Exploring the association between acute pancreatitis and biliary tract cancer: A large-scale population-based matched cohort study.

BACKGROUND: Biliary tract cancer (BTC) often goes undetected until its advanced stages, resulting in a poor prognosis. Given the anatomical closeness of the gallbladder and bile ducts to the pancreas, the inflammatory processes triggered by acute pancreatitis might increase the risk of BTC. OBJECTIVE: To assess the association between acute pancreatitis and the risk of BTC. METHODS: Using the Swedish Pancreatitis Cohort (SwePan), we compared the BTC risk in patients with a first-time episode of acute pancreatitis during 1990-2018 to a 1:10 matched pancreatitis-free control group. Multivariable Cox regression models, stratified by follow-up duration, were used to calculate hazard ratios (HRs), adjusting for socioeconomic factors, alcohol use, and comorbidities. RESULTS: BTC developed in 0.94% of 85,027 acute pancreatitis patients and in 0.23% of 814,993 controls. The BTC risk notably increased within 3 months of hospital discharge (HR 82.63; 95% CI: 63.07-108.26) and remained elevated beyond 10 years of follow-up (HR 1.82; 95% CI: 1.35-2.47). However, the long-term risk of BTC subtypes did not increase with anatomical proximity to the pancreas, with a null association for gallbladder and extrahepatic tumors. Importantly, patients with acute pancreatitis had a higher occurrence of early-stage BTC within 2 years of hospital discharge than controls (13.0 vs. 3.6%; p-value <0.01). CONCLUSION: Our nationwide study found an elevated BTC risk in acute pancreatitis patients; however, the risk estimates for BTC subtypes were inconsistent, thereby questioning the causality of the association. Importantly, the amplified detection of early-stage BTC within 2 years after a diagnosis of acute pancreatitis underscores the necessity for proactive BTC surveillance in these patients.

Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries: population based cohort study.

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.

Decreased Risk of Esophageal Adenocarcinoma After Gastric Bypass Surgery in a Cohort Study From 3 Nordic Countries.

OBJECTIVE: The objective of this study was to test the hypothesis that bariatric surgery decreases the risk of esophageal and cardia adenocarcinoma. BACKGROUND: Obesity is strongly associated with esophageal adenocarcinoma and moderately with cardia adenocarcinoma, but whether weight loss prevents these tumors is unknown. 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 nonoperated group. The incidence of esophageal and cardia adenocarcinoma (ECA) was first compared with the corresponding background population by calculating standardized incidence ratios (SIR) with 95% CIs. Second, the bariatric surgery group and the nonoperated 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 after gastric bypass, from SIR=2.2 (95% CI, 0.9-4.3) after 2 to 5 years to SIR=0.6 (95% CI, <0.1-3.6) after 10 to 40 years. Gastric bypass patients were also at a decreased risk of ECA compared with nonoperated 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. CONCLUSIONS: Gastric bypass surgery may counteract the development of esophageal adenocarcinoma in morbidly obese individuals.

Proton pump inhibitor use and risk of pneumonia: a self-controlled case series study.

BACKGROUND: Recent research indicates that use of proton pump inhibitors (PPIs) is associated with pneumonia, but existing evidence is inconclusive because of methodological issues. This study aimed to answer whether PPI-use increases risk of pneumonia while taking the methodological concerns of previous research into account. METHODS: This population-based and nationwide Swedish study conducted in 2005-2019 used a self-controlled case series design. Data came from national registries for medications, diagnoses, and mortality. Conditional fixed-effect Poisson regression provided incidence rate ratios (IRR) with 95% confidence intervals (CI) for pneumonia comparing PPI-exposed periods with unexposed periods in the same individuals, thus controlling for confounding. Analyses were stratified by PPI-treatment duration, sex, age, and smoking-related diseases. Use of histamine type-2 receptor antagonists (used for the same indications as PPIs) and risk of pneumonia was analysed for assessing the validity and specificity of the results for PPI-therapy and pneumonia. RESULTS: Among 519,152 patients with at least one pneumonia episode during the study period, 307,709 periods of PPI-treatment occurred. PPI-use was followed by an overall 73% increased risk of pneumonia (IRR 1.73, 95% CI 1.71-1.75). The IRRs were increased across strata of PPI-treatment duration, sex, age, and smoking-related disease status. No such strong association was found between histamine type-2 receptor antagonist use and risk of pneumonia (IRR 1.08, 95% CI 1.02-1.14). CONCLUSIONS: PPI-use seems to be associated with an increased risk of pneumonia. This finding highlights a need for caution in using PPIs in individuals with a history of pneumonia.

