Colorectal cancer(CRC)is the third most commonly diagnosed cancer in the world.The incidence and mortality show wide geographical variations.Screening is recommended to reduce both incidence and mortality.However,ther...Colorectal cancer(CRC)is the third most commonly diagnosed cancer in the world.The incidence and mortality show wide geographical variations.Screening is recommended to reduce both incidence and mortality.However,there are significant differences among studies in implementation strategies and detection.This review aimed to present the results and strategies of different screening programs worldwide.We reviewed the literature on national and international screening programs published in Pub Med,on web pages,and in clinical guidelines.CRC Screening programs are currently underway in most European countries,Canada,specific regions in North and South America,Asia,and Oceania.The most extensive screening strategies were based on fecal occult blood testing,and more recently,the fecal immunochemical test(FIT).Participation in screening has varied greatly among different programs.The Netherlands showed the highest participation rate(68.2%)and some areas of Canada showed the lowest(16%).Participation rates were highest among women and in programs that used the FIT test.Men exhibited the greatest number of positive results.The FIT test has been the most widely used screening program worldwide.The advent of this test has increased participation rates and the detection of positive results.展开更多
Gastrin is the main hormone responsible for the stimulation of gastric acid secretion;in addition,gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types.Gastrin synthesis and s...Gastrin is the main hormone responsible for the stimulation of gastric acid secretion;in addition,gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types.Gastrin synthesis and secretion are increased in certain situations,for example,when proton pump inhibitors are used.The impact of sustained hypergastrinemia is currently being investigated.In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates;although,this relationship is less clear in human beings.Higher gastrin levels have been shown to cause hyperplasia of several cell types;yet,the risk for developing cancer seems to be the same in normo-and hypergastrinemic patients.Some tumors also produce their own gastrin,which can act in an autocrine manner promoting tumor growth.Certain cancers are extremely dependent on gastrin to proliferate.Initial research focused only on the effects of amidated gastrins,but there has been an interest in intermediates of gastrin in the last few decades.These intermediates aren't biologically inactive;in fact,they may exert greater effects on proliferation and apoptosis than the completely processed forms.In certain gastrin overproduction states,they are the most abundant gastrin peptides secreted.The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production,levels,and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett's and colorectal carcinogenesis.展开更多
Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the devel...Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.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 evaluate an evidence-based educational program for improving strategies for prevention of non-steroidal anti-inflammatory drug(NSAID)-associated gastrointestinal(GI)complications. METHODS:Four hundred and fifty...AIM:To evaluate an evidence-based educational program for improving strategies for prevention of non-steroidal anti-inflammatory drug(NSAID)-associated gastrointestinal(GI)complications. METHODS:Four hundred and fifty-six specialists replied to a questionnaire that covered issues related to NSAID-induced adverse effects.They also collected data from their last five consecutive patients before and after they had attended an evidence-based seminar on GI prevention strategies. RESULTS:Four hundred and forty-one of 456 specialists(96.7%)participated in the survey,and 382(83.7%)in the education-based study that recorded data from 3728 patients.The specialists overestimated the risk of GI complications with NSAIDs,underestimated the GI safety profile of coxibs,but were aware of the risk factors and of the current prevention strategies.Proton pump inhibitors were co-prescribed with NSAIDs in>80% of patients with and without risk factors.The educational program had little impact on prescribing habits.CONCLUSION:Specialists are informed of advances in NSAID-associated adverse effects and have high rates of GI-prevention therapy.Our educational program did not alter these rates.展开更多
