Prompt Upper Endoscopy Is an Appropriate Initial Management in Uninvestigated Chinese Patients With Typical Reflux Symptoms

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1 nature publishing group ORIGINAL CONTRIBUTIONS 1947 Prompt Upper Endoscopy Is an Appropriate Initial Management in Uninvestigated Chinese Patients With Typical Reflux Symptoms Sui Peng, MD 1, Li-Shou Xiong, MD 1, Ying-Lian Xiao, MD 1, Jin-Kun Lin, MM 1, An-Jiang Wang, MD 1, Ning Zhang, MD 1, Pin-Jin Hu, MM 1 and Min-Hu Chen, MD, PhD 1 OBJECTIVES: METHODS: RESULTS: We sought to investigate the prevalence of clinically significant endoscopic findings (CSEFs) in Chinese patients presenting with uninvestigated typical reflux symptoms in the absence of alarm symptoms, and to evaluate whether prompt endoscopy is an appropriate initial management in these patients. Consecutive patients presenting with uninvestigated typical reflux symptoms (i.e., heartburn or acid regurgitation) as chief complaints were recruited for symptom evaluation and upper endoscopy, followed by a 2-week proton pump inhibitor (PPI) therapy. Of 469 patients recruited, CSEFs were observed in 180 (38.4 % ): 154 (32.8 % ) with erosive esophagitis (EE), 18 (3.8 % ) with Barrett s esophagus (BE), 24 (5.1 % ) with peptic ulcer disease (PUD), and 4 (0.9 % ) with carcinomas (1 esophageal carcinoma and 3 gastric adenocarcinomas). Multivariate analysis identified that an age >50 years (odds ratio (OR) = 1.94, P = 0.008), male gender (OR = 4.11, P < 0.001), being overweight or obese (OR = 2.99, P < 0.001), and alcohol use (OR = 9.96, P < 0.001) were independent risk factors for EE; an age >50 years (OR = 4.61, P = 0.003) and alcohol use (OR = 5.50, P = 0.003) were independent risk factors for BE; and Helicobacter pylori infection (OR = 8.52, P < 0.001) and alcohol use (OR = 4.08, P = 0.004) were independent risk factors for PUD. Symptom evaluation and response to PPI treatment were not correlated with EE, BE, and PUD in these patients. CONCLUSIONS: CSEFs other than gastroesophageal reflux disease are present in a considerable proportion of Chinese patients with uninvestigated typical reflux symptoms but without alarm features. Symptom evaluation is of limited practical value, and thus prompt endoscopy seems to be an appropriate initial management option in these patients. Am J Gastroenterol 2010; 105: ; doi: /ajg ; published online 30 March 2010 INTRODUCTION The initial management strategy for gastroesophageal reflux disease (GERD) is controversial. It is generally agreed that typical reflux symptoms such as heartburn and acid regurgitation are specific to GERD ( 1 ). However, it has been reported that typical reflux symptoms may have causes other than GERD ( 2 ). Particularly in the Chinese, the prevalence of upper gastrointestinal (GI) malignancy and Helicobacter pylori infection-associated gastroduodenal diseases is higher than that in Western populations ( 3 ), and thus, GERD has to be differentiated from these upper GI diseases. Although it is currently recommended that patients with typical reflux symptoms together with alarm symptoms require prompt endoscopy ( 1 ), the role of prompt endoscopy in patients with uninvestigated typical reflux symptoms suggested for GERD in the absence of alarm symptoms has not been well defined, especially in the Chinese. The aim of this study was to investigate the prevalence of clinically significant endoscopic findings (CSEFs) in Chinese patients presenting to gastroenterology clinics with uninvestigated typical reflux symptoms in the absence of alarm symptoms, and to evaluate whether prompt endoscopy is an appropriate initial management in these patients. METHODS Subjects From April 2007 to March 2008, consecutive Chinese patients who visited the Gastroenterology Division of the First Affiliated 1 Division of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. Correspondence: Min-Hu Chen, MD, PhD, Division of Gastroenterology and Hepatology, The First Affi liated Hospital of Sun Yat-Sen University, Guangzhou , China. chenminhu@vip.163.com Received 24 September 2009; accepted 17 February by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY

2 1948 Peng et al. Hospital, Sun Yat-Sen University, due to typical reflux symptoms, but had not been extensively examined for the symptoms, were primarily screened for eligibility for this prospective study. Patients who had experienced heartburn or acid regurgitation as the predominant symptom for at least 6 months were considered as having typical reflux symptoms. The exclusion criteria included a history of GI surgery, major co-existent disease known to aggravate gastroesophageal reflux, pregnancy, or lactation, H. pylori eradication treatment in the previous 6 months, and / or certain alarm features (weight loss, vomiting, odynophagia, dysphagia, bleeding, anemia, family history of gastric and / or esophageal cancer). Patients treated with proton pump inhibitors (PPIs) or H 2 -receptor antagonists 30 days before enrollment were also excluded. This prospective study was approved by the Human Subjects Committee of Sun Yat-Sen University. All patients gave written informed consent. Questionnaire Before endoscopy, clinical information was recorded in a standard structured questionnaire that was based on a previously established version ( 4 ), with some modifications to suit this study. Heartburn was defined as a burning sensation in the retrosternal area (behind the breastbone), and regurgitation as a bitter or sour-tasting fluid coming into the throat or mouth ( 1 ). Severity and frequency of the most bothersome reflux symptoms (either heartburn or acid regurgitation) were assessed with a 4- point Likert scale ( 5 ) and the duration of the reflux symptom (i.e., the time from first onset of the reflux symptom to the visit) were also assessed. The symptom was defined as frequent when the episodes of self-reported heartburn or acid regurgitation occurred at least weekly, and as infrequent when the episodes occurred fewer than weekly. Alcohol use for each patient was defined as consumption of >75 g alcohol per week. A smoker was defined as a current smoker who smoked over two cigarettes per day. Endoscopy and definitions of endoscopic findings Within 7 days of the primary screening, an upper endoscopy was performed for patients who consented to participate. Endoscopically, reflux esophagitis (EE) was defined as visible breaks of the distal esophageal mucosa and evaluated for severity according to the LA classification of EE ( 6 ). When a suspected columnar-lined esophagus was identified based on salmon-pink mucosa in either a circumferential upward shift of the squamocolumnar junction or in adjacent mucosal tongues or islands, biopsies were taken for histological examination (7 ). The diagnosis of Barrett s esophagus (BE) was confirmed by the presence of specialized intestinal metaplasia containing goblet cells. Peptic ulcers were defined as mucosal breaks ( 0.5 cm in diameter) in the stomach and / or duodenum. Mucosal breaks < 0.5 cm in diameter were considered to be gastric or duodenal erosions only. For the purpose of this study, CSEFs were defined as the presence of EE, BE, peptic ulcer disease (PUD), and / or gastroesophageal carcinomas. As hiatus hernia and endoscopic gastroduodenitis have not been proven to cause specific symptoms, these were not regarded as clinically significant for the purposes of this study. In addition, multiple biopsy specimens were taken in any areas where the appearance raised a suspicion of malignancy. H. pylori status was determined by using a 24-h rapid urease test on antral biopsy specimens taken from each patient. This rapid urease test has been validated in the Chinese with a sensitivity and specificity of 99 and 100 %, respectively ( 8 ). Treatment and outcome assessment After endoscopy, patients with serious findings such as carcinomas were refereed to oncologists for