gastric ulceration is a common worldwide problem which can often lead to dyspeptic symptoms , epigastric pain , gastrointestinal bleeding and/or anemia . while helicobacter pylori is commonly implicated in the pathogenesis of benign ulceration 1 , the risk of malignant change in gastric ulcer has long been recognized 2 . in the literature , the rate of malignancy in endoscopically diagnosed gastric ulcers varies considerably , ranging from 2.4    21  % 3 
 4 . subsequently there has been disagreement over the requirements for follow - up in patients with gastric ulcers . a number of studies have reported low rates of additional gastric cancer diagnoses when following up patients with gastric ulcers 3 
 5 . this was especially the case if initial histology showed benign features and if no endoscopic suspicion was raised 5 . the british national institute for health and care excellence ( nice ) recommends a follow - up endoscopy ( fu - ogd ) for every patient with a gastric ulcer 8 weeks after index endoscopy 6 
 7 . in contrast , the american society for gastrointestinal endoscopy recommends follow - up endoscopy only for selected cases of gastric ulcers 8 . neither guideline advises on the need for biopsies of gastric ulcers at index endoscopy or follow - up . the aim of this study was to determine the malignancy yield in gastric ulcers in a british setting , assess the impact of nice guidance , and establish predictive factors potentially allowing a more targeted follow - up program . leeds teaching hospitals nhs trust is the main secondary care provider for a population of 770,000 . the endoscopy department operates 10 endoscopy rooms at 3 sites performing approximately 20,000 procedures per annum . for this study we searched gastroscopy records within the electronic endoscopy reporting system ( adam , fujifilm europe gmbh , 2011 ) and included all patients with a first endoscopic diagnosis of gastric ulcer between january 2012 and september 2013 . patients with known gastric ulcers prior to the study period or those referred for tertiary assessment were excluded . patient demographics , data on endoscopic appearance and histological reports were recorded from adam and the electronic patient record system . endoscopy procedures were performed by a group of certified endoscopists comprising gastroenterologists , surgeons , trainees , and nurse endoscopists . gastric ulcers were defined as a mucosal break of 5  mm or larger in diameter with unequivocal depth , and erosion by mucosal change with white necrotic substance 9 . the primary analysis of the whole study cohort included analysis of endoscopic assessments , compliance with nice guidance , and the overall combined dysplasia and malignancy yield . to assess compliance with required service standards we analyzed the proportion of fu - ogd performed within 8 weeks of index endoscopy ( national standard ) and the number of fu - ogd performed within 2 weeks of index endoscopy if no biopsies were taken ( locally agreed standard ) . for the secondary analysis of predictors of benign and malignant disease , we excluded patients with insufficient follow - up to ensure that no patient with a potential malignant transformation within 1 year was classified as benign disease . insufficient follow - up was therefore defined as the lack of follow - up endoscopy and lack of data within the medical records to ascertain cancer - free survival of at least 360 days . benign disease was defined as patients with complete ulcer healing , those with at least 2 sets of benign biopsies and no endoscopic suspicion of malignant disease , or in cases without fu - ogd , 1 set of negative biopsies and at least 360 days cancer - free survival . patients with insufficient follow - up ( as judged by the above criteria ) were excluded from the secondary analysis . ulcers were classified as superficial , cratered or linear , which are the preset classification criteria on the endoscopy reporting system . the endoscopist s subjective impression was recorded dichotomously ( suspicious appearance / non - suspicious appearance ) by analysing the free text comment on the endoscopy reports ( if suspicious features were not documented the ulcer was classed as showing  non - suspicious appearance  ) . we analyzed the influence of demographic , endoscopic , and histologic factors on the likelihood of benign disease using chi - square test for categorical and t - test for continuous variables . independence of variables was analyzed by entering variables showing statistical significance on univariate analysis into binary logistic regression analysis . the hosmer - lemeshow s test was used to test the null hypothesis that there was a linear relationship between predictor variable and the log odds of the outcome variable . if collinearity was detected we planned to minimize this by inputting the variable separately in the multivariate analysis . all statistical tests were done using pasw version 21 ( ibm corp , ny ) . clinical audits are exempt from the need of ethics committee approval and the need for written informed consent under uk regulations 10 . the primary analysis cohort consisted of 432 patients ( 53  % male ) with a mean age of 65 years ( table  1 ) . the presenting feature leading to endoscopy was a gastrointestinal bleed in 38  % , anaemia in 13  % , dyspepsia in 18  % and other symptoms ( including weight loss or any combination of symptoms ) in 31  % . 