Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma.

BACKGROUND: Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour. METHODS: This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5 years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers. RESULTS: Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46-0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56-1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56-1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location. CONCLUSION: Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.

Survival among patients cured from gastric adenocarcinoma compared to the background population.

BACKGROUND: It is unknown if gastric adenocarcinoma survivors have longer, shorter, or similar survival compared to the background population. This knowledge could contribute to evidence-based monitoring strategies, healthcare recommendations, and information for patients and families. METHODS: This population-based cohort study included all patients who underwent gastrectomy for gastric adenocarcinoma between 2006-2015 in Sweden and survived ≥ 5 years after surgery. They were followed up until death, postoperative year 10, or end of study period (31 December, 2020). Division of the observed by the expected survival yielded relative survival rates with 95% confidence intervals (CIs) using the life table method. The expected survival was derived from the entire Swedish population of the corresponding age, sex, and calendar year. Data came from medical records and nationwide registers. RESULTS: The survival among all 767 gastric adenocarcinoma survivors was shorter than the expected. The reduction in relative survival increased for each follow-up year, from 97.3% (95% CI 95.4-99.1%) year 6 to 86.6% (95% CI 82.3-90.9%) year 10. The decline in relative survival was more pronounced among patients who had gastrectomy in earlier calendar years (82.9% [95% CI 77.4-88.4%] year 10 for years 2011-2015), shorter education (85.2% [95% CI 77.4-93.0%] year 10 for education ≤ 9 years), more comorbidities (78.0% [95% CI 63.9-92.0%] year 10 for Charlson comorbidity score ≥ 2), and no neoadjuvant therapy (83.2% [95% CI 77.4-89.0%] year 10). CONCLUSION: Gastric adenocarcinoma survivors seem to have poorer survival than the corresponding background population, particularly in certain subgroups.

Statin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma: a Swedish population-based cohort study.

BACKGROUND: Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma. METHODS: This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality. Data came from medical records and national healthcare registries. The exposure was statin use during the year prior to gastrectomy which was compared to no such use during the same period. The outcomes were 5-year disease-specific mortality (main) and 5-year all-cause mortality (secondary). Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, low-dose aspirin use, tumour sublocation, pathological tumour stage, neoadjuvant chemotherapy, annual surgeon volume, and surgical radicality. RESULTS: Among 1515 participating patients, the mean age was 69 years and 58.4% were men. Statin use, identified in 399 (26.3%) patients, was not associated with any statistically significantly decreased 5-year disease-specific mortality (HR 0.99, 95% CI 0.82-1.21) or 5-year all-cause mortality (HR 0.94, 95% CI 0.79-1.12). No risk reductions were found across subgroups of age, sex, aspirin user status, or tumour stage, or in patients with long-term preoperative of postoperative use of statins, all with point estimates close to 1. CONCLUSIONS: Perioperative use of statins does not seem to improve the 5-year survival in patients who undergo gastrectomy with curative intent for gastric adenocarcinoma in Sweden.

Extent of Lymphadenectomy and Long-term Survival in Esophageal Cancer.

OBJECTIVE: To examine the hypothesis that survival in esophageal cancer increases with more removed lymph nodes during esophagectomy up to a plateau, after which it levels out or even decreases with further lymphadenec-tomy. SUMMARY OF BACKGROUND DATA: There is uncertainty regarding the ideal extent of lymphadenectomy during esophagectomy to optimize long-term survival in esophageal cancer. METHODS: This population-based cohort study included almost every patient who underwent esophagectomy for esophageal cancer in Sweden or Finland in 2000-2016 with follow-up through 2019. Degree of lymphadenectomy, divided into deciles, was analyzed in relation to all-cause 5-year mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for all established prognostic factors. RESULTS: Among 2306 patients, the second (4-8 nodes), seventh (21-24 nodes) and eighth decile (25-30 nodes) of lymphadenectomy showed the lowest all-cause 5-year mortality compared to the first decile [hazard ratio (HR) = 0.77, 95% CI 0.61-0.97, HR = 0.76, 95% CI 0.59-0.99, and HR = 0.73, 95% CI 0.57-0.93, respectively]. In stratified analyses, the survival benefit was greatest in decile 7 for patients with pathological T-stage T3/T4 (HR = 0.56, 95% CI0.40-0.78), although it was statistically improved in all deciles except decile 10. For patients without neoadjuvant chemotherapy, survival was greatest in decile 7 (HR = 0.60, 95% CI 0.41-0.86), although survival was also statistically significantly improved in deciles 2, 6, and 8. CONCLUSION: Survival in esophageal cancer was not improved by extensive lymphadenectomy, but resection of a moderate number (20-30) of nodes was prognostically beneficial for patients with advanced T-stages (T3/T4) and those not receiving neoadjuvant therapy.

