Minimising warm ischaemia time during robot-assisted partial nephrectomy. A video-based assessment of tumour excision, kidney reconstruction and intermediate time.

INTRODUCTION: Surgical video review is an emerging tool for assessing patient outcomes, especially in complex surgeries such as robot-assisted partial nephrectomy (RAPN). Assessing and measuring warm ischaemia time (WIT) during RAPN by dividing it into the time used for tumour excision time (ExcT), time used for kidney reconstruction time (RecT) and intermediate time (IntT) has not been performed before. This study aimed to analyse the factors that can influence all surgical times and assess their impact on positive surgical margins (PSMs) and complication rates. METHODS: We evaluated 32 surgical video recordings from patients undergoing RAPN and measured WIT, ExcT, RecT and IntT with a stopwatch. Factors such as tumour characteristics and surgeon experience were also recorded. SPSS software was used to identify the predictors for all surgical times and to correlate ExcT with PSM and RecT with complication rate. RESULTS: We recorded a median WIT of 1,048 s (17 min and 28 s). The median of ExcT, RecT and IntT was 398 s (37.1% of WIT), 518 s (46.7% of WIT) and 180 s (16.2% of WIT), respectively. We found a significant correlation (P < 0.001) between R.E.N.A.L. score and all surgical times. No correlation was found between ExcT and PSM (P = 0.488) and between RecT and the probability of developing complications (P = 0.544). CONCLUSION: Tumour morphology influences all surgical times, and surgeon experience influences only ExcT. We observed a short RecT during RAPN though at the cost of increased ExcT, and we believe that improving surgical experience, especially for the excision of more complex tumours, can reduce WIT during RAPN.

IARC monographs: 40 years of evaluating carcinogenic hazards to humans.

BACKGROUND: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. OBJECTIVES: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. DISCUSSION: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.

Long-term experience with surgical treatment of selected patients with bladder pain syndrome/interstitial cystitis.

OBJECTIVE: The role of major surgery in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) is not fully established. This report presents a single-institution experience with major surgery in patients with disabling BPS/IC where conservative treatment had failed. MATERIAL AND METHODS: Forty-one patients (34 women, seven men) with BPS/IC refractory to conservative treatment underwent major surgery from 1983 to 2004. Surgical approach was determined on a case-by-case basis. Postoperative pain and satisfaction were assessed by a questionnaire. RESULTS: Cystectomy was the primary procedure in five patients. The remaining 36 patients were primarily operated on with subtotal cystectomy and bladder augmentation (n = 16) or supravesical urinary diversion with intact bladder (n = 20). Thirteen of these patients were later operated on with cystectomy due to persisting pain 12 (6-146) months after the primary procedure. The questionnaire was answered by 38 of 41 patients after a median follow-up of 66 (6-238) months. In total, 28 patients (74%) were free of pain, and 26 patients (68%) were satisfied with the end result. There was no difference in reported pain between cystectomized and non-cystectomized patients. When comparing patients who reported pain at follow-up with those who did not report pain, preoperative length of symptoms was significantly increased, with 12.1 compared to 5.4 years (p = 0.02). CONCLUSIONS: Major surgery is associated with good symptom relief in strictly selected patients with disabling BPS/IC, where conservative treatment has failed. Extended preoperative duration of symptoms may be a predictor for persisting pain after major surgery for BPS/IC.

Unrecognized risks of nickel-related respiratory cancer among Canadian electrolysis workers.

OBJECTIVES: Nickel compounds, inclusive of water-soluble salts, have been classified as human carcinogens by the International Agency for Research on Cancer (IARC). Nickel producers have disputed the classification of soluble nickel compounds for three decades with reference to an alleged absence of excess respiratory cancer among Canadian nickel-exposed electrolysis workers. We evaluated historical data from two electrolytic refineries in Ontario, both included in prominent Canadian reports on occupational nickel-related cancer. METHODS: For Port Colborne nickel refinery (PCNR) and Copper Cliff copper refinery (CCCR), we identified process descriptions, exposure estimates, and original reports on cancer mortality using reference lists, libraries, and state archives. The documents were written or published between 1930 and 1992. RESULTS: For PCNR, a 1977 US National Institute of Occupational Safety and Health criteria document demonstrated an excess nasal cancer risk among electrolysis workers independent of furnace exposure. PCNR studies published after 1980 excluded 26% of long-term refiners who died from respiratory cancer according to earlier reports, and 42% of the workers had unknown vital status at the end of follow-up, biasing the standardized observed-to-expected mortality ratios downwards, most pronounced in recent reports and for workers without pension or company benefits. CCCR reports did not adequately address soluble nickel exposure in the evaluation of an observed occupational lung cancer excess. CONCLUSIONS: While acknowledging important contributions to the recognition of nickel carcinogenicity from highly exposed Canadian refiners, we conclude that the claimed absence of nickel-related respiratory cancer among electrolysis workers has resulted from an arbitrary overemphasis of biased and inconclusive findings.

Evidence of carcinogenicity in humans of water-soluble nickel salts.

BACKGROUND: Increased risks of nasal cancer and lung cancer in nickel refiners have been investigated scientifically and discussed since they were detected in the 1930s. Nickel compounds are considered to be the main cause of the cancer excess. Parts of the nickel producing industry and their consultants oppose the classification of water-soluble nickel salts as human carcinogens, and argue that the risk in exposed workers should be ascribed to other occupational exposures and smoking. DISCUSSION: Respiratory cancer risks in Welsh, Finnish, and Norwegian nickel refiners add to the evidence of carcinogenicity of water-soluble nickel. In Norwegian refiners, the first epidemiological study in 1973 identified high risks of lung cancer and nasal cancer among long-term electrolysis workers. Risk analyses based on exposure estimates developed in the 1980s supported the view that water-soluble nickel compounds were central in the development of cancer. Recently, new exposure estimates were worked out for the same cohort based on personal monitoring of total nickel and chemical determination of four forms of nickel. Additional data have been collected on life-time smoking habits, and on exposure to arsenic, asbestos, sulphuric acid mists, cobalt, and occupational lung carcinogens outside the refinery. After adjustment for these potential confounding exposures in case-control analyses, the risk pattern added to the evidence of an important role of water-soluble nickel compounds as causes of lung cancer. These Norwegian cancer studies rely on national Cancer Registry data, considered close to complete from 1953 onwards; and on National Population Register data continuously updated with mortality and emigration. Canadian mortality studies--perceived to offer the strongest support to the industry position not to recognise carcinogenicity of water-soluble nickel--appear to suffer from limitations in follow-up time, loss to follow-up, absence of risk analysis with individual exposure estimates, no confounder control, and a likely underestimation of cancer mortality. CONCLUSIONS: Rejection to recognise water-soluble nickel as a human carcinogen seems to contradict material epidemiological evidence that demonstrates a strong association between water-soluble nickel compounds and risks of lung cancer and nasal cancer. Independent international scientific bodies have classified nickel compounds as carcinogenic to humans, inclusive of water-soluble nickel.

Prediagnostic serum concentrations of organochlorine compounds and risk of testicular germ cell tumors.

BACKGROUND: Recent findings suggest that exposure to organochlorine (OC) compounds, chlordanes and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) in particular, may increase the risk of developing testicular germ cell tumors (TGCTs). OBJECTIVE: To further investigate this question, we conducted a nested case-control study of TGCTs within the Norwegian Janus Serum Bank cohort. METHODS: The study was conducted among individuals with serum collected between 1972 and 1978. TGCT cases diagnosed through 1999 (n = 49; 27-62 years of age at diagnosis) were identified through linkage to the Norwegian Cancer Registry. Controls (n =51) were matched to cases on region, blood draw year, and age at blood draw. Measurements of 11 OC insecticide compounds and 34 polychlorinated biphenyl (PCB) congeners were performed using gas chromatography/high-resolution mass spectrometry. Case-control comparisons of lipid-adjusted analyte concentrations were performed using the Wilcoxon signed-rank test. Odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles of analyte concentration were calculated using conditional logistic regression. RESULTS: TGCT cases had elevated concentrations of p,p'-DDE (tertile 3 vs. tertile 1 OR (OR(T3)) 2.2; 95% CI, 0.7-6.5; p(Wilcoxon) = 0.07), oxychlordane (OR(T3) 3.2; 95% CI, 0.6-16.8; p(Wilcoxon) = 0.05), trans-nonachlor (OR(T3) 2.6; 95% CI, 0.7-8.9; p(Wilcoxon) = 0.07), and total chlordanes (OR(T3) 2.0; 95% CI, 0.6-7.2; p(Wilcoxon) = 0.048) compared with controls, although no ORs were statistically significant. Seminoma cases had significantly lower concentrations of PCB congeners 44, 49, and 52 and significantly higher concentrations of PCBs 99, 138, 153, 167, 183, and 195. CONCLUSIONS: Our study provides additional but qualified evidence supporting an association between exposures to p,p'-DDE and chlordane compounds, and possibly some PCB congeners, and TGCT risk.