Mortality in small bowel cancers and adenomas - A nationwide, population-based matched cohort study.

BACKGROUND: Small bowel adenocarcinoma (SBA), neuroendocrine tumors (NET) and gastrointestinal stromal tumors (GIST) are neoplastic lesions of the small bowel while small bowel adenomas are precursors of SBA. AIM: To examine mortality in patients diagnosed with SBA, small bowel adenomas, NET and GIST. METHODS: We performed a population-based matched cohort study encompassing all individuals with SBA (n = 2289), adenomas (n = 3700), NET (n = 1884) and GIST (n = 509) in the small bowel diagnosed at any of Sweden's 28 pathology departments between 2000 and 2016 (the "ESPRESSO study"). Each case was matched by sex, age, calendar year and county of residence to up to 5 comparators from the general population. Through Cox regression we estimated hazard ratios (HRs) and 95% confidence intervals (95%CIs) for death and cause-specific death adjusting for education. RESULTS: During follow-up until December 31, 2017, 1836 (80%) deaths occurred in SBA patients, 1615 (44%) in adenoma, 866 (46%) in NET and 162 (32%) in GIST patients. This corresponded to incidence rates of 295, 74, 80 and 62/1000 person-years respectively and adjusted HRs of 7.60 (95%CI=6.95-8.31), 2.21 (2.07-2.36), 2.74 (2.50-3.01) and 2.33 (1.90-2.87). Adjustment for education had a substantial impact on the HR for death in SBA but not for other neoplasias. The predominant cause of excess death was cancer in all groups. CONCLUSION: This study confirms earlier findings of increased death rates in patients with SBA and NET in a modern study population. We also demonstrate a more than 2-fold increased risk of death in both GIST and the SBA precursor adenoma.

Appendectomy and Future Risk of Microscopic Colitis: A Population-Based Case-Control Study in Sweden.

BACKGROUND AND AIMS: Microscopic colitis (MC) is an inflammatory bowel disease and a common cause of chronic diarrhea. Appendectomy has been suggested to have immunomodulating effects in the colon, influencing the risk of gastrointestinal disease. The relationship between appendectomy and MC has only been sparsely studied. METHODS: This was a case-control study based on the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, consisting of histopathological examinations in Sweden, linked to national registers. Patients with MC were matched to population controls by age, sex, calendar year of biopsy, and county of residence. Data on antecedent appendectomy and comorbidities were retrieved from the Patient Register. Unconditional logistic regression models were conducted presenting odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for country of birth and matching factors. Further subanalyses were made based on MC subtypes (lymphocytic colitis and collagenous colitis), follow-up time postappendectomy and severity of appendicitis. RESULTS: The study included 14,520 cases of MC and 69,491 controls, among these 7.6% (n = 1103) and 5.1% (n = 3510), respectively, had a previous appendectomy ≥1 year prior to MC or matching date. Patients with a previous appendectomy had an increased risk of MC in total (OR, 1.50; 95% CI, 1.40-1.61) and per the collagenous colitis subtype (OR, 1.67; 95% CI, 1.48-1.88) or lymphocytic colitis subtype (OR, 1.42; 95% CI, 1.30-1.55). The risk remained elevated throughout follow-up, and the highest risk was observed in noncomplicated appendicitis. CONCLUSIONS: This nationwide case-control study found a modestly increased risk of developing MC following appendectomy.

Objectively confirmed gastroesophageal reflux disease and risk of atrial fibrillation: a population-based cohort study in Sweden.

