Changes in Indications for Upper Gastrointestinal Tract Endoscopy and Endoscopic Findings during the Last Fifteen Years in South-Western Greece

Changes in Indications for Upper Gastrointestinal Tract Endoscopy and Endoscopic Findings during the Last Fifteen Years in South-Western Greece STELIOS F. ASSIMAKOPOULOS, MD, PHD; KONSTANTINOS C. THOMOPOULOS, MD, PHD; EMANUEL LOUVROS, MD; GEORGE THEOCHARIS, MD; CHRISTOS GIANNIKOULIS, MD; EVANGELOS KATSAKOULIS, MD; VASSILIKI N. NIKOLOPOULOU, MD, PHD

ABSTRACT: Background: During the past years, major advances in the management of upper gastrointestinal diseases have been achieved. The aim of this study was to determine if changes in indications for upper gastrointestinal endoscopy and endoscopic findings have occurred during the last 15 years in our area. Methods: Indications for upper gastrointestinal tract endoscopy and endoscopy findings of patients who underwent upper endoscopy in years 1990, 1995, 2000, and 2005 in our department were compared. Results: Over the 15year period, the number of diagnostic endoscopies performed in our department in years 1990, 1995, 2000, and 2005 increased (953, 1245, 2350, and 2528, respectively). Acute upper gastrointestinal bleeding had become less frequent (40%, 42.8%, 19.7%, 14.3%, P ⬍ 0.001), but dyspepsia (24.4%, 33.6%, 54.3%, 51.3%, P ⫽ 0.002) and reflux (1.8%, 1.3%, 5.1%, 10.8%, P ⫽ 0.005) more frequent indications for upper endoscopy. The endoscopic findings of duodenal ulcer (39.1%,

22.5%, 20.5%, 9.3%, P ⬍ 0.001), gastric ulcer (15.9%, 8.3%, 5.7%, 4.6%, P ⫽ 0.036) as well as erosive gastroduodenitis (35.6%, 22.2%, 15.3%, 4.7%, P ⬍ 0.001) decreased, whereas that of reflux esophagitis (3.1%, 10.1%, 12%, 16%, P ⫽ 0.034) increased. Moreover, the percentage of patients with negative endoscopy or minimal endoscopic findings (eg, nonerosive gastritis) increased (12.8%, 33.7%, 54.1%, 64.4%, P ⬍ 0.001). Conclusions: In south-western Greece, dyspepsia and reflux as an indication for upper endoscopy have been increasing, whereas acute upper gastrointestinal bleeding has been decreasing. The finding of peptic ulcers at the upper gastrointestinal tract endoscopy has become significantly less frequent, while the percentage of patients with negative results of endoscopy seems to have been increasing rapidly. KEY INDEXING TERMS: Upper gastrointestinal tract endoscopy; Peptic ulcer; Reflux esophagitis; Endoscopic findings; Dyspepsia. [Am J Med Sci 2008;336(1):21–26.]

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ing lesions such as nonerosive gastritis. Although the appropriate time to perform endoscopy in patients with typical or atypical dyspeptic symptoms remains to be established, upper endoscopy is the method of choice to distinguish between organic causes of symptoms and functional dyspepsia.1–3 During the past years, major advances in the management of upper GI tract diseases have been achieved mainly in peptic ulcer disease.4 –9 Eradication of Helicobacter pylori (HP), the offending agent for ulcer formation, has changed the natural history of peptic ulcer disease and has led to a reduction in ulcer recurrences and complications, especially bleeding. On the other hand, the population is aging and due to coexisting illnesses the need for nonsteroidal anti-inflammatory drugs (NSAIDs) consumption in these patients is increasing, with a parallel increase in ulcer prevalence and bleeding complications.10,11

pper gastrointestinal (GI) tract endoscopy is a highly accurate and safe method of evaluating the mucosal surface of the esophagus, stomach, and duodenum, and it is performed for a variety of indications. Endoscopy is the first diagnostic procedure undertaken in the evaluation of patients presenting with chronic upper GI tract symptoms. A significant percentage of patients with dyspeptic symptoms have a normal upper GI tract or minimal nonoffend-

From the Department of Internal Medicine (SFA), School of Medicine, University of Patras, Patras, Greece; and Department of Internal Medicine, Division of Gastroenterology (KCT, EL, GT, CG, EK, VNN), School of Medicine, University of Patras, Patras, Greece. Submitted May 29, 2007; accepted in revised form September 11, 2007. Correspondence: Stelios F. Assimakopoulos, MD, PhD, Department of Internal Medicine, School of Medicine, University of Patras, Vironos 18, 26224 Patras, Greece (E-mail: [email protected]). THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES

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Changes in Indications and Findings at Upper GI Tract Endoscopy

