All-cause and cancer-specific mortality in GORD in a population-based cohort study (the HUNT study)

OBJECTIVE: Gastro-oesophageal reflux is a public health concern which could have associated oesophageal complications, including adenocarcinoma, and possibly also head-and-neck and lung cancers. The aim of this study was to test the hypothesis that reflux increases all-cause and cancer-specific mortalities in an unselected cohort. DESIGN: The Nord-Trondelag health study (HUNT), a Norwegian population-based cohort study, was used to identify individuals with and without reflux in 1995-1997 and 2006-2008, with follow-up until 2014. All-cause mortality and cancer-specific mortality were assessed from the Norwegian Cause of Death Registry and Cancer Registry. Multivariable Cox regression was used to calculate HRs with 95% CIs for mortality with adjustments for potential confounders. RESULTS: We included 4758 participants with severe reflux symptoms and 51 381 participants without reflux symptoms, contributing 60 323 and 747 239 person-years at risk, respectively. Severe reflux was not associated with all-cause mortality, overall cancer-specific mortality or mortality in cancer of the head-and-neck or lung. However, for men with severe reflux a sixfold increase in oesophageal adenocarcinoma-specific mortality was found (HR 6.09, 95% CI 2.33 to 15.93) and the mortality rate was 0.27 per 1000 person-years. For women, the corresponding mortality was not significantly increased (HR 3.68, 95% CI 0.88 to 15.27) and the mortality rate was 0.05 per 1000 person-years. CONCLUSIONS: Individuals with severe reflux symptoms do not seem to have increased all-cause mortality or overall cancer-specific mortality. Although the absolute risk is small, individuals with severe reflux symptoms have a clearly increased oesophageal adenocarcinoma-specific mortality.Swedish Research CouncilAccepte

Improved surgical treatment of oesophageal cancer

Oesophageal cancer is the 7thmost common cancer globally and the 5-year survival is poor (below 20%). Curative treatment usually involves surgical resection of the tumour (oesophagectomy), with or without neoadjuvant chemo(radio)therapy. The aim of the thesis was to identify surgery-related factors of importance for improved long-term survival inoesophageal cancer. Study I was a nationwide Swedish cohort study ofpatients who underwent oesophagectomyfor oesophageal cancer between1987 and 2010, with follow-up until 2016. The study included 1,384 patients who had undergone surgery by any of 36 surgeons. Risk adjusted cumulative sum analysis was used to create proficiency gain curves for “lower volume surgeons” (<4 cases per year)and“higher volume surgeons” (≥4 cases per year), as well as“younger surgeons” (<45 years) and “older surgeons” (≥45 years) regarding all-cause 1 to 5-year mortality(main outcome). The results were adjusted for confounders. “Higher volume surgeons” reached proficiency at 14 cases compared to 31 cases for “lower volume surgeons”. “Younger surgeons” reached proficiency at 13 cases compared to 48 cases for “older surgeons”. Study II was a systematic review and meta-analysis comparing long-term survival afterminimally invasive oesophagectomy (MIO) withopen oesophagectomy (OO) for oesophageal cancer in studies published up until 2018. Based on 55 relevant studies and 14,592 patients (7,358 MIO and 7,234 OO), random effects meta-analysis was used to produce hazard ratios (HR) with 95% confidence intervals (CI) for all-cause 5-year mortality(main outcome)with adjustment for confounders. MIO was associated with 18% lower risk of all-cause 5-year mortality compared to OO (HR 0.82, 95% CI 0.76-0.88). Study III was a population-basedcohort study including almost all patients operated for oesophageal cancer in Sweden from 2011until 2015 and in Finland from 2010 until 2016, with follow-up throughout2019. Multivariable Cox regression was used to produce HRs with 95% CIs comparing MIO (n=459) with OO (n=771) for the main outcome all-cause 5-year mortality. The results were adjusted for confounders. MIO was associated with 18% lower risk of all-cause 5-year mortality compared to OO (HR 0.82, 95% CI 0.67-1.00 [P=0.048]). Study IV was a population-basedcohort study including almost allpatients who underwent surgery for oesophageal cancer from 2000 until 2015 in Sweden and from 2000 until 2016 in Finland, with follow-up throughout2019. The 2,306 included patients were divided into deciles (10 about equal size group) by the level of lymphadenectomy during oesophagectomy. Multivariable Cox regression was used to produce HRs with 95% CIs for the main outcome all-cause 5-year mortalitywith adjustment for confounders. Compared to the 1stdecile (0-3 nodes) the lowest risk for all-cause 5-year mortality was found in decile 8 (25-30 nodes). Upon stratification, this survival benefit was especially apparent for T3/T4 tumours and forpatients who did not receive neoadjuvant therapy. In conclusion, this thesis indicates that intense training in oesophagectomy of younger surgeons,use of minimally invasive oesophagectomy and moderate extent of lymphadenectomyimprove long-term survivalin patients who undergo surgery for oesophageal cancer

