| 1. |
- Brusselaers, Nele, et al.
(författare)
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Menopausal hormone therapy and the risk of esophageal and gastric cancer
- 2017
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- A protective effect of female sex hormones has been suggested to explain the male predominance in esophageal and gastric adenocarcinoma, but evidence is lacking. We aimed to test whether menopausal hormone therapy (MHT) decreases the risk of these tumors. For comparison, esophageal squamous cell carcinoma was also assessed. This population-based matched cohort study included all women who had ever used systemic MHT in Sweden in 2005-2012. A comparison cohort of non-users of MHT was matched to the MHT-users regarding age, parity, thrombotic events, hysterectomy, diabetes, obesity, smoking-related diseases, and alcohol-related diseases. Individuals with any previous cancer were excluded. Data on MHT use, cancer, comorbidity, and mortality were collected from well-established Swedish nationwide registers. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using conditional logistic regression. Different MHT regimens and age groups were compared in sub-group analyses. We identified 290,186 ever-users and 870,165 non-users of MHT. Ever-users had decreased ORs of esophageal adenocarcinoma (OR=0.62, 95% CI 0.45-0.85, n=46), gastric adenocarcinoma (OR=0.61, 95% CI 0.50-0.74, n=123), and esophageal squamous cell carcinoma (OR=0.57, 95% CI 0.39-0.83, n=33). The ORs were decreased for both estrogen-only MHT and estrogen and progestin combined MHT, and in all age groups. The lowest OR was found for esophageal adenocarcinoma in MHT-users younger than 60 years (OR=0.20, 95% CI 0.06-0.65). Our study suggests that MHT-users are at a decreased risk of esophageal and gastric adenocarcinoma, and also of esophageal squamous cell carcinoma. The mechanisms behind these associations remain to be elucidated.
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| 2. |
- Holmberg, Dag, et al.
(författare)
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Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease
- 2022
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 162:2, s. 431-438.e4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with decreased incidence and mortality in upper gastrointestinal cancer (ie, esophageal, gastric, or duodenal cancer).METHODS: We conducted a population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs).RESULTS: Among 1,062,740 patients with GERD (median age 58 years; 52% were women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper gastrointestinal cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper gastrointestinal cancer compared with those who did not undergo endoscopy (HR, 0.45; 95% CI, 0.43-0.48), a decrease that was more pronounced during more recent years (HR, 0.34; 95% CI, 0.30-0.38 from 2008 onward), and was otherwise stable across sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR, 0.39; 95% CI, 0.37-0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for 5 and at least 10 years, respectively.CONCLUSIONS: Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.
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| 3. |
- Holmberg, Dag, et al.
(författare)
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Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries : population based cohort study
- 2023
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Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 382, s. e076017-
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess the incidence rate of oesophageal adenocarcinoma among patients with non-erosive gastro-oesophageal reflux disease compared with the general population.Design Population based cohort study.Setting All patients in hospital and specialised outpatient healthcare in Denmark, Finland, and Sweden from 1 January 1987 to 31 December 2019.Participants 486 556 adults (>18 years) who underwent endoscopy were eligible for inclusion: 285 811 patients were included in the non-erosive gastro-oesophageal reflux disease cohort and 200 745 patients in the validation cohort with erosive gastro-oesophageal reflux disease.Exposures Non-erosive gastro-oesophageal