Introduction

Obesity is strongly associated with esophageal adenocarcinoma and moderately with cardia adenocarcinoma, but whether weight loss prevents these tumors is unknown. We examined whether bariatric surgery decreases the risk of these tumors.

Aims & Methods

This population-based cohort study included patients with an obesity diagnosis in Sweden, Finland, or Denmark. Participants were divided into a bariatric surgery group and a non-operated group. The incidence of esophageal and cardia adenocarcinoma (ECA) was first compared with the corresponding background population by calculating standard incidence ratios (SIR) with 95% confidence intervals (CI). Second, the bariatric surgery group and the non-operated group were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CI, adjusted for sex, age, comorbidity, calendar year, and country.

Results

Among 748,932 participants with an obesity diagnosis, 91,731 underwent bariatric surgery, predominantly gastric bypass (n=70,176; 76.5%). The SIRs of ECA decreased over time following gastric bypass, from SIR=2.2 (95% CI 0.9-4.3) after 2-5 years to SIR=0.6 (95% CI 0.1-3.6) after 10-40 years. Gastric bypass patients were also at a decreased risk of ECA compared to non-operated patients with obesity (adjusted HR=0.6, 95% CI 0.4-1.0 [0.98]), with decreasing point estimates over time. Gastric bypass was followed by a strongly decreased adjusted risk of esophageal adenocarcinoma (HR=0.3, 95% CI 0.1-0.8), but not of cardia adenocarcinoma (HR=0.9, 95% CI 0.5-1.6), when analyzed separately. There were no consistent associations between other bariatric procedures (mainly gastroplasty, gastric banding, sleeve gastrectomy, and biliopancreatic diversion) and ECA.

Conclusion

Gastric bypass surgery may counteract the development of esophageal adenocarcinoma in morbidly obese individuals.

Introduction

Hypergastrinemia, caused by chronic atrophic gastritis or Helicobacter pylori (H. pylori) associated pangastritis, is associated with an increased risk of non-cardia gastric cancer. Recent studies have also found an increased risk of gastric cancer in long-term proton pump inhibitor (PPI) users. Patients with chronic atrophic gastritis also have an increased risk of neuroendocrine neoplasms (NEN) due to hypergastrinemia. However, whether long-term PPI use increases the risk of gastric NEN has not been assessed in the general population.

Aims & Methods

The aim of the present study was to assess the risk of gastric NEN among long-term PPI users in a multinational population-based study from the Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). The study was based on the Nordic Gastric and Esophageal Tumor Study (NordGETS), which is a population-based multinational sex, age, calendar year, and country matched case-control study including all adults (≥18 years of age) with a diagnosis of gastric or esophageal tumor in the Nordic countries. In the present study, the cases were incident gastric NEN identified in the cancer registries and the exposure was long-term use of PPI categorised into three equal-sized groups (tertiles) of defined daily doses (DDDs) from the medication registries of the Nordic countries between 1996 and 2020. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for chronic atrophic gastritis, NEN in the duodenum or pancreas, and H. pylori infection identified in the patient registries and medication registries.

Results

In total, 1,790 gastric NEN case patients were compared to 17,897 control participants. After a one-year run-in period, the median follow-up was 11.8 years. The risk of incident gastric NEN increased in PPI users compared to non-users in a dose-dependent manner. The adjusted OR for incident gastric NEN was 1.83 (95% CI 1.56 to 2.15) in the highest tertile of PPI use (>385 DDDs, entire drug history) compared to no PPI use (Table). The risk was higher in the younger age group (<65 years) than the older age group (≥65 years) and the estimates were consistent when excluding individuals with chronic atrophic gastritis, other NENs, and H. pylori.

Conclusion

In this population-based study from the five Nordic countries the risk of gastric NEN was increased in PPI users compared to non-users of PPI in a seemingly dose-dependent manner. The risk was higher in younger age groups of PPI users compared to older age groups.

Disclosure

No conflicts of interest

Introduction

Antireflux surgery (fundoplication) may counteract gastroesophageal reflux of all types of carcinogenic gastric contents, not only acid, and reduce esophageal acid exposure to a greater extent than antireflux medication (proton pump inhibitors). We therefore examined the hypothesis that antireflux surgery prevents esophageal adenocarcinoma to a larger degree than antireflux medication in high-risk patients of esophageal adenocarcinoma, i.e. those with Barrett’s esophagus.

