Johanna Adami

Cancer risk following organ transplantation: a nationwide cohort study in Sweden

A substantial excess risk of lymphomas and nonmelanoma skin cancer has been demonstrated following organ transplantation. Large sample size and long follow-up time may, however, allow more accurate risk estimates and detailed understanding of long-term cancer risk. The objective of the study was to assess the risk of cancer following organ transplantation. A nationwide cohort study comprising 5931 patients who underwent transplantation of kidney, liver or other organs during 1970–1997 in Sweden was conducted. Complete follow-up was accomplished through linkage to nationwide databases. We used comparisons with the entire Swedish population to calculate standardised incidence ratios (SIRs), and Poisson regression for multivariate internal analyses of relative risks (RRs) with 95% confidence intervals (CI). Overall, we observed 692 incident first cancers vs 171 expected (SIR 4.0; 95% CI 3.7–4.4). We confirmed marked excesses of nonmelanoma skin cancer (SIR 56.2; 95% CI 49.8–63.2), lip cancer (SIR 53.3; 95% CI 38.0–72.5) and of non-Hodgkins lymphoma (NHL) (SIR 6.0; 95% CI 4.4–8.0). Compared with patients who underwent kidney transplantation, those who received other organs were at substantially higher risk of NHL (RR 8.4; 95% CI 4.3–16). Besides, we found, significantly, about 20-fold excess risk of cancer of the vulva and vagina, 10-fold of anal cancer, and five-fold of oral cavity and kidney cancer, as well as two- to four-fold excesses of cancer in the oesophagus, stomach, large bowel, urinary bladder, lung and thyroid gland. In conclusion, organ transplantation entails a persistent, about four-fold increased overall cancer risk. The complex pattern of excess risk at many sites challenges current understanding of oncogenic infections that might become activated by immunologic alterations.

Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial.

Objective:To determine whether an intervention with smoking cessation starting 4 weeks before general and orthopedic surgery would reduce the frequency of postoperative complications. Summary Background Data:Complications are a major concern after elective surgery and smokers have an increased risk. There is insufficient evidence concerning how the duration of preoperative smoking intervention affects postoperative complications. Methods:A randomized controlled trial, conducted between February 2004 and December 2006 at 4 university-affiliated hospitals in the Stockholm region, Sweden. The outcome assessment was blinded. The follow-up period for the primary outcome was 30 days. Eligibility criteria were active daily smokers, aged 18 to 79 years. Of the 238 patients assessed, 76 refused participating, and 117 men and women undergoing surgery for primary hernia repair, laparoscopic cholecystectomy, or a hip or knee prosthesis were enrolled. Intervention:Smoking cessation therapy with individual counseling and nicotine substitution started 4 weeks before surgery and continued 4 weeks postoperatively. The control group received standard care. The main outcome measure was frequency of any postoperative complication. Results:An intention-to-treat analysis showed that the overall complication rate in the control group was 41%, and in the intervention group, it was 21% (P = 0.03). Relative risk reduction for the primary outcome of any postoperative complication was 49% and number needed to treat was 5 (95% CI, 3–40). An analysis per protocol showed that abstainers had fewer complications (15%) than those who continued to smoke or only reduced smoking (35%), although this difference was not statistically significant. Conclusion:Perioperative smoking cessation seems to be an effective tool to reduce postoperative complications even if it is introduced as late as 4 weeks before surgery.

