Testicular Cancer in the Cisplatin Era: Causes of Death and Mortality Rates in a Population-Based Cohort

PURPOSE Using complete information regarding testicular cancer (TC) treatment burden, this study aimed to investigate cause-specific non-TC mortality with impact on previous treatment with platinum-based chemotherapy (PBCT) or radiotherapy (RT). METHODS Overall, 5,707 men identified by the Cancer Registry of Norway diagnosed with TC from 1980 to 2009 were included in this population-based cohort study. By linking data with the Norwegian Cause of Death Registry, standardized mortality ratios (SMRs), absolute excess risks (AERs; [(observed number of deaths − expected number of deaths)/person-years of observation] ×10,000), and adjusted hazard ratios (HRs) were calculated. RESULTS Median follow-up was 18.7 years, during which non-TC death was registered for 665 (12%) men. Overall excess non-TC mortality was 23% (SMR, 1.23; 95% CI, 1.14 to 1.33; AER, 11.14) compared with the general population, with increased risks after PBCT (SMR, 1.23; 95% CI, 1.07 to 1.43; AER, 7.68) and RT (SMR, 1.28; 95% CI, 1.15 to 1.43; AER, 19.55). The highest non-TC mortality was observed in those < 20 years at TC diagnosis (SMR, 2.27; 95% CI, 1.32 to 3.90; AER, 14.42). The most important cause of death was non-TC second cancer with an overall SMR of 1.53 (95% CI, 1.35 to 1.73; AER, 7.94), with increased risks after PBCT and RT. Overall noncancer mortality was increased by 15% (SMR, 1.15; 95% CI, 1.04 to 1.27; AER, 4.71). Excess suicides appeared after PBCT (SMR, 1.65; 95% CI, 1.01 to 2.69; AER, 1.39). Compared with surgery, increased non-TC mortality appeared after 3 (HR, 1.47; 95% CI, 0.91 to 2.39), 4 (HR, 1.41; 95% CI, 1.01 to 1.99), and more than four (HR, 2.04; 95% CI, 1.25 to 3.35) cisplatin-based chemotherapy cycles after > 10 years of follow-up. CONCLUSION TC treatment with PBCT or RT is associated with a significant excess risk of non-TC mortality, and increased risks emerged after more than two cisplatin-based chemotherapy cycles after > 10 years of follow-up.

Industrial pollution and mortality from digestive cancers at the small area level in a Spanish industrialized province

The province of Cadiz, Spain, is a highly industrialized area with numerous registered industrial plants, which has led to major concern regarding the possible influence of these facilities on the high rate of cancer-related mortality observed. Our objective was to evaluate the association between digestive cancer mortality and proximity to industrial installations in the province of Cadiz over the period 1992-2014 and to analyse this risk according to different categories of carcinogenic substances. An ecological study at the census tract level was carried out. Mortality due to digestive cancer (involving the oral cavity, pharynx, oesophagus, stomach, liver, pancreas, gallbladder, colon and rectum) was analysed. Using the spatial Besag, York and Mollié (BYM) approach, we assessed the relative risk of dying from these cancers for people living between 500 m and 5 km from industrial installations. The models were adjusted to account for socioeconomic deprivation. We detected a significant, excess risk of dying due to cancer in the following organs (expressed as relative risk with 95% confidence intervals): colon/rectum (1.13; 1.04-1.22 at 4 km), stomach (1.13; 1.00-1.29 at 2 km), liver (1.28; 1.02-1.61 at 1 km), pancreas (1.19; 1.03-1.39 at 2 km), oral and pharyngeal (1.40; 1.08-1.82 at 1 km), oesophagus (2.05; 1.18-3.56 at 500 m) and gallbladder (2.80; 1.14-6.89 at 500 m) for men; and from colorectal (1.21; 1.00-1.46 at 1 km), stomach (1.15; 1.01-1.31 at 4 km) and liver (1.58; 1.20- 2.07 at 1 km) cancers for women. The results support the hypothesis of an association between several digestive cancers and proximity to polluting industrial plants.