appropriate treatment options. All other patients with or without CSEFs started a 2-week treatment with a PPI, esomeprazole (20 mg twice daily). Follow-up symptom assessment was conducted within 1 week after the therapy, when the patient visited the department, or by a nurse who made a telephone interview if the patient could not make the visit. The patients who reported being symptom-free for 1 week before the assessment were considered as achieving symptom elimination ( 9 ). Statistical analysis Univariate analysis was performed using the χ 2 test or Fisher exact test for categorical variables to assess the risk factors associated with different CSEFs. The odds ratio (OR) and 95 % confidence interval (CI) were calculated. Variables with a P value of < 0.20 in the univariate analysis were entered as candidate risk factors in the multivariate forward stepwise logistic regression analysis, in order not to miss any potential risk factors in view of the small sample size. All statistical calculations were performed by the Statistical Package for Social Science (SPSS 13.0, Chicago, IL). A P value of < 0.05 was considered to be statistically significant, and all reported P values were two sided. RESULTS Patients During the period of the study, a total of 515 consecutive patients presenting with uninvestigated typical reflux symptoms as chief complaints were enrolled for further evaluation. Among them, 46 were excluded from the study due to inclusion criteria not fulfilled ( n = 36), unwillingness to consent to endoscopy ( n = 7), and noncompliance with the protocol ( n = 3). Thus, 469 patients (258 males and 211 females, with a mean ( ± s.d.) age of ± years were recruited for symptom evaluation and endoscopy. A total of 141 (30.1 % ) patients were positive for H. pylori infection. Of the patients, 202 (43.0 % ) presented with both heartburn and acid regurgitation, 188 (40.1 % ) with heartburn alone, and 79 (16.8 % ) with acid regurgitation alone. Prevalence of CSEFs Of the 469 patients, one or more CSEFs were observed in 180 (38.4 % ). Specifically, EE, BE, PUD, and carcinomas were presented in 154 (32.8 % ), 18 (3.8 % ), 24 (5.1 % ), and 4 (0.9 % ) patients, respectively. The majority ( n = 141 or 91.6 % ) of EE cases were classified as LA grade A or B. One patient with BE had low-grade The American Journal of GASTROENTEROLOGY VOLUME 105 SEPTEMBER

3 Prompt Upper Endoscopy for Typical Reflux Symptoms in the Chinese 1949 Table 1. Comparison of characteristics of patients with and without clinically significant endoscopic findings (CSEFs) With CSEFs ( n =180) Without CSEFs ( n = 289) Multivariate analysis Odds ratio (95% CI) P value Age >50 years (%) 61 (33.9%) 79 (27.3%)* 2.59 ( ) < Male gender (%) 138 (76.7%) 118 (40.8%)** 4.21 ( ) < H. pylori infection (%) 57 (31.7%) 84 (29.1%) NA Cigarette use (%) 49 (27.2%) 27 (9.3%)** 1.35 ( ) Alcohol use (%) 52 (28.9%) 12 (4.2%)** ( ) < BMI >25 (%) 48 (26.7%) 35 (12.1%)** 2.31 ( ) Symptom-free after PPI therapy (%) a 124 (75.2%) 160 (60.0%)* 1.61 ( ) Duration of reflux symptom >2 years (%) 88 (48.9%) 138 (43.6%) NA Score of symptom frequency >2 66 (36.7%) 87 (30.1%) NA Score of symptom severity >2 49 (27.2%) 68 (23.5%) NA BMI, body mass index (kg / m 2 ); CI, confi dence interval; NA, not applicable (not used in the fi nal models); PPI, proton pump inhibitor. * P < 0.05, ** P < when compared with patients without CSEFs. a Data on PPI therapy were unavailable for 15 patients with CSEFs (including four patients with carcinoma) and 22 patients without CSEFs. dysplasia. Of the PUD patients, 5 had gastric ulcers, 15 had duodenal ulcers, and 4 had both, with the mean size ( ± s.d.) and number ( ± s.d.) of the ulcers being 7.0 ± 2.6 mm and 1.5 ± 0.6, respectively. Of the patients with carcinomas, an esophageal squamous cell carcinoma was observed in the mid-esophagus of one 70-yearold female patient, and gastric adenocarcinomas were observed in three patients (in the cardia of a 65-year-old