73  % gastrointestinal bleed no biopsies were taken in 142 patients at index endoscopy as 73  % of these had presented with a gastrointestinal bleed ( fig .  1 ) and 6  % were fully anticoagulated at the time of endoscopy . in 21  % of these 142 , 67  % ( 96 patients ) received a fu - ogd for biopsies after a median of 7 days ( range 1    363 days , interquartile range 3    38 days ) . two hundred and ninety patients had an average of 4.8 biopsies taken on index endoscopy . of these , 194 underwent fu - ogd after a median of 70 days ( range 3    639 days , interquartile range 52 only 33  % underwent fu - ogd within the recommended time frame of 8 weeks . reasons for not undergoing fu - ogd included failure to request the procedure by the medical team in 10  % . a repeat procedure was deemed medically inappropriate ( comorbidities , life expectancy , etc ) by the clinical team in a further 19  % . other reasons for a lack of fu - ogd included patient non - attendance ( 24  % ) and malignant disease on first biopsy ( 9  % ) . gastric neoplasia was found in 27 patients ( 19 adenocarcinomas , 2 cases of low - grade dysplasia 11 , 5 lymphomas , 1 melanoma ) leading to a diagnosis of malignancy in 6  % of patients with gastric ulcers ( fig .  1 ) . three hundred and fifty - eight patients were at least biopsied once during the study . after excluding patients with dysplasia or malignancy on first biopsy ( n  =  25 ) , without biopsies on repeat endoscopy ( n  =  28 ) , and those without sufficient follow - up and/or no further endoscopy after index biopsy ( n  =  80 ) , the cancer yield of fu - ogd after initially benign biopsy was 2 of 225 patients ( 0.9  % ) . no cases of gastric cancer were detected in the group of patients without fu - ogd . after excluding those patients with insufficient follow - up ( as outlined in the methods section ) the cohort for the secondary analysis consisted of 377 patients . of these , 350 ( 92  % ) had benign disease and 27 had dysplastic or neoplastic disease . patient sex , indication for gastroscopy , and h pylori status did not influence the likelihood of benign disease . benign disease was significantly associated (  table 2 ) with ulcer location in the antrum ( p  =  0.001 ) , endoscopic benign appearance as judged by the endoscopist at the time of procedure ( fig .  2 , p  <  0.001 ) , non - cratered ulcer morphology (  fig . 3 , p  <  0.001 ) , benign histology on first biopsy ( p  <  0.001 ) , younger age ( mean 64 vs 73 years , p  =  0.02 ) , lower number of ulcers ( mean 1.4 vs 2 , p  <  0.001 ) , and smaller ulcer size ( mean 10 vs 28  mm , p  <  0.001 ) . the number of biopsies taken was not associated with the likelihood of benign or malignant disease . after binary logistic regression analysis , endoscopic benign appearance ( odds ratio 0.004 95  % ci 0    0.576 ; p  =  0.029 ) , benign histology on first biopsy ( odds ratio 0 95  % ci 0    0.39 ; p  =  0.011 ) , and lower number of ulcers ( odds ratio 0.22 ( 95  % ci 0.05    0.99 ) ; p  =  0.049 ) were independent predictors of benign disease ( table  2 ) . to rule out selection bias by including patients without fu - ogd , those without fu - ogd had significantly fewer biopsies ( mean 4.59 vs 5.14 ; p  =  0.023 ) and were more likely to have presented with other symptoms  rather than a gastrointestinal bleed ( p  =  0.001 ) . no differences in age , number of ulcers , ulcer size , location , or macroscopic or histologic appearance were found . no significant collinearity was detected on correlation matrices and the hosmer - lemeshows test was not significant , suggesting that the data fit the model well . all dysplastic and neoplastic cases would have been correctly identified if a combination of at least 1 set of biopsies for all ulcers and repeat endoscopy with further biopsies for patients with ulcers displaying suspicious features on index endoscopy had been applied . medical opinion and international guidelines on the appropriate follow - up for patients with gastric ulcers remain divided . while british guidelines mandate fu - ogd for all patients 6 