AIM： To test whether antioxidant treatment could prevent the progression of Barrett＇s esophagus to adenocarcinoma. METHODS： In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastr...AIM： To test whether antioxidant treatment could prevent the progression of Barrett＇s esophagus to adenocarcinoma. METHODS： In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric preservation, groups of 6-10 rats were randomized to receive treatment with superoxide dismutase （SOD） or vehicle and followed up for 4 too. Rat＇s esophagus was assessed by histological analysis, superoxide anion and peroxinitrite generation, SOD levels and DNA oxidative damage. RESULTS： All rats undergoing esophagojejunostomy developed extensive esophageal mucosal ulceration and inflammation by mo 4. The process was associated with a progressive presence of intestinal metaplasia beyond the anastomotic area （9% 1st mo and 50% 4th too） （94% at the anastomotic level） and adenocarcinoma （11% 1^ST mo and 60% 4th too）. These changes were associated with superoxide anion and peroxinitrite mucosal generation, an early and significant increase of DNA oxidative damage and a significant decrease in SOD levels （P〈0.05）. Exogenous administration of SOD decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the risk of developing intestinal metaplasia beyond the anastomotic area （odds ratio = 0.326; 95%CI： 0.108-0.981; P = 0.046）, and esophageal adenocarcinoma （odds ratio = 0.243; 95%CI： 0.073-0.804; P = 0.021）. CONCLUSION： Superoxide dismutase prevents the progression of esophagitis to Barrett＇s esophagus and adenocarcinoma in this rat model of gastrointestinal reflux, supporting a role of antioxidants in the chemoprevention of esophageal adenocarcinoma.展开更多
Colorectal cancer(CRC)is the third most common type of cancer worldwide.Screening measures are far from adequate and not widely available in resourcepoor settings.Primary prevention strategies therefore remain necessa...Colorectal cancer(CRC)is the third most common type of cancer worldwide.Screening measures are far from adequate and not widely available in resourcepoor settings.Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC.Increasing evidence from epidemiological studies,randomized clinical trials and basic science supports the effectiveness of aspirin,as well as other non-steroidal anti-inflammatory drugs,for chemoprevention of several types of cancer,including CRC.This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality.The detectable benefit of daily low-dose aspirin(at least 75 mg),as used to prevent cardiovascular disease events,strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy.Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase(COX)-1 in platelets(in pre-systemic circulation)while causing alimited and rapidly reversible inhibitory effect on COX-2and/or COX-1 expressed in nucleated cells.Aspirin has a short half-life in human circulation(about 20 minutes);nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours,while platelets do not.COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.展开更多
AIM： To evaluate the effects of indomethacin [dual cyclooxygenase （COX）-I/COX-2 inhibitor] and 3-（3,4-difluorophenyl）-4-（4-（methylsulfonyl） phenyl）- 2-（5H）-furanone （MF-tricyclic） （COX-2 selective inhibi...AIM： To evaluate the effects of indomethacin [dual cyclooxygenase （COX）-I/COX-2 inhibitor] and 3-（3,4-difluorophenyl）-4-（4-（methylsulfonyl） phenyl）- 2-（5H）-furanone （MF-tricyclic） （COX-2 selective inhibi- tor） in a rat experimental model of Barrett＇s esophagus and esophageal adenocarcinoma.METHODS： A total of 112 surviving post-surgery rats were randomly divided into three groups： the control group （n = 48）, which did not receive any treatment; the indomethacin group （n = 32）, which were given 2 mg/kg per day of the COX-I/COX-2 inhibitor; and the MF-tricyclic group （n = 32）, which received 10 mg/kg per day of the selective COX-2 inhibitor. Randomly se- lected rats were killed either 8 wk or 16 wk after sur- gery. The timing of the deaths was in accordance with a previous study performed in our group. Only rats that were killed at the times designated by the protocol were included in the study. We then assessed the histology and prostaglandin E2 （PGE2） expression levels in the rat esophagi. An additional group of eight animals that did not undergo esophagojejunostomy were included in order to obtain normal esophageal tissue as a control. RESULTS： Compared to a control group with no treat- ment （vehicle-treated rats）, indomethacin treatment was associated with decreases in ulcerated esophageal mucosa （16% vs 35% and 14% vs 17%, 2 mo and 4 mo after surgery, respectively; P = 0.021）, length of intestinal metaplasia in continuity with anastomosis （2 4- 1.17 mm vs 2.29 ＋ 0.75 mm and 1.25 4- 0.42 mm vs 3.5 4- 1.54 mm, 2 mo and 4 mo after surgery, respec- tively; P = 0.007）, presence of intestinal metaplasia beyond anastomosis （20% vs 71.4% and 0% vs 60%, 2 mo and 4 mo after surgery, respectively; P = 0.009）, severity of dysplasia （0% vs 71.4% and 20% vs 85.7% high-grade dysplasia, 2 mo and 4 mo after surgery, re- spectively; P = 0.002）, and adenocarcinoma incidence （0% vs 57.1% and 0% vs 60%, 2 mo and 4 mo after surgery, respectively; P 〈 0.0001）. Treatment with the selective COX-2 inhibitor, MF-tricyclic, did not prevent development of intestinal metaplasia or adenocarci- noma. In parallel, we observed a significant decrease in PGE2 levels in indomethacin-treated rats, but not in those treated with MF-tricyclic, at both 2 mo and 4 mo. Compared to control rats that did not undergo surgery （68 ＋ 8 ng/g, P = 0.0022 Kruskal-Wallis test） there was a significant increase in PGE2 levels in the esophageal tissue of the rats that underwent surgery either 2 mo （1332 ＋ 656 ng/g） or 4 mo （1121 ＋ 1015 ng/g） after esophagojejunostomy. However, no differences were found when esophageal PGE2 levels were compared 2 mo vs 4 mo post-esophagojejunostomy. At both the 2- and 4-mo timepoints, we observed a significant decrease in PGE2 levels in indomethacin-treated rat esophagi compared to those in either the control or MF-tricyclic groups （P = 0.049 and P = 0.017, respec- tively）. No differences in PGE2 levels were found when we compared levels in rats treated with MF-tricyclic to not-treated rats. CONCLUSION： In this rat model of gastrointestinal reflux, indomethacin was associated with a decrease in the severity of esophagitis and reduced development of esophageal intestinal metaplasia and adenocarcinoma.展开更多