female patient, in the corpus of a 45-year-old male patient and in the antrum of a 48-year-old male patient). The esophageal squamous cell carcinoma (T1N0M0) and the gastric adenocarcinoma in the gastric cardia (T1N0M0) were in the early stage, whereas adenocarcinomas in the gastric corpus and antrum were both in the advanced stage T2N1M0, with metastatic lymph nodes as revealed in the surgical resection specimens. Concomitant EE was identified in 14 (58.3 % ) of the patients with PUD, in 5 (27.8 % ) of the patients with BE, and in 1 patient with both BE and PUD. Response to PPI therapy A total of 432 patients completed the 2-week esomeprazole therapy. After the therapy, 283 (65.5 % ) patients had the reflux symptoms eliminated. The rates were 74.5 % (108 /145), 66.7 % (12 /18), 77.3 % (17 / 22), and 59.6 % (159 / 267), respectively, for patients with EE, BE, PUD, and those without CSEFs. There was no significant difference in the symptom elimination rate among the patients with different CSEFs. Risk factors associated with different CSEFs Patients with CSEFs were more likely to be older, overweight or obese (defined as a body mass index >25 kg / m 2 ) ( 10 ), male, alcohol users, and smokers, compared with those without CSEFs ( Table 2 ). Multivariate analysis showed that an age older than 50 (OR = 2.59, 95 % CI = , P < 0.001), the male gender (OR = 4.21, 95 % CI = , P < 0.001), being overweight or obese (OR = 2.31, 95 % CI = , P = 0.007), and alcohol use (OR = 10.87, 95 % CI = , P < 0.001) were the independent factors for CSEFs ( Table 1 ). The risk factors for the individual CSEFs are summarized in Table 2. Briefly, an age older than 50, the male gender, being overweight or obese, smoking, and alcohol use were associated with EE in the univariate analysis, and multivariate analysis identified that an age >50 (OR = 1.94, 95 % CI = P = 0.008), the male gender (OR = 4.11, 95 % CI = , P < 0.001), being overweight or obese (OR = 2.99, 95 % CI = , P < 0.001), and alcohol use (OR = 9.96, 95 % CI = , P < 0.001) were independent risk factors for EE ( Table 2 ). On the other hand, alcohol use was associated with BE in the univariate analysis, and multivariate analysis identified that an age >50 (OR = 4.61, 95 % CI = P = 0.003) and alcohol use (OR = 5.50, 95 % CI = , P = 0.003) were independent risk factors (Table 2 ). In addition, the male gender, alcohol use, and H. pylori infection were associated with PUD in the univariate analysis, and multivariate analysis identified that H. pylori infection (OR = 8.52, 95 % CI = , P < 0.001) and alcohol use (OR = 4.08, 95 % CI = , P = 0.004) were the independent risk factors (Table 2 ). DISCUSSION This study showed that CSEFs were present in 38.4 % of Chinese patients presenting to the gastroenterology clinic with uninvestigated typical reflux symptoms. EE was the most common finding (32.8 % ) in this study, whereas PUD and BE were found in 5.1 and 3.8 %, respectively. More importantly, gastroesophageal carcinomas were found in 0.9 % of patients. We believe that these rates are reflective of the clinical practice in China because almost all hospitals in China are open access settings, and provide primary, secondary, and tertiary levels of health care. Currently, the role of prompt endoscopy in the management of GERD is unclear. It has been pointed out that the validity of typical reflux symptoms also depends on the relative prevalence of 2010 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY

4 1950 Peng et al. Table 2. Different potential predictors for clinically significant endoscopic findings (CSEFs) in patients with typical reflux symptoms as determined in univariate and multivariate analyses a Erosive esophagitis (n =154) c Univariate analysis Multivariate analysis b Prevalence ( % ) Odds ratio (95 % CI) P value Odds ratio (95 % CI) P value Age (>50 vs. 50 years old) 57.4 vs ( ) < ( ) Gender (males vs. females) 48.6 vs ( ) < ( ) < H. pylori infection (positive vs. negative) 33.1 vs ( ) NA Smoking (yes vs. no) 60.0 vs ( ) < ( ) Alcohol use (yes vs. no) 73.0 vs ( ) < ( ) < Overweight / obese (BMI >25 vs. BMI 25) 56.1 vs ( ) < ( ) < Symptom-free after PPI therapy (yes vs. no) d 34.4 vs ( ) NA Duration of refl ux symptom >2 years (yes vs. no) 37.8 vs ( ) NA Symptom frequency (frequent vs. infrequent) 32.5 vs ( ) NA Symptom severity (mild moderate vs. severe) 28.1 vs ( ) NA Barrett s esophagus (n =18) c Age (>50 vs. 50 years old) 7.3 vs ( ) ( ) Gender (males vs. females) 3.5 vs ( ) NA H. pylori infection (positive vs. negative) 2.9 vs ( ) NA Overweight / obese (BMI >25 vs. BMI 25) 6.1 vs ( ) NA Symptom-free after PPI therapy (yes vs. no) d 6.1 vs ( ) ( ) Smoking (yes vs. no) 4.0 vs ( ) NA Alcohol use (yes vs. no) 9.5 vs ( ) ( ) Duration of refl ux symptom >2 years (yes vs. no) 4.8 vs ( ) NA Symptom frequency (frequent vs. infrequent) 4.0 vs ( ) NA Symptom severity (mild moderate vs. severe) 5.3 vs ( ) NA Peptic ulcer disease (n = 24) c Age (>50 vs. 50 years old) 5.8 vs ( ) NA Gender (males vs. females) 8.3 vs ( ) < NA H. pylori infection (positive vs. negative) 12.9 vs ( ) < ( ) < Overweight / obese (BMI >25 vs. BMI 25) 6.1 vs ( ) NA Symptom-free after PPI therapy (yes vs. no) d 6.0 vs ( ) NA Smoking (yes vs. no) 8.0 vs ( ) NA Alcohol use (yes vs. no) 12.7 vs ( ) ( ) Duration of refl ux symptom >2 years (yes vs. no) 6,2 vs ( ) NA Symptom frequency (frequent vs. infrequent) 6.0 vs ( ) NA Symptom severity (mild moderate vs. severe) 7.0 vs ( ) NA BMI, body mass index (kg/ m 2 ); CI, confi dence interval; EE, esophagitis; NA, not applicable (not used in the fi nal models); PPI, proton pump inhibitor; PUD, peptic ulcer disease. a Four patients with carcinoma were excluded from the analyses due to the small number of cases. b Variables with a P value of < 0.20 in the univariate analysis were entered as candidate risk factors in the multivariate analysis. c Some cases may have more than one CSEF. d Data on PPI therapy were unavailable for 9 patients with EE, 2 patients with PUD, and 22 patients without CSEFs. The American Journal of GASTROENTEROLOGY VOLUME 105 SEPTEMBER

5 Prompt Upper Endoscopy for Typical Reflux Symptoms in the Chinese 1951 GERD and other upper GI disorders in the study population ( 11 ). As we know, there is a high incidence of gastroesophageal carcinomas and PUD in some Asian populations ( 12 ), especially in the Chinese, and the prevalence of GERD is relatively lower. Therefore, in 2007, the Chinese GERD Consensus Conference had cautiously recommended prompt endoscopy as the initial management in Chinese patients with reflux symptoms, even without sufficient direct evidence of the utility of prompt endoscopy in such a population ( 13 ). According to our data, some of these patients with so-called typical reflux symptoms actually had symptoms caused by other GI diseases. Recent studies have suggested that frequent heartburn was associated with an eightfold increase in the risk of developing esophageal adenocarcinoma ( 14 ). Therefore, GERD symptoms are clinically important and may be a warning for upper GI malignancy. This study showed that in the 469 patients who presented with typical reflux symptoms suggestive of GERD, esophageal carcinoma and gastric carcinoma were identified in one and three cases, respectively, by upper endoscopy. It is clear from other studies that the empirical use of antisecretory drugs, particularly PPIs, before diagnosis can mask carcinoma or delay diagnosis through the modification of symptoms and / or the potential healing of early malignant ulcers ( 15,16 ). Although we did not evaluate the empirical PPI test in patients with gastroesophageal carcinomas in this study, it is conceivable that if upper endoscopy were restricted to patients with persistent symptoms after empirical PPI treatment, the diagnosis of gastroesophageal carcinomas would have been unduly delayed in patients whose symptoms were initially improved with successful