 7 , the american position of the asge advises that it is only required in selected cases 8 . in this large cohort of patients , it was demonstrated that gastric ulcers are associated with a significant risk of dysplasia or malignancy of 6  % . the major strength of this study is the non - selected secondary care cohort of patients thus reducing selection bias , which may explain the wide variation of malignancy rates reported in previously published case series . the large size of the cohort also allows for accurate determination of factors predicting benign or malignant disease . furthermore , the endoscopies were performed by a diverse group of endoscopists rather than purely tertiary referral expert endoscopists . the need for biopsies of all gastric ulcers has so far not been recognized by international guidelines . in this study 90 % of cases of dysplasia or neoplasia were diagnosed with first biopsy , highlighting the need for all gastric ulcers to be biopsied . this is especially important as a number of ulcers with neoplasia on histology did not show endoscopically suspicious features . it follows that all gastric ulcers should be biopsied with an appropriate number of samples ( at least 4 ) reflecting the ulcer size . the number of biopsies taken was not associated with the likelihood of malignant disease in this study , but a number of studies have suggested that 3 to 4 biopsy samples are usually sufficient to diagnose cancer in gastric ulcers with 95  % sensitivity 12 
 13 . if biopsies can not be performed on index endoscopy ( because of anticoagulation , gastrointestinal bleeding , etc ) , a repeat procedure for biopsies should be scheduled at the earliest opportunity to avoid delays in a potential diagnosis of neoplasia . this study also highlighted that for many patients , fu - ogd was deemed inappropriate due to comorbidities and patient frailty . this is also reflected in the number of patients who died before a follow - up procedure was due . gastric ulcers are often found in patients who have acute severe illnesses or are elderly with multiple medical issues . in such circumstances the need for fu - ogd needs to be balanced against overall life expectancy and the potential suitability for definitive treatment if a gastric malignancy were found . the high non - attendance rate noted in this study may relate to the uncomfortable and invasive nature of endoscopy . furthermore patients may have not have been made aware of the reasons for fu - ogd and the implications of non - attendance . we have demonstrated in this study that early fu - ogd for biopsies in those with no initial biopsies can be achieved in a very busy endoscopy department . unfortunately many patients waited longer than the recommended 8 weeks after initial benign biopsies for a fu - ogd . strategies to reduce the burden of fu - ogd for both patients and the health service would therefore be highly desirable . we have demonstrated that several simple factors collected during index endoscopy and ulcer biopsy can predict benign disease . risk stratification using the endoscopist s impression of the gastric ulcer and initial biopsy identified all cases of neoplasia in this study . it therefore may be that the need for fu - ogd in all patients with benign endoscopy and histology should be reconsidered . these data are supported by experience from another center 5 and suggest that the need for fu - ogd may not need to be a blanket approach for all gastric ulcers but would benefit from evaluation of individual patient risk factors . there are a number of limitations to our study . while this is a large study , all of the patients came from 1 geographical area in northern england . case identification via the endoscopy reporting system allowed capture of all cases of gastric ulcers as these were entered prospectively on the reporting system . data collection , however , used retrospective methodology by examining endoscopy reports and medical and histology records . consequently we were unable to examine the influence of other presenting features , particularly weight loss . furthermore the endoscopist s overall impression of a gastric ulcer was taken from endoscopists comments in the report s free comment boxes . this method introduces a large degree of subjectivity , but the use of free text is a matter of routine in endoscopy reporting practice . lesion identification and characterization is a key part of endoscopy training , yet such training often varies in different institutions . it is therefore possible that the practice of endoscopists may vary between different locations . importantly and in contrast to other studies this highlights that endoscopic interpretation by any jag - certified endoscopist was sufficiently accurate for differentiation between suspicious and non - suspicious appearance . this study is also limited in that a number of risk factors for gastric cancer could not be addressed . ethnicity can influence the risk of gastric cancer and japanese race is associated with an increased risk 14 