Impact of Age on the Treatment and Survival in Esophagogastric Cancer.

BACKGROUND: The age-specific risks of mortality for patients with esophagogastric cancer and their probability of surgical treatment are not well-known. METHODS: This population-based, nationwide cohort study included all patients with esophageal or gastric (esophagogastric) cancer in Sweden between 1990 and 2013, with follow-up evaluation throughout 2018. Age at diagnosis (exposure) was categorized into nine 5-year groups. The main outcome was 5-year all-cause mortality. The secondary outcomes were 90-day all-cause mortality, 5-year disease-specific mortality, 5-year disease-specific mortality excluding 90-day all-cause mortality, and non-operation. For mortality outcomes, Cox regression provided hazard ratios (HRs) with 95% confidence intervals (95% CIs) adjusted for confounders. For non-operation, logistic regression provided odds ratios (ORs) with 95% CIs. RESULTS: Among 28,725 patients, 11,207 (39.0%) underwent surgery. For those who underwent surgery, the HRs of 5-year all-cause mortality were stable before the ages of 65 to 69 years. After that, it gradually increased for patients 65 to 69 years old (HR, 1.13; 95% CI, 1.01-1.26), patients 75 to 79 years old (HR, 1.29; 95% CI, 1.56-1.44), and patients older than 85 years (HR, 1.84; 95% CI, 1.60-2.11) compared with those younger than 50 years. Analyses of age as a continuous variable, other mortality outcomes and stratification by comorbidity and tumor type showed similar results. The odds of non-operation increased for patients 75 to 79 years old (OR, 2.09 [95% CI, 1.84-2.94] for patients 80 to 84 years old and OR, 5.00 [95% CI, 4.31-5.78] for patients ≥85 years old or older), compared with those younger than 50 years. CONCLUSION: Older age, starting from 65 years, is associated with worse survival after surgery for esophagogastric cancer, and from 75 years with lower odds of surgical treatment.

Aspirin or statin use in relation to survival after surgery for esophageal cancer: a population-based cohort study.

BACKGROUND: Adjuvant postoperative treatment with aspirin and statins may improve survival in several solid tumors. This study aimed to assess whether these medications improve the survival after curatively intended treatment (including esophagectomy) for esophageal cancer in an unselected setting. METHODS: This nationwide cohort study included nearly all patients who underwent esophagectomy for esophageal cancer in Sweden from 2006 to 2015, with complete follow-up throughout 2019. Risk of 5-year disease-specific mortality in users compared to non-users of aspirin and statins was analyzed using Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI). The HRs were adjusted for age, sex, education, calendar year, comorbidity, aspirin/statin use (mutual adjustment), tumor histology, pathological tumor stage, and neoadjuvant chemo(radio)therapy. RESULTS: The cohort included 838 patients who survived at least 1 year after esophagectomy for esophageal cancer. Of these, 165 (19.7%) used aspirin and 187 (22.3%) used statins during the first postoperative year. Neither aspirin use (HR 0.92, 95% CI 0.67-1.28) nor statin use (HR 0.88, 95% CI 0.64-1.23) were associated with any statistically significant decreased 5-year disease-specific mortality. Analyses stratified by subgroups of age, sex, tumor stage, and tumor histology did not reveal any associations between aspirin or statin use and 5-year disease-specific mortality. Three years of preoperative use of aspirin (HR 1.26, 95% CI 0.98-1.65) or statins (HR 0.99, 95% CI 0.67-1.45) did not decrease the 5-year disease-specific mortality. CONCLUSIONS: Use of aspirin or statins might not improve the 5-year survival in surgically treated esophageal cancer patients.

