Magnus Kaijser

Long-term solid cancer risk among 5-year survivors of Hodgkin's lymphoma.

PURPOSE Hodgkins lymphoma (HL) survivors are known to be at substantially increased risk of solid cancers (SC). However, no investigation has used multivariate modeling to estimate the relative risk (RR), excess absolute risk (EAR), and cumulative incidence for specific attained ages and ages at HL diagnosis. PATIENTS AND METHODS We identified 18,862 5-year HL survivors from 13 population-based cancer registries in North America and Europe. Poisson regression was used to evaluate the effects of age at diagnosis, attained age, latency, sex, treatment, and year of diagnosis on the RR and EAR of SC. RESULTS Among 1,490 identified SC, 850 were estimated to be in excess. For most cancer sites, both RR and EAR decreased with age at HL diagnosis and showed strong dependencies on attained age. For a patient diagnosed at age 30 years and survived to > or = 40 years, modeled risks were significantly elevated for cancers of the breast (RR = 6.1), other supradiaphragmatic sites (RR = 6.0), and infradiaphragmatic sites (RR = 3.7); the largest RR (20-fold) was observed for malignant mesothelioma. Thirty-year cumulative risks of SC for men and women diagnosed at 30 years were 18% and 26%, respectively, compared with 7% and 9%, respectively, in the general population. For young HL patients, risks of breast and colorectal cancers were elevated 10 to 25 years before the age when routine screening would be recommended in the general population. CONCLUSION Multivariable modeling demonstrates for the first time temporal changes in SC risk not evident in unadjusted analyses, and can facilitate the development of individualized risk assessment and the creation of screening strategies for early detection.

Perinatal Risk Factors for Ischemic Heart Disease Disentangling the Roles of Birth Weight and Preterm Birth

Background— Several studies have reported an association between low birth weight and ischemic heart disease, but it remains unclear whether the association is mediated through poor fetal growth or short gestational duration. Methods and Results— In a cohort study, we have identified all subjects born preterm or with a low birth weight at 4 major delivery units in Sweden from 1925 through 1949. For comparison, an equal number of subjects with none of these criteria were identified within the same source population. The study population consists of 6425 subjects, of whom 2931 were born before 37 weeks of gestation and 2176 had a birth weight <2500 g. Fetal growth was estimated through birth weight for gestational age. The cohort was followed up for occurrence of ischemic heart disease through the nationwide Hospital Discharge and Cause of Death Registries during the period of 1987 through 2002. In the cohort, 617 cases of ischemic heart disease occurred. Compared with subjects with a normal fetal growth, those born small for gestational age (birth weight ≤−2 SD below the mean) were at increased risk of ischemic heart disease (adjusted hazard ratio, 1.64; 95% confidence interval, 1.23 to 2.18). The negative association between fetal growth and risk of ischemic heart disease was independent of gestational duration. Conclusions— The association between low birth weight and adult risk of ischemic heart disease appears to be mediated entirely by poor fetal growth.

Maternal pregnancy estriol levels in relation to anamnestic and fetal anthropometric data.

In epidemiologic studies of perinatal exposures, birth weight has been proposed as a proxy variable for intrauterine estrogen exposure. To assess the validity of this assumption, we performed analyses of the association between estriol levels in 188 women in the 17th, 25th, 33rd, and 37th weeks of pregnancy and the birth weights of their infants. We found a general increase in mean cumulative estriol dose with increasing birth weight category throughout pregnancy. In late pregnancy, mean pregnancy estriol level of mothers of infants in the highest birth weight category (>4,500 gm) was twice as high as that of mothers of infants in the lowest category (<2,500 gm), 775 nmol/liter and 392 nmol/liter, respectively. Smoking lowered the maternal estriol levels by 20% or more throughout pregnancy. With smoking and birth weight included in a regression analysis, maternal age, placental weight, and infant ponderal index did not add any explanatory power to the model. Our data suggest that, on an aggregate level, birth weight can be used as a proxy variable of intrauterine estriol exposure.