Gastric cancer is the most common cancer worldwide and it is often diagnosed in an advanced stage. In countries where screening endoscopy is performed widely, early detection is possible. In fact, early gastric cancer...Gastric cancer is the most common cancer worldwide and it is often diagnosed in an advanced stage. In countries where screening endoscopy is performed widely, early detection is possible. In fact, early gastric cancer incidence is increasing during the last years worldwide and screening could be a major factor in such increase. In the past, the standard treatment of gastric cancer was surgical resection;however, the endoscopic treatment has increased due to advances in the instruments available and clinician experience. In fact, endoscopic resection has become one of the greatest advances in EGC treatment. It is the standard treatment in most of the cases because early gastric cancer is associated with a low rate of lymph node metastasis and a high survival rate. Endoscopic Mucosal Resection and more recently Endoscopic Submucosal Dissection are the two main developed procedures. Endoscopic Submucosal Dissection achieves a higher rate of en-bloc resection, complete resection, curative resection and lower local recurrence compared with Endoscopic Mucosal Resection group. The disadvantages associated with Endoscopic Submucosal Dissection, such as higher perforation rates and longer procedure time, will probably improve as the endoscopists experience increases and new endoscopic tools are developed. The aim of this paper is to review the management of EGC with a special focus on endoscopic detection, staging, therapy, surveillance, and prevention.展开更多
文摘Colorectal cancer(CRC)is the third most commonly diagnosed cancer in the world.The incidence and mortality show wide geographical variations.Screening is recommended to reduce both incidence and mortality.However,there are significant differences among studies in implementation strategies and detection.This review aimed to present the results and strategies of different screening programs worldwide.We reviewed the literature on national and international screening programs published in Pub Med,on web pages,and in clinical guidelines.CRC Screening programs are currently underway in most European countries,Canada,specific regions in North and South America,Asia,and Oceania.The most extensive screening strategies were based on fecal occult blood testing,and more recently,the fecal immunochemical test(FIT).Participation in screening has varied greatly among different programs.The Netherlands showed the highest participation rate(68.2%)and some areas of Canada showed the lowest(16%).Participation rates were highest among women and in programs that used the FIT test.Men exhibited the greatest number of positive results.The FIT test has been the most widely used screening program worldwide.The advent of this test has increased participation rates and the detection of positive results.
基金Supported by Instituto de Salud Carlos Ⅲ with Grants FIS 08/1047 and CIBERehdInstituto de Salud Carlos Ⅲ FI10/00167, to Chueca E
文摘Gastrin is the main hormone responsible for the stimulation of gastric acid secretion;in addition,gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types.Gastrin synthesis and secretion are increased in certain situations,for example,when proton pump inhibitors are used.The impact of sustained hypergastrinemia is currently being investigated.In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates;although,this relationship is less clear in human beings.Higher gastrin levels have been shown to cause hyperplasia of several cell types;yet,the risk for developing cancer seems to be the same in normo-and hypergastrinemic patients.Some tumors also produce their own gastrin,which can act in an autocrine manner promoting tumor growth.Certain cancers are extremely dependent on gastrin to proliferate.Initial research focused only on the effects of amidated gastrins,but there has been an interest in intermediates of gastrin in the last few decades.These intermediates aren't biologically inactive;in fact,they may exert greater effects on proliferation and apoptosis than the completely processed forms.In certain gastrin overproduction states,they are the most abundant gastrin peptides secreted.The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production,levels,and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett's and colorectal carcinogenesis.