Evidence of an association between non-Hodgkin's lymphoma and skin cancer

Abstract Objective: To investigate a possible link between exposure to ultraviolet light and the almost epidemic increase in non-Hodgkins lymphoma worldwide. Because ultraviolet light is known to cause skin cancers, the association between non-Hodgkins lymphoma and skin cancer was studied. Design: Secondary occurrence of either malignant melanoma or squamous cell skin cancer in cohorts of patients with a first diagnosis of either non-Hodgkins lymphoma or chronic lymphocytic leukaemia, and vice versa, were studied. Expected numbers of subsequent cancers were calculated by sex, age, and period specific national incidence rates multiplied by the person years under observation in the cohorts. Setting: Denmark (1943-89) and Sweden (1958-89). Subjects: Four population based cohorts identified in the nationwide cancer registries (34641 people with non-Hodgkins lymphoma, 17400 with chronic lymphocytic leukaemia, 34989 with malignant melanoma, 25980 with squamous cell skin cancer). A total of 562085 person years were accrued for the analysis. Main outcome measures: The ratios of observed to expected cancers (the standardised incidence ratio) served as a measure of the relative risk. Results: The relative risk for developing squamous cell skin cancer was 5.5 (95% confidence interval 4.6 to 6.6) among patients with non-Hodgkins lymphoma and 8.6 (7.2 to 10.3) among patients with chronic lymphocytic leukaemia. The relative risks remained high over more than 15 years of follow up. Relative risks for malignant melanoma were 2.4 (1.8 to 3.2) for patients with non-Hodgkins lymphoma and 3.1 (2.1 to 4.4) for patients with chronic lymphocytic leukaemia. After squamous cell skin cancer had been diagnosed there was a twofold excess risk for non-Hodgkins lymphoma and chronic lymphocytic leukaemia. By contrast, in each of the cohorts the general cancer risks excluding skin and lymphoproliferative malignancies were close to the expected. Conclusions: The occurrence of non-Hodgkins lymphoma and skin cancer are strongly associated; this supports the hypothesis that the secular increase in exposure to ultraviolet light may have contributed to the increasing incidence of non-Hodgkins lymphoma in recent decades Key messages Key messages Ultraviolet light is known to be immunosuppressive and to have causal links to skin cancer Non-Hodgkins lymphoma is strongly associated with skin cancer Exposure to ultraviolet light may have contributed to the increasing incidence of non-Hodgkins lymphoma in recent decades

Fractures of the shaft of the humerus. An epidemiological study of 401 fractures.

We studied the epidemiology of 401 fractures of the shaft of the humerus in 397 patients aged 16 years or older. The incidence was 14.5 per 100,000 per year with a gradually increasing age-specific incidence from the fifth decade, reaching almost 60 per 100, 000 per year in the ninth decade. Most were closed fractures in elderly patients which had been sustained as the result of a simple fall. The age distribution in women was characterised by a peak in the eighth decade while that in men was more even. Simple fractures were by far the most common and most were located in the middle or proximal shaft. The incidence of palsy of the radial nerve was 8% and fractures in the middle and distal shaft were most likely to be responsible. Only 2% of the fractures were open and 8% were pathological. These figures are representative of a population with a low incidence of high-energy and penetrating trauma, which probably reflects the situation in most European countries.

Oral use of Swedish moist snuff (snus) and risk for cancer of the mouth, lung, and pancreas in male construction workers: a retrospective cohort study.

BACKGROUND Although classified as carcinogenic, snuff is used increasingly in several populations. Scandinavian moist snuff (snus) has been proposed as a less harmful alternative to smoking, but precise data on the independent associations of snus use with site-specific cancers are sparse. We aimed to assess the risks for cancer of the oral cavity, lung, and pancreas. METHODS Detailed information about tobacco smoking and snus use was obtained from 279 897 male Swedish construction workers in 1978-92. Complete follow-up until end of 2004 was accomplished through links with population and health registers. To distinguish possible effects of snus from those of smoking, we focused on 125 576 workers who were reported to be never-smokers at entry. Adjusted relative risks were derived from Cox proportional hazards regression models. FINDINGS 60 cases of oral, 154 of lung, and 83 of pancreatic cancer were recorded in never-smokers. Snus use was independently associated with increased risk of pancreatic cancer (relative risk for ever-users of snus 2.0; 95% CI 1.2-3.3, compared with never-users of any tobacco), but was unrelated to incidence of oral (0.8, 95% CI 0.4-1.7) and lung cancer (0.8, 0.5-1.3). INTERPRETATION Use of Swedish snus should be added to the list of tentative risk factors for pancreatic cancer. We were unable to confirm any excess of oral or lung cancer in snus users.

