Proton pump inhibitors(PPIs) are one of the most frequently used medications for upper gastrointestinal diseases. However, a number of physicians have raised concern about the serious side effects of long-term use of ...Proton pump inhibitors(PPIs) are one of the most frequently used medications for upper gastrointestinal diseases. However, a number of physicians have raised concern about the serious side effects of long-term use of PPIs, including the development of gastric cancer. Recent epidemiological studies have reported a significant association between long-term PPI intake and the risk of gastric cancer, even after successful Helicobacter pylori eradication. However, the effects of PPIs on the development of pre-malignant conditions such as atrophic gastritis or intestinal metaplasia are not fully known, suggesting the need for comprehensive and confirmative studies are needed in the future. Meanwhile,several experimental studies have demonstrated the effects of PPIs in reducing chemoresistance in gastric cancer cells by modulating the acidic microenvironment, cancer stemness and signal transducer and activator of transcription 3(STAT3) signaling pathway. The inhibitory effects of PPIs on STAT3 activity may overcome drug resistance and enhance the efficacy of conventional or targeted chemotherapeutic agents. Taken together, PPIs may"play dual role" in gastric carcinogenesis and treatment of gastric cancer.展开更多
Over the past two decades,proton pump inhibitors (PPIs)have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders.Unfortunately,this desirable pharmacologi...Over the past two decades,proton pump inhibitors (PPIs)have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders.Unfortunately,this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings.While generally well-tolerated,research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired(CAP)and hospital-acquired pneumonias(HAP).The mechanism behind PPI-associated pneumonia may be multifactorial,but is thought to stem from compromising the stomach's"acid mantle"against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated.A secondary postulate is that PPIs,through their inhibition of extra-gastric H+/K+ATPase enzymes,may reduce the acidity of the upper aerodigestive tract,thus resulting in increased bacterial colonization of the larynx,esophagus and lungs.To date,several retrospective case control studies have been published looking at the association between PPI use and CAP.Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia,but only two could define a dose-response re-lationship.Furthermore,other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP,we reviewed two retrospective cohort studies and one prospective study.One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy,while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H2RAs.The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H2RAs.In conclusion,the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H2RAs,but the findings are not consistent across all studies.Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP.Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations.In the interim,it appears prudent to limit the use of PPIs to situations where they are clinically indicated and,in such cases,use them at the lowest effective dose.In the case of prescribing for stress ulcer prophylaxis in ICU patients,perhaps H2RAs should be used as the preferred agents over PPIs.展开更多
AIM To determine the prognostic factors associated with mortality in patients with gastric fundal variceal (GFV) bleeding.METHODS In total, 42 patients were endoscopically diagnosed with GFV bleeding from January 2000...AIM To determine the prognostic factors associated with mortality in patients with gastric fundal variceal (GFV) bleeding.METHODS In total, 42 patients were endoscopically diagnosed with GFV bleeding from January 2000 to March 2014. We retrospectively reviewed the patients' medical records and assessed their history, etiology of liver cirrhosis, disease conditions, treatment options for GFV bleeding, medications administered before and after onset of GFV bleeding, blood test results(hemoglobin, albumin, and bilirubin concentrations), and imaging results(including computed tomography and abdominal ultrasonography). We also assessed the prognostic factors associated with short-term mortality(up to 90 d) and long-term mortality in all patients.RESULTS Multivariate analysis showed that prophylactic administration of antibiotics was an independent prognostic factor associated with decreases in short-term mortality (OR = 0.08, 95%CI: 0.01-0.52) and longterm mortality (OR = 0.27, 95%CI: 0.08-0.91) in patients with GFV bleeding. In contrast, concurrent hepatocellular carcinoma (HCC) and regular use of proton pump inhibitors (PPI) were independent prognostic factors associated with increases in shortterm mortality(HCC: OR = 15.4, 95%CI: 2.08-114.75; PPI: OR = 12.76, 95%CI: 2.13-76.52) and long-term mortality (HCC: OR = 7.89, 95%CI: 1.98-31.58; PPI: OR = 10.91, 95%CI: 2.86-41.65) in patients with GFV bleeding. The long-term overall survival rate was significantly lower in patients who regularly used PPI than in those who did not use PPI(P = 0.0074).CONCLUSION Administration of antibiotics is associated with decreased short- and long-term mortality, while concurrent HCC and regular PPI administration are associated with increased short- and long-term mortality.展开更多
AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the ...AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H 2 RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS: Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I2 = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H 2 RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I2 = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I2 = 0.0%, P = 0.377). CONCLUSION: Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.展开更多
