inguinal or femoral hernia repair. To test the validity of the questionnaire, 100 patients received the IPQ and the Brief Pain Inventory (BPI) 1 and 4 weeks after surgery (group 1). To test reliability and internal consistency, 100 patients received the IPQ on two occasions 1 month apart, 3 years after surgery (group 2). Non-surgery-related pain was analysed in group 3 (2853 patients). RESULTS: A significant decrease in IPQ-rated pain intensity was observed in the first 4 weeks after surgery (P < 0.001). Significant correlations with corresponding BPI pain intensity items corroborated the criterion validity (P < 0.050). Logical incoherence did not exceed 5.5 per cent for any item. Values for kappa in the test-retest in group 2 were higher than 0.5 for all but three items. Cronbach's alpha was 0.83 for questions on pain intensity and 0.74 for interference with daily activities. CONCLUSION: This study found good validity and reliability for the IPQ, making it a useful instrument for assessing pain following groin hernia repair.

Intake of vitamin C, vitamin E, selenium, zinc and polyunsaturated fatty acids and upper respiratory tract infection-a prospective cohort study.

BACKGROUND/OBJECTIVES: Antioxidants and polyunsaturated fatty acids (PUFAs) have a role in the human immune defense and may affect the susceptibility to upper respiratory tract infection (URTI). To examine dietary intake of vitamin C, vitamin E, selenium, zinc and PUFAs in relation to URTI incidence in a prospective cohort study. SUBJECTS/METHODS: A total of 1533 Swedish women and men aged 25-64 years were followed for nine months during 2011-2012. Information on dietary intake was assessed through a web-based food frequency questionnaire, and events of URTI were self-reported prospectively as they occurred. Cox proportional hazards regression was applied to obtain incidence rate ratios with 95% confidence intervals. RESULTS: The mean number of URTI events was 0.9 among all participants, 1.0 among women and 0.7 among men. In women, the incidence rate ratios (95% confidence interval) for high compared with low intake were 0.69 (0.55-0.88) for vitamin C, 0.77 (0.62-0.96) for vitamin E, 0.57 (0.39-0.83) for docosahexaenoic acid (DHA) and 0.80 (0.65-0.99) for arachidonic acid (AA). No association was found for selenium or zinc among women. In men, an increased URTI incidence was seen with medium vitamin E intake (1.42 (1.09-1.85)) and high zinc intake (1.50 (1.04-2.16)). No association was found for vitamin C, selenium or PUFAs among men. CONCLUSIONS: We found an inverse association of URTI incidence among women for vitamin C, vitamin E, DHA and AA intake and a positive association among men for vitamin E and zinc intake. The observed gender differences warrant further investigation.

Airborne occupational exposures and risk of oesophageal and cardia adenocarcinoma.

BACKGROUND: The reasons for the increasing incidence of and strong male predominance in patients with oesophageal and cardia adenocarcinoma remain unclear. The authors hypothesised that airborne occupational exposures in male dominated industries might contribute. METHODS: In a nationwide Swedish population based case control study, 189 and 262 cases of oesophageal and cardia adenocarcinoma respectively, 167 cases of oesophageal squamous cell carcinoma, and 820 frequency matched controls underwent personal interviews. Based on each study participant's lifetime occupational history the authors assessed cumulative airborne occupational exposure for 10 agents, analysed individually and combined, by a deterministic additive model including probability, frequency, and intensity. Furthermore, occupations and industries of longest duration were analysed. Relative risks were estimated by odds ratios (OR), with 95% confidence intervals (CI), using conditional logistic regression, adjusted for potential confounders. RESULTS: Tendencies of positive associations were found between high exposure to pesticides and risk of oesophageal (OR 2.3 (95% CI 0.9 to 5.7)) and cardia adenocarcinoma (OR 2.1 (95% CI 1.0 to 4.6)). Among workers highly exposed to particular agents, a tendency of an increased risk of oesophageal squamous cell carcinoma was found. There was a twofold increased risk of oesophageal squamous cell carcinoma among concrete and construction workers (OR 2.2 (95% CI 1.1 to 4.2)) and a nearly fourfold increased risk of cardia adenocarcinoma among workers within the motor vehicle industry (OR 3.9 (95% CI 1.5 to 10.4)). An increased risk of oesophageal squamous cell carcinoma (OR 3.9 (95% CI 1.2 to 12.5)), and a tendency of an increased risk of cardia adenocarcinoma (OR 2.8 (95% CI 0.9 to 8.5)), were identified among hotel and restaurant workers. CONCLUSIONS: Specific airborne occupational exposures do not seem to be of major importance in the aetiology of oesophageal or cardia adenocarcinoma and are unlikely to contribute to the increasing incidence or the male predominance.