The impact of tobacco use and body mass index on the length of stay in hospital and the risk of post-operative complications among patients undergoing total hip replacement

We carried out a retrospective cohort study of 3309 patients undergoing primary total hip replacement to examine the impact of tobacco use and body mass index on the length of stay in hospital and the risk of short term post-operative complications. Heavy tobacco use was associated with an increased risk of systemic post-operative complications (p = 0.004). Previous and current smokers had a 43% and 56% increased risk of systemic complications, respectively, when compared with non-smokers. In heavy smokers, the risk increased by 121%. A high body mass index was significantly associated with an increased mean length of stay in hospital of between 4.7% and 7%. The risk of systemic complications was increased by 58% in the obese. Smoking and body mass index were not significantly related to the development of local complications. Greater efforts should be taken to reduce the impact of preventable life style factors, such as smoking and high body mass index, on the post-operative course of total hip replacement.

Sunlight and non-Hodgkin's lymphoma: a population-based cohort study in Sweden

Indirect evidence, notably ecological comparisons and an association with skin cancer, links non‐Hodgkins lymphoma (NHL) with exposure to sunlight. We conducted a population‐based, nationwide cohort study with exposure to outdoor work inferred from job titles reported in the population and housing censuses in 1960 and/or 1970 and by classifying each individuals work and home addresses according to latitude. Follow‐up for cancer incidence was accomplished through record linkages with the virtually complete Swedish Cancer Registry. The cohort included all Swedish residents who were recorded as gainfully employed in both censuses. Altogether 4,171,175 individuals contributing 69,639,237 person‐years accrued through 1989 were included in the analyses. We identified 10,381 cases of NHL, 4,018 cases of chronic lymphocytic leukemia (CLL), 11,398 cases of malignant melanoma (MM) and 11,913 cases of squamous cell skin cancer (SCC). We calculated age‐adjusted relative risks for NHL, CLL, MM and SCC in strata based on estimated residential and occupational sunlight exposure. Interaction effects were considered for pesticide and solvent exposure. NHL, MM and SCC, but not CLL, were positively associated with increasingly southerly residential latitude, with stronger associations seen for skin cancer compared to NHL. Occupational sun exposure was not associated with the risk of developing any of the studied cancers. Pesticides and solvents also were not related to an increased risk of NHL, nor did these exposures enhance effects of residential or occupational sunlight exposure. Our results provide some support for an association of sunlight exposure with NHL incidence based on the associations seen using geographic latitude of residence as a proxy for exposure. Although type of occupation may be an imperfect index of the biologically relevant ultraviolet (UV) light dose, our data on individual exposure are not consistent with an important role of sunlight in the etiology of NHL. Int. J. Cancer 80:641–645, 1999.

High body mass index is associated with increased risk of implant dislocation following primary total hip replacement: 2,106 patients followed for up to 8 years

Background and purpose Implant dislocation is one of the commonest complications following primary total hip replacement (THR). We investigated the effect of body mass index (BMI) and tobacco use on the risk of this complication. Subjects and methods Through linkage between the Swedish Construction Workers’ cohort and the Swedish Inpatient Register, 2,106 male patients who had undergone primary THR between 1997 and 2004 were identified. We used Cox multivariable regression analysis to study the association between BMI and tobacco use and the risk of implant dislocation. Results 53 patients (2.5%) developed implant dislocation during a mean of 2 (0–3) years of follow-up. We found overweight and obesity to be associated with increased risk of implant dislocation (HR = 2.5,95% CI: 1.1–5.5 and HR = 3.7, 95% CI: 1.5–9.3, respectively as compared to those of normal weight). There was no statistically significant association between tobacco use and the risk of dislocation. Interpretation Greater attention should be given to high BMI as a risk factor for implant dislocation following THR.