OBJECTIVE: This study aimed to determine the risk of atrial fibrillation in patients with objectively confirmed GERD. METHODS: This was a nationwide population-based cohort study between 2005 and 2018, including the majority ( n = 8 421 115) of all Swedish adult residents (≥18 years). Within this cohort, the exposed group were all individuals with a diagnosis of esophagitis or Barrett's esophagus, and the unexposed group was made up of five times as many individuals without any GERD, matched by age, sex, and calendar year. The outcome was the first diagnosis of atrial fibrillation. Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for confounders. RESULTS: Among 118 013 individuals with esophagitis or Barrett's esophagus and 590 065 without GERD, 7042 (6.0%) and 40 962 (6.9%) developed atrial fibrillation, respectively. The risk of atrial fibrillation among patients with GERD was 13% increased within the first year of diagnosis (HR, 1.13; 95% CI, 1.06-1.20), but was not increased after that. Among individuals aged less than 60 years, the HR of atrial fibrillation was 55% increased within the first year of diagnosis (HR, 1.55; 95% CI, 1.27-1.88), and this association remained increased after the first year (HR, 1.14; 95% CI, 1.06-1.22). No association was found in older participants (≥60 years). Results were similar in men and women. CONCLUSION: This large population-based cohort study indicates that objectively determined GERD increases the risk of atrial fibrillation shortly after diagnosis in men and women younger than 60 years.

Cohort profile: the Swedish Pancreatitis Cohort (SwePan).

PURPOSE: The Swedish Pancreatitis Cohort (SwePan) was designed to study long-term outcomes following an episode of acute pancreatitis. It can also be used to study various risk factors for developing acute pancreatitis. PARTICIPANTS: The SwePan is a register-based nationwide matched cohort. It includes all Swedish cases of acute pancreatitis during 1990-2019. It contains 95 632 individuals with acute pancreatitis and 952 783 pancreatitis-free individuals matched on sex, age and municipality of residence. Follow-up was censored at death, emigration or end of study (31 December 2019). The dataset includes comprehensive information based on several registries, and includes diagnoses, prescribed medications and socioeconomic factors both prior to inclusion and during follow-up. FINDINGS TO DATE: During the study period, the number of cases of acute pancreatitis in Sweden has more than doubled from 1977 cases in 1990 to 4264 cases in 2019. The median age of first episode of acute pancreatitis has increased from 58 years (IQR 44-73 years) in 1990 to 64 years (IQR 49-76 years) in 2019. Cases with acute pancreatitis were generally less healthy compared with the pancreatitis-free individuals (Charlson Comorbidity Index of 0 in 59.2% and 71.4%, respectively). FUTURE PLANS: SwePan will be used to determine the incidence of acute pancreatitis in Sweden over time and assess long-term all-cause and cause-specific mortality after an episode of acute pancreatitis. Some examples of additional planned studies are (1) assessment of long-term risk of diabetes and (2) risk of malignancy in adjacent organs following acute pancreatitis and (3) assessment of risk factors for development of acute pancreatitis including various drugs.

Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease.

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.

Proton Pump Inhibitor and Clopidogrel Use After Percutaneous Coronary Intervention and Risk of Major Cardiovascular Events.

PURPOSE: Due to shared hepatic metabolism, concomitant medication with a proton pump inhibitor (PPI) and clopidogrel might reduce the effectiveness of clopidogrel in the prevention of cardiovascular events after percutaneous coronary intervention (PCI). We aimed to examine the risk of major cardiovascular events after PCI comparing patients who used clopidogrel together with PPI with those who used clopidogrel alone. METHODS: This Swedish nationwide cohort study included patients who received clopidogrel after primary PCI in 2005-2019. Patients were followed for up to 12 months after PCI. Data were retrieved from the Swedish Prescribed Drug Registry, Patient Registry, Cancer Registry, and Cause of Death Registry. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular events comparing PPI users (exposed) with non-users of PPI (non-exposed). The HRs were adjusted for sex, age, comorbidity, calendar period, obesity, diabetes, anti-diabetic medication, tobacco-related diseases, hypertension, and congestive heart failure. RESULTS: The cohort included 99,836 patients who received clopidogrel after primary PCI. Among these, 35,772 (35.8%) received concomitant PPI. Compared to non-users, PPI users had increased adjusted HRs of all study outcomes, i.e., the main outcome myocardial infarction (HR = 1.23, 95% CI 1.15-1.32) and the secondary outcomes coronary heart disease (HR = 1.28, 95% CI 1.24-1.33), stroke (HR = 1.21, 95% CI 1.05-1.40), and death due to coronary heart disease (HR = 1.52, 95% CI 1.37-1.69). The results were similar in analyses including both primary and secondary PCIs. CONCLUSIONS: In patients who receive clopidogrel after PCI, concomitant use of PPI seems to increase the risk of major cardiovascular events.