Human papillomavirus infection and esophageal cancer: a nationwide seroepidemiologic case-control study in Sweden.

BACKGROUND: Infection with human papillomavirus (HPV) type 16 has been implicated as a risk factor for esophageal squamous cell carcinoma in three seroepidemiologic studies. We conducted a larger, population-based study to verify this association and to investigate possible confounding factors. METHODS: We performed a nationwide case-control study in Sweden of HPV16 or HPV18 infection and risk of esophageal squamous cell carcinoma or esophageal/gastroesophageal adenocarcinoma. Tumors were strictly classified by their location and histologic type. Case subjects with incident cancers and population-based control subjects donated blood samples and were interviewed in person about potential confounding factors. An enzyme-linked immunosorbent assay was used to detect HPV seropositivity. Multivariate analyses were conducted to study relationships between HPV seropositivity, level of education, smoking (all tobacco) status, alcohol consumption, and cancer risk. RESULTS: We compared 121 case subjects with esophageal squamous cell carcinoma and 173 case subjects with adenocarcinoma of the esophagus or gastroesophageal junction with 302 population-based control subjects. The age- and sex-adjusted odds ratios (ORs) for squamous cell carcinoma were 1.0 (95% confidence interval [CI] = 0.5-2.0) for persons seropositive for HPV16 and 0.5 (95% CI = 0.2-1.1) for persons seropositive for HPV18 in comparison with seronegative individuals. The corresponding ORs for adenocarcinoma were 1.2 (95% CI = 0.7-2.2) and 0.2 (95% CI = 0.1-0.7), respectively. Adjustments for smoking status, alcohol consumption, and level of education did not alter the results. CONCLUSIONS: We found no evidence of a positive association between HPV16 or HPV18 infection and either form of esophageal cancer. Our results do not support conclusions from previous studies.

Cancer risk after hip replacement with metal implants: a population-based cohort study in Sweden.

BACKGROUND: Joint replacement with metal implants has been the standard procedure for surgical treatment of irreversible degeneration of hip and knee joints for more than two decades. However, reports of local malignancy after joint replacement and experimental studies that suggest a carcinogenic action of metal ions and polymethylmethacrylate (an acrylic compound used to stabilize the implant in the host) have raised concern about the possible long-term risks associated with metal implants. PURPOSE: Our aim was to study cancer risk in a Swedish cohort of patients who had hip replacement surgery during the period 1965 through 1983. METHODS: We studied the risk of cancer in a cohort of 39 154 patients (14 869 men and 24 285 women), identified in the nationwide Swedish Inpatient Register with at least one hip replacement during the period 1965 through 1983. The patients were followed through 1989 by means of record linkage to the Swedish Cancer Register. The cohort contributed a total of 327 922 person-years at risk. Standardized incidence ratios (SIRs) were computed using age-, sex-, and period-specific incidence rates derived from the entire Swedish population. RESULTS: The overall relative risk of cancer was increased by only 3%. Bone cancer--the focus of previous concerns--occurred in six cases versus 4.3 expected, and connective tissue cancer occurred in 28 cases versus 25.9 expected. Increased risks were observed for kidney cancer (SIR = 1.31; 95% confidence interval [CI] = 1.13-1.51), prostate cancer (SIR = 1.13; 95% CI = 1.04-1.22), and melanoma (SIR = 1.23; 95% CI = 1.00-1.50). The relative risk of gastric cancer steadily declined with increasing follow-up time, in both men and women (SIR = 0.58; 95% CI = 0.39-0.84 more than 10 years after hip replacement). CONCLUSION: In this study, the largest study to date to evaluate hip replacement and subsequent cancer risk, the overall cancer risk appears to be negligible from a public health perspective, and our results have not produced any strong evidence against the continued use of these devices. Nevertheless, the small but statistically significant increases in kidney and prostate cancers and the decrease in gastric cancer deserve further study.