reflux disease was defined by an absence of oesophagitis and any other oesophageal diagnosis at endoscopy. Erosive gastro-oesophageal reflux disease was examined for comparison reasons and was defined by the presence of oesophagitis at endoscopy.Main outcome measures The incidence rate of oesophageal adenocarcinoma was assessed for up to 31 years of follow-up. Standardised incidence ratios with 95% confidence intervals were calculated by dividing the observed number of oesophageal adenocarcinomas in each of the gastro-oesophageal reflux disease cohorts by the expected number, derived from the general populations in Denmark, Finland, and Sweden of the corresponding age, sex, and calendar period.Results Among 285 811 patients with non-erosive gastro-oesophageal reflux disease, 228 developed oesophageal adenocarcinomas during 2 081 051 person-years of follow-up. The incidence rate of oesophageal adenocarcinoma in patients with non-erosive gastro-oesophageal reflux disease was 11.0/100 000 person-years. The incidence was similar to that of the general population (standardised incidence ratio 1.04 (95% confidence interval 0.91 to 1.18)), and did not increase with longer follow-up (1.07 (0.65 to 1.65) for 15-31 years of follow-up). For validity reasons, we also analysed people with erosive oesophagitis at endoscopy (200 745 patients, 1 750 249 person-years, and 542 oesophageal adenocarcinomas, corresponding to an incidence rate of 31.0/100 000 person-years) showing an increased overall standardised incidence ratio of oesophageal adenocarcinoma (2.36 (2.17 to 2.57)), which became more pronounced with longer follow-up.Conclusions Patients with non-erosive gastro-oesophageal reflux disease seem to have a similar incidence of oesophageal adenocarcinoma as the general population. This finding suggests that endoscopically confirmed non-erosive gastro-oesophageal reflux disease does not require additional endoscopic monitoring for oesophageal adenocarcinoma.
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| 4. |
- Maret-Ouda, John, et al.
(författare)
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Antireflux surgery and risk of esophageal adenocarcinoma : a systematic review and meta-analysis
- 2016
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Ingår i: Annals of Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0003-4932. ; 263:2, s. 251-257
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the preventive effect of antireflux surgery against esophageal adenocarcinoma (EAC), compared to medical treatment of gastroesophageal reflux disease (GERD) and to the background population. Background: GERD is causally associated with EAC. Effective symptomatic treatment can be achieved with medication and antireflux surgery, yet the possible preventive effect on EAC development remains unclear. Methods: This systematic review identified 10 studies comparing EAC risk following antireflux surgery with non-operated GERD patients, including 7 studies of patients with Barrett’s esophagus; and 2 studies comparing EAC risk after antireflux surgery to the background population. A fixed-effects Poisson meta-analysis was conducted to calculate pooled incidence rate ratios (IRR) and 95% confidence intervals (CI). Results: The pooled IRR in patients following antireflux surgery was 0.76 (95% CI 0.42-1.39) compared to medically treated GERD patients. In patients with Barrett’s esophagus, the corresponding IRR was 0.46 (95% CI 0.20-1.08), and 0.26 (95% CI 0.09-0.79) when restricted to publications after 2000. There was no difference in EAC risk between antireflux surgery and medical treatment in GERD patients without known Barrett’s esophagus (IRR 0.98, 95% CI 0.72-1.33). The EAC risk remained elevated in patients following antireflux surgery compared to the background population (IRR 10.78, 95% CI 8.48-13.71). While the clinical heterogeneity of the included studies was high, the statistical heterogeneity was low. Conclusions: Antireflux surgery may prevent EAC better than medical therapy in patients with Barrett’s esophagus. The EAC risk following antireflux surgery does not seem to revert to that of the background population.
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| 5. |
- Maret-Ouda, John, et al.
(författare)
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Aspiration pneumonia after antireflux surgery among neurologically impaired children with GERD
- 2020
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Ingår i: Journal of Pediatric Surgery. - : Elsevier BV. - 0022-3468 .- 1531-5037. ; 55:11, s. 2408-2412
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Aspiration pneumonia is a common and serious complication to gastroesophageal reflux disease (GERD) among neurologically impaired children. Medication of GERD does not effectively prevent aspiration pneumonia, and whether antireflux surgery with fundoplication is better in this respect is uncertain. The objective was to determine whether fundoplication prevents aspiration pneumonia among children with neurological impairment and GERD.METHODS: This was a population-based cohort study from Denmark, Finland, Norway and Sweden, consisting of neurologically impaired children with GERD who underwent fundoplication. The risk of aspiration pneumonia before fundoplication (preoperative person-time) was compared with the risk after surgery (postoperative person-time). Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs). Except for confounding adjusted for by means of the "crossover like" design, the HRs were adjusted for age, sex, year of entry and respiratory diseases.RESULTS: Among 578 patients (median age 3.5 years), the preoperative person-time was 956 years and the postoperative person-time was 3324 years. Fundoplication was associated with 56% decreased overall HR of aspiration pneumonia (HR 0.44, 95% CI 0.27-0.72), and the HRs decreased over time after surgery. The risk of other types of pneumonia than aspiration pneumonia was not clearly decreased after fundoplication (HR 0.79, 95% CI 0.59-1.08). The 30-day mortality rate was 0.7% and the complication rate was 3.6%.CONCLUSIONS: Antireflux surgery decreases, but does not eliminate, the risk of aspiration pneumonia among neurologically impaired children with GERD. Fundoplication may be a treatment option when aspiration pneumonia is a recurrent problem in these children.TYPE OF STUDY: Cohort study.LEVEL OF EVIDENCE: Prognosis study-level I.
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| 6. |
- Maret-Ouda, John, et al.
(författare)
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Association between laparoscopic antireflux surgery and recurrence of gastroesophageal reflux
- 2017
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Ingår i: Journal of the American Medical Association. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0098-7484 .- 1538-3598.
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Cohort studies, mainly based on questionnaires and interviews, have reported high rates of reflux recurrence after antireflux surgery, which may have contributed to a decline in its use. Reflux recurrence after laparoscopic antireflux surgery has not been assessed in a long-term population-based study of unselected patients. OBJECTIVES: To determine the risk of reflux recurrence after laparoscopic antireflux surgery and to identify risk factors for recurrence. DESIGN AND SETTING: Nationwide population-based retrospective cohort study in Sweden between January 1, 2005, and December 31, 2014, based on all Swedish health care and including 2655 patients who underwent laparoscopic antireflux surgery according to the Swedish Patient Registry. Their records were linked to the Swedish Causes of Death Registry and Prescribed Drug Registry. EXPOSURES: Primary laparoscopic antireflux surgery due to gastroesophageal reflux disease in adults (>18 years). MAIN OUTCOMES AND MEASURES: The outcomewas recurrence of reflux, defined as use of antireflux medication (proton pump inhibitors or histamine2 receptor antagonists for >6 months) or secondary antireflux surgery. Multivariable Cox regression was used to assess risk factors for reflux recurrence. RESULTS: Among all 2655 patients who underwent antireflux surgery (median age, 51.0 years; interquartile range, 40.0-61.0 years; 1354 men [51.0%]) and were followed up for a median of 5.6 years, 470 patients (17.7%) had reflux recurrence; 393 (83.6%) received long-term antireflux medication and 77 (16.4%) underwent secondary antireflux surgery. Risk factors for reflux recurrence included female sex (hazard ratio [HR], 1.57 [95%CI, 1.29-1.90]; 286 of 1301 women [22.0%] and 184 of 1354 men [13.6%] had recurrence of reflux), older age (HR, 1.41 [95%CI, 1.10-1.81] for age 61 years compared with 45 years; recurrence among 156 of 715 patients and 133 of 989 patients, respectively), and comorbidity (HR, 1.36 [95%CI, 1.13-1.65] for Charlson comorbidity index score 1 compared with 0; recurrence among 180 of 804 patients and 290 of 1851 patients, respectively). Hospital volume of antireflux surgery was not associated with risk of reflux recurrence (HR, 1.09 [95%CI, 0.77-1.53] for hospital volume 24 surgeries compared with 76 surgeries; recurrence among 38 of 266 patients [14.3%] and 271 of 1526 patients [17.8%], respectively). CONCLUSIONS AND RELEVANCE: Among patients who underwent primary laparoscopic antireflux surgery, 17.7%experienced recurrent gastroesophageal reflux requiring long-term medication use or secondary antireflux surgery. Risk factors for recurrence were older age, female sex, and comorbidity. Laparoscopic antireflux surgery was associated with a relatively high rate of recurrent gastroesophageal reflux disease requiring treatment, diminishing some of the benefits of the operation.