Aims & Methods

This multi-national and population-based cohort study included all patients with a recorded diagnosis of Barrett’s esophagus from Denmark (in 2012-2020), Finland (1987-1996 and 2010-2020), Norway (2008-2020), or Sweden (2006-2020) in a national patient registry. Patients who underwent antireflux surgery were compared with non-operated patients using antireflux medication. The risk of esophageal adenocarcinoma was calculated using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, sex, country, calendar year, and comorbidity.

Results

The cohort consisted of 33,939 patients with Barrett’s esophagus. Of these, 542 (1.6%) had undergone antireflux surgery. During up to 32 years of follow-up, the overall HR was not decreased in patients having undergone antireflux surgery compared to non-operated patients using antireflux medications, but rather increased (adjusted HR 1.9, 95% CI 1.1-3.5). The point estimates did not decrease with longer follow-up, but instead increased for each follow-up category, from 1.8 (95% CI 0.6-5.0) within 1-4 years of follow-up to 4.4 (95% CI 1.4-13.5) after >10 years of follow-up.

Conclusion

Antireflux surgery does not seem to be superior to antireflux medication in the prevention of esophageal adenocarcinoma among patients with Barrett’s esophagus.

Introduction

The incidence of oesophago-gastric cancer has an age-dependent male predominance mirroring physiological changes in sex hormonal levels. Some previous studies suggest that menopausal hormone therapy (MHT) counteracts the occurrence of these tumours, but larger studies with longer follow-up and adjustment for confounders are needed, which prompted the present study.

Aims & Methods

To investigate the hypothesis that MHT decreases the risk of developing oesophago-gastric cancer, especially oesophageal adenocarcinoma.
This population-based case-control study included women aged ≥45 years in all five Nordic countries (Denmark, Finland, Iceland, Norway, Sweden) between 1995-2020. Prospectively collected data came from national complete registries for medications, cancer, diagnoses, total populations, and death. The study included 19,518 case patients with oesophago-gastric cancer and 195,094 randomly identified control participants matched for age, country and calendar year. The participants were categorised into three equal-sized groups (tertiles) of defined daily doses (DDD) of MHT, with non-users as the reference group. MHT was also categorized as systemic or local, and oestrogen only or oestrogen combined with progesterone MHT. Oesophago-gastric cancer was divided into oesophageal or cardia adenocarcinoma, oesophageal squamous cell carcinoma, and gastric non-cardia adenocarcinoma as separate outcomes. Conditional logistic regression provided odds ratios (OR) with 95% confidence intervals (CI), adjusted for age, calendar year, country, obesity, gastroesophageal reflux disease, smoking, alcohol, Helicobacter pylori eradication, use of statins and non-steroidal anti-inflammatory drugs.

Results

​Compared to non-users of MHT, the adjusted ORs of oesophageal or cardia adenocarcinoma were 0.74 (95% CI 0.67-0.81) for low MHT-use (<158 DDDs), 0.68 (95% CI 0.61-0.75) for intermediate MHT-use (158-848 DDDs), and 0.68 (95% CI 0.61-0.75) for high MHT-use (>848 DDDs). The corresponding ORs were 0.69 (95% CI 0.62-0.77), 0.70 (95% CI 0.62-0.77), and 0.71 (95% CI 0.64-0.79) for oesophageal squamous cell carcinoma, and 0.90 (95% CI 0.84-0.96), 0.85 (95% CI 0.79-0.91), and 0.80 (95% CI 0.74-0.86) for gastric non-cardia adenocarcinoma.

Table. Odds ratios (OR) and 95% confidence intervals (CI) of oesophago-gastric cancer by tertiles of defined daily doses (DDD) of menopausal hormone therapy (MHT), MHT hormonal constitution and administration of MHT.

Conclusion

This study provides support for the hypothesis of an inverse association between MHT and risk of developing oesophago-gastric cancer, and particularly for oesophageal adenocarcinoma where the association was seemingly dose-dependent and stronger for combined oestrogen and progesterone MHT and for systemic MHT. A limitation to the study was the inability to adjust for socioeconomic factors as confounders.