Use of 5α-reductase inhibitors and survival of oesophageal and gastric cancer in a nationwide Swedish cohort study.

BACKGROUND: We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. METHODS: This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. RESULTS: Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). CONCLUSION: This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer.

Long-term Survival in Esophageal Cancer After Minimally Invasive Esophagectomy Compared to Open Esophagectomy.

OBJECTIVE: To examine 5-year survival in esophageal cancer after MIE compared to OE. SUMMARY BACKGROUND DATA: MIE is becoming an increasingly common approach in the surgical treatment of esophageal cancer. A recent meta-analysis suggested 18% lower 5-year all-cause mortality after MIE compared to OE, but the quality of the included studies was limited. METHODS: Population-based cohort study including almost all patients who underwent elective esophagectomy for esophageal cancer in Sweden or Finland in 2010 to 2016, with follow-up until end of 2019. Cox regression was used to provide hazard ratios (HRs) with 95% confidence intervals (CIs) of all-cause 5-year mortality (main outcome) after MIE (hybrid or total) versus OE. Adjustments were made for age, sex, comorbidity, pathological tumor stage, histological tumor type, neoadjuvant chemo(radio)therapy, country, and annual hospital volume of esophagectomy. RESULTS: Among all 1264 patients, 470 (37.2%) underwent MIE and 794 (62.8%) underwent OE. MIE was associated with an 18% decreased risk of all-cause 5-year mortality, compared to OE [adjusted HR 0.82, 95% CI 0.67- 1.00 ( P = 0.048)]. The HR of all-cause 5-year mortality was seemingly lower after total MIE compared to OE (adjusted HR 0.77, 95% CI 0.60-0.98) than after hybrid MIE compared to OE (adjusted HR 0.87, 95% CI 0.68-1.11). CONCLUSIONS: This bi-national study indicates that MIE is associated with a higher 5-year survival than OE in patients with esophageal cancer, and that the survival benefit is greater after total MIE than hybrid MIE.

Life Expectancy in Survivors of Esophageal Cancer Compared with the Background Population.

It is unknown whether the survival of patients cured of esophageal cancer differs from that of the corresponding background population. This nationwide and population-based cohort study included all patients who survived for at least 5 years after surgery for esophageal cancer in Sweden between 1987 and 2015, with follow-up throughout 2020. Relative survival rates with 95% confidence intervals (95% CI) were calculated by dividing the observed with the expected survival. The expected survival was assessed from the entire Swedish population of the corresponding age, sex, and calendar year. Yearly relative survival rates were calculated between 6 and 10 years postoperatively. Among all 762 participants, the relative survival was initially similar to the background population (96.1%, 95% CI 94.3-97.9%), but decreased each following postoperative year to 83.5% (95% CI 79.5-87.6%) by year 10. The drop in relative survival between 6 and 10 years was more pronounced in participants with a history of squamous cell carcinoma [from 94.5% (95% CI 91.2-97.8%) to 70.8% (95% CI 64.0-77.6%)] than in those with adenocarcinoma [from 96.9% (95% CI 94.8-99.0%) to 91.5% (95% CI 86.6-96.3%)], and in men [from 96.0% (95% CI 93.8-98.1%) to 81.8% (95% CI 76.8-86.8%)] than in women [from 96.4% (95% CI 93.4-99.5%) to 88.1% (95% CI 81.5-94.8%)]. No major differences were found between age groups. In conclusion, esophageal cancer survivors had a decline in survival between 6 and 10 years after surgery compared with the corresponding general population, particularly those with a history of squamous cell carcinoma of the esophagus and male sex.