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| 7. |
- Maret-Ouda, John, et al.
(författare)
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Cohort profile : the Nordic antireflux surgery cohort (NordASCo)
- 2017
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Ingår i: BMJ Open. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2044-6055.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To describe a newly created all-Nordic cohort of patients with gastro-oesophageal reflux disease (GORD), entitled the Nordic Antireflux Surgery Cohort (NordASCo), which will be used to compare participants having undergone antireflux surgery with those who have not regarding risk of cancers, other diseases and mortality. PARTICIPANTS: Included were individuals with a GORD diagnosis recorded in any of the nationwide patient registries in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) in 1964-2014 (with various start and end years in different countries). Data regarding cancer, other diseases and mortality were retrieved from the nationwide registries for cancer, patients and causes of death, respectively. FINDINGS TO DATE: The NordASCo includes 945 153 individuals with a diagnosis of GORD. Of these, 48 433 (5.1%) have undergone primary antireflux surgery. Median age at primary antireflux surgery ranged from 47 to 52 years in the different countries. The coding practices of GORD seem to have differed between the Nordic countries. FUTURE PLANS: The NordASCo will initially be used to analyse the risk of developing known or potential GORD-related cancers, that is, tumours of the oesophagus, stomach, larynx, pharynx and lung, and to evaluate the mortality in the short-term and long-term perspectives. Additionally, the cohort will be used to evaluate the risk of non-malignant respiratory conditions that might be caused by aspiration of gastric contents.
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| 8. |
- Maret-Ouda, John, et al.
(författare)
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Esophageal adenocarcinoma after obesity surgery in a population-based cohort study
- 2015
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Ingår i: Surgery for Obesity and Related Diseases. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1550-7289. ; 13:1, s. 28-34
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is strongly associated with esophageal adenocarcinoma (EAC), yet whether weight loss reduces the risk of EAC is unclear. Objectives: To test the hypothesis that the risk of EAC decreases following weight reduction achieved by obesity surgery. Setting: Nationwide register-based cohort study. Methods: This study included a majority of individuals who underwent obesity surgery in Sweden in 1980-2012. The incidence of EAC following obesity surgery was compared to the incidence in the corresponding background population of Sweden by means of calculation of standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). The risk of EAC after obesity surgery was also compared with the risk in non-operated obese individuals by means of multivariable Cox regression, providing hazard ratios (HRs) with 95% CIs, adjusted for potential confounders. Results: Among 34,437 study participants undergoing obesity surgery and 239,775 person- 15" years of follow-up, 8 cases of EAC occurred (SIR 1.6, 95% CI 0.7-3.2). No clear trend of decreased SIRs was seen in relation to increased follow-up time after surgery. The SIR of EACs (n=53) among 123,695 non-operated obese individuals (673,238 person-years) was increased to a similar extent as in the obesity surgery cohort (SIR=1.9, 95% CI 1.4-2.5). Cox regression showed no difference in risk of EAC between operated and non-operated participants (adjusted HR=0.9, 95% CI 0.4-1.9). Conclusions: The risk of EAC might not decrease following obesity surgery, but even larger studies with longer follow-up are needed to establish this association.
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| 9. |
- Maret-Ouda, John, et al.
(författare)
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Gastroesophageal Reflux Disease : A Review.