Laryngeal and Pharyngeal Squamous Cell Carcinoma After Antireflux Surgery in the 5 Nordic Countries.

OBJECTIVE: The aim of this study was to clarify whether antireflux surgery prevents laryngeal and pharyngeal squamous cell carcinoma. SUMMARY BACKGROUND DATA: Gastroesophageal reflux disease (GERD) seems to increase the risk of laryngeal and pharyngeal squamous cell carcinoma. METHODS: All-Nordic (Denmark, Finland, Iceland, Norway, and Sweden) population-based cohort study of adults with documented GERD in 1980 to 2014. First, cancer risk after antireflux surgery was compared to the expected risk in the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). Second, cancer risk among antireflux surgery patients was compared to nonoperated GERD patients using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs, adjusted for sex, age, calendar period, and diagnoses related to tobacco smoking, obesity, and alcohol overconsumption. RESULTS: Among 814,230 GERD patients, 47,016 (5.8%) underwent antireflux surgery. The overall SIRs and HRs of the combined outcome laryngeal or pharyngeal squamous cell carcinoma (n=39) were decreased after antireflux surgery [SIR=0.62 (95% CI 0.44-0.85) and HR=0.55 (95% CI 0.38-0.80)]. The point estimates were further decreased >10 years after antireflux surgery [SIR=0.48 (95% CI 0.26-0.80) and HR=0.47 (95% CI 0.26-0.85)]. The risk estimates of laryngeal squamous cell carcinoma were particularly decreased >10 years after antireflux surgery [SIR=0.28 (95% CI 0.08-0.72) and HR=0.23 (95% CI 0.08-0.69)], whereas no such decrease over time after surgery was found for pharyngeal squamous cell carcinoma. Analyses of patients with severe GERD (reflux esophagitis or Barrett esophagus) showed similar results. CONCLUSION: Antireflux surgery may decrease the risk of laryngeal squamous cell carcinoma and possibly also of pharyngeal squamous cell carcinoma.

Mortality, Reoperation, and Hospital Stay Within 90 Days of Primary and Secondary Antireflux Surgery in a Population-Based Multinational Study.

BACKGROUND & AIMS: Absolute rates and risk factors of short-term outcomes after antireflux surgery remain largely unknown. We aimed to clarify absolute risks and risk factors for poor 90-day outcomes of primary laparoscopic and secondary antireflux surgery. METHODS: This population-based cohort study included patients who had primary laparoscopic or secondary antireflux surgery in the 5 Nordic countries in 2000-2018. In addition to absolute rates, we analyzed age, sex, comorbidity, hospital volume, and calendar period in relation to all-cause 90-day mortality (main outcome), 90-day reoperation, and prolonged hospital stay (≥2 days over median stay). Multivariable logistic regression provided odds ratios (ORs) with 95% confidence intervals (95% CI), adjusted for confounders. RESULTS: Among 26,193 patients who underwent primary laparoscopic antireflux surgery, postoperative 90-day mortality and 90-day reoperation rates were 0.13% (n = 35) and 3.0% (n = 750), respectively. The corresponding rates after secondary antireflux surgery (n = 1 618) were 0.19% (n = 3) and 6.2% (n = 94). Higher age (56-80 years vs 18-42 years: OR, 2.66; 95% CI 1.03-6.85) and comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 6.25; 95% CI 2.42-16.14) increased risk of 90-day mortality after primary surgery, and higher hospital volume suggested a decreased risk (highest vs lowest tertile: OR, 0.58; 95% CI, 0.22-1.57). Comorbidity increased the risk of 90-day reoperation. Higher age and comorbidity increased risk of prolonged hospital stay after both primary and secondary surgery. Higher annual hospital volume decreased the risk of prolonged hospital stay after primary surgery (highest vs lowest tertile: OR, 0.74; 95% CI, 0.67-0.80). CONCLUSION: These findings suggest that laparoscopic antireflux surgery has an overall favorable safety profile in the treatment of gastroesophageal reflux disease, particularly in younger patients without severe comorbidity who undergo surgery at high-volume centers.