Recent incidence trends of oesophago-gastric cancer in Sweden.

BACKGROUND: Oesophago-gastric cancers have had sharply different and changing incidence patterns depending on subsite and histology, but incidence data for the last few years are missing. We aimed to provide updated incidence trends of oesophago-gastric tumours by subsite and histology in Sweden. MATERIAL AND METHODS: The Swedish Cancer Registry provided data for 74,303 patients with oesophago-gastric cancer aged ≥50 years in 1970-2020. The focus was on the last available 6-year period, i.e., from 2015 until 2020 inclusive. We calculated yearly age-standardized and sex-specific incidence rates per 100,000 person-years, with the age distribution (in 5-year age groups) of the Swedish population in year 2000 as reference. RESULTS: For oesophageal squamous cell carcinoma, the incidence continued to decrease between 2015 and 2020 (from 6.46 to 5.53/100,000 person-years in men, and from 4.26 to 3.78/100,000 person-years in women). For oesophageal adenocarcinoma, the earlier increasing incidence rates rather slightly decreased in men between 2015 and 2020 (from 12.39 to 11.70/100,000 person-years) and increased marginally in women (from 2.49 to 2.85/100,000 person-years). The incidence rates of cardia adenocarcinoma were stable between 2015 and 2020 (from 9.83 to 10.13/100,000 person-years in men, and from 2.21 to 2.41/100,000 person-years in women). For gastric non-cardia adenocarcinoma, the incidence rates continued to decrease between 2015 and 2020 (from 14.67 to 13.29/100,000 person-years in men, and from 9.37 to 8.14/100,000 person-years in women). There were no major age-group differences in recent incidence trends. CONCLUSION: The 6-year period from 2015 to 2020 inclusive has witnessed stabilising incidence rates of oesophageal and cardia adenocarcinoma in Sweden, whereas the incidence rates of oesophageal squamous cell carcinoma and non-cardia gastric adenocarcinoma have continued to decrease.

Annual surgeon and hospital volume of gastrectomy and gastric adenocarcinoma survival in a population-based cohort study.

BACKGROUND: It is uncertain whether centralization of gastrectomy to fewer surgeons and larger centers improves survival in gastric adenocarcinoma in Western populations. The aim of this study was to examine if higher annual surgeon or hospital volumes of gastrectomy increase gastric adenocarcinoma survival in a population-based Swedish cohort. METHODS: This study included almost all patients who underwent curatively intended gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2020. Data were collected from medical records and national registries. Annual surgeon and hospital volumes of gastrectomies were analyzed by categorization into four equal-sized groups and as continuous variables. The outcomes were 5-year all-cause mortality (main) and 5-year disease-specific mortality. Cox regression produced hazard ratios (HR) with 95% confidence intervals (95% CI), adjusted for sex, age, education, comorbidity, pathological tumor stage, pre-operative therapy, calendar period, and mutually for hospital or surgeon volume. RESULTS: The study included 1774 patients. Higher annual surgeon volume did not decrease the risk of 5-year all-cause mortality when comparing the highest and lowest quartiles (HR = 1.07, 95% CI 0.86-1.34) or when analyzed as a continuous variable (HR = 1.03, 95% 1.00-1.06). Higher annual hospital volume did not significantly decrease the risk of 5-year all-cause mortality (highest versus lowest quartiles: HR = 0.89, 95% CI 0.71-1.10; continuous variable: HR = 0.98, 95% CI 0.95-1.02). The results for 5-year disease-specific mortality were similar. CONCLUSIONS: This study, mirroring routine clinical practices in an entire Western country, indicates that neither annual surgeon volume nor annual hospital volume of gastrectomy influences the long-term survival in gastric adenocarcinoma.

Aspirin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma.