Perinatal Risk Factors for Diabetes in Later Life

OBJECTIVE—Low birth weight is consistently associated with an increased risk of type 2 diabetes in adulthood, but the individual contributions from poor fetal growth and preterm birth are not known. We therefore investigated the significance of these two factors separately. RESEARCH DESIGN AND METHODS—We identified a cohort of subjects born preterm or with low birth weight at term at four major delivery units in Sweden from 1925 through 1949. A comparison cohort of subjects was identified from the same source population. Of 6,425 subjects in all, 2,931 were born at <37 weeks of gestation and 2,176 had a birth weight <2,500 g. Disease occurrence among participants was assessed through nationwide hospital registers from 1987 through 2006. RESULTS—During follow-up, there were 508 cases of diabetes. Low birth weight was strongly negatively associated with risk of diabetes (P for trend <0.0001). Both short gestational duration and poor fetal growth were associated with later diabetes (P for trend <0.0001 and <0.0004, respectively). Very preterm birth (≤32 weeks of gestation at birth) was associated with a hazard ratio (HR) of 1.67 (95% CI 1.33–2.11) compared with term birth. Birth weights below 2 SDs of mean birth weight for gestational age were associated with an HR of 1.76 (1.30–2.38) compared with birth weights between the mean weight and the weight at 1 SD above the mean. CONCLUSIONS—Our results suggest that the association between low birth weight and diabetes is due to factors associated with both poor fetal growth and short gestational age.

Sickness in pregnancy and sex of child

We report a female predominance among the offspring of mothers with hyperemesis gravidarum.

Women smoking and testicular cancer: one epidemic causing another?

In many countries the incidence of testicular cancer has increased epidemically, but the aetiology remains obscure. Maternal smoking during pregnancy has been suggested to be a cause, but a satisfactorily valid assessment of the hypothesis is still lacking. To evaluate the epidemiological relevance, we assessed the ecological correlation between female smoking habits and testicular cancer incidence in the Nordic countries. Data on smoking prevalence among women in 5‐year birth cohorts 1910–1940, at 25–29 years of age, were obtained through past studies of smoking habits in Sweden, Denmark, Norway and Finland. Testicular cancer incidence in the presumed offspring birth cohorts 1938–1968, was calculated using data from the respective cancer registries. For comparison, a similar analysis of male smoking and testicular cancer in the presumed offspring cohorts was carried out. The Pearson correlation coefficient between female smoking prevalence and testicular cancer incidence in the generation of the presumed offspring was 0.9 (p < 0.0001) for all countries combined. With the exception of Finland, the country‐specific correlations were of the same magnitude. In multivariate analysis, there was no correlation with male smoking. The strong geographical and temporal correlations between female smoking and testicular cancer indicate that if smoking during pregnancy is a cause of testicular cancer in the offspring, part of the increasing trends could be explained, and more importantly: avoided, by primary prevention.

Stomach Cancer Risk After Treatment for Hodgkin Lymphoma

PURPOSE Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with specific HL treatments are unclear. PATIENTS AND METHODS We conducted an international case-control study of stomach cancer nested in a cohort of 19,882 HL survivors diagnosed from 1953 to 2003, including 89 cases and 190 matched controls. For each patient, we quantified cumulative doses of specific alkylating agents (AAs) and reconstructed radiation dose to the stomach tumor location. RESULTS Stomach cancer risk increased with increasing radiation dose to the stomach (Ptrend < .001) and with increasing number of AA-containing chemotherapy cycles (Ptrend = .02). Patients who received both radiation to the stomach ≥ 25 Gy and high-dose procarbazine (≥ 5,600 mg/m(2)) had strikingly elevated stomach cancer risk (25 cases, two controls; odds ratio [OR], 77.5; 95% CI, 14.7 to 1452) compared with those who received radiation < 25 Gy and procarbazine < 5,600 mg/m(2) (Pinteraction < .001). Risk was also elevated (OR, 2.8; 95% CI, 1.3 to 6.4) among patients who received radiation to the stomach ≥ 25 Gy but procarbazine < 5,600 mg/m(2); however, no procarbazine-related risk was evident with radiation < 25 Gy. Treatment with dacarbazine also increased stomach cancer risk (12 cases, nine controls; OR, 8.8; 95% CI, 2.1 to 46.6), after adjustment for radiation and procarbazine doses. CONCLUSION Patients with HL who received subdiaphragmatic radiotherapy had dose-dependent increased risk of stomach cancer, with marked risks for patients who also received chemotherapy containing high-dose procarbazine. For current patients, risks and benefits of exposure to both procarbazine and subdiaphragmatic radiotherapy should be weighed carefully. For patients treated previously, GI symptoms should be evaluated promptly.