Utility of collagen-derived peptides as markers of organ injury in patients with acute heart failure

ObjectiveThis study aims to investigate the time-dependent prognostic utility of two fibrosis markers representing organ fibrogenesis (N-terminal propeptide of procollagen III (PIIINP) and type IV collagen 7S (P4NP 7S)) in patients with acute heart failure (HF).Methods390 patients with acute HF were dichotomised based on the median value of fibrosis markers at discharge. The primary outcome measure was a composite of cardiac death and HF hospitalisation.ResultsP4NP 7S significantly declined during hospitalisation, whereas PIIINP did not. The cumulative 90-day and 365-day incidence of the primary outcome measure was 16.6% vs 16.0% (p=0.42) and 33.3% vs 28.4% (p=0.34) in the patients with high versus low PIIINP; 19.9% vs 13.0% (p=0.04) and 32.3% vs 29.0% (p=0.34) in the patients with high and low P4NP 7S, respectively. After adjusting for confounders, high P4NP 7S correlated with significant excess risk relative to low P4NP 7S for both 90-day and 365-day primary outcome measure (adjusted HR, 1.50; 95% CI, 1.02 to 2.21; p=0.04 and adjusted HR, 1.89; 95% CI, 1.11 to 3.26; p=0.02, respectively), which was driven by significant association of high P4NP 7S with higher incidence of HF hospitalisation. Furthermore, P4NP 7S exhibited an additive value to conventional prognostic factors for predicting 90-day outcome (p=0.038 for net reclassification improvement; p=0.0068 for integrated discrimination improvement). High PIIINP did not correlate with significant excess risk for both 90-day and 365-day outcome.ConclusionsThis study suggests a possible role of P4NP 7S in the risk stratification of patients with acute HF.

P6359Utility of collagen-derived peptides as markers of organ injury in patients with acute heart failure: a prospective cohort study

Background Organ injury in heart failure (HF) might evoke profibrotic response, which might adversely affect prognosis.In patients with HF, liver fibrogenesis marker, type IV collagen 7S (P4NP 7S), correlates with pulmonary artery pressure and right-side cardiac pressure such as right atrial and ventricular pressure. The present study aimed to investigate the prognostic utility of two collagen markers (N-terminal propeptide of procollagen III [PIIINP] and P4NP 7S) in patients with acute HF. Methods and results We conducted a prospective cohort study including 390 patients admitted for HF to three territorial hospitals. The pre-specified primary outcome measure was cardiac death and HF hospitalization at early (90-day) and late (365-day) post-discharge period. Follow-up ratio was 99% at 90 day and 97% at 365 day, respectively. Cardiac death and HF hospitalization occurred in 61 and 114 patients at 90 days and 365 days, respectively. The dichotomization the patients based on the median value of the collagen marker at discharge revealed that patients with high P4NP 7S correlated with significant excess risk relative to those with low P4NP 7S for 90-day (adjusted hazard ratio [HR]; 1.89, 95% confidence interval [CI]); 1.11–3.26, P=0.02) and 365-day (adjusted HR; 1.50, 95% CI; 1.02–2.21, P=0.04) outcome. 10% increase in P4NP 7S was associated with 8% increase for primary outcome measure at 90 day (P=0.04). P4NP 7S showed incremental prognostic value on top of the conventional prognostic factors including age, sex, estimated glomerular filtration rate (eGFR), ejection fraction (EF) <40%, B-type natriuretic peptide (BNP), hemoglobin and sodium <140mmol/L (P=0.038 for net reclassification improvement, P=0.0068 for integrated discrimination improvement). PIIINP weakly correlated with P4NP 7S (Spearman's r=0.24, P<0.0001), but it neither correrated with the marked excess risk not associated with significant excess risk for 90 and 365-day primary outcome measure nor enhanced the discrimination. Conclusions This study suggests a possible role of P4NP 7S in the risk stratification of patients with acute HF. Acknowledgement/Funding None

Association between Mortality and Short-Term Exposure to Particles, Ozone and Nitrogen Dioxide in Stockholm, Sweden