BACKGROUND: Low-dose aspirin use may reduce cancer incidence and mortality, but its influence on gastric adenocarcinoma survival is unclear. This study aimed to assess whether aspirin use improves long-term survival following gastrectomy for gastric adenocarcinoma. METHODS: This population-based cohort study included almost all patients who underwent gastrectomy for gastric adenocarcinoma in Sweden from 2006 to 2015, with follow-up throughout 2020. Preoperative exposure to a daily low-dose (75-160 mg) aspirin for 1 (main exposure), 2 and 3 years and for 1 year after gastrectomy was examined in relation to 5-year all-cause mortality (primary outcome) and disease-specific mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, statin use, tumour location, tumour stage, neoadjuvant chemotherapy, surgeon volume of gastrectomy and surgical radicality. RESULTS: Among 2025 patients, 545 (26.9%) used aspirin at the date of gastrectomy. Aspirin use within 1 year before surgery did not decrease the adjusted risk of 5-year all-cause mortality (HR = 0.98, 95% CI 0.85-1.13) or disease-specific mortality (HR = 1.00, 95% CI 0.86-1.17). Preoperative aspirin use for 2 years (HR = 0.98, 95% CI 0.84-1.15) or 3 years (HR = 0.94, 95% CI 0.79-1.12) did not decrease the risk of 5-year all-cause mortality. Patients remaining on aspirin during the first year after gastrectomy had a similar 5-year all-cause mortality as non-users of aspirin (HR = 1.01, 95% CI 0.82-1.25). CONCLUSIONS: Low-dose aspirin use might not improve long-term survival after gastrectomy for gastric adenocarcinoma and may thus not be a target for adjuvant therapy in this group of patients.

Using Novel Molecular-Level Chemical Composition Observations of High Arctic Organic Aerosol for Predictions of Cloud Condensation Nuclei.

Predictions of cloud droplet activation in the late summertime (September) central Arctic Ocean are made using κ-Köhler theory with novel observations of the aerosol chemical composition from a high-resolution time-of-flight chemical ionization mass spectrometer with a filter inlet for gases and aerosols (FIGAERO-CIMS) and an aerosol mass spectrometer (AMS), deployed during the Arctic Ocean 2018 expedition onboard the Swedish icebreaker Oden. We find that the hygroscopicity parameter κ of the total aerosol is 0.39 ± 0.19 (mean ± std). The predicted activation diameter of ∼25 to 130 nm particles is overestimated by 5%, leading to an underestimation of the cloud condensation nuclei (CCN) number concentration by 4-8%. From this, we conclude that the aerosol in the High Arctic late summer is acidic and therefore highly cloud active, with a substantial CCN contribution from Aitken mode particles. Variability in the predicted activation diameter is addressed mainly as a result of uncertainties in the aerosol size distribution measurements. The organic κ was on average 0.13, close to the commonly assumed κ of 0.1, and therefore did not significantly influence the predictions. These conclusions are supported by laboratory experiments of the activation potential of seven organic compounds selected as representative of the measured aerosol.

Lung function and self-rated symptoms in healthy volunteers after exposure to hydrotreated vegetable oil (HVO) exhaust with and without particles.

