Improved survival in gastric adenocarcinoma

Despite advances in surgical treatment and systemic therapy during recent decades, the prognosis of gastric adenocarcinoma remains poor. This thesis aims to identify factors that may contribute to improving long-term survival in patients with gastric adenocarcinoma. Four population-based cohort studies were conducted:

Study I tested two hypotheses: (1) that gastric bypass for obesity is followed by an increased risk of adenocarcinoma in the excluded stomach (i.e., gastric non- cardia adenocarcinoma), and (2) that the diagnosis of such tumors is delayed if they occur. In a cohort of 98,881 patients who underwent bariatric surgery in Denmark (1996-2019), Finland (1997-2019), and Sweden (1980-2019), with follow-up through 31 December 2019, 31 cases of gastric non-cardia adenocarcinoma were identified. Gastric bypass was associated with an increased risk of gastric non-cardia adenocarcinoma 10-40 years after surgery compared to other bariatric surgeries, but not within the first 1-9 years. The rates of gastrectomy and survival seemed decreased following gastric bypass, indicating delayed tumor detection.

Study II tested the hypothesis that a later weekday of surgery is associated with increased 5-year mortality after gastrectomy for gastric adenocarcinoma. Among 1,678 patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006-2015, surgery performed in later weekdays (Thursday- Friday) was not associated with increased 5-year mortality compared to early- mid weekdays (Monday-Wednesday). When analyzing each weekday separately, Friday showed an increased point estimate for 5-year mortality, but statistically non-significant. These findings suggest that weekday of gastrectomy may not influence long-term survival in gastric adenocarcinoma, at least on Monday through Thursday.

Study III tested the hypothesis that surgeon age influences 5-year survival after gastrectomy for gastric adenocarcinoma. Among 1,647 patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006-2015, surgeon age 247 years was associated with increased 5-year mortality compared to <47 years. The association attenuated and became non-significant when adjusting for lymph node yield, resection margin status, and postoperative complications. These findings suggest that surgeon age 247 years may increase 5-years mortality after gastrectomy for gastric adenocarcinoma, possibly mediated by lower lymph node yield, higher frequency of tumor-involved resection margins, and increased postoperative complications.

Study IV evaluated whether survivors of gastric adenocarcinoma have a longer, shorter, or similar survival compared to the general Swedish population of the same age, sex, and calendar year. Among 767 patients who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006-2015 and survived at least 5 years (these were considered cured), observed survival was lower than expected survival. The decline was more pronounced among patients who underwent gastrectomy in earlier calendar years, had lower education level, more comorbidities, and had not undergone neoadjuvant therapy. These findings suggest that gastric adenocarcinoma survivors have a decreased survival compared to the general population, particularly if they belong to certain subgroups.

List of scientific papers

I. Leijonmarck W, Santoni G, Holmberg D, von Euler-Chelpin M, Ness- Jensen E, Kauppila JH, Lagergren J. Cancer in the excluded stomach after gastric bypass surgery for obesity. [Manuscript]

II. Leijonmarck W, Asplund J, Markar SR, Mattsson F, Lagergren J. Weekday of gastrectomy and long-term survival in gastric adenocarcinoma. Eur J Surg Oncol. 2023;49(1):83-88.
https://doi.org/10.1016/j.ejso.2022.07.011

III. Leijonmarck W, Mattsson F, Asplund J, Markar S, Lagergren J. Surgeon age in relation to patients' long-term survival after gastrectomy for gastric adenocarcinoma: nationwide population-based cohort study. BJS Open. 2024;8(2):zrae015. https://doi.org/10.1093/bjsopen/zrae015

IV. Leijonmarck W, Mattsson F, Lagergren J. Survival among patients cured from gastric adenocarcinoma compared to the background population. Gastric Cancer. 2024;27(6):1180-1188. https://doi.org/10.1007/s10120-024-01545-y