AIM:To assess risk factors for bleeding after gastric endoscopic submucosal dissection(ESD) and to develop preventive measures.METHODS:This retrospective study was performed in a tertiary referral center.A total of 32...AIM:To assess risk factors for bleeding after gastric endoscopic submucosal dissection(ESD) and to develop preventive measures.METHODS:This retrospective study was performed in a tertiary referral center.A total of 328 patients underwent ESD for 398 gastric neoplasms between July 2007 and June 2009.The main outcome was association between post-ESD bleeding and the following:age;sex;comorbidities;daily use of medicine potentially related to gastric injury/bleeding;location,size,and histological depth of lesions;ulceration;experience of operator coagulating the ulcer floor,and duration of operation.We also determined the relationship between the location of post-ESD bleeding and risk factors for hemorrhage.RESULTS:Univariate analysis revealed significant risk factors:tumor location [odds ratio(OR),2.86;95% CI:1.21-6.79,P=0.024],coagulator experience(OR,4.29;95% CI:1.43-12.86,P=0.009),and medicine potentially related to gastric injury/bleeding(OR,2.80;95% CI:1.14-6.90,P=0.039).Multivariate logistic regression analysis confirmed significant,independent risk factors:tumor in lower third of stomach(OR,2.47;95% CI:1.02-5.96,P=0.044),beginner coagulator(OR,3.93;95% CI:1.29-11.9,P=0.016),and medicine(OR,2.76;95% CI:1.09-6.98,P=0.032).We classif ied cases of post-ESD bleeding into two groups(bleeding at the ulcer margin vs bleeding at the center) and found that bleeding at the margin occurred more frequently with beginner coagulators compared with experts(OR,16.00;95% CI:1.22-210.59,P=0.040).CONCLUSION:Beginner coagulators,tumor in the antrum,and medicines were significant risk factors for post-ESD bleeding.Bleeding at the ulcer margin frequently occurred with beginner operators.展开更多
This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvement...This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAID-enteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e., proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAID-enteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small intestinal damage in animal models offer hope for a solution to this serious adverse effect of one of the most widely used classes of drugs.展开更多
AIM: To investigate the clinical differences between small intestinal injuries in low-dose aspirin (LDA) users and in non-steroidal anti-inflammatory drug (NSAID) users who were examined by capsule endoscopy (CE) for ...AIM: To investigate the clinical differences between small intestinal injuries in low-dose aspirin (LDA) users and in non-steroidal anti-inflammatory drug (NSAID) users who were examined by capsule endoscopy (CE) for obscure gastrointestinal bleeding (OGIB).展开更多
Proton pump inhibitors(PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal antiinfl...Proton pump inhibitors(PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal antiinflammatory drugs(NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding(LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients.展开更多
AIM:To investigate the clinical characteristics and outcomes of idiopathic Helicobacter pylori(H.pylori)-negative and drug-negative]peptic ulcer bleeding(PUB).METHODS:A consecutive series of patients who experienced P...AIM:To investigate the clinical characteristics and outcomes of idiopathic Helicobacter pylori(H.pylori)-negative and drug-negative]peptic ulcer bleeding(PUB).METHODS:A consecutive series of patients who experienced PUB between 2006 and 2012 was retrospectively analyzed.A total of 232 patients were enrolled in this study.The patients were divided into four groups according to the etiologies of PUB:idiopathic,H.pylori-associated,drug-induced and combined(H.pylori-associated and drug-induced)types.We compared the clinical characteristics and outcomes between the groups.When the silver stain or rapid urease tests were H.pylori-negative,we obtained an additional biopsy specimen by endoscopic re-examination and performed an H.pylori antibody test 6-8 wk after the initial endoscopic examination.For a diagnosis of idiopathic PUB,a negative result of an H.pylori antibody test was confirmed.In all cases,re-bleeding was confirmed by endoscopic examination.For the risk assessment,the Blatchford and the Rockall scores were calculated for all patients.RESULTS:For PUB,the frequency of H.pylori infection was 59.5%(138/232),whereas the frequency of idiopathic cases was 8.6%(20/232).When idiopathic PUB was compared to H.pylori-associated PUB,the idiopathic PUB group showed a higher rate of rebleeding after initial hemostasis during the hospital stay(30%vs 7.4%,P = 0.02).When idiopathic PUB was compared to drug-induced PUB,the patients in the idiopathic PUB group showed a higher rate of rebleeding after initial hemostasis upon admission(30%vs 2.7%,P < 0.01).When drug-induced PUB was compared to H.pylori-associated PUB,the patients in the drug-induced PUB were older(68.49 ± 14.76 years vs 47.83 ± 15.15 years,P< 0.01) and showed a higher proportion of gastric ulcer(77%vs 49%,P < 0.01).However,the Blatchford and the Rockall scores were not significantly different between the two groups.Among the patients who experienced drug-induced PUB,no significant differences were found with respect to clinical characteristics,irrespective of H展开更多
AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in children.METHODS: A retrospective, multicenter study was conducted between January 2005 and Januar...AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in children.METHODS: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber(physician or selfmedication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled(median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients(68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients(56.9%)]. Seven patients had positive family history of Helicobacter pylori(H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four(47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom(33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51(62%) patients, duodenal lesions in 17(33%) and esophageal lesions in 8(15%). In 10/51(19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight(94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51(6%) patients, an endoscopic hemostasis was needed.CONCLUSION: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in展开更多
AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indo...AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indomethacin （20 mg/kg）, an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethadn （3 mg/kg）. In cultured human gastric mucous cells, EP4 agonist effect on indomethacin- induced apoptosis was assessed by flow cytometry. RESULTS： The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.CONCLUSION： EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and i ulcers, via promoting mucous epithelial cells. proliferation and survival of mucous epithelial cells.展开更多
Promoting intestinal epithelial regeneration remains a major medical challenge.Female patients taking nonsteroidal anti-inflammatory drugs are less likely to have upper gastrointestinal bleeding and ulcers than males....Promoting intestinal epithelial regeneration remains a major medical challenge.Female patients taking nonsteroidal anti-inflammatory drugs are less likely to have upper gastrointestinal bleeding and ulcers than males.Using a nonsteroidal anti-inflammatory druginduced intestinal damage mouse model,we verified that female mice recover faster than males following acute intestinal insult.Using ex vivo intestinal organoid cultures,we showed that estrogen is necessary and sufficient in enhancing the female organoid formation from breached isolated crypts via the estrogen receptor b receptor.Thus,estrogen promotes female intestinal epithelial organoid regeneration to lower the incidence of intestinal bleeding and ulceration.Animal studies were approved by University of Utah IACUC under protocol number 16-05012 and 18-02010.展开更多
文摘AIM:To assess risk factors for bleeding after gastric endoscopic submucosal dissection(ESD) and to develop preventive measures.METHODS:This retrospective study was performed in a tertiary referral center.A total of 328 patients underwent ESD for 398 gastric neoplasms between July 2007 and June 2009.The main outcome was association between post-ESD bleeding and the following:age;sex;comorbidities;daily use of medicine potentially related to gastric injury/bleeding;location,size,and histological depth of lesions;ulceration;experience of operator coagulating the ulcer floor,and duration of operation.We also determined the relationship between the location of post-ESD bleeding and risk factors for hemorrhage.RESULTS:Univariate analysis revealed significant risk factors:tumor location [odds ratio(OR),2.86;95% CI:1.21-6.79,P=0.024],coagulator experience(OR,4.29;95% CI:1.43-12.86,P=0.009),and medicine potentially related to gastric injury/bleeding(OR,2.80;95% CI:1.14-6.90,P=0.039).Multivariate logistic regression analysis confirmed significant,independent risk factors:tumor in lower third of stomach(OR,2.47;95% CI:1.02-5.96,P=0.044),beginner coagulator(OR,3.93;95% CI:1.29-11.9,P=0.016),and medicine(OR,2.76;95% CI:1.09-6.98,P=0.032).We classif ied cases of post-ESD bleeding into two groups(bleeding at the ulcer margin vs bleeding at the center) and found that bleeding at the margin occurred more frequently with beginner coagulators compared with experts(OR,16.00;95% CI:1.22-210.59,P=0.040).CONCLUSION:Beginner coagulators,tumor in the antrum,and medicines were significant risk factors for post-ESD bleeding.Bleeding at the ulcer margin frequently occurred with beginner operators.
基金Supported by A grant from the Canadian Institutes of Health Research
文摘This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAID-enteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e., proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAID-enteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small intestinal damage in animal models offer hope for a solution to this serious adverse effect of one of the most widely used classes of drugs.
文摘AIM: To investigate the clinical differences between small intestinal injuries in low-dose aspirin (LDA) users and in non-steroidal anti-inflammatory drug (NSAID) users who were examined by capsule endoscopy (CE) for obscure gastrointestinal bleeding (OGIB).