BACKGROUND: Diesel engine exhaust causes adverse health effects. Meanwhile, the impact of renewable diesel exhaust, such as hydrotreated vegetable oil (HVO), on human health is less known. Nineteen healthy volunteers were exposed to HVO exhaust for 3 h in a chamber with a double-blind, randomized setup. Exposure scenarios comprised of HVO exhaust from two modern non-road vehicles with 1) no aftertreatment system ('HVOPM+NOx' PM1: 93 µg m-3, EC: 54 µg m-3, NO: 3.4 ppm, NO2: 0.6 ppm), 2) an aftertreatment system containing a diesel oxidation catalyst and a diesel particulate filter ('HVONOx' PM1: ~ 1 µg m-3, NO: 2.0 ppm, NO2: 0.7 ppm) and 3) filtered air (FA) as control. The exposure concentrations were in line with current EU occupational exposure limits (OELs) of NO, NO2, formaldehyde, polycyclic aromatic hydrocarbons (PAHs), and the future OEL (2023) of elemental carbon (EC). The effect on nasal patency, pulmonary function, and self-rated symptoms were assessed. Calculated predicted lung deposition of HVO exhaust particles was compared to data from an earlier diesel exhaust study. RESULTS: The average total respiratory tract deposition of PM1 during HVOPM+NOx was 27 µg h-1. The estimated deposition fraction of HVO PM1 was 40-50% higher compared to diesel exhaust PM1 from an older vehicle (earlier study), due to smaller particle sizes of the HVOPM+NOx exhaust. Compared to FA, exposure to HVOPM+NOx and HVONOx caused higher incidence of self-reported symptoms (78%, 63%, respectively, vs. 28% for FA, p < 0.03). Especially, exposure to HVOPM+NOx showed 40-50% higher eye and throat irritation symptoms. Compared to FA, a decrement in nasal patency was found for the HVONOx exposures (- 18.1, 95% CI: - 27.3 to - 8.8 L min-1, p < 0.001), and for the HVOPM+NOx (- 7.4 (- 15.6 to 0.8) L min-1, p = 0.08). Overall, no clinically significant change was indicated in the pulmonary function tests (spirometry, peak expiratory flow, forced oscillation technique). CONCLUSION: Short-term exposure to HVO exhaust concentrations corresponding to EU OELs for one workday did not cause adverse pulmonary function changes in healthy subjects. However, an increase in self-rated mild irritation symptoms, and mild decrease in nasal patency after both HVO exposures, may indicate irritative effects from exposure to HVO exhaust from modern non-road vehicles, with and without aftertreatment systems.

Prediagnostic circulating levels of sex hormones and survival in esophageal adenocarcinoma.

Sex hormonal differences may contribute to the strong male predominance in esophageal adenocarcinoma (EAC), but whether sex hormone levels influence survival in EAC is unstudied. Our study aimed to assess associations between prediagnostic sex hormone levels and survival in EAC. In a population-based cohort study, 244 male EAC patients from the Janus Serum Bank Cohort in Norway were followed up through 2018. Associations between prediagnostic serum levels of 12 sex hormone measures and disease-specific mortality were assessed using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, body mass index, tobacco smoking, physical activity and surgical resection. Higher levels of sex hormone-binding globulin (SHBG) indicated decreased disease-specific mortality (HR 0.68, 95% CI 0.44-1.07, highest vs lowest tertile). In stratified analyses by surgery, such associations remained in nonoperated patients (HR 0.58, 95% CI 0.35-0.96, highest vs lowest tertile), but not in operated patients. Higher levels of follicle-stimulating hormone (FSH) were associated with increased disease-specific mortality in an exposure-response pattern; HRs for the middle and highest tertiles vs the lowest tertile were 1.35 (95% CI 0.89-2.05) and 1.61 (95% CI 1.06-2.43), respectively. No clear associations were observed with serum levels of dehydroepiandrosterone sulfate, luteinizing hormone, prolactin, testosterone, 17-OH-progesterone, progesterone, estradiol, androstenedione, testosterone:estradiol ratio or free testosterone index. These findings suggest that higher endogenous levels of SHBG and lower levels of FSH may increase the survival in EAC. The other 10 examined sex hormone measures may not influence the survival.

Hypergastrinemia is associated with an increased risk of gastric adenocarcinoma with proximal location: A prospective population-based nested case-control study.