In this study, the effects on daily mortality in Stockholm associated with short-term exposure to ultrafine particles (measured as number of particles with a diameter larger than 4 nm, PNC4), black carbon (BC) and coarse particles (PM2.5–10) have been compared with the effects from more common traffic-pollution indicators (PM10, PM2.5 and NO2) and O3 during the period 2000–2016. Air pollution exposure was estimated from measurements at a 20 m high building in central Stockholm. The associations between daily mortality lagged up to two days (lag 02) and the different air pollutants were modelled by using Poisson regression. The pollutants with the strongest indications of an independent effect on daily mortality were O3, PM2.5–10 and PM10. In the single-pollutant model, an interquartile range (IQR) increase in O3 was associated with an increase in daily mortality of 2.0% (95% CI: 1.1–3.0) for lag 01 and 1.9% (95% CI: 1.0–2.9) for lag 02. An IQR increase in PM2.5–10 was associated with an increase in daily mortality of 0.8% (95% CI: 0.1–1.5) for lag 01 and 1.1% (95% CI: 0.4–1.8) for lag 02. PM10 was associated with a significant increase only at lag 02, with 0.8% (95% CI: 0.08–1.4) increase in daily mortality associated with an IQR increase in the concentration. NO2 exhibits negative associations with mortality. The significant excess risk associated with O3 remained significant in two-pollutant models after adjustments for PM2.5–10, BC and NO2. The significant excess risk associated with PM2.5–10 remained significant in a two-pollutant model after adjustment for NO2. The significantly negative associations for NO2 remained significant in two-pollutant models after adjustments for PM2.5–10, O3 and BC. A potential reason for these findings, where statistically significant excess risks were found for O3, PM2.5–10 and PM10, but not for NO2, PM2.5, PNC4 and BC, is behavioral factors that lead to misclassification in the exposure. The concentrations of O3 and PM2.5–10 are in general highest during sunny and dry days during the spring, when exposure to outdoor air tend to increase, while the opposite applies to NO2, PNC4 and BC, with the highest concentrations during the short winter days with cold weather, when people are less exposed to outdoor air.

Chlorination disinfection by-products in drinking water and congenital anomalies: review and meta-analyses

This study aims to review epidemiologic evidence of the association between exposure to chlorination disinfection by-products (DBPs) and congenital anomalies. All epidemiologic studies that evaluated a relationship between an index of DBP exposure and risk of congenital anomalies were analyzed. For all congenital anomalies combined, the meta-analysis gave a statistically significant excess risk for high versus low exposure to water chlorination or TTHM (17%; 95% CI, 3-34) based on a small number of studies. The meta-analysis also suggested a statistically significant excess risk for ventricular septal defects (58%; 95% CI, 21-107), but based on only three studies, and there was little evidence of an exposure-response relationship. It was observed no statistically significant relationships in the other meta-analyses and little evidence for publication bias, except for urinary tract defects and cleft lip and palate. Although some individual studies have suggested an association between chlorination disinfection by-products and congenital anomalies, meta-analyses of all currently available studies demonstrate little evidence of such association.

Fatal accidents among Danes with multiple sclerosis

We compared the rate of fatal accidents among Danes with multiple sclerosis (MS) with that of the general population. The study was based on linkage of the Danish Multiple Sclerosis Registry to the Cause of Death Registry and covered all 10 174 persons in whom MS was diagnosed during the period 1953-1996. The end of follow-up was 1 January 1999. We calculated standardized mortality ratios (SMRs) for various types of fatal accidents. A total of 76 persons (48 men and 28 women) died from accidents, whereas the expected number of fatalities from such causes was 55.7 (31.4 men and 24.3 women). Thus, the risk for death from accidents among persons with MS was 37% higher than that of the general population (SMR=1.37). We found no significant excess risk for fatal road accidents (SMR=0.80). The risk for falls was elevated (SMR=1.29) but not statistically significantly so. The risks were particularly high for deaths from burns (SMR=8.90) and suffocation (SMR=5.57). We conclude that persons with MS are more prone to fatal accidents than the general population. The excess risk is due not to traffic accidents but to burns and suffocation.