文摘Proton pump inhibitors(PPIs) represent a milestone in the treatment of acid-related diseases, and are the mainstay in preventing upper gastrointestinal bleeding in high-risk patients treated with nonsteroidal antiinflammatory drugs(NSAIDs) or low-dose aspirin. However, this beneficial effect does not extend to the lower gastrointestinal tract. PPIs do not prevent NSAID or aspirin-associated lower gastrointestinal bleeding(LGB). PPIs may increase both small bowel injury related to NSAIDs and low-dose aspirin treatment and the risk of LGB. Recent studies suggested that altering intestinal microbiota by PPIs may be involved in the pathogenesis of NSAID-enteropathy. An increase in LGB hospitalization rates may occur more frequently in older patients with more comorbidities and are associated with high hospital resource utilization, longer hospitalization, and increased mortality. Preventive strategies for NSAID and aspirin-associated gastrointestinal bleeding should be directed toward preventing both upper and lower gastrointestinal damage. Future research should be directed toward identifying patients at low-risk for gastrointestinal events associated with the use of NSAIDs or aspirin to avoid inappropriate PPI prescribing. Alternatively, the efficacy of new pharmacologic strategies should be evaluated in high-risk groups, with the aim of reducing the risk of both upper and lower gastrointestinal bleeding in these patients.
文摘AIM:To investigate the clinical characteristics and outcomes of idiopathic Helicobacter pylori(H.pylori)-negative and drug-negative]peptic ulcer bleeding(PUB).METHODS:A consecutive series of patients who experienced PUB between 2006 and 2012 was retrospectively analyzed.A total of 232 patients were enrolled in this study.The patients were divided into four groups according to the etiologies of PUB:idiopathic,H.pylori-associated,drug-induced and combined(H.pylori-associated and drug-induced)types.We compared the clinical characteristics and outcomes between the groups.When the silver stain or rapid urease tests were H.pylori-negative,we obtained an additional biopsy specimen by endoscopic re-examination and performed an H.pylori antibody test 6-8 wk after the initial endoscopic examination.For a diagnosis of idiopathic PUB,a negative result of an H.pylori antibody test was confirmed.In all cases,re-bleeding was confirmed by endoscopic examination.For the risk assessment,the Blatchford and the Rockall scores were calculated for all patients.RESULTS:For PUB,the frequency of H.pylori infection was 59.5%(138/232),whereas the frequency of idiopathic cases was 8.6%(20/232).When idiopathic PUB was compared to H.pylori-associated PUB,the idiopathic PUB group showed a higher rate of rebleeding after initial hemostasis during the hospital stay(30%vs 7.4%,P = 0.02).When idiopathic PUB was compared to drug-induced PUB,the patients in the idiopathic PUB group showed a higher rate of rebleeding after initial hemostasis upon admission(30%vs 2.7%,P < 0.01).When drug-induced PUB was compared to H.pylori-associated PUB,the patients in the drug-induced PUB were older(68.49 ± 14.76 years vs 47.83 ± 15.15 years,P< 0.01) and showed a higher proportion of gastric ulcer(77%vs 49%,P < 0.01).However,the Blatchford and the Rockall scores were not significantly different between the two groups.Among the patients who experienced drug-induced PUB,no significant differences were found with respect to clinical characteristics,irrespective of H
文摘AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in children.METHODS: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber(physician or selfmedication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled(median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients(68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients(56.9%)]. Seven patients had positive family history of Helicobacter pylori(H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four(47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom(33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51(62%) patients, duodenal lesions in 17(33%) and esophageal lesions in 8(15%). In 10/51(19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight(94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51(6%) patients, an endoscopic hemostasis was needed.CONCLUSION: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in
文摘AIM： To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS： In a mouse model of gastric bleeding with high dose of indomethacin （20 mg/kg）, an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethadn （3 mg/kg）. In cultured human gastric mucous cells, EP4 agonist effect on indomethacin- induced apoptosis was assessed by flow cytometry. RESULTS： The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.CONCLUSION： EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and i ulcers, via promoting mucous epithelial cells. proliferation and survival of mucous epithelial cells.
基金funded by grants to WZ(R01EY025342,and R01HL077671)to SJO(R01AR064788,R01CA202778,and R01HL130541)from NIH.
文摘Promoting intestinal epithelial regeneration remains a major medical challenge.Female patients taking nonsteroidal anti-inflammatory drugs are less likely to have upper gastrointestinal bleeding and ulcers than males.Using a nonsteroidal anti-inflammatory druginduced intestinal damage mouse model,we verified that female mice recover faster than males following acute intestinal insult.Using ex vivo intestinal organoid cultures,we showed that estrogen is necessary and sufficient in enhancing the female organoid formation from breached isolated crypts via the estrogen receptor b receptor.Thus,estrogen promotes female intestinal epithelial organoid regeneration to lower the incidence of intestinal bleeding and ulceration.Animal studies were approved by University of Utah IACUC under protocol number 16-05012 and 18-02010.