empirical treatment or in patients who did not attend the follow-up visits when the empirical treatment was unsuccessful. Considering that delaying the diagnosis of gastroesophageal carcinoma has a major detrimental impact on patient management and so carries a poorer prognosis, routine use of endoscopy for individuals with typical reflux symptoms is conceivably a reasonable choice. It is well known that treatment strategies vary for different patterns of GERD. For example, symptom control is the primary goal of management for patients with bothersome symptoms in the absence of endoscopic findings, whereas patients with endoscopic positive findings such as EE and BE should be treated with more aggressive acid suppression, and patients with BE should also be enrolled into a surveillance program. Some published guidelines ( 1 ) support that patients with GERD symptoms for 5 years but without alarm features should undergo endoscopy to exclude BE. However, among patients with predominant reflux symptoms in our study, neither the frequency and / or severity nor the duration of reflux symptoms predicted the presence of EE and BE. These data send a message to physicians that symptom evaluation is of very limited predictive value for predicting the patterns of GERD. In addition, contrary to our expectation, the response to PPI therapy seems to be poorly predictive of the underlying endoscopic findings, which support the presumption that the PPI test is a less discriminatory tool than predicted in the Chinese population. Therefore, in the absence of alarm features, foregoing prompt endoscopy is likely to reveal more significant underlying pathologies such as carcinomas, BE, and peptic ulcers, particularly in patients who are older than 50 years, overweight or obese, male, and / or alcohol users. Interestingly, peptic ulcers were detected in 24 cases presenting with dominant reflux symptoms. Similar results were obtained in a study of a population in the southern Italy where the relatively high prevalence of H. pylori infection was associated with the coexistence of GERD and PUD ( 17 ). The reason why patients with PUD present with typical reflux symptoms remains unclear, but the observation that EE was present in 58.0 % of patients with PUD suggests that either typical symptoms of PUD were overshadowed by reflux symptoms, or that typical reflux symptoms were actually caused by peptic ulcers per se. It might be argued that the patients with PUD still require acid-suppression therapy. However, without an early endoscopic diagnosis of PUD, these patients would have been treated empirically with acid-suppression therapy without knowing the status of the H. pylori infection and thus without eradication of the infection, which may result in the recurrence of ulcers in a substantial proportion of patients. Many physicians prefer empiric PPI therapy as the initial management for uninvestigated GERD without alarm symptoms, assuming that it can reduce the workload and avoid the cost of endoscopy. However, the incremental cost-effectiveness of management is very sensitive to the cost of endoscopy ( 18 ). In China, upper endoscopy has been generally accepted as a practical approach to diagnosis and provide re-assurance to the patient, and the cost of a diagnostic upper endoscopy is between US $ ( $ 40 in our hospital), which was comparable with the average cost (US $ 52.31) for a 14-day treatment with esomeprazole (20 mg bid). Moreover, although the CSEFs other than GERD were relatively low, gastroesophageal carcinomas were detected in 0.9 % of our patients. This rate is much higher than that in the general population of South China (i.e., annual incidence of 51 per 100,000) ( 19 ). As we known, the morbidity and mortality associated with gastroesophageal carcinomas are much greater than those associated with GERD ( 3 ), which further emphasizes the importance of prompt upper endoscopy. The main concern of our study would be that the 2-week PPI treatment might have a low specificity for the diagnosis of refluxrelated symptoms, and the response rate would have been higher if we used the PPI for 4 weeks. However, the optimal period of the short-term PPI trial (1 12 weeks) is controversial ( 20 ). It has been shown that a 2-week treatment duration is reasonable for PPI because of low placebo response rates and high compliance of patients for this duration ( 21,22 ). In addition, an absence of reflux symptoms after 1 week of PPI therapy predicts sustained symptom reduction after 4 weeks of therapy ( 23 ). Also, due to the high cost of PPIs, the Chinese GERD Consensus Conference recommended the 2-week PPI treatment as empirical PPI therapy trial in 2007 (13 ). Therefore, we think that the 2-week treatment in this study was justifiable. In conclusion, CSEFs other than GERD, such as gastroesophageal carcinoma and PUD are present in a considerable proportion of Chinese patients with uninvestigated typical reflux symptoms but without alarm features. Symptom evaluation is of very limited practical value for the diagnosis of different CSEFs. Thus, as a prac by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY

6 1952 Peng et al. tical and inexpensive approach to the diagnosis and management of upper GI diseases, prompt endoscopy seems to be an appropriate initial management option in those Chinese patients with typical reflux symptoms but without alarm features, particularly in patients who are older than 50 years, overweight or obese, male, and /or alcohol users. ACKNOWLEDGMENTS We thank Medjaden Bioscience Limited for assisting in the preparation of the manuscript. CONFLICT OF INTEREST Guarantor of the article: Min-Hu Chen, MD, PhD. Specific author contributions: Designing and conducting the study and drafting and revising the manuscript: Sui Peng; designing and conducting the study and critically reviewing the manuscript: Min-Hu Chen; conducting the study: Li-Shou Xiong; conducting the study: Ying-Lian Xiao; conducting the study: Jin-Kun Lin; conducting the study: An-Jiang Wang; conducting the study: Ning Zhang; designing the study: Pin-Jin Hu. Financial support: This work was supported by the Natural Science Foundation of Guangdong Province of China (no ). Potential competing interests: None. Study Highlights WHAT IS CURRENT KNOWLEDGE 3 Typical reflux symptoms may have causes other than gastroesophageal reflux disease (GERD). The prevalence of upper gastrointestinal malignancy and Helicobacter pylori infection-associated gastroduodenal diseases is higher and the prevalence of GERD is relatively lower in the Asian population, particularly in the Chinese, than in Western populations. 3 Although many physicians support empiric proton pump inhibitor therapy as the initial management for GERD because it offers a low-cost, noninvasive, curative alternative to endoscopy, the role of prompt endoscopy in the initial management strategy of GERD is controversial. WHAT IS NEW HERE 3 This study showed that in 469 Chinese patients presenting to a gastroenterology center with uninvestigated typical reflux symptoms but without alarm features, esophageal erosion (EE), Barrett s esophagus (BE), and peptic ulcer disease (PUD) were found in 32.8 %, 3.8 %, and 5.1 %, respectively. More importantly, gastroesophageal carcinomas were found in 0.9 % of patients. 3 Symptom evaluation and response to proton pump inhibitor treatment did not correlate with EE, BE, and PUD in Chinese patients with uninvestigated typical reflux symptoms, and thus prompt endoscopy seems to be an appropriate initial management option in these patients. REFERENCES 1. Va k i l N, v an Z anten S V, Ka h r i l as P, et al., Glob a l C ons ensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006 ;101 : Vaezi MF. Refractory GERD acid, nonacid or not GERD? 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Aliment Pharmacol Ther 2006 ;24 : The American Journal of GASTROENTEROLOGY VOLUME 105 SEPTEMBER