- 2020
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Ingår i: Journal of the American Medical Association (JAMA). - CHICAGO USA : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 324:24, s. 2536-2547
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Gastroesophageal reflux disease (GERD) is defined by recurrent and troublesome heartburn and regurgitation or GERD-specific complications and affects approximately 20% of the adult population in high-income countries.Observations: GERD can influence patients' health-related quality of life and is associated with an increased risk of esophagitis, esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Obesity, tobacco smoking, and genetic predisposition increase the risk of developing GERD. Typical GERD symptoms are often sufficient to determine the diagnosis, but less common symptoms and signs, such as dysphagia and chronic cough, may occur. Patients with typical GERD symptoms can be medicated empirically with a proton pump inhibitor (PPI). Among patients who do not respond to such treatment or if the diagnosis is unclear, endoscopy, esophageal manometry, and esophageal pH monitoring are recommended. Patients with GERD symptoms combined with warning symptoms of malignancy (eg, dysphagia, weight loss, bleeding) and those with other main risk factors for esophageal adenocarcinoma, such as older age, male sex, and obesity, should undergo endoscopy. Lifestyle changes, medication, and surgery are the main treatment options for GERD. Weight loss and smoking cessation are often useful. Medication with a PPI is the most common treatment, and after initial full-dose therapy, which usually is omeprazole 20 mg once daily, the aim is to use the lowest effective dose. Observational studies have suggested several adverse effects after long-term PPI, but these findings need to be confirmed before influencing clinical decision making. Surgery with laparoscopic fundoplication is an invasive treatment alternative in select patients after thorough and objective assessments, particularly if they are young and healthy. Endoscopic and less invasive surgical techniques are emerging, which may reduce the use of long-term PPI and fundoplication, but the long-term safety and efficacy remain to be scientifically established.Conclusions and Relevance: The clinical management of GERD influences the lives of many individuals and is responsible for substantial consumption of health care and societal resources. Treatments include lifestyle modification, PPI medication, and laparoscopic fundoplication. New endoscopic and less invasive surgical procedures are evolving. PPI use remains the dominant treatment, but long-term therapy requires follow-up and reevaluation for potential adverse effects.
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| 10. |
- Maret-Ouda, John, et al.
(författare)
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Mortality from laparoscopic antireflux surgery in a nationwide cohort of the working-age population
- 2016
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Ingår i: British Journal of Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0007-1323 .- 1365-2168.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Effective treatment of severe gastro-oesophageal reflux disease is available through medication or surgery. Postoperative risks have contributed to decreased use of antireflux surgery. We aimed to assess short-term mortality following primary laparoscopic fundoplication. Method: Population-based nationwide Swedish cohort study including all Swedish hospitals performing laparoscopic fundoplication, between 1997 and 2013. All patients aged 18-65 years with gastro-oesophageal reflux disease who underwent primary laparoscopic fundoplication during the study period were included. Main outcome was absolute all-cause and surgery-related 90-day and 30-day mortality. Secondary outcomes were reoperation and length of hospital stay. Logistic regression was used to calculate odds ratios with 95% confidence intervals of reoperation within 90 days and prolonged hospital stay (>4 days). Results: Of 8947 included patients, 5306 (59.3%) were men, and 551 (6.2%) had a significant comorbidity (Charlson comorbidity score >0). Median age at surgery was 48 years, and median hospital stay was 2 days. Annual rate of laparoscopic fundoplication decreased from 15.3 to 2.4 cases per 100 000 inhabitants during the study period, while the proportion of patients with comorbidity increased more than 2-fold. All-cause 90- and 30-day mortality were 0.08% (n=7) and 0.03% (n=3), respectively. Only 1 death (0.01%) was directly surgery-related. 90-day reoperation rate was 0.4% (n=39). Comorbidity and higher age entailed increased risk for prolonged hospital stay, but not for reoperation. Conclusion: This population-based study revealed a remarkably low 90-day mortality and reoperation rate following laparoscopic, results which might influence clinical decision-making in the treatment of severe gastro-oesophageal reflux disease.
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