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.

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.

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.

Survival Trends in Gastric Adenocarcinoma: A Population-Based Study in Sweden.

BACKGROUND: Gastric adenocarcinoma is the second most common cancer-related death globally. Assessing survival trends can help evaluate changes in detection and treatment. We aimed to determine recent prognosis trends in gastric non-cardia and cardia adenocarcinoma in an unselected cohort with complete follow-up. METHODS: Population-based nationwide cohort study, including 17,491 patients with gastric non-cardia adenocarcinoma and 4698 with cardia adenocarcinoma recorded in the Swedish Cancer Registry in 1990-2013 with follow-up until 2017. Observed and relative 5-year survival was calculated and stratified by resectional surgery and no such surgery. Prognostic factors were evaluated using multivariable Cox regression. RESULTS: The relative overall 5-year survival remained stable at 18% for gastric non-cardia adenocarcinoma throughout the study period and increased from 12 to 18% for cardia adenocarcinoma. Concurrently, the proportion of patients who underwent resectional surgery decreased from 49 to 38% for non-cardia adenocarcinoma and from 48 to 33% for cardia adenocarcinoma. The relative postoperative 5-year survival increased from 33 to 44% for non-cardia adenocarcinoma and from 21 to 43% for cardia adenocarcinoma, whereas in nonoperated patients it decreased from 3 to 2% in non-cardia adenocarcinoma and increased from 3 to 5% in cardia adenocarcinoma. Poor prognostic factors were higher tumor stage, older age, and more comorbidity. CONCLUSIONS: Despite decreasing resectional rates, the 5-year overall survival has remained unchanged for gastric non-cardia adenocarcinoma and improved for cardia adenocarcinoma over the last two decades in Sweden and is now similar for these sublocations. The postoperative survival has improved for both sublocations, but particularly for cardia adenocarcinoma.

Surgeon age in relation to patients' long-term survival after gastrectomy for gastric adenocarcinoma: nationwide population-based cohort study.

BACKGROUND: Increasing surgeon age may influence patient outcomes after complex procedures due to gained experience but also decreased technical and cognitive abilities. This study aimed to clarify whether surgeon age influences patients' long-term survival after gastrectomy for gastric adenocarcinoma. METHODS: Population-based cohort study including all patients who underwent open and curatively intended gastrectomy for gastric adenocarcinoma between 2006 and 2015 in Sweden, with follow-up throughout 2020. Surgeon age, categorized into three equal-sized groups (tertiles), was assessed in relation to 5-year all-cause mortality rate (main outcome) and 5-year disease-specific death (secondary outcome) using multivariable Cox regression adjusted for patient age, sex, education, co-morbidity, pathological tumour stage, tumour sublocation and neoadjuvant therapy. Lymph node yield, resection margin status, in-hospital complications and annual surgeon volume of gastrectomy were considered potential mediators. RESULTS: Among 1647 patients, the 5-year all-cause mortality rate was increased for surgeon age ≥55 years (adjusted HR 1.21, 95% c.i. 1.04 to 1.41) and borderline elevated for age 47-54 years (HR 1.16, 95% c.i. 0.99 to 1.36), compared with age ≤46 years. Five-year disease-specific death was increased for surgeon age ≥55 years (HR 1.25, 95% c.i. 1.06 to 1.48) and 47-54 years (HR 1.22, 95% c.i. 1.02 to 1.44), compared with age ≤46 years. The associations attenuated and became statistically non-significant after adjustment for lymph node yield, resection margin status and complications. CONCLUSION: Surgeon age ≥47 years might be associated with worse long-term survival in patients who undergo gastrectomy for gastric adenocarcinoma, possibly mediated in part by differences in lymph node yield, resection margin status and complications.

Incidence Trends and Survival in Early-Onset Esophagogastric Adenocarcinoma: A Swedish Population-Based Cohort Study.