Mortality in gastro-oesophageal reflux disease in a population-based nationwide cohort study of Swedish twins

Objectives The public health disorder gastro-oesophageal reflux disease (GORD) is linked with several comorbidities, including oesophageal adenocarcinoma (OAC), but whether life expectancy is reduced by GORD is uncertain. This study assessed all-cause and cancer-specific mortality in GORD after controlling for confounding by heredity and other factors. Design Population-based cohort study from 1998 to 2015. Setting Swedish nationwide study. Participants Twins (n=40 961) born in 1958 or earlier in Sweden. Exposure GORD symptoms reported in structured computer-assisted telephone interviews. Outcomes The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality among twins with GORD and twins without GORD. HRs and 95% CIs were analysed using parametric survival models, both in individual twin analyses and co-twin pair analyses, with adjustment for body mass index, smoking, education and comorbidity. Results Among 40 961 individual twins, 5812 (14.2%) had GORD at baseline and 8062 (19.7%) died during follow-up of up to 16 years. The risks of all-cause mortality (HR=1.00, 95% CI: 0.94–1.07) and cancer-specific mortality (HR=0.99, 95% CI: 0.89–1.10) were not increased in individual twins with GORD compared with individual twins without GORD. Similarly, there were no differences in mortality outcomes in within-pair analyses. The OAC-specific mortality rate was 0.45 (95% CI: 0.32–0.66) per 1000 person-years in individual twins with GORD and 0.22 (95% CI: 0.18–0.27) per 1000 person-years without GORD, rendering an adjusted HR of 2.01 (95% CI: 1.35–2.98). Conclusions GORD did not increase all-cause or cancer-specific mortality when taking heredity and other confounders into account. The increased relative risk of mortality in OAC was low in absolute numbers

Mortality in gastro-oesophageal reflux disease in a population-based nationwide cohort study of Swedish twins

Objectives The public health disorder gastro-oesophageal reflux disease (GORD) is linked with several comorbidities, including oesophageal adenocarcinoma (OAC), but whether life expectancy is reduced by GORD is uncertain. This study assessed all-cause and cancer-specific mortality in GORD after controlling for confounding by heredity and other factors. Design Population-based cohort study from 1998 to 2015. Setting Swedish nationwide study. Participants Twins (n=40 961) born in 1958 or earlier in Sweden. Exposure GORD symptoms reported in structured computer-assisted telephone interviews. Outcomes The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality among twins with GORD and twins without GORD. HRs and 95% CIs were analysed using parametric survival models, both in individual twin analyses and co-twin pair analyses, with adjustment for body mass index, smoking, education and comorbidity. Results Among 40 961 individual twins, 5812 (14.2%) had GORD at baseline and 8062 (19.7%) died during follow-up of up to 16 years. The risks of all-cause mortality (HR=1.00, 95% CI: 0.94–1.07) and cancer-specific mortality (HR=0.99, 95% CI: 0.89–1.10) were not increased in individual twins with GORD compared with individual twins without GORD. Similarly, there were no differences in mortality outcomes in within-pair analyses. The OAC-specific mortality rate was 0.45 (95% CI: 0.32–0.66) per 1000 person-years in individual twins with GORD and 0.22 (95% CI: 0.18–0.27) per 1000 person-years without GORD, rendering an adjusted HR of 2.01 (95% CI: 1.35–2.98). Conclusions GORD did not increase all-cause or cancer-specific mortality when taking heredity and other confounders into account. The increased relative risk of mortality in OAC was low in absolute numbers

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

Treatment and outcome among patients with laryngeal squamous cell carcinoma in Stockholm-A population-based study

Objective Survival of patients with advanced laryngeal squamous cell carcinoma (LSCC) remains poor and management protocols warrant further development. We thus investigated treatment and outcome-related factors for LSCC in Stockholm, Sweden.Methods In a retrospective setting, 520 patients with LSCC diagnosed during 2000-2014, were included. Data on stage, treatment, and outcome were correlated with recurrence-free and overall survival (RFS and OS, respectively).Results Five-year OS for all patients was 65%. Five-year RFS for T1a, T1b, T2, T3, and T4 glottic LSCC was 90%, 91%, 77%, 47%, and 80%, respectively. The corresponding figures for T1, T2, T3, and T4 supraglottic LSCC were 64%, 66%, 64%, and 86%.Conclusion Patients with a T3 glottic LSCC had unexpectedly poor survival, especially when compared with patients with a T4 tumor. Patients with T4 disease were primarily treated with laryngectomy and postoperative radiotherapy (RT)/chemoradiotherapy (CRT), while most patients with T3 LSCC were treated with RT/CRT.Peer reviewe