The incidence of proximal gastric adenocarcinoma is increasing among younger adults. Rodent models have shown that hypergastrinemia causes carcinogenesis in the proximal stomach. The aim of our study was therefore to assess if hypergastrinemia was associated with an increased risk of developing gastric adenocarcinoma also in humans. A prospective population-based nested case-control study within the Nord-Trøndelag Health Study (HUNT) cohort, Norway, was used to assess this association. Serum was collected from 78 962 participants in 1995 to 1997 and 2006 to 2008. In the cohort, 181 incident gastric adenocarcinoma cases were identified from the Norwegian Cancer and Patient Registries through 2015 and matched with 359 controls. The risk of gastric adenocarcinoma was compared between participants with prediagnostic hypergastrinemia (>60 pmol/L) and normal serum gastrin (≤60 pmol/L). Logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for body mass index, tobacco smoking and comorbidity. Hypergastrinemia was associated with increased risk of gastric adenocarcinoma overall (OR 2.2, 95% CI 1.4-3.4) and in particular for gastric adenocarcinoma with proximal location (OR 6.1, 95% CI 2.7-13.8), but not with gastric adenocarcinoma with distal location (OR 1.7, 95% CI 0.9-3.4). Moreover, hypergastrinemia was associated with an increased risk of gastric adenocarcinoma of intestinal histological type (OR 3.8, 95% CI 1.8-7.9), but not for diffuse histological type (OR 1.6, 95% CI 0.7-3.7). In conclusion, hypergastrinemia was associated with an increased risk of proximal and intestinal type gastric adenocarcinoma.

Esophageal Adenocarcinoma After Antireflux Surgery in a Cohort Study From the 5 Nordic Countries.

OBJECTIVE: We aimed to clarify the long-term risk development of EAC after antireflux surgery. SUMMARY OF BACKGROUND DATA: Gastroesophageal reflux disease (GERD) increases EAC risk, but whether antireflux surgery prevents EAC is uncertain. METHODS: Multinational, population-based cohort study including individuals with GERD from all 5 Nordic countries in 1964-2014. First, EAC risk after antireflux surgery in the cohort was compared with the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). Second, multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95% CIs, compared EAC risk in GERD patients with antireflux surgery with those with nonsurgical treatment. RESULTS: Among 942,071 GERD patients, 48,863 underwent surgery and 893,208 did not. Compared to the corresponding background population, EAC risk did not decrease after antireflux surgery [SIR 4.90 (95% CI 3.62-6.47) 1-<5 years and SIR 4.57 (95% CI 3.44-5.95) ≥15 years after surgery]. Similarly, no decrease was found for patients with severe GERD (esophagitis or Barrett esophagus) after surgery [SIR 6.09 (95% CI 4.39-8.23) 1-<5 years and SIR = 5.27 (95% CI 3.73-7.23) ≥15 years]. The HRs of EAC were stable comparing the surgery group with the nonsurgery group with GERD [HR 1.71 (95% CI 1.26-2.33) 1-<5 years and HR 1.69 (95% CI 1.24-2.30) ≥15 years after treatment], or for severe GERD [HR 1.56 (95% CI 1.11-2.20) 1-<5 years and HR 1.57 (95% CI 1.08-2.26) ≥15 years after treatment]. CONCLUSIONS: Surgical treatment of GERD does not seem to reduce EAC risk.

Prognosis after surgery for gastric adenocarcinoma in the Swedish Gastric Cancer Surgery Study (SWEGASS).