Esophageal Adenocarcinoma After Antireflux Surgery in a Cohort Study From the 5 Nordic Countries.

OBJECTIVE: We aimed to clarify the long-term risk development of EAC after antireflux surgery. SUMMARY OF BACKGROUND DATA: Gastroesophageal reflux disease (GERD) increases EAC risk, but whether antireflux surgery prevents EAC is uncertain. METHODS: Multinational, population-based cohort study including individuals with GERD from all 5 Nordic countries in 1964-2014. First, EAC risk after antireflux surgery in the cohort was compared with the corresponding background population by calculating standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs). Second, multivariable Cox proportional hazards regression, providing hazard ratios (HRs) with 95% CIs, compared EAC risk in GERD patients with antireflux surgery with those with nonsurgical treatment. RESULTS: Among 942,071 GERD patients, 48,863 underwent surgery and 893,208 did not. Compared to the corresponding background population, EAC risk did not decrease after antireflux surgery [SIR 4.90 (95% CI 3.62-6.47) 1-<5 years and SIR 4.57 (95% CI 3.44-5.95) ≥15 years after surgery]. Similarly, no decrease was found for patients with severe GERD (esophagitis or Barrett esophagus) after surgery [SIR 6.09 (95% CI 4.39-8.23) 1-<5 years and SIR = 5.27 (95% CI 3.73-7.23) ≥15 years]. The HRs of EAC were stable comparing the surgery group with the nonsurgery group with GERD [HR 1.71 (95% CI 1.26-2.33) 1-<5 years and HR 1.69 (95% CI 1.24-2.30) ≥15 years after treatment], or for severe GERD [HR 1.56 (95% CI 1.11-2.20) 1-<5 years and HR 1.57 (95% CI 1.08-2.26) ≥15 years after treatment]. CONCLUSIONS: Surgical treatment of GERD does not seem to reduce EAC risk.

Hospital Volume of Antireflux Surgery in Relation to Endoscopic and Surgical Re-interventions.

OBJECTIVE: To test the hypothesis that higher hospital volume decreases endoscopic and surgical re-intervention rates after antireflux surgery. BACKGROUND: Antireflux surgery for gastro-esophageal reflux disease is followed by varying rates of re-interventions. Whether hospital volume influences re-intervention rates is uncertain. METHODS: This population-based cohort study used nationwide data from Denmark, Finland, and Sweden for patients having undergone primary antireflux surgery. Hospitals were divided into tertiles based upon annual volume, that is, 3 equal-sized groups. The outcomes were 30-day surgical re-intervention, endoscopic re-intervention, and secondary antireflux surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for risk of the first outcome occurrence. Incidence rate ratios were calculated to count all outcome occurrences. All risk estimates were adjusted for age, sex, comorbidity, type of antireflux surgery, year of surgery, and country. RESULTS: Among 33,060 patients and a median follow-up of 12 years after antireflux surgery, the frequencies of 30-day re-intervention, endoscopic re-intervention, and secondary antireflux surgery were 1.2%, 4.6%, and 7.0%, respectively. When comparing the highest with the lowest tertiles, higher hospital volume did not decrease HRs of 30-day re-intervention (adjusted HR = 1.14, 95% CI 0.73-1.77), endoscopic re-intervention (HR = 1.21, 95% CI 0.96-1.51), or secondary antireflux surgery (HR = 1.28, 95% CI 1.05-1.54), but rather increased point estimates. The incidence rate ratios showed similar patterns. CONCLUSIONS: Higher hospital volume of primary antireflux surgery may not decrease risk of endoscopic or surgical re-intervention, suggesting that centralization will not decrease rates of postoperative complications or recurrence of gastro-esophageal reflux disease.