文摘Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.
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.
基金Supported by Unrestricted grant from AstraZeneca Spain
文摘AIM:To evaluate an evidence-based educational program for improving strategies for prevention of non-steroidal anti-inflammatory drug(NSAID)-associated gastrointestinal(GI)complications. METHODS:Four hundred and fifty-six specialists replied to a questionnaire that covered issues related to NSAID-induced adverse effects.They also collected data from their last five consecutive patients before and after they had attended an evidence-based seminar on GI prevention strategies. RESULTS:Four hundred and forty-one of 456 specialists(96.7%)participated in the survey,and 382(83.7%)in the education-based study that recorded data from 3728 patients.The specialists overestimated the risk of GI complications with NSAIDs,underestimated the GI safety profile of coxibs,but were aware of the risk factors and of the current prevention strategies.Proton pump inhibitors were co-prescribed with NSAIDs in>80% of patients with and without risk factors.The educational program had little impact on prescribing habits.CONCLUSION:Specialists are informed of advances in NSAID-associated adverse effects and have high rates of GI-prevention therapy.Our educational program did not alter these rates.
基金Supported by grants from CICYT (SAF2000-0123) and Instituto de Salud Carlos Ⅲ (C03/02). Elena Piazuelo is supported by Instituto de Salud Carlos Ⅲ and Instituto Aragones de Ciencias de la Salud
文摘AIM： To test whether antioxidant treatment could prevent the progression of Barrett＇s esophagus to adenocarcinoma. METHODS： In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric preservation, groups of 6-10 rats were randomized to receive treatment with superoxide dismutase （SOD） or vehicle and followed up for 4 too. Rat＇s esophagus was assessed by histological analysis, superoxide anion and peroxinitrite generation, SOD levels and DNA oxidative damage. RESULTS： All rats undergoing esophagojejunostomy developed extensive esophageal mucosal ulceration and inflammation by mo 4. The process was associated with a progressive presence of intestinal metaplasia beyond the anastomotic area （9% 1st mo and 50% 4th too） （94% at the anastomotic level） and adenocarcinoma （11% 1^ST mo and 60% 4th too）. These changes were associated with superoxide anion and peroxinitrite mucosal generation, an early and significant increase of DNA oxidative damage and a significant decrease in SOD levels （P〈0.05）. Exogenous administration of SOD decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the risk of developing intestinal metaplasia beyond the anastomotic area （odds ratio = 0.326; 95%CI： 0.108-0.981; P = 0.046）, and esophageal adenocarcinoma （odds ratio = 0.243; 95%CI： 0.073-0.804; P = 0.021）. CONCLUSION： Superoxide dismutase prevents the progression of esophagitis to Barrett＇s esophagus and adenocarcinoma in this rat model of gastrointestinal reflux, supporting a role of antioxidants in the chemoprevention of esophageal adenocarcinoma.
基金Supported by Funds from FIS(P108/1301)Dr.Lanas A has received speaking and consultancy fees from AstraZeneca,Pfizer and Bayer
文摘Colorectal cancer(CRC)is the third most common type of cancer worldwide.Screening measures are far from adequate and not widely available in resourcepoor settings.Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC.Increasing evidence from epidemiological studies,randomized clinical trials and basic science supports the effectiveness of aspirin,as well as other non-steroidal anti-inflammatory drugs,for chemoprevention of several types of cancer,including CRC.This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality.The detectable benefit of daily low-dose aspirin(at least 75 mg),as used to prevent cardiovascular disease events,strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy.Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase(COX)-1 in platelets(in pre-systemic circulation)while causing alimited and rapidly reversible inhibitory effect on COX-2and/or COX-1 expressed in nucleated cells.Aspirin has a short half-life in human circulation(about 20 minutes);nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours,while platelets do not.COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.