BACKGROUND: Most studies examining prognostic factors after gastrectomy come from selected patients and non-Western populations. This nationwide population-based cohort study aims to identify prognostic factors after surgery for gastric adenocarcinoma in an unselected Western cohort. METHODS: This study included 98% of patients who underwent gastrectomy for gastric adenocarcinoma in Sweden in 2006-2015, with follow-up through 2019. Data were collected from medical records and national registries. Exposures were sex, age, education, comorbidity, tumor sub-localization, tumor stage, calendar period, and pre-operative chemotherapy. Outcomes were 3-year all-cause and disease-specific mortality. Cox regression produced hazard ratios (HRs) with 95% confidence intervals (95% CIs), adjusted for the other study exposures. RESULTS: Among all 2154 patients, 3-year all-cause mortality was 53.3%. Factors influencing 3-year all-cause mortality after multivariable adjustment were tumor stage (stage IV vs. stage 0-I: HR 8.72, 95% CI 6.77-11.24), comorbidity (Charlson comorbidity score ≥2 vs. 0: HR 1.63, 95% CI 1.39-1.90), age (>75 vs. <65 years: HR 1.48, 95% CI 1.24-1.78), and calendar period (2006-2010 vs. 2011-2015: HR 0.83, 95% CI 0.73-0.95). No independent prognostic influence was found for sex (women vs. men: HR 1.01, 95% CI 0.85-1.09), pre-operative chemotherapy (yes vs. no: HR 0.92, 95% CI 0.78-1.08), tumor sub-localization (non-cardia vs. cardia: HR 1.01, 95% CI 0.83-1.22), or education (≥13 vs. ≤9 years: HR 0.89, 95% CI 0.74-1.07). The results were similar for 3-year disease-specific mortality. CONCLUSION: Survival after gastrectomy for gastric adenocarcinoma needs further improvement. Tumor stage, comorbidity, age, and calendar period were independently prognostic, while sex, pre-operative chemotherapy, tumor sub-localization, and education were not.

Emissions of soot, PAHs, ultrafine particles, NOx, and other health relevant compounds from stressed burning of candles in indoor air.

Burning candles release a variety of pollutants to indoor air, some of which are of concern for human health. We studied emissions of particles and gases from the stressed burning of five types of pillar candles with different wax and wick compositions. The stressed burning was introduced by controlled fluctuating air velocities in a 21.6 m3 laboratory chamber. The aerosol physicochemical properties were measured both in well-mixed chamber air and directly above the candle flame with online and offline techniques. All candles showed different emission profiles over time with high repeatability among replicates. The particle mass emissions from stressed burning for all candle types were dominated by soot (black carbon; BC). The wax and wick composition strongly influenced emissions of BC, PM2.5 , and particle-phase polycyclic aromatic hydrocarbons (PAHs), and to lower degree ultrafine particles, inorganic and organic carbon fraction of PM, but did not influence NOx , formaldehyde, and gas-phase PAHs. Measurements directly above the flame showed empirical evidence of short-lived strong emission peaks of soot particles. The results show the importance of including the entire burn time of candles in exposure assessments, as their emissions can vary strongly over time. Preventing stressed burning of candles can reduce exposure to pollutants in indoor air.

Endoscopy for gastroesophageal reflux disease and survival in esophageal adenocarcinoma.

Gastroesophageal reflux disease (GERD) is a risk factor of esophageal adenocarcinoma (EAC) and the most common indication for upper gastrointestinal endoscopy. Yet, whether GERD or endoscopy practice influence survival in EAC is largely unknown and was assessed in our study.This nationwide cohort study included all Swedish residents diagnosed with EAC in 1997-2013 with follow-up to 2018. Exposures were history of GERD and endoscopies prior to EAC. The main outcome was EAC-specific 5-year mortality. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential confounders. Among 6,600 EAC patients (79.3% males, median age 70 years) followed for 9,138 person-years, 440 (6.7%) had GERD and 592 (9.0%) had ≥1 endoscopy before EAC diagnosis. GERD was associated with a decreased risk of mortality (adjusted HR 0.71, 95% CI 0.64-0.80), which was only slightly attenuated by adjustment for prior endoscopies (HR 0.79, 95% CI 0.70-0.90), and further adjustments also for tumor stage and surgical resection (HR 0.74, 95% CI 0.62-0.89). Compared to EAC patients without prior endoscopy, mortality was unchanged in GERD patients having undergone 1 or 2 endoscopies before EAC diagnosis (HR 1.02, 95% CI 0.80-1.31, for 1 endoscopy; HR 0.90, 95% CI 0.63-1.30, for 2 endoscopies), while the mortality was decreased in patients with ≥3 endoscopies (HR 0.55, 95% CI 0.36-0.85). Our study indicates that GERD may be associated with a better prognosis in the event of EAC; however, the use of endoscopy screening has a limited impact on survival unless performed very frequently.