Mechanical thrombectomy as the primary treatment for acute basilar artery occlusion: experience from 5 years of practice

Background Most studies of the treatment for acute basilar occlusion focus on intravenous or intra-arterial thrombolysis whereas data on mechanical thrombectomy as the preferred treatment for acute basilar occlusion are scarce. In this study, data are presented on 28 patients treated with mechanical thrombectomy as the preferred treatment for basilar artery occlusion. Methods Retrospective study comprising all patients who were treated for acute basilar occlusion at the Karolinska University Hospital from September 2005 to November 2010. Favorable outcome was defined as a modified Rankin score of ≤2 at 3–8 months after thrombectomy. Results Of 28 patients treated with mechanical thrombectomy, the proportion reaching a favorable outcome was 57% (95% CI 37% to 75%), and if there were no signs of acute infarction prior to treatment the proportion was 73% (95% CI 50% to 89%). Only 21% died (95% CI 8% to 41%). Conclusions The results for mechanical thrombectomy for basilar artery occlusion were superior to those presented previously for intravenous and intra-arterial thrombolysis. The study suggests that mechanical thrombectomy is a method distinct from therapies based on thrombolysis and that any randomized clinical trial on treatment for acute basilar occlusion must consider mechanical thrombectomy as a separate entity.

Expected day of delivery from ultrasound dating versus last menstrual period—obstetric outcome when dates mismatch

Objective  To analyse the association between fetal size at time of dating ultrasound and risk for preterm delivery and small‐for‐gestational‐age (SGA) birth and to evaluate if timing of ultrasound, that is before 14 weeks of gestation or after 16 weeks affects this association.

Second Cancers After Squamous Cell Carcinoma and Adenocarcinoma of the Cervix

PURPOSE Although cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) are both caused by human papillomavirus (HPV) infection, they differ in cofactors such as cigarette smoking. We assessed whether these cofactor differences translate into differences in second cancer risk. PATIENTS AND METHODS We assessed second cancer risk among 85,109 cervical SCC and 10,280 AC survivors reported to population-based cancer registries in Denmark, Finland, Norway, Sweden, and the United States. Risks compared to the general population were assessed using standardized incidence ratios (SIR). RESULTS Overall cancer risk was significantly increased among both cervical SCC survivors (n = 10,559 second cancers; SIR, 1.31; 95% CI, 1.29 to 1.34) and AC survivors (n = 920 second cancers; SIR, 1.29; 95% CI, 1.22 to 1.38). Risks of HPV-related and radiation-related cancers were increased to a similar extent among cervical SCC and AC survivors. Although significantly increased in both groups when compared with the general population, risk of smoking-related cancers was significantly higher among cervical SCC than AC survivors (P = .015; SIR for cervical SCC = 2.07 v AC = 1.78). This difference was limited to lung cancer (SIR for cervical SCC = 2.69 v AC = 2.18; P = .026). The increased lung cancer risk among cervical AC survivors was observed for both lung SCC and lung AC. SIRs for second cancers of the colon, soft tissue, melanoma, and non-Hodgkins lymphoma were significantly higher among cervical AC than SCC survivors. CONCLUSION The second cancer profiles among cervical SCC and AC survivors mirror the similarities and differences in cofactors for these two histologies. Because smoking is not a cofactor for cervical AC, the increased lung cancer risk suggests a role for additional factors.