AIM:To compare the effects of rabeprazole and lafutidine on post-endoscopic submucosal dissection(ESD) gastric ulcers.METHODS:Patients with gastric tumors indicated for ESD were prospectively studied.After ESD,all pat...AIM:To compare the effects of rabeprazole and lafutidine on post-endoscopic submucosal dissection(ESD) gastric ulcers.METHODS:Patients with gastric tumors indicated for ESD were prospectively studied.After ESD,all patients were treated with intravenous omeprazole for the first 3 d.Patients were then randomly assigned to oral lafutidine or rabeprazole.Ulcer size,ulcer size reduction rate,and ulcer stage were evaluated 4 wk later.Occurrence of complication was monitored throughout the 4-wk period.RESULTS:Sixty five patients were enrolled in the study,and 60 patients were subjected to the final analysis.In the lafutidine group(30 lesions in 29 patients),initial and 4-wk post-ESD ulcer sizes were 33.3 ± 9.2 and 10.5 ± 4.8 mm,respectively.In the rabeprazole group(34 lesions in 31 patients),the values were 34.7 ± 11.3 and 11.8 ± 6.7 mm,respectively.Ulcer size reduction rates in lafutidine and rabeprazole groups were 32.3% and 33.5%,respectively(P=0.974).Ulcer stage 4 wk post-ESD did not differ significantly between the two groups(P=0.868).Two cases in the rabeprazole group and no cases in the lafutidine group developed ulcer bleeding during the oral dose period,although the difference of bleeding rate between the two groups was not statistically significant(P=0.157).CONCLUSION:Lafutidine and rabeprazole have equivalent therapeutic effects on post-ESD gastric ulcers.展开更多
As patients with carcinoma of the esophagus live longer, complications associated with the use of a gastric conduit are increasing. Ulcers form in the gastric conduit in 6.6% to 19.4% of patients. There are a few repo...As patients with carcinoma of the esophagus live longer, complications associated with the use of a gastric conduit are increasing. Ulcers form in the gastric conduit in 6.6% to 19.4% of patients. There are a few reports of perforation of a gastric conduit in the English literature. Almost all of these were associated with serious complications. We report a patient who developed a tension pneumothorax consequent to spontaneous perforation of an ulcer in the gastric conduit 7 years after the index surgery in a patient with carcinoma of the gastroesophageal junction. He responded well to conservative management. Complications related to a gastric conduit can be because of multiple factors. Periodic endoscopic surveillance of gastric conduits should be considered as these are at a higher risk of ulcer formation than a normal stomach. Long term treatment with proton pump inhibitors may decrease complications. There are no guidelines for the treatment of a perforated gastric conduit ulcer and the management should be individualized.展开更多
基金Supported by Basic Science Research Program through the National Research Foundation of Korea,No.NRF-2016R1D1A1A02936964
文摘Proton pump inhibitors(PPIs) are one of the most frequently used medications for upper gastrointestinal diseases. However, a number of physicians have raised concern about the serious side effects of long-term use of PPIs, including the development of gastric cancer. Recent epidemiological studies have reported a significant association between long-term PPI intake and the risk of gastric cancer, even after successful Helicobacter pylori eradication. However, the effects of PPIs on the development of pre-malignant conditions such as atrophic gastritis or intestinal metaplasia are not fully known, suggesting the need for comprehensive and confirmative studies are needed in the future. Meanwhile,several experimental studies have demonstrated the effects of PPIs in reducing chemoresistance in gastric cancer cells by modulating the acidic microenvironment, cancer stemness and signal transducer and activator of transcription 3(STAT3) signaling pathway. The inhibitory effects of PPIs on STAT3 activity may overcome drug resistance and enhance the efficacy of conventional or targeted chemotherapeutic agents. Taken together, PPIs may"play dual role" in gastric carcinogenesis and treatment of gastric cancer.
文摘Over the past two decades,proton pump inhibitors (PPIs)have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders.Unfortunately,this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings.While generally well-tolerated,research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired(CAP)and hospital-acquired pneumonias(HAP).The mechanism behind PPI-associated pneumonia may be multifactorial,but is thought to stem from compromising the stomach's"acid mantle"against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated.A secondary postulate is that PPIs,through their inhibition of extra-gastric H+/K+ATPase enzymes,may reduce the acidity of the upper aerodigestive tract,thus resulting in increased bacterial colonization of the larynx,esophagus and lungs.To date,several retrospective case control studies have been published looking at the association between PPI use and CAP.Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia,but only two could define a dose-response re-lationship.Furthermore,other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP,we reviewed two retrospective cohort studies and one prospective study.One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy,while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H2RAs.The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H2RAs.In conclusion,the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H2RAs,but the findings are not consistent across all studies.Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP.Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations.In the interim,it appears prudent to limit the use of PPIs to situations where they are clinically indicated and,in such cases,use them at the lowest effective dose.In the case of prescribing for stress ulcer prophylaxis in ICU patients,perhaps H2RAs should be used as the preferred agents over PPIs.