Smoking and colorectal cancer: a 20-year follow-up study of Swedish construction workers.

BACKGROUND: Although cigarette smoking has consistently been shown to be positively related to the risk of adenomatous polyp development (benign neoplastic growth of epithelial tissue in the colon), most studies of cigarette smoking and the risk of colorectal cancer have been negative. However, in two large prospective studies in women and men, a statistically significant association between cigarette smoking and an increased risk of colorectal cancer was found, but only after more than 35 years of smoking. PURPOSE: To shed further light on the alleged relationship between long-term smoking and colorectal cancer risk, we performed a retrospective cohort study among Swedish construction workers, with many long-term smokers, complete long-term follow-up, and a large number of observed cases. METHODS: We analyzed the association of smoking with colon cancer and with rectal cancer, using data on a cohort of approximately 135000 male construction workers. High-quality exposure information was collected with the use of a comprehensive questionnaire filled out at the time of enrollment in the cohort, from 1971 through 1975. Complete follow-up was achieved through 1991 and the subjects were observed for an average of 17.6 years, thereby contributing approximately 2375000 person-years of follow-up. We calculated age-adjusted rate ratios (RRs) with the use of Poisson-based multiplicative multivariate models followed by further multivariate modeling that adjusted for other variables. RESULTS: A total of 713 incident colon cancers and 505 rectal cancers were observed. There was no statistically significant association between current smoking status, number of cigarettes smoked or number of years smoking, and risk of colorectal cancer. The age-adjusted RRs were 0.98 (95% confidence interval [CI] = 0.82-1.17) and 1.16 (95% CI = 0.94-1.44) for colon and rectal cancers, respectively, among current smokers, and 1.07 (95% CI = 0.63-1.82) and 1.08 (95% CI = 0.58-2.03) among smokers of 25 or more cigarettes per day, relative to nonsmokers. Among smokers for more than 30 years at the start of follow-up, the age-adjusted RRs were 1.03 (95% CI = 0.85-1.25) and 1.21 (95% CI = 0.96-1.53) for colon and rectal cancers, respectively, relative to nonsmokers. Heavy smokers of cigars and pipes had a statistically nonsignificant tendency toward excess risk for colon cancer, but there was no clear dose-risk trend. CONCLUSION: Our large cohort study did not indicate any excess risk of colon cancer in males who were long-term heavy smokers and provided only weak support for an association with rectal cancer. Our data are thus consistent with the majority of previous reports. The reasons for the discrepancies in comparison with recent U.S. data have yet to be identified.

Evaluating gastric cancer misclassification: a potential explanation for the rise in cardia cancer incidence.

BACKGROUND: Reports of dramatic increases in gastric cardia cancer incidence warrant concern. However, the recent introduction of a separate diagnostic code, the lack of a consensus definition of the cardia area, and the accelerating interest in cardia cancer may affect classification practices. Little is known about the magnitude of cardia cancer misclassification in large cancer registries. METHODS: In a well-defined Swedish population (1.3 million), we uniformly classified all patients with newly diagnosed gastric adenocarcinoma (from 1989 through 1994) with respect to gastric subsite, and we used this patient group as our gold standard. We then evaluated the completeness of the Swedish Cancer Registry in registering gastric adenocarcinomas against this gold standard and, further, assessed the completeness of cardia cancer registration and the rate of falsely included cases to estimate the potential impact on observed incidence trends. RESULTS: Our gold standard contained 1337 case subjects with gastric adenocarcinoma. Overall, the Swedish Cancer Registry was 98% complete with regard to gastric adenocarcinomas and had a 4% rate of falsely included cases. The completeness of coding cardia cancer was only 69%, and the positive predictive value for cardia cancer was 82%, with no improvement over time. CONCLUSIONS: Although overall completeness of gastric cancer registration by the Swedish Cancer Registry was excellent, accuracy in registering cardia tumors was surprisingly low. Our estimates suggest that true cardia cancer incidence could be up to 45% higher or 15% lower than that reported in the Cancer Registry. This margin of error could accommodate the observed increase in cardia cancer in Sweden. Therefore, secular trends in cardia cancer incidence should be interpreted cautiously.

Body size and prostate cancer: a 20-year follow-up study among 135006 Swedish construction workers.

BACKGROUND: Obesity is associated with endocrine changes (e.g., increased estrogen and decreased testosterone in the blood) that have been implicated in the cause of prostate cancer and, therefore, an association between body weight and the risk of developing prostate cancer would be expected. However, because of bias or low statistical power in previous epidemiologic studies, associations between anthropometric measurements (height and weight), body mass index (BMI), and the risk of prostate cancer may have been inadvertently overlooked. PURPOSE: We performed a large, retrospective cohort study among Swedish construction workers to evaluate possible associations of adult weight, height, BMI, and lean body mass (LBM) by age at entry in the study with the incidence and mortality rate of prostate cancer. METHODS: We analyzed data that had been compiled in a computerized central register on a cohort of approximately 135000 male construction workers. Information on height and weight had been collected with the use of a comprehensive questionnaire filled out by nurses at the time of enrollment in the cohort, from 1971 through 1975. Complete follow-up was achieved through 1991 by means of record linkage to the Swedish National Cancer Register, the Death Register, and the Migration Register. A total of 2368 incident cases and 708 deaths from prostate cancer occurred in the cohort during a follow-up period averaging 18 years. We used only information obtained at the index visit from 1971 through 1975 to determine age-adjusted rate ratios (RRs) in a Poisson-based multiplicative multivariate model with age and the relevant exposure variable (e.g., weight, height, BMI, and LBM) as independent variables. RESULTS: All anthropometric measurements were positively associated with the risk of prostate cancer and were more strongly related to mortality than to incidence. The excess risk of death from prostate cancer was statistically significant in all BMI categories above the reference category: RR = 1.40 (95% confidence interval [CI] = 1.09-1.81) in the highest category compared with the lowest (P for trend = .04). For height and LBM, the excess risk in the highest compared with the lowest categories was somewhat less pronounced: RR = 1.28 (95% CI = 1.02-1.60) and RR = 1.26 (95% CI = 1.02-1.57), respectively. Statistically significant linear dose-response relationships were also found with the incidence of prostate cancer, with the exception of BMI (P for trend = .10). CONCLUSION: Our large cohort study indicates that various aspects of body size are related to the risk of prostate cancer and that future studies are needed to study the role of body size and prostate cancer.

Risk of urinary tract cancers following kidney or ureter stones.

BACKGROUND: A relationship has been suggested between kidney or ureter stones and the development of urinary tract cancers. In this study, a population-based cohort of patients hospitalized for kidney or ureter stones in Sweden was followed for up to 25 years to examine subsequent risks for developing renal cell, renal pelvis/ureter, or bladder cancer. METHODS: Data from the national Swedish In-patient Register and the national Swedish Cancer Registry were linked to follow 61,144 patients who were hospitalized for kidney or ureter stones from 1965 through 1983. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were computed on the basis of nationwide cancer incidence rates, after adjustment for age, sex, and calendar year. RESULTS: Risk of renal cell cancer was not elevated in this cohort. Significant excesses of renal pelvis/ureter cancer (SIR = 2.5; 95% CI = 1.8-3.3) and bladder cancer (SIR = 1.4; 95% CI = 1.3-1.6) were observed, but the SIRs for women were more than twice those for men. Risks varied little by age or duration of follow-up. Risks of renal pelvis/ureter cancer and bladder cancer among patients with an associated diagnosis of urinary tract infection were more than double those among patients without such infection, although the risks were significantly elevated in both groups. CONCLUSIONS: Individuals hospitalized for kidney or ureter stones are at increased risk of developing renal pelvis/ureter or bladder cancer, even beyond 10 years of follow-up. Chronic irritation and infection may play a role, since kidney or ureter stones were located on the same side of the body as the tumors in most patients with renal pelvis/ureter cancer evaluated in our study.

Excess risk of primary liver cancer in patients with diabetes mellitus.