Outcome after closed functional treatment of humeral shaft fractures.

Objective: The aim of this study was to investigate the outcome after an isolated humeral shaft fracture treated primarily nonoperatively with a fracture brace. Setting: University hospital. Design: Descriptive study. Retrospective assessment of clinical and radiographic healing. Prospective assessment of functional outcome and health-related quality of life (HRQoL). Patients: Seventy-eight patients (female, n = 45), mean age 58 (range, 16-91) years with isolated humeral shaft fractures. Intervention: Closed functional treatment with a fracture brace. Main Outcome Measurements: Fracture healing, need for revision surgery, Short Musculoskeletal Functional Assessment (SMFA), HRQoL according to the Short Form 36 (SF-36) and patient-reported recovery. Results: Ninety percent of the fractures healed after nonoperative treatment, and nearly 90% of the nonunions healed after revision surgery. There was a trend toward more frequent nonunions in simple fractures, that is, type A according to the Orthopedic Trauma Association (OTA) classification (P = 0.08). The nonunion rate in type A fractures located in the proximal and middle part of the shaft was approximately 20%. Nearly 50% of the patients reported full recovery after successful nonoperative treatment, but none of the patients with a healed nonunion did after revision surgery (P < 0.05). The SMFA scores for arm/hand function were acceptable for the patients who healed after the primary fracture-brace treatment, but the values were worse for those with a healed nonunion after revision surgery. The SF-36 scores were generally slightly lower compared with a Swedish reference population. Conclusion: This study confirms the high overall rate of union of humeral shaft fractures and an acceptable functional outcome after successful fracture-brace treatment. However, in simple (type A) fractures, the nonunion rate seems to be higher, and patients with healed nonunions after revision surgery reported worse functional outcomes. Based on these findings, it seems reasonable to explore the use of plate fixation compared with nonoperative treatment for selected fracture types in a randomized controlled trial.

Subarachnoid haemorrhage in Sweden 1987-2002: regional incidence and case fatality rates

Background: Incidence estimates of subarachnoid haemorrhage (SAH) in Sweden vary, which may be caused by regional variations. Reliable estimates of age-specific case fatality rates are lacking. We analysed regional incidence rates and case fatality rates of SAH in Sweden. Methods: The Swedish Hospital Discharge and Cause of Death Registries from 1987 to 2002 yielded data on 18 443 patients with SAH. Incidence and case fatality rates by age, gender, region and time period were calculated by Poisson regression. Results: The incidence rate was 12.4 per 100 000 person-years (95% CI 12.2 to 12.6) and increased with age, from 6.4/100 000 person-years in patients who were 30–39 years old to 25.8/100 000 person-years in patients who were older than 80 years. Incidence was higher for women (14.4 (95% CI 14.2 to 14.7)) than for men (10.3 (95% CI 10.3 to 10.6)), and higher in the north than in the south (RR 1.31 (95% CI 1.25 to 1.37)). This geographical gradient was more evident in women (RR 1.41 (95% CI 1.33 to1.49)) than in men (RR 1.23 (95% CI 1.15 to 1.33)). The 28-day case fatality rate was 31.7% (95% CI 31.0 to 32.3). It increased with age from 18.1% (95% CI 16.0 to 20.3) in patients who were 30–39 years old to 57.6% (95% CI 55.2 to 59.9) in patients over 80 years, then levelling off. Over time (1995–2002 compared with 1987–1994), the incidence rate decreased (RR 0.93 (95% CI 0.90 to 0.96)) and case fatality rate decreased (RR 0.89 (95% CI 0.85 to 0.93)). Conclusions: SAH incidence rates in Sweden increase from south to north, more in women than in men. Octogenarians have a quadrupled incidence and a tripled case fatality compared with young adults. During 16 years, both incidence and case fatality have decreased.