文摘AIM To determine the prognostic factors associated with mortality in patients with gastric fundal variceal (GFV) bleeding.METHODS In total, 42 patients were endoscopically diagnosed with GFV bleeding from January 2000 to March 2014. We retrospectively reviewed the patients' medical records and assessed their history, etiology of liver cirrhosis, disease conditions, treatment options for GFV bleeding, medications administered before and after onset of GFV bleeding, blood test results(hemoglobin, albumin, and bilirubin concentrations), and imaging results(including computed tomography and abdominal ultrasonography). We also assessed the prognostic factors associated with short-term mortality(up to 90 d) and long-term mortality in all patients.RESULTS Multivariate analysis showed that prophylactic administration of antibiotics was an independent prognostic factor associated with decreases in short-term mortality (OR = 0.08, 95%CI: 0.01-0.52) and longterm mortality (OR = 0.27, 95%CI: 0.08-0.91) in patients with GFV bleeding. In contrast, concurrent hepatocellular carcinoma (HCC) and regular use of proton pump inhibitors (PPI) were independent prognostic factors associated with increases in shortterm mortality(HCC: OR = 15.4, 95%CI: 2.08-114.75; PPI: OR = 12.76, 95%CI: 2.13-76.52) and long-term mortality (HCC: OR = 7.89, 95%CI: 1.98-31.58; PPI: OR = 10.91, 95%CI: 2.86-41.65) in patients with GFV bleeding. The long-term overall survival rate was significantly lower in patients who regularly used PPI than in those who did not use PPI(P = 0.0074).CONCLUSION Administration of antibiotics is associated with decreased short- and long-term mortality, while concurrent HCC and regular PPI administration are associated with increased short- and long-term mortality.
基金Supported by A National Research Foundation of Korea Grant funded by the Korean Government, No. 2010-0004429
文摘AIM: To evaluate the association between acid suppressive drug use and the development of gastric cancer. METHODS: A systematic search of relevant studies that were published through June 2012 was conducted using the MEDLINE (PubMed), EMBASE, and Cochrane Library databases. The search included observational studies on the use of histamine 2-receptor antagonists (H 2 RAs) or proton pump inhibitors and the associated risk of gastric cancer, which was measured using the adjusted odds ratio (OR) or the relative risk and 95%CI. An independent extraction was performed by two of the authors, and a consensus was reached. RESULTS: Of 4595 screened articles, 11 observational studies (n = 94558) with 5980 gastric cancer patients were included in the final analyses. When all the studies were pooled, acid suppressive drug use was associated with an increased risk of gastric cancer risk (adjusted OR = 1.42; 95%CI: 1.29-1.56, I2 = 48.9%, P = 0.034). The overall risk of gastric cancer increased among H 2 RA users (adjusted OR = 1.40; 95%CI: 1.24-1.59, I2 = 59.5%, P = 0.008) and PPI users (adjusted OR = 1.39; 95%CI: 1.19-1.64, I2 = 0.0%, P = 0.377). CONCLUSION: Acid suppressive drugs are associated with an increased risk of gastric cancer. Further studies are needed to test the effect of acid suppressive drugs on gastric cancer.
文摘AIM:To compare the effects of rabeprazole and lafutidine on post-endoscopic submucosal dissection(ESD) gastric ulcers.METHODS:Patients with gastric tumors indicated for ESD were prospectively studied.After ESD,all patients were treated with intravenous omeprazole for the first 3 d.Patients were then randomly assigned to oral lafutidine or rabeprazole.Ulcer size,ulcer size reduction rate,and ulcer stage were evaluated 4 wk later.Occurrence of complication was monitored throughout the 4-wk period.RESULTS:Sixty five patients were enrolled in the study,and 60 patients were subjected to the final analysis.In the lafutidine group(30 lesions in 29 patients),initial and 4-wk post-ESD ulcer sizes were 33.3 ± 9.2 and 10.5 ± 4.8 mm,respectively.In the rabeprazole group(34 lesions in 31 patients),the values were 34.7 ± 11.3 and 11.8 ± 6.7 mm,respectively.Ulcer size reduction rates in lafutidine and rabeprazole groups were 32.3% and 33.5%,respectively(P=0.974).Ulcer stage 4 wk post-ESD did not differ significantly between the two groups(P=0.868).Two cases in the rabeprazole group and no cases in the lafutidine group developed ulcer bleeding during the oral dose period,although the difference of bleeding rate between the two groups was not statistically significant(P=0.157).CONCLUSION:Lafutidine and rabeprazole have equivalent therapeutic effects on post-ESD gastric ulcers.
文摘As patients with carcinoma of the esophagus live longer, complications associated with the use of a gastric conduit are increasing. Ulcers form in the gastric conduit in 6.6% to 19.4% of patients. There are a few reports of perforation of a gastric conduit in the English literature. Almost all of these were associated with serious complications. We report a patient who developed a tension pneumothorax consequent to spontaneous perforation of an ulcer in the gastric conduit 7 years after the index surgery in a patient with carcinoma of the gastroesophageal junction. He responded well to conservative management. Complications related to a gastric conduit can be because of multiple factors. Periodic endoscopic surveillance of gastric conduits should be considered as these are at a higher risk of ulcer formation than a normal stomach. Long term treatment with proton pump inhibitors may decrease complications. There are no guidelines for the treatment of a perforated gastric conduit ulcer and the management should be individualized.