Protective effect from solar exposure, risk of an ecological fallacy.

Solar exposure, vitamin D, and their possible beneficial effect on cancer risk and cancer prognosis are a topic for research. Despite the distinct nature of sunlight, it has proved difficult to assess the exposure quantitatively in epidemiological studies. Skin cancers, latitude, and sunny climate have been used as proxy indicators of solar exposure above a reference level. The interpretation of such data may still be hampered by incomplete cancer registration, difference in protection against sunbeams, selection mechanisms, and absence of information on potential confounders. A recently published paper -- on second primary cancer following the diagnosis of a skin cancer -- is discussed to illustrate the difficulties. Further epidemiological studies of potentially protective effects from carcinogenic ultraviolet rays should include individual information on solar exposure and vitamin D levels, as well as on other recognised and relevant risk factors.

Impact of respiratory symptoms on lung cancer: 30-year follow-up of an urban population.

We investigated the relationship between respiratory symptoms reported at one time and incidence of lung cancer the subsequent 30 years in an urban Norwegian population. A cohort of 19,998 persons, aged 15-70 years living in Oslo, was randomly selected for a respiratory survey in 1972. The response-rate was 89% and 17,670 respondents were followed up. The relationship between respiratory symptoms and lung cancer incidence was investigated separately for each symptom group, symptom score and sex, with adjustment for age, smoking habits and occupational exposure. Lung cancer developed in 352 persons (228 men and 124 women) during follow up. We found a significant positive association between the incidence of lung cancer and cough symptoms in both sexes, asthma-like symptoms among women and dyspnoea when walking uphill among men. The relative risk for lung cancer increased with the number of symptoms reported at baseline and was strongest the first decade and decreased with duration of follow up. This association was more pronounced for non-small cell lung cancer than for small cell lung cancer.

Respiratory symptoms and long-term cardiovascular mortality.

BACKGROUND: Our aim was to investigate the association between respiratory symptoms and mortality from ischaemic heart disease (IHD) and stroke in a population during 30 years follow-up. METHODS: In 1972, 19998 persons aged 15-70 years, living in Oslo, were selected for a respiratory survey (response 89%). Respiratory symptoms were divided into four groups and given a score. The association between respiratory symptoms and mortality from IHD and stroke were investigated separately for men and women, with adjustment for age, occupational exposure to air pollution and smoking habits. RESULTS: IHD accounted for 1572 and stroke for 653 of all deaths. The adjusted hazard ratio (HR) for mortality from IHD in men varied from 1.3 (95% confidence interval, 1.1-1.5) to 3.0 (2.3-3.8) and in women from 1.2 (1.0-1.5) to 1.9 (1.4-2.5) for cough symptoms and severe dyspnoea, respectively. Symptom score predicted death from IHD, in a dose-response manner. The HR for mortality from stroke varied from 1.0 to 2.3 in men and from 1.1 to 1.5 in women for the symptom groups, but was significant only among men reporting severe dyspnoea and among women reporting moderate dyspnoea. For all respiratory symptoms, the excess risk for cardiovascular mortality decreased during follow-up, but IHD-mortality was still significantly increased the last decade. CONCLUSION: We found a significant, positive association between respiratory symptoms and 30-year mortality from IHD. The positive association was weaker between respiratory symptoms and long-term mortality from stroke.

Polychlorinated biphenyl levels in peripheral blood and non-Hodgkin's lymphoma: a report from three cohorts.

The incidence of non-Hodgkin's lymphoma (NHL) unrelated to HIV infection has steadily increased over the past several decades and remains substantially unexplained. Limited evidence suggests that increased concentrations of polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated with increased risk of NHL. Although PCB congeners vary in their biological activity, the relation between individual congeners and NHL risk has not been examined previously using prospectively collected biospecimens. We examined congener-specific associations in three prospective cohorts. Prediagnostic serum or plasma concentrations of selected PCB congeners were measured among NHL cases and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and CLUE I (74 cases and 147 controls) and the Nurses' Health Study (30 cases and 78 controls) in the United States. All blood samples were collected in the 1970s or 1980s. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the relations between risk of NHL and lipid-corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and 153) that were present at higher levels and were moderately to highly correlated with each other showed exposure-response trends with risk of NHL in all three cohorts. These associations were observed primarily among subjects diagnosed closer to the date of blood collection in the two cohorts with sufficient cases to permit stratification by time. Among cases diagnosed within the median years of follow-up (16 years in Janus and 12 years in CLUE I), ORs and 95% CIs for increasing fourths of concentration of congener 118 relative to the lowest fourth were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8; P(trend) < 0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8; P(trend) < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for total PCBs. Limited evidence of exposure-response trends was also observed for several other congeners. The primary 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane metabolite, p,p'-DDE, was not significantly associated with NHL in most analyses but slightly to moderately confounded the PCB associations. The results from these three cohorts suggest that concentrations of certain PCBs in blood are associated with increased risk of NHL.

Noncancer causes of death in survivors of testicular cancer.

BACKGROUND: Although modern treatments for testicular cancer are associated with increased survival, the long-term health effects of these treatments are unclear. We conducted a population-based study to quantify the long-term risks of mortality from noncancer causes among men with testicular cancer. METHODS: We identified 38,907 one-year survivors of testicular cancer within 14 population-based cancer registries in North America and Europe (from 1943 through 2002). We used data from these registries to calculate standardized mortality ratios (SMRs) for noncancer deaths and to evaluate associations between histology, age at testicular cancer diagnosis, calendar year of diagnosis, and initial treatment and the risk of noncancer mortality. All statistical tests were two-sided. RESULTS: A total of 2942 deaths from all noncancer causes were reported after a median follow-up of 10 years, exceeding the expected number of deaths from all noncancer causes in the general population by 6% (SMR = 1.06, 95% confidence interval [CI] = 1.02 to 1.10); the noncancer standardized mortality ratios did not differ statistically significantly between patients diagnosed before and after 1975, when cisplatin-based chemotherapy came into widespread use. Compared with the general population, testicular cancer survivors had higher mortality from infections (SMR = 1.28, 95% CI = 1.12 to 1.47) and from digestive diseases (SMR = 1.44, 95% CI = 1.26 to 1.64). Mortality from all circulatory diseases was statistically significantly elevated in men diagnosed with testicular cancer before age 35 years (1.23, 95% CI = 1.09 to 1.39) but not in men diagnosed at older ages (SMR = 0.94; 95% CI = 0.89 to 1.00). Men treated with chemotherapy (with or without radiotherapy) in 1975 or later had higher mortality from all noncancer causes (SMR = 1.34, 95% CI = 1.15 to 1.55), all circulatory diseases (SMR = 1.58, 95% CI = 1.25 to 2.01), all infections (SMR = 2.48, 95% CI = 1.70 to 3.50), and all respiratory diseases (SMR = 2.53, 95% CI = 1.26 to 4.53). Testicular cancer patients who were younger than 35 years at diagnosis and were treated with radiotherapy alone in 1975 or later had higher mortality from all circulatory diseases (SMR = 1.70, 95% CI = 1.21 to 2.31) compared with the general population. CONCLUSION: Men who have survived for at least 1 year after being diagnosed with testicular cancer have a slightly higher risk of dying from noncancer causes, including infections, digestive diseases, and circulatory diseases, than the general population. Men treated with chemotherapy in 1975 or later may be at particularly high risk.

Nordic biological specimen banks as basis for studies of cancer causes and control--more than 2 million sample donors, 25 million person years and 100,000 prospective cancers.

The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at -20 degrees C to -135 degrees C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.

Cancer risk among 43000 Norwegian nurses.

OBJECTIVES: This study evaluated the influence of occupational exposure on cancer risk among female Norwegian nurses. METHODS: A historical prospective cohort study was performed. The cohort was established from the Norwegian Board of Health's registry of nurses and included women who graduated from a nursing school before 1985. The cohort (N=43 316) was linked to the Cancer Registry of Norway. The observed number of cases was compared with the expected number on the basis of national rates. Time since first employment, period of first employment, and duration of employment were used as indicators of exposure. Poisson regression analyses were used for internal comparisons, adjusting for age, period, and fertility. RESULTS: The nurses were followed over 1473931 person-years. During the follow-up (1953-2002), 6193 cancer cases were observed. The standardized incidence ratio (SIR) for all cancers combined was close to unity. Significantly lower risks were found for cancers with a known association with alcohol and tobacco consumption and sexual activity. A significantly increased risk was found for breast cancer (SIR 1.14, 95% confidence interval (95% CI) 1.09-1.19), ovarian cancer (SIR 1.14, 95% CI 1.04-1.25), malignant melanoma (SIR 1.15, 95% CI 1.04-1.28), and borderline significant risk appeared for other skin cancer (SIR 1.12, 95% CI 0.98-1.29). A positive trend for increasing time since first exposure was found for breast cancer and malignant melanoma. CONCLUSIONS: The results indicate an association between working as a nurse and an increased risk of breast cancer and malignant melanoma. Decreased risks, found for several cancers, indicate favorable lifestyle habits among nurses.

Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples.

The rhesus monkey virus Simian Virus 40 (SV40) is a member of the polyomavirus family. It was introduced inadvertently to human populations through contaminated polio vaccine during the years 1956-1963, can induce experimental tumors in animals and transform human cells in culture. SV40 DNA has been identified in mesothelioma and other human tumors in some but not all studies. We tested prediagnostic sera from 49 mesothelioma cases and 147 matched controls for antibodies against the viral capsid protein VP1 and the large T antigen of SV40 and of the closely related human polyomaviruses BK and JC, and for SV40 DNA. Cases and controls were identified among donors to the Janus Serum Bank, which was linked to the Cancer Registry of Norway. Antibodies were analyzed by recently developed multiplex serology based on recombinantly expressed fusions of glutathione-S transferase with viral proteins as antigens combined with fluorescent bead technology. BKV and JCV specific antibodies cross- reactive with SV40 were preabsorbed with the respective VP1 proteins. Sera showing SV40 reactivity after preabsorption with BKV and JCV VP1 were further analyzed in SV40 neutralization assays. SV40 DNA was analyzed by SV40 specific polymerase chain reactions. The odds ratio for being a case when tested positive for SV40 VP1 in the antibody capture assay was 1.5 (95% CI 0.6-3.7) and 2.0 (95% CI 0.6-7.0) when only strongly reactive sera where counted as positive. Although some sera could neutralize SV40, preabsorption with BKV and JCV VP1 showed for all such sera that this neutralizing activity was due to cross-reacting antibodies and did not represent truly SV40-specific antibodies. No viral DNA was found in the sera. No significant association between SV40 antibody response in prediagnostic sera and risk of mesothelioma was seen.

Serum cotinine level as predictor of lung cancer risk.

BACKGROUND: No prospective studies are available on serum cotinine level as a marker of lung cancer risk. METHODS: We analyzed serum cotinine level among 1,741 individuals enrolled since the 1970s in a prospective study of Norwegian volunteers who developed lung cancer during the follow-up and 1,741 matched controls free from lung cancer. Serum cotinine was measured with a competitive immunoassay. Regression dilution was corrected for based on repeated measures on samples from 747 subjects. RESULTS: Mean serum cotinine level was higher in cases than in controls. Compared with subjects with a cotinine level of < or = 5 ng/mL, the odds ratio of lung cancer was increasing linearly, reaching 55.1 (95% confidence interval, 35.7-85.0) among individuals with a serum cotinine level of > 378 ng/mL. There was no clear suggestion of a plateau in risk at high exposure levels. Odds ratios were very similar in men and women. We found no association between serum cotinine level (range, 0.1-9.9 ng/mL) and lung cancer risk among self-reported nonsmokers and long-term quitters (79 cases and 350 controls). DISCUSSION: The association between tobacco smoking and lung cancer risk might be stronger than is estimated from questionnaire-based studies. Serum cotinine level is a predictor of risk of lung cancer among smokers. The reported plateau in risk at high doses is likely due mainly to artifacts. There is no difference between men and women in the carcinogenicity of tobacco smoking.

Acute myeloid leukemia following Hodgkin lymphoma: a population-based study of 35,511 patients.

Treatments for Hodgkin lymphoma are associated with large relative risks of acute myeloid leukemia (AML), but there are few estimates of the excess absolute risk (EAR), a useful measure of disease burden. One-year Hodgkin lymphoma survivors (N = 35,511) were identified within 14 population-based cancer registries in Nordic countries and North America from January 1, 1970, through December 31, 2001. We used Poisson regression analysis to model the EAR of AML, per 10,000 person-years. A total of 217 Hodgkin lymphoma survivors were diagnosed with AML (10.8 expected; unadjusted EAR = 6.2; 95% confidence interval = 5.4 to 7.1). Excess absolute risk for AML was highest during the first 10 years after Hodgkin lymphoma diagnosis but remained elevated thereafter. In subsequent analyses, adjusted for time since Hodgkin lymphoma diagnosis and presented for the 5-9 year interval, the EAR was statistically significantly (P < .001) larger in patients diagnosed with Hodgkin lymphoma at age 35 years and older than in those diagnosed before 35 years of age. The EAR of AML declined statistically significantly after 1984 (7.0 to 4.2 and 16.4 to 9.9 in the < 35 and > or = 35 age groups, respectively), which may be associated with modifications in chemotherapy.

Cancer in persons working in dry cleaning in the Nordic countries.

U.S. studies have reported an increased risk of esophageal and some other cancers in dry cleaners exposed to tetrachloroethylene. We investigated whether the U.S. findings could be reproduced in the Nordic countries using a series of case-control studies nested in cohorts of laundry and dry-cleaning workers identified from the 1970 censuses in Denmark, Norway, Sweden, and Finland. Dry-cleaning work in the Nordic countries during the period when tetrachloroethylene was the dominant solvent was not associated with an increased risk of esophageal cancer [rate ratio (RR) = 0.76; 95% confidence interval (CI), 0.34-1.69], but our study was hampered by some unclassifiable cases. The risks of cancer of the gastric cardia, liver, pancreas, and kidney and non-Hodgkin lymphoma were not significantly increased. Assistants in dry-cleaning shops had a borderline significant excess risk of cervical cancer not found in women directly involved in dry cleaning. We found an excess risk of bladder cancer (RR = 1.44; 95% CI, 1.07-1.93) not associated with length of employment. The finding of no excess risk of esophageal cancer in Nordic dry cleaners differs from U.S. findings. Chance, differences in level of exposure to tetrachloroethylene, and confounding may explain the findings. The overall evidence on bladder cancer in dry cleaners is equivocal.

A pooled analysis of second primary pancreatic cancer.

Studies of pancreatic cancer in the setting of second primary malignant neoplasms can provide etiologic clues. An international multicenter study was carried out using data from 13 cancer registries with a registration period up to year 2000. Cancer patients were followed up from the initial cancer diagnosis, and the occurrence of second primary malignant neoplasms was compared with expected values derived from local rates, adjusting for age, sex, and period of diagnosis. Results from individual registries were pooled by use of a fixed-effects model. People were at higher risk of developing pancreatic cancer within 10 years of a diagnosis of cancers of the pharynx, stomach, gallbladder, larynx, lung, cervix, corpus uteri, bladder, and eye and 10 years or later following a diagnosis of cancers of the stomach, colon, gallbladder, breast, cervix, placenta, corpus uteri, ovary, testis, bladder, kidney, and eye, as well as Hodgkin's and non-Hodgkin's lymphomas. Pancreatic cancer was connected with smoking-related cancers, confirming the etiologic role of tobacco. The associations with uterine and ovarian cancers suggest that reproductive factors might be implicated in pancreatic carcinogenesis. The elevated pancreatic cancer risk in young patients observed among several types of cancer implies a role of genetic factors. Radiotherapy is also suggested as a risk factor.

Associations between small intestine cancer and other primary cancers: an international population-based study.

Cancer of the small intestine is a rare neoplasm, and its etiology remains poorly understood. Analysis of other primary cancers in individuals with small intestine cancer may help elucidate the causes of this neoplasm and the underlying mechanisms. We included 10,946 cases of first primary small intestine cancer from 13 cancer registries in a pooled analysis. The observed numbers of 44 types of second primary cancer were compared to the expected numbers derived from the age-, gender- and calendar period-specific cancer incidence rates in each registry. We also calculated the standardized incidence ratios (SIR) for small intestine cancer as a second primary after other cancers. There was a 68% overall increase in the risk of a new primary cancer after small intestine carcinoma (SIR = 1.68, 95% confidence interval [CI] = 1.47-1.71), that remained constant over time. The overall SIR was 1.18 (95% CI = 1.05-1.32) after carcinoid, 1.29 (1.01-1.63) after sarcoma, and 1.27 (0.78-1.94) after lymphoma. Significant (p < 0.05) increases were observed for cancers of the oropharynx, colon, rectum, ampulla of Vater, pancreas, corpus uteri, ovary, prostate, kidney, thyroid gland, skin and soft tissue sarcomas. Small intestine cancer as a second primary was increased significantly after all these cancers, except after oropharyngeal and kidney cancers. Although some of the excess may be attributable to overdiagnosis, it is plausible that most additional cases of second primary cancers were clinically relevant and were due to common genetic (e.g., defects in mismatch or other DNA repair pathways) and environmental (e.g., dietary) factors.

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.