BACKGROUND: Early-onset adenocarcinomas of different sites are increasing in high-income countries, data on esophagogastric adenocarcinoma are sparse. METHODS: We performed a Swedish population-based cohort study over 1993 to 2019 to delineate differences in incidence and survival in early-onset (age 20-54 years) compared with later-onset (55-99 years) esophageal, cardia, and noncardia gastric adenocarcinoma. Temporal incidence trends were quantified as annual percentage changes (APC) and survival differences as excess mortality rate ratios (EMRR) using Poisson regression and including 95% confidence intervals (CI). RESULTS: Among 27,854 patients with esophagogastric adenocarcinoma, 2,576 were early-onset whereof 470 were esophageal, 645 were cardia, and 1,461 were noncardia gastric. Except noncardia gastric, the male predominance was larger in early-onset compared with later-onset disease. Advanced stage and signet ring cell morphology were more common among early-onset patients. Early-onset and later-onset APC estimates were comparable and esophageal adenocarcinoma incidence increased, cardia remained stable, and noncardia gastric decreased. Early-onset patients had better survival than later-onset, which was amplified when adjusting for prognostic factors including stage [adjusted EMRR 0.73 (95% CI, 0.63-0.85) in esophageal, 0.75 (95% CI, 0.65-0.86) in cardia, and 0.67 (95% CI, 0.61-0.74) in noncardia gastric adenocarcinoma]. The early-onset survival advantage was more pronounced in localized stages 0 to II (all sites) and women (esophageal and noncardia gastric). CONCLUSIONS: We found no major differences in incidence trends comparing early-onset and later-onset esophagogastric adenocarcinoma. Despite unfavorable prognostic features, early-onset esophagogastric adenocarcinoma survival was better than later-onset, particularly in localized stages and women. IMPACT: Our findings suggest delayed diagnosis in younger individuals and especially men.

Weekday of gastrectomy and long-term survival in gastric adenocarcinoma.

BACKGROUND: Cancer surgery conducted late during the working week might decrease long-term survival for some tumours. Studies on how weekday of gastrectomy influences long-term survival following gastric cancer are few and show conflicting results, which prompted the present investigation. METHODS: This population-based cohort study included almost all patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015, with follow-up throughout 2020. Associations between weekday of gastrectomy and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome) were analysed using multivariable Cox regression. The hazard ratios (HR) with 95% confidence intervals (CI) were adjusted for age, sex, education, comorbidity, pathological tumour stage, tumour sub-location, neoadjuvant therapy, annual surgeon volume of gastrectomy, and calendar year. RESULTS: Among 1678 patients, surgery on Thursday-Friday was not associated with any statistically significantly increased risk of 5-year all-cause mortality (HR 1.05, 95% CI 0.91-1.22) or 5-year disease-specific mortality (HR 1.04, 95% CI 0.89-1.23) compared to Monday-Wednesday. No associations were found when each weekday was analysed separately, with point estimates close to 1.00 (range 0.98-1.00) Monday-Thursday, but increased for Friday (HR 1.22, 95% CI 0.89-1.68) when fewer patients underwent surgery (4% of all). Stratified analyses by age, comorbidity, tumour stage, neoadjuvant therapy, surgeon volume, and tumour sub-location did not reveal any associations between weekday of surgery on Thursday-Friday compared with Monday-Wednesday and risk of 5-year all-cause mortality. CONCLUSIONS: Weekday of gastrectomy might not influence the 5-year survival in patients with gastric adenocarcinoma.

Surgeon proficiency gain and survival after gastrectomy for gastric adenocarcinoma: A population-based cohort study.

OBJECTIVE: Quality of surgery is essential for survival in gastric adenocarcinoma, but studies examining surgeons' proficiency gain of gastrectomies are scarce. This study aimed to reveal potential proficiency gain curves for surgeons operating patients with gastric cancer. METHODS: Population-based cohort study of patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2020. Data were retrieved from national registries and medical records. Risk prediction models were used to calculate outcome probabilities, and risk-adjusted cumulative sum curves were plotted to assess differences (change points) between observed and expected outcomes. The main outcome was long-term (>3-5 years) all-cause mortality after surgery. Secondary outcomes were all-cause mortality within 30 days, 31-90 days, 91 days to 1 year and>1-3 years of surgery, resection margin status, and lymph node yield. RESULTS: The study included 261 surgeons and 1636 patients. The>3- to 5-year mortality was improved after 20 cases, and decreased from 12.4% before to 8.6% after this change point (p = 0.027). Change points were suggested, but not statistically significant, after 22 cases for 30-day mortality, 28 cases for 31- to 90-day mortality, 9 cases for 91-day to 1-year mortality, and 10 cases for>1- to 3-year all-cause mortality. There were statistically significant improvements in tumour-free resection margins after 28 cases (p < 0.005) and greater lymph node yield after 13 cases (p < 0.001). CONCLUSIONS: This study reveals proficiency gain curves regarding long-term survival, resection margin status, and lymph node yield in gastrectomy for gastric adenocarcinoma, and that at least 20 gastrectomies should be conducted with experienced support before doing these operations independently.