Gustaf Edgren

Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008—A Swedish population-based study

Organ transplant recipients are at increased risk of a wide range of malignancies, especially cutaneous squamous cell carcinomas (SCC). Few previous population‐based studies have quantified and compared cancer risks according to graft type and with long‐term follow‐up. Using nationwide Swedish registers, we identified 10,476 recipients transplanted from 1970 to 2008 and followed them for cancer occurrence. Relative risks of cancer in comparison with the general population were expressed as standardized incidence ratios (SIR) and within the transplanted cohort as incidence rate ratios (IRR). During a total follow‐up of 93,432 person‐years, patients were diagnosed with 1,175 cancers excluding SCC, and with 2,231 SCC, SIRcancer excl SCC 2.4 (95% CI, 2.2–2.5); SIRSCC 121 (95% CI, 116–127). Cancer risks were most increased among heart and/or lung recipients SIRcancer excl SCC 3.3 (95% CI, 2.8–4.0); SIRSCC 198 (95% CI, 174–224), followed by kidney SIRcancer excl SCC 2.3 (95% CI, 2.1–2.4); SIRSCC 121 (95% CI, 116–127) and liver recipients SIRcancer excl SCC 2.3 (95% CI, 1.9–2.8); SIRSCC 32 (95% CI, 24–42). During follow‐up, risk of cancer excluding SCC remained stable while risk of SCC tripled over 20 years irrespective of graft type, partly due to a subgroup of patients developing new SCCs at a rapidly increasing rate. In summary, post‐transplant cancer risk varied by transplanted organ and by cancer site, with the bulk of the excess risk driven by an exceptionally high and accelerating risk of SCC. These findings underscore the importance of regular skin screening in organ transplant recipients.

Duration of red blood cell storage and survival of transfused patients (CME)

BACKGROUND: Disquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time.

Risk of anogenital cancer after diagnosis of cervical intraepithelial neoplasia: a prospective population-based study

BACKGROUND The first vaccine against human papillomavirus (HPV)-related disease is now available. Although it has been designed and tested mainly to protect against cervical lesions, it is also expected to be effective against other anogenital cancers. Associations between HPV and vaginal, vulvar, and anal cancers are well established, but the full extent in terms of age and time since diagnosis of these associations is not well known. METHODS We established a cohort of all women in Sweden who were aged 18-50 years at some timepoint from 1968 to 2004. Using national registration numbers, we linked this cohort to nationwide population, migration, cancer, and death registers. The incidence rate ratios (IRRs) of vaginal, vulvar, anal, and rectal cancer in women with a history of a cervical intraepithelial neoplasm (CIN), grade 3, compared with women with no such history were estimated by use of multivariate Poisson regression. FINDINGS Women with a history of grade 3 CIN had increased risks of cancer of the vagina (6.74 [95% CI 5.24-8.56]), vulva (2.22 [1.79-2.73]), and anus (IRR 4.68 [3.87-5.62]). No excess risk was found for rectal cancer. For all four anatomical sites, the IRRs varied substantially with the amount of time that had elapsed since the date of first diagnosis of grade 3 CIN. Analyses stratified by attained age during follow-up showed that the risk of cancer conferred by a history of diagnosis of grade 3 CIN was highly age dependent. The observed increased risks were not explained by smoking or socioeconomic status. INTERPRETATION This study confirms the known association between history of CIN, presumed HPV infection, and increased risk of cancers of the vagina, vulva, and anus by use of large and complete databases, but also shows that this risk varies both by the time from initial diagnosis of grade 3 CIN and by the age of the individual. Further studies are needed to clarify the type of HPV associated with this increase in risk to determine the clinical applicability of the new HPV vaccines.

Mammographic Density Reduction Is a Prognostic Marker of Response to Adjuvant Tamoxifen Therapy in Postmenopausal Patients With Breast Cancer

PURPOSE Tamoxifen treatment is associated with a reduction in mammographic density and an improved survival. However, the extent to which change in mammographic density during adjuvant tamoxifen therapy can be used to measure response to treatment is unknown. PATIENTS AND METHODS Overall, 974 postmenopausal patients with breast cancer who had both a baseline and a follow-up mammogram were eligible for analysis. On the basis of treatment information abstracted from medical records, 474 patients received tamoxifen treatment and 500 did not. Mammographic density was measured by using an automated thresholding method and expressed as absolute dense area. Change in mammographic density was calculated as percentage change from baseline. Survival analysis was performed by using delayed-entry Cox proportional hazards regression models, with death as a result of breast cancer as the end point. Analyses were adjusted for a range of patient and tumor characteristics. RESULTS During a 15-year follow-up, 121 patients (12.4%) died from breast cancer. Women treated with tamoxifen who experienced a relative density reduction of more than 20% between baseline and first follow-up mammogram had a reduced risk of death as a result of breast cancer of 50% (hazard ratio, 0.50; 95% CI, 0.27 to 0.93) compared with women with stable mammographic density. In the no-tamoxifen group, there was no statistically significant association between mammographic density change and survival. The survival advantage was not observed when absolute dense areas at baseline or follow-up were evaluated separately. CONCLUSION A decrease in mammographic density after breast cancer diagnosis appears to serve as a prognostic marker for improved long-term survival in patients receiving adjuvant tamoxifen, and these data should be externally validated.