基金Supported by Instituto de Salud Carlos III (CIBERehd)MFtricyclic was supplied free of charge by Merck Frosst Canada Inc
文摘AIM： To evaluate the effects of indomethacin [dual cyclooxygenase （COX）-I/COX-2 inhibitor] and 3-（3,4-difluorophenyl）-4-（4-（methylsulfonyl） phenyl）- 2-（5H）-furanone （MF-tricyclic） （COX-2 selective inhibi- tor） in a rat experimental model of Barrett＇s esophagus and esophageal adenocarcinoma.METHODS： A total of 112 surviving post-surgery rats were randomly divided into three groups： the control group （n = 48）, which did not receive any treatment; the indomethacin group （n = 32）, which were given 2 mg/kg per day of the COX-I/COX-2 inhibitor; and the MF-tricyclic group （n = 32）, which received 10 mg/kg per day of the selective COX-2 inhibitor. Randomly se- lected rats were killed either 8 wk or 16 wk after sur- gery. The timing of the deaths was in accordance with a previous study performed in our group. Only rats that were killed at the times designated by the protocol were included in the study. We then assessed the histology and prostaglandin E2 （PGE2） expression levels in the rat esophagi. An additional group of eight animals that did not undergo esophagojejunostomy were included in order to obtain normal esophageal tissue as a control. RESULTS： Compared to a control group with no treat- ment （vehicle-treated rats）, indomethacin treatment was associated with decreases in ulcerated esophageal mucosa （16% vs 35% and 14% vs 17%, 2 mo and 4 mo after surgery, respectively; P = 0.021）, length of intestinal metaplasia in continuity with anastomosis （2 4- 1.17 mm vs 2.29 ＋ 0.75 mm and 1.25 4- 0.42 mm vs 3.5 4- 1.54 mm, 2 mo and 4 mo after surgery, respec- tively; P = 0.007）, presence of intestinal metaplasia beyond anastomosis （20% vs 71.4% and 0% vs 60%, 2 mo and 4 mo after surgery, respectively; P = 0.009）, severity of dysplasia （0% vs 71.4% and 20% vs 85.7% high-grade dysplasia, 2 mo and 4 mo after surgery, re- spectively; P = 0.002）, and adenocarcinoma incidence （0% vs 57.1% and 0% vs 60%, 2 mo and 4 mo after surgery, respectively; P 〈 0.0001）. Treatment with the selective COX-2 inhibitor, MF-tricyclic, did not prevent development of intestinal metaplasia or adenocarci- noma. In parallel, we observed a significant decrease in PGE2 levels in indomethacin-treated rats, but not in those treated with MF-tricyclic, at both 2 mo and 4 mo. Compared to control rats that did not undergo surgery （68 ＋ 8 ng/g, P = 0.0022 Kruskal-Wallis test） there was a significant increase in PGE2 levels in the esophageal tissue of the rats that underwent surgery either 2 mo （1332 ＋ 656 ng/g） or 4 mo （1121 ＋ 1015 ng/g） after esophagojejunostomy. However, no differences were found when esophageal PGE2 levels were compared 2 mo vs 4 mo post-esophagojejunostomy. At both the 2- and 4-mo timepoints, we observed a significant decrease in PGE2 levels in indomethacin-treated rat esophagi compared to those in either the control or MF-tricyclic groups （P = 0.049 and P = 0.017, respec- tively）. No differences in PGE2 levels were found when we compared levels in rats treated with MF-tricyclic to not-treated rats. CONCLUSION： In this rat model of gastrointestinal reflux, indomethacin was associated with a decrease in the severity of esophagitis and reduced development of esophageal intestinal metaplasia and adenocarcinoma.
文摘Gastric cancer is the most common cancer worldwide and it is often diagnosed in an advanced stage. In countries where screening endoscopy is performed widely, early detection is possible. In fact, early gastric cancer incidence is increasing during the last years worldwide and screening could be a major factor in such increase. In the past, the standard treatment of gastric cancer was surgical resection;however, the endoscopic treatment has increased due to advances in the instruments available and clinician experience. In fact, endoscopic resection has become one of the greatest advances in EGC treatment. It is the standard treatment in most of the cases because early gastric cancer is associated with a low rate of lymph node metastasis and a high survival rate. Endoscopic Mucosal Resection and more recently Endoscopic Submucosal Dissection are the two main developed procedures. Endoscopic Submucosal Dissection achieves a higher rate of en-bloc resection, complete resection, curative resection and lower local recurrence compared with Endoscopic Mucosal Resection group. The disadvantages associated with Endoscopic Submucosal Dissection, such as higher perforation rates and longer procedure time, will probably improve as the endoscopists experience increases and new endoscopic tools are developed. The aim of this paper is to review the management of EGC with a special focus on endoscopic detection, staging, therapy, surveillance, and prevention.
