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, according to a Nordic retrospective study.
Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.
“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”
Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.
“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.
For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.
In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.
After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.
The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).
“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”
Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.
“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.
“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.
The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.
Esophageal adenocarcinoma (EAC) has been increasing in frequency for decades. EAC’s only known precursor is Barrett’s esophagus (BE), a complication of GERD with chronic esophageal inflammation (reflux esophagitis). Chronic inflammation can predispose to cancer and refluxed acid itself can cause potentially carcinogenic double-strand DNA breaks in Barrett’s metaplasia. PPIs, which block secretion of the gastric acid that causes reflux esophagitis and DNA damage, are recommended to BE patients for cancer prevention. Logical as that practice may seem, meta-analyses have reached contradictory conclusions regarding the cancer-preventive benefits of PPIs. PPIs do not stop the reflux of other potential carcinogens such as bile salts, and thus it has been argued that fundoplication, which blocks the reflux of all gastric material, should be superior to PPIs for cancer prevention. Plausible as that argument sounds, meta-analyses of the generally small and heterogeneous studies on this issue have not found consistently that antireflux surgery is superior to medical therapy for cancer prevention in BE.
Now, a large, population-based cohort study by Åkerström et al. of Nordic BE patients followed for up to 32 years has found that the overall risk of EAC was higher for patients treated with fundoplication than for those treated with medication (adjusted HR 1.9, 95%CI 1.1-3.5). Furthermore, the EAC risk increased over time in the surgical patients. Well done as this study was, it has important limitations. The overall BE population was large (n=33,939), but only 1.6% (542 patients) had antireflux surgery, and only 14 of those developed EAC during follow-up. Those small numbers limit statistical power. Moreover, important residual confounding cannot be excluded. The surgical patients might have had more severe GERD than medical patients, and it is difficult to make a plausible argument for why fundoplication should increase EAC risk. Nevertheless, this study provides a good lesson on why a plausible argument needs supportive evidence before acting on it in clinical practice. While there may be some excellent reasons for recommending antireflux surgery over medication for patients with severe GERD, better esophageal cancer prevention does not appear to be one of them.
Stuart Jon Spechler, MD, is chief of the division of gastroenterology and codirector of the Center for Esophageal Diseases at Baylor University Medical Center, and codirector of the Center for Esophageal Research at Baylor Scott & White Research Institute, Dallas, Texas. Dr. Spechler is a consultant for Phathom Pharmaceuticals and ISOThrive, LLC.
Esophageal adenocarcinoma (EAC) has been increasing in frequency for decades. EAC’s only known precursor is Barrett’s esophagus (BE), a complication of GERD with chronic esophageal inflammation (reflux esophagitis). Chronic inflammation can predispose to cancer and refluxed acid itself can cause potentially carcinogenic double-strand DNA breaks in Barrett’s metaplasia. PPIs, which block secretion of the gastric acid that causes reflux esophagitis and DNA damage, are recommended to BE patients for cancer prevention. Logical as that practice may seem, meta-analyses have reached contradictory conclusions regarding the cancer-preventive benefits of PPIs. PPIs do not stop the reflux of other potential carcinogens such as bile salts, and thus it has been argued that fundoplication, which blocks the reflux of all gastric material, should be superior to PPIs for cancer prevention. Plausible as that argument sounds, meta-analyses of the generally small and heterogeneous studies on this issue have not found consistently that antireflux surgery is superior to medical therapy for cancer prevention in BE.
Now, a large, population-based cohort study by Åkerström et al. of Nordic BE patients followed for up to 32 years has found that the overall risk of EAC was higher for patients treated with fundoplication than for those treated with medication (adjusted HR 1.9, 95%CI 1.1-3.5). Furthermore, the EAC risk increased over time in the surgical patients. Well done as this study was, it has important limitations. The overall BE population was large (n=33,939), but only 1.6% (542 patients) had antireflux surgery, and only 14 of those developed EAC during follow-up. Those small numbers limit statistical power. Moreover, important residual confounding cannot be excluded. The surgical patients might have had more severe GERD than medical patients, and it is difficult to make a plausible argument for why fundoplication should increase EAC risk. Nevertheless, this study provides a good lesson on why a plausible argument needs supportive evidence before acting on it in clinical practice. While there may be some excellent reasons for recommending antireflux surgery over medication for patients with severe GERD, better esophageal cancer prevention does not appear to be one of them.
Stuart Jon Spechler, MD, is chief of the division of gastroenterology and codirector of the Center for Esophageal Diseases at Baylor University Medical Center, and codirector of the Center for Esophageal Research at Baylor Scott & White Research Institute, Dallas, Texas. Dr. Spechler is a consultant for Phathom Pharmaceuticals and ISOThrive, LLC.
Esophageal adenocarcinoma (EAC) has been increasing in frequency for decades. EAC’s only known precursor is Barrett’s esophagus (BE), a complication of GERD with chronic esophageal inflammation (reflux esophagitis). Chronic inflammation can predispose to cancer and refluxed acid itself can cause potentially carcinogenic double-strand DNA breaks in Barrett’s metaplasia. PPIs, which block secretion of the gastric acid that causes reflux esophagitis and DNA damage, are recommended to BE patients for cancer prevention. Logical as that practice may seem, meta-analyses have reached contradictory conclusions regarding the cancer-preventive benefits of PPIs. PPIs do not stop the reflux of other potential carcinogens such as bile salts, and thus it has been argued that fundoplication, which blocks the reflux of all gastric material, should be superior to PPIs for cancer prevention. Plausible as that argument sounds, meta-analyses of the generally small and heterogeneous studies on this issue have not found consistently that antireflux surgery is superior to medical therapy for cancer prevention in BE.
Now, a large, population-based cohort study by Åkerström et al. of Nordic BE patients followed for up to 32 years has found that the overall risk of EAC was higher for patients treated with fundoplication than for those treated with medication (adjusted HR 1.9, 95%CI 1.1-3.5). Furthermore, the EAC risk increased over time in the surgical patients. Well done as this study was, it has important limitations. The overall BE population was large (n=33,939), but only 1.6% (542 patients) had antireflux surgery, and only 14 of those developed EAC during follow-up. Those small numbers limit statistical power. Moreover, important residual confounding cannot be excluded. The surgical patients might have had more severe GERD than medical patients, and it is difficult to make a plausible argument for why fundoplication should increase EAC risk. Nevertheless, this study provides a good lesson on why a plausible argument needs supportive evidence before acting on it in clinical practice. While there may be some excellent reasons for recommending antireflux surgery over medication for patients with severe GERD, better esophageal cancer prevention does not appear to be one of them.
Stuart Jon Spechler, MD, is chief of the division of gastroenterology and codirector of the Center for Esophageal Diseases at Baylor University Medical Center, and codirector of the Center for Esophageal Research at Baylor Scott & White Research Institute, Dallas, Texas. Dr. Spechler is a consultant for Phathom Pharmaceuticals and ISOThrive, LLC.
, according to a Nordic retrospective study.
Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.
“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”
Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.
“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.
For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.
In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.
After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.
The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).
“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”
Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.
“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.
“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.
The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.
, according to a Nordic retrospective study.
Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.
“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”
Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.
“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.
For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.
In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.
After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.
The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).
“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”
Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.
“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.
“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.
The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY