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Esophageal adenocarcinoma (EAC) is characterized by 6 striking features: increasing incidence, male predominance, lack of preventive measures, opportunities for early detection, demanding surgical therapy and care, and poor prognosis. Reasons for its rapidly increasing incidence include the rising prevalence of gastroesophageal reflux and obesity, combined with the decreasing prevalence of Helicobacter pylori infection. The strong male predominance remains unexplained, but hormonal influence might play an important role. Future prevention might include the treatment of reflux or obesity or chemoprevention with nonsteroidal antiinflammatory drugs or statins, but no evidence-based preventive measures are currently available. Likely future developments include endoscopic screening of better defined high-risk groups for EAC. Individuals with Barrett esophagus might benefit from surveillance, at least those with dysplasia, but screening and surveillance strategies need careful evaluation to be feasible and cost-effective. The surgery for EAC is more extensive than virtually any other standard procedure, and postoperative survival, health-related quality of life, and nutrition need to be improved (eg, by improved treatment, better decision-making, and more individually tailored follow-up). Promising clinical developments include increased survival after preoperative chemoradiotherapy, the potentially reduced impact on health-related quality of life after minimally invasive surgery, and the new endoscopic therapies for dysplastic Barrett esophagus or early EAC. The overall survival rates are improving slightly, but poor prognosis remains a challenge. [PUBLICATION ABSTRACT]

Esophagectomy is the mainstay of curative treatment for most patients with a diagnosis of esophageal cancer. This procedure needs to be optimized to secure the best possible chance of cure for these patients. Research comparing various surgical approaches of esophagectomy generally has failed to identify any major differences in long-term prognosis. Comparisons between minimally invasive and open esophagectomy, transthoracic and transhiatal approaches, radical and moderate lymphadenectomy, and high and moderate hospital volume generally have provided only moderate alterations in long-term survival rates after adjustment for established prognostic factors. In contrast, some direct surgeon-related factors, which remain independent of known prognostic factors, seem to influence the long-term survival more strongly in esophageal cancer. Annual surgeon volume is strongly prognostic, and recent studies have suggested the existence of long surgeon proficiency gain curves for achievement of stable 5-year survival rates and possibly also a prognostic influence of surgeon age and weekday of surgery. The available literature indicates a potentially more critical role of the individual surgeon’s skills than that of variations in surgical approach for optimizing the long-term survival after esophagectomy for esophageal cancer. This finding points to the value of paying more attention to how the skills of the individual esophageal cancer surgeon can best be achieved and maintained. Careful selection and evaluation of the most suitable candidates, appropriate and structured training programs, and regular peer-review assessments of experienced surgeons may be helpful in this respect.

ObjectiveGastric infection with Helicobacter pylori is a strong risk factor for non-cardia gastric adenocarcinoma. The aim of this study was to assess whether the risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma decreases after eradication treatment for H. pylori in a Western population.DesignThis was a nationwide, population-based cohort study in Sweden in 2005–2012. Data from the Swedish Prescribed Drug Registry provided information on H. pylori eradication treatment, whereas information concerning newly developed gastric adenocarcinoma was retrieved from the Swedish Cancer Registry. The risk of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in individuals who had received H. pylori eradication treatment was compared with the background population of the corresponding age, sex and calendar year distribution, yielding standardised incidence ratios (SIRs) with 95% CIs.ResultsDuring the follow-up of 95 176 individuals who had received eradication treatment (351 018 person-years at risk), 75 (0.1%) developed gastric adenocarcinoma and 69 (0.1%) developed non-cardia gastric adenocarcinoma. The risk of gastric adenocarcinoma decreased over time after eradication treatment to levels below that of the corresponding background population. The SIRs were 8.65 (95% CI 6.37 to 11.46) for 1–3 years, 2.02 (95% CI 1.25 to 3.09) for 3–5 years and 0.31 (95% CI 0.11 to 0.67) for 5–7.5 years after eradication treatment. When restricted to non-cardia adenocarcinoma, the corresponding SIRs were 10.74 (95% CI 7.77 to 14.46), 2.67 (95% CI 1.63 to 4.13) and 0.43 (95% CI 0.16 to 0.93).ConclusionEradication treatment for H. pylori seems to counteract the development of gastric adenocarcinoma and non-cardia gastric adenocarcinoma in this Western population.