BACKGROUND: Chronic infection with hepatitis B virus, alcohol consumption, and cirrhosis of the liver are recognized risk factors for primary liver cancer. A few, but not all, studies have suggested that diabetes mellitus also increases risk for this cancer. PURPOSE: We conducted a population-based cohort study to analyze the risk of developing primary liver cancer and biliary tract (gallbladder, extrahepatic bile ducts, and ampulla of Vater) cancers among patients with diabetes. METHODS: A cohort of 153 852 patients with a hospital discharge diagnosis of diabetes in the period from 1965 through 1983 was identified by use of the Swedish In-patient Register. Follow-up for these patients extended from the date of cohort entry through December 31, 1989. Incident cases of cancer during follow-up were identified through the Swedish Cancer Registry. To minimize the impact of selection bias, we excluded from the analysis patients who were diagnosed with liver and biliary tract cancers during the first year of follow-up. Standardized incidence ratios (SIRs) and their 95% confidence intervals (CIs) were computed by use of nationwide rates of liver and biliary tract cancers, adjusted for age, sex, and calendar year, for comparison. RESULTS: During 1-24 years of follow-up, 819 incident cancers in the combined category of primary liver (n = 533) and biliary tract (n = 286) were identified in the cohort, yielding an overall SIR of 2.5 (95% CI = 2.3-2.6). The risk was higher in men (SIR = 3.2; 95% CI = 2.9-3.6) than in women (SIR = 2.0; 95% CI = 1.8-2.2). The incidence of primary liver cancer alone was increased fourfold (SIR = 4.1; 95% CI = 3.8-4.5); again, the risk was higher in men (SIR = 4.7; 95% CI = 4.2-5.2) than in women (SIR = 3.4; 95% CI = 2.9-3.9). Smaller increases in risk were seen for cancers of the gallbladder, the extrahepatic bile ducts, and the ampulla of Vater. After exclusion of diabetic patients with concomitant diseases that predispose to primary liver cancer, such as alcoholism, cirrhosis, and hepatitis, the persistence of an approximately threefold excess risk was observed. CONCLUSIONS: Our findings suggest that patients with diabetes are at increased risk of developing primary liver cancer and perhaps cancers of the biliary tract. The mechanisms involved in the association of diabetes and liver cancer remain to be clarified. Additional studies are needed to determine whether patients with insulin-dependent diabetes mellitus and those with non-insulin-dependent diabetes mellitus differ in their risk for primary liver cancer or whether the risk is affected by the type of diabetes treatment.

Nationwide study of cancer risk among hip replacement patients in Sweden.

BACKGROUND: Orthopedic implants and their fixatives contain materials with carcinogenic potential. Whether these implants are linked to subsequent cancer development remains unknown, mainly because large-scale, long-term follow-up data are scarce. METHODS: We conducted a nationwide cohort study in Sweden to examine cancer incidence among 116,727 patients who underwent hip replacement surgery during the period from 1965 through 1994. Through record linkage to the Swedish Cancer Register, we identified all incident cancers through 1995 in this population (693,954 person-years of observation). For each cancer type, the observed number of cases was divided by that expected in the general Swedish population to produce standardized incidence ratios (SIRs). RESULTS: Relative to the general population, the cohort had no overall cancer excess (SIR = 1.01; 95% confidence interval [CI] = 0.99 to 1.03). However, we observed elevated SIRs for prostate cancer (SIR = 1.16; 95% CI = 1.11 to 1.22) and melanoma (SIR = 1.15; 95% CI = 1.01 to 1.30) and a reduction in stomach cancer risk (SIR = 0.83; 95% CI = 0.75 to 0.92). Long-term follow-up (>or=15 years) revealed an excess of multiple myeloma (SIR = 1.86; 95% CI = 1.01 to 3.11) and a statistically nonsignificant increase in bladder cancer (SIR = 1.42; 95% CI = 0.98 to 1.99). There was no material increase in risk for bone or connective tissue cancer for either men or women in any follow-up period. CONCLUSIONS: In this, the largest study to date, hip implant patients had similar rates of most types of cancer to those in the general population. Although the excesses of melanoma, multiple myeloma, and prostate and bladder cancers may be due to chance, confounding, or detection bias and should be interpreted cautiously, they warrant further investigation because of the ever-increasing use of hip implants at younger ages.