Hospital volume of esophageal cancer surgery in relation to outcomes from primary anti-reflux surgery.

No previous study has sought to identify the effect of hospital volume of esophagectomy on anti-reflux surgery outcomes. The hypothesis under investigation was hospitals performing esophagectomies, particularly those of higher annual volume, have better outcomes from primary anti-reflux surgery. This population-based cohort study included adult individuals (≥18 years) in Sweden receiving primary anti-reflux surgery for a recorded gastro-esophageal reflux disease in 1997-2010, with follow-up until 2013 The 'exposure' was hospital volume of esophagectomy, with hospitals conducting esophagectomies divided into 0, >0-1, >1-3 and ≥ 4 based on annual volume, and hospitals not conducting esophagectomies were the reference category. The outcomes were 30-day re-intervention and surgical re-intervention during the entire follow-up after anti-reflux surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, sex, comorbidity, type of anti-reflux surgery, and year of anti-reflux surgery. Among 10,959 participants having undergone primary anti-reflux surgery, the 30-day re-intervention rate was 1.1%, and the rate of surgical re-intervention during the entire follow-up was 6.8%. Compared with hospitals not performing esophagectomy, hospitals in the highest volume group of esophagectomy showed no decreased risks of 30-day re-intervention (HR = 1.46, 95% CI 0.89-2.39) or surgical re-intervention (HR = 1.21, 95%CI 0.91-1.60) during follow-up. Similarly, the intermediate hospital volume categories of esophageal cancer surgery had no decreased risk of surgical re-interventions after anti-reflux surgery. This study provides no evidence for centralization of primary anti-reflux surgery to centers for esophageal cancer surgery.

Gastroesophageal Reflux Disease: A Review.

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.

Antireflux surgery and risk of lung cancer by histological type in a multinational cohort study.

INTRODUCTION: Airway micro-aspiration might contribute to the proposed associations between gastroesophageal reflux disease (GERD) and some lung diseases, including lung cancer. This study aimed to examine the hypothesis that antireflux surgery decreases the risk of small cell carcinoma, squamous cell carcinoma and adenocarcinoma of the lung differently depending on their location in relation to micro-aspiration. METHODS: Population-based cohort study including patients having undergone antireflux surgery during 1980-2014 in Denmark, Finland, Iceland, Norway or Sweden. Patients having undergone antireflux surgery were compared with two groups: 1) the corresponding background population, by calculating standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) and 2) non-operated GERD-patients, by calculating hazard ratios (HRs) with 95% CIs using multivariable Cox regression with adjustment for sex, age, calendar period, country, chronic obstructive pulmonary disease and obesity diagnosis or type 2 diabetes. RESULTS: Among all 812,617 GERD-patients, 46,996 (5.8%) had undergone antireflux surgery. The SIRs were statistically significantly decreased for small cell carcinoma (SIR = 0.57, 95% CI 0.41-0.77) and squamous cell carcinoma (SIR = 0.75, 95% CI 0.60-0.92), but not for adenocarcinoma of the lung (SIR = 0.90, 95% CI 0.76-1.06). The HRs were also below unity for small cell carcinoma (HR = 0.63, 95% CI 0.44-0.90) and squamous cell carcinoma (HR = 0.80, 95% CI 0.62-1.03), but not for adenocarcinoma of the lung (HR = 1.03, 95% CI 0.84-1.26). Analyses restricted to patients with objective GERD (reflux oesophagitis or Barrett's oesophagus) showed similar results. CONCLUSIONS: This all-Nordic study indicates that patients who undergo antireflux surgery are at decreased risk of small cell carcinoma and squamous cell carcinoma of the lung, but not of adenocarcinoma of the lung.