Background Centralisation of healthcare, especially for advanced cancer surgery, has been a matter of debate. Clear short-term mortality benefits have been described for oesophageal cancer surgery conducted at high-volume hospitals and by high-volume surgeons. Objective To clarify the association between hospital volume, surgeon volume and hospital type in relation to long-term survival after oesophagectomy for cancer, by a meta-analysis. Design The systematic literature search included PubMed, Web of Science, Cochrane library, EMBASE and Science Citation Index, for the period 1990–2013. Eligible articles were those which reported survival (time to death) as HRs after oesophagectomy for cancer by hospital volume, surgeon volume or hospital type. Fully adjusted HRs for the longest follow-up were the main outcomes. Results were pooled by a meta-analysis, and reported as HRs and 95% CIs. Results Sixteen studies from seven countries met the inclusion criteria. These studies reported hospital volume (N=13), surgeon volume (N=4) or hospital type (N=4). A survival benefit was found for high-volume hospitals (HR=0.82, 95% CI 0.75 to 0.90), and possibly also, for high-volume surgeons (HR=0.87, 95% CI 0.74 to 1.02) compared with their low-volume counterparts. No association with survival remained for hospital volume after adjustment for surgeon volume (HR=1.01, 95% CI 0.97 to 1.06; N=2), while a survival benefit was found in favour of high-volume surgeons after adjustment for hospital volume (HR=0.91, 95% CI 0.85 to 0.98; N=2). Conclusions This meta-analysis demonstrated better long-term survival (even after excluding early deaths) after oesophagectomy with high-volume surgery, and surgeon volume might be more important than hospital volume. These findings support centralisation with fewer surgeons working at large centres.

BackgroundEsophagectomy for esophageal cancer is associated with a substantial risk of life-threatening complications and a limited long-term survival. This study aimed to clarify the controversial questions of how age influences short-term and long-term survival.MethodsThis population-based cohort study included almost all patients who underwent curatively intended esophagectomy for esophageal cancer in Sweden in 1987–2010, with follow-up through 2016. The exposure was age, analyzed both as a continuous and categorical variable. The probability of mortality was computed using a novel flexible parametric model approach. The reported probabilities are proper measures of the risk of dying, and the related odds ratios (OR) are therefore more suitable measures of association than hazard ratios. The outcomes were 90-day all-cause mortality, 5-year all-cause mortality, and 5-year disease-specific mortality. A novel flexible parametric model was used to derive the instantaneous probability of dying and the related OR along with 95% confidence intervals (CIs), adjusted for sex, education, comorbidity, tumor histology, pathological tumor stage, and resection margin status.ResultsAmong 1737 included patients, the median age was 65.6 years. When analyzed as a continuous variable, older age was associated with slightly higher odds of 90-day all-cause mortality (OR 1.05, 95% CI 1.02–1.07), 5-year all-cause mortality (OR 1.02, 95% CI 1.01–1.03), and 5-year disease-specific mortality (OR 1.01, 95% CI 1.01–1.02). Compared with patients aged < 70 years, those aged 70–74 years had no increased risk of any mortality outcome, while patients aged ≥ 75 years had higher odds of 90-day mortality (OR 2.85, 95% CI 1.68–4.84), 5-year all-cause mortality (OR 1.56, 95% CI 1.27–1.92), and 5-year disease-specific mortality (OR 1.38, 95% CI 1.09–1.76).ConclusionsPatient age 75 years or older at esophagectomy for esophageal cancer appears to be an independent risk factor for higher short-term mortality and lower long-term survival.

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.

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.

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.

Background Results are conflicting and no population-based studies are available regarding the postoperative mortality after intrathoracic anastomotic leakage. The current study addressed the unselected and independent fatality rate of intrathoracic esophageal anastomotic leaks after resection for cancer. Methods A prospective, nationwide study was conducted in Sweden in April 2001 through December 2005. Details concerning patient and tumor characteristics, surgical procedures, postoperative anastomotic leakage, and mortality were collected prospectively. Logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for age, tumor stage, comorbidity, and hospital volume. Results Among 559 resected patients with an intrathoracic anastomosis, 44 patients (7.9%) sustained an anastomotic leak within 30 days of surgery. Of these, 8 patients (18.2%) died within 90 days of surgery, compared with 32 of the 515 patients without leakage (6.2%) ( P  = .003). The adjusted OR of postoperative death following intrathoracic anastomotic leakage was increased 3-fold compared with those without such a complication (OR 3.0, 95% CI 1.2–7.2). Conclusion Intrathoracic anastomotic leakage after esophageal resection for cancer remains a major risk factor for short-term postoperative death in an unselected, population-based setting.