Pancreatitis and pancreatic cancer: a population-based study.

BACKGROUND: Little is known about the etiology of cancer of the exocrine portion of the pancreas, which produces a variety of digestive enzymes. Smoking, certain dietary factors, and diabetes mellitus are considered to be risk factors, although the risk estimates are modest in most instances. A recent cohort study of patients with chronic pancreatitis indicated a ninefold to 16-fold increased risk for pancreatic cancer. PURPOSE: Our purpose was to evaluate the relationship between various clinical types of pancreatitis and pancreatic cancer. METHODS: Data for this study were collected from all inpatient medical institutions in Sweden from 1965 until 1983 by the Swedish National Board of Health and Welfare. Data were recorded on individual hospital admissions and discharges in the Inpatient Register. All patients with records in the Inpatient Register coded for acute, chronic, or unspecified pancreatitis were considered for inclusion in the study. A population-based cohort of 7956 patients with at least one discharge diagnosis of pancreatitis was monitored (up to 19 years of follow-up) for the occurrence of pancreatic cancer by record linkages to the Swedish Cancer Registry and Registry of Causes of Death. RESULTS: A total of 46 pancreatic cancers were diagnosed during follow-up compared with 21 expected (standardized incidence ratio [SIR] of 2.2; 95% confidence interval [CI] 1.6-2.9) for the Uppsala Health Care Region. The excess risk for women and men was similar--most pronounced during the first period of follow-up (2-4 years) after discharge and close to unity after more than 10 years of follow-up. Patients with chronic pancreatitis and patients with more than one discharge diagnosis of either acute or unspecified pancreatitis were at higher risk (SIR = 3.8; 95% CI 1.4-8.2 and SIR = 4.8; 95% CI 1.9-9.9, respectively) compared with those with only one discharge of acute (SIR = 1.6; 95% CI 0.9-2.7) or unspecified (SIR = 2.1; 95% CI 1.2-3.2) pancreatitis. CONCLUSIONS: Our finding of a moderate excess of pancreatic cancer among patients with pancreatitis, especially the chronic or recurrent forms, supports some earlier clinical and case-control studies, but it is not consistent with the ninefold to 16-fold risk reported in a recent cohort study. The absence of an increased risk 10 years or more after first discharge for pancreatitis argues against a straight-forward causal relationship. Because of the relatively short interval between diagnosis of pancreatitis and pancreatic cancer, it is possible that some forms of pancreatitis are a precursor to pancreatic cancer or that shared risk factors for both diseases (e.g., cigarette smoking) may also be involved.

Risk for gastric cancer after antibiotic prophylaxis in patients undergoing hip replacement.

Despite strong evidence of an association between Helicobacter pylori and gastric cancer, the benefit of eradicating H. pylori infection is unknown. Our aim was to test the hypothesis that exposure to high doses of antibiotics reduces risk for gastric cancer via possible eradication of H. pylori We conducted a nationwide case-control study nested in a cohort of 39,154 patients who underwent hip replacement surgery between 1965 and 1983. Such patients frequently receive prophylactic antibiotic treatment. During follow-up through 1989, we identified 189 incident cases of gastric cancer. For each case, three controls were selected from the cohort. Exposure data were abstracted from hospital records. Blood samples from a separate cohort undergoing hip replacement surgery were analyzed for anti-H. pylori IgG before and after surgery. Both long-term antibiotic treatment before surgery [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7] and prophylactic antibiotic treatment (OR, 0.7; 95% CI, 0.5-1.1) conferred a reduction in gastric cancer risk. The reduction appeared stronger after 5 years (OR, 0.6; 95% CI, 0.3-1.2) than during shorter follow-up after hip replacement (OR, 0.8; 95% CI, 0.4-1.7). There was an apparent decrease in risk with increasing body weight-adjusted doses of antibiotics (P = 0.13). However, the rate of H. pylori antibody disappearance was not strikingly higher in the cohort of patients undergoing hip replacement than in a control cohort. Our findings provide indirect support for the hypothesis that treatment with antibiotics at a relatively advanced age reduces the risk of gastric cancer.