 15 . however , fewer than 37,000 people of japanese origin reside in the uk ( 0.06  % of the general population ) 16 and it is unlikely that japanese ethnicity would have influenced our results . unfortunately , h pylori status was not documented for some patients and our results should be interpreted with caution with regard to that status . other risk factors such as atrophic gastritis were not included in our analysis as no biopsies were obtained from non - ulcerated areas of the stomach in accordance with local histopathology guidelines . furthermore no data on medication usage especially on aspirin or nonsteroidal anti - inflammatory drugs were available . for this study the authors chose to report a combined outcome of dysplasia and malignancy . in clinical practice it is of utmost importance for the endoscopist to differentiate benign from potentially malignant ( ie dysplastic ) and malignant disease . hence differentiation between clearly benign and the combined outcome of dysplastic / neoplastic disease was considered clinically more relevant . the study identified predictors of benign versus malignant disease ( rather than malignant versus benign ) and therefore promotes the identification of benign disease which may not require close follow - up . ideally all of our patients should have undergone fu - ogd but it was important to report on the full cohort rather than just selecting those with fu - ogd . the authors included patients without fu - ogd who survived more than 360 days without a cancer diagnosis in the group of patients with benign disease . given the fast - growing nature of upper gastrointestinal malignancies , the authors opine that this is a clinically justified characterization . because this group of patients differed from those with fu - ogd only marginally ( the numeric differences in number of biopsies obtained are of doubtful clinical importance ) , that is unlikely to influence the outcome of our analysis . in japanese cohorts very early - stage cancers and dysplasia may be slowly progressive and it would be possible , but unlikely , to have missed such cases through the 360-day follow - up period 19 . however , all our patients presented with symptoms in the first instance , whereas in japanese patients , detection was usually through screening and they would have been asymptomatic . because median survival from gastric cancer is unfortunately only 35 weeks in the united kingdom 20 , the choice of 360-day follow - up is very unlikely to influence the outcomes or our conclusions . this study has demonstrated a 6  % combined dysplasia and malignancy risk in gastric ulcers . biopsies of all gastric ulcers should be performed as a matter of routine and , if not possible , at time of first endoscopy , should be scheduled as soon as possible afterwards . however , routine fu - ogd may not be required for all patients with gastric ulcers , as a combination of benign endoscopy appearance and benign histology accurately predicted benign disease in this study .
background and study aim : malignant change can occur in gastric ulcer but guideline recommendations for follow - endoscopy ( fu - ogd ) are conflicting . 
 this study aims to determine rate of malignancy and need for follow - up for gastric ulcers . 
 patients and methods : patients with a first diagnosis of gastric ulcer between january 2012 and september 2013 were studied by analyzing endoscopic assessments , dysplasia , and malignancy yield and the influence of risk factors on the likelihood of benign disease . 
 results : in a cohort of 432 patients with gastric ulcer ( 53  % male , mean age 65 years ) dysplasia or neoplasia were found in 27 ( 19 adenocarcinomas , 2 cases of dysplasia , 5 lymphomas , 1 melanoma ; malignancy yield 6  % ) . 
 twenty - five ( 93  % ) cases were diagnosed on first biopsy . the cancer yield of fu - ogd after initially benign biopsy was 0.9  % . 
 binary logistic regression analysis revealed that endoscopically benign appearance ( odds ratio 0.004 95  % ci 0    0.576 ; p 
 =  0.029 ) , benign histology on first biopsy ( odds ratio 0 95  % ci 0    0.39 ; p  =  0.011 ) and lower number of ulcers ( odds ratio 0.22 ( 95  % ci 0.05    0.99 ) ; p  =  0.049 ) were independent predictors of benign disease . 
 all dysplastic and neoplastic cases would have been identified by a combination of initial biopsies plus repeat endoscopy with further biopsies for endoscopically suspicious appearances . 
 conclusions : in this large cohort 6  % of gastric ulcers were found to be malignant , highlighting the need for all gastric ulcers to be biopsied . 
 the cancer yield of fu - ogd after benign biopsies was low . 
 we have demonstrated that the combination of benign index histology and no endoscopic suspicion of malignancy can predict benign disease . 
 we recommend that all gastric ulcers to be biopsied . 
 risk stratification could potentially reduce need for fu - ogd .