Enigmatic sex disparities in cancer incidence

In this study we aimed to identify cancers where there is a consistent sex disparity, with the goal of identifying unexplained sex disparities that may offer promising opportunities for etiologic research. Age- and sex-specific cancer incidence data from Cancer Incidence in Five Continents, provided by the International Agency for Research on Cancer, were used to calculate incidence rate ratios for 35 cancer sites, comparing men to women, adjusting for attained age, gross domestic product (GDP), and geographical region. Genital cancers and breast cancer were excluded. The consistency of relative risks was examined by GDP and geographical region and, in a subset of longstanding cancer registers, by calendar year. For each cancer site, the sex disparity was broadly classified as plausibly explained by established environmental risk factors, partly explained, or unexplained. Cancer incidence was statistically significantly higher in men than women at 32 of 35 sites, with disparities >2-fold for 15 sites and >4-fold for 5 sites. For nearly all sites, the sex disparity was consistent across GDP groups and geographical regions. However, the incidence rate ratios varied considerably by age at diagnosis. The sex disparity for 13 cancer sites was considered to be entirely unexplained by known risk factors; these sites showed strikingly little variation in the incidence rate ratios over decades. Thus, the basis of many of the largest sex disparities in cancer incidence seems mostly unknown, highlighting the need for intensified research into its origins.

Survival after blood transfusion

BACKGROUND: Long‐term survival of transfusion recipients has rarely been studied. This study examines short‐ and long‐term mortality among transfusion recipients and reports these as absolute rates and rates relative to the general population.

Temporal Trends in Cause of Death Among Swedish and US Men with Prostate Cancer

BACKGROUND A growing proportion of men diagnosed with localized prostate cancer detected through prostate-specific antigen testing are dying from causes other than prostate cancer. Temporal trends in specific causes of death among prostate cancer patients have not been well described. METHODS We analyzed causes of death among all incident prostate cancer cases recorded in the nationwide Swedish Cancer Registry (1961-2008; n = 210 112) and in the US Surveillance, Epidemiology, and End Results Program (1973-2008; n = 490 341). We calculated the cumulative incidence of death due to seven selected causes that accounted for more than 80% of the reported deaths (including ischemic heart disease and non-prostate cancer) and analyzed mortality trends by calendar year and age at diagnosis and length of follow-up. RESULTS During follow-up through 2008, prostate cancer accounted for 52% of all reported deaths in Sweden and 30% of reported deaths in the United States among men with prostate cancer; however, only 35% of Swedish men and 16% of US men diagnosed with prostate cancer died from this disease. In both populations, the cumulative incidence of prostate cancer-specific death declined during follow-up, while the cumulative incidences of death from ischemic heart disease and non-prostate cancer remained constant. The 5-year cumulative incidence of death from prostate cancer among all men was 29% in Sweden and 11% in the United States. CONCLUSIONS In Sweden and the United States, men diagnosed with prostate cancer are less likely to die from prostate cancer than from another cause. Because many of these other causes of death are preventable through changes in lifestyle, interventions that target lifestyle factors should be integrated into prostate cancer management.

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.

Epidemiology of adult ankle fractures in Sweden between 1987 and 2004: A population-based study of 91,410 Swedish inpatients

Background and purpose Previous national epidemiological data on the characteristics and trends of patients with ankle fractures have been limited. We therefore analyzed data on Swedish inpatients with ankle fractures in this nationwide population study, based on data from 1987 through 2004. Patients and methods Data on all inpatients aged 15 years and older with ankle fracture were extracted from the Swedish National Patient Register for the period 1987–2004. Results We identified 91,410 hospital admissions with ankle fracture, corresponding to an annual incidence rate of 71 per 105 person-years. During the study period, the number of hospital admissions increased by 0.2% annually, mainly from increase in fracture incidence in the elderly women. Mean age at admission was 45 (SD 19) years for men and 58 (18) for women. The major mechanism of injury was falling at the same level (64%). Interpretation This nationwide study of inpatients with ankle fractures showed an increase in fracture incidence, particularly in elderly women.

Risk of cancer after blood transfusion from donors with subclinical cancer: a retrospective cohort study

BACKGROUND Although mechanisms for detection of short-term complications after blood transfusions are well developed, complications with delayed onset, notably transmission of chronic diseases such as cancer, have been difficult to assess. Our aim was to investigate the possible risk of cancer transmission from blood donors to recipients through blood transfusion. METHODS We did a register-based retrospective cohort study of cancer incidence among patients who received blood from donors deemed to have a subclinical cancer at the time of donation. These precancerous donors were diagnosed with a cancer within 5 years of the donation. Data from all computerised blood bank registers in Sweden and Denmark gathered between 1968 and 2002 were merged into a common database. Demographic and medical data, including mortality and cancer incidence, were ascertained through linkages with nationwide, and essentially complete, population and health-care registers. The risk of cancer in exposed recipients relative to that in recipients who received blood from non-cancerous donors was estimated with multivariate Poisson regression, adjusting for potential confounding factors. FINDINGS Of the 354 094 transfusion recipients eligible for this analysis, 12,012 (3%) were exposed to blood products from precancerous donors. There was no excess risk of cancer overall (adjusted relative risk 1.00, 95% CI 0.94-1.07) or in crude anatomical subsites among recipients of blood from precancerous donors compared with recipients of blood from non-cancerous donors. INTERPRETATION Our data provide no evidence that blood transfusions from precancerous blood donors are associated with increased risk of cancer among recipients compared with transfusions from non-cancerous donors.