Table 1. Patients Characteristics and Use of Drugs Year Patients Characteristics

1990

1995

2000

2005

Statistics

N Age (mean ⫾ SD) Gender (males %) Use of drugs over past 3 mo (%) Aspirin NSAIDs (nonaspirin) H2-blockers Proton pump inhibitors

953 55.4 ⫾ 17.23 64.5

1245 56.58 ⫾ 17.15 62.8

2350 56.43 ⫾ 17.51 58.45

2528 57.45 ⫾ 18.32 59

NS NS

16.8 4 12 0.5

11.5 9.3 28 3

14 3.7 19 15

17 3.9 6 22

NS NS 0.001 ⬍0.001

Furthermore, there are several other factors that have a significant influence on the epidemiology of GI tract diseases, such as the body mass index, smoking, and alcohol consumption, which have changed over the last decades worldwide. Epidemiological studies regarding the Greek population noticed that the prevalence of overweight and obesity has been dramatically increasing.12,13 Greeks are also suffering from a smoking epidemic, characterized of antitobacco policy failure,14 whereas there is a decreasing trend in alcohol consumption over the last decades.15 The aim of this study was to determine if changes in indications for upper GI tract endoscopy and endoscopic findings have occurred during the last 15 years in our area. Methods Medical records of patients who underwent upper endoscopy in years 1990, 1995, 2000, and 2005 in our department were retrospectively evaluated. Our department is the major endoscopic centre in our area with a population of over 300.000 people. Data for this retrospective study were retrieved from a computerized endoscopy database. All procedures were performed by 3 experienced endoscopists or by a resident in gastroenterology under the supervision of an experienced endoscopist. Indications for upper GI tract endoscopy (dyspepsia, acute upper GI bleeding, anemia, etc) and endoscopic findings of patients who underwent upper GI tract endoscopy were recorded. A substantial number of patients had more than 1 endoscopic finding, eg, erosive gastritis and ulcer. The collection of these data was made in the same way for all periods. All patients older than 18 years were included. Excluded from analysis were those patients who had undergone scheduled therapeutic endoscopy and those with previous endoscopic evaluation for the same reason. ⌻he diagnosis of reflux esophagitis was made when at least 1 erosion more than 5 mm was observed. Erythema edema or mucosal friability was not considered diagnostic of reflux esophagitis. Macroscopic nonerosive gastritis was defined when there were erythema edema and/or mucosal friability without erosions in the stomach. Cancer was defined as a mass, polypoid lesion, or distorted mucosa that was proven by biopsy to be malignant. Acute upper GI bleeding was diagnosed when hematemesis, bloody nasogastric aspiration, or melena as well as other clinical or laboratory evidence of acute blood loss from the upper GI tract were present. Data were analyzed using the SPSS statistical package (SPSS Inc, 2001, Release 11.0.0, USA). Analysis of variance was used to compare the means of patients’ age in each study period. The ␹2 (␹2) test, with Yates’ correction if required, was used to compare

22

the proportional data, (use of drugs, indications for upper endoscopy and endoscopic findings) over the study period. A P value of less than 0.05 was considered as significant.

Results Overall, 7076 patient files were recruited in the study. Their age (mean ⫾ SD) was 56,15 ⫾ 17,33 years. There were no significant differences in age or gender proportion over the study period. The number of diagnostic endoscopies performed in our department was 953 in 1990 1245 in 1995, 2350 in 2000, and 2528 in 2005. Over the 15-year period, the number of diagnostic endoscopies increased. There was no difference regarding the use of aspirin and other NSAIDs, whereas the use of proton pump inhibitors was significantly increased (0.5%, 3%, 15%, 22%, P ⬍ 0.001) and H2blockers were reduced (12%, 28%, 19%, 6%, P ⫽ 0.001) (Table 1, Figure 1). Over the 15 years, acute upper GI bleeding had become less frequent (40%, 42.8%, 19.7%, 14.3%, P ⬍ 0.001) but dyspepsia (24.4%, 33.6%, 54.3%, 51.3%, P ⫽ 0.002) and reflux (1.8%, 1.3%, 5.1%, 10.8%, P ⫽ 0.005) more frequent indications for upper endoscopy (Table 2, Figure 2).

Figure 1. Trends in use of ulcerogenic and antisecretory drugs during the last 15 years: There is a significant increase of PPIs’ use, while use of H2-blockers is decreased. The use of ASA and NSAIDs remain unchanged. ASA, acetyl-salicylic acid; NSAIDs, nonsteroidal anti-inflammatory drugs; PPIs, proton pump inhibitors.

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Table 2. Main Indications for Upper Gastrointestinal Endoscopy Year Indications (%)

1990

1995

2000

2005

Statistics

Total number of endoscopies per year Acute upper gastrointestinal bleeding Dyspepsia Anaemia Gastric surgery history Dysphagia Reflux symptoms Acute epigastric pain Vomiting Cirrhosis—detection of varices Weight loss—anorexia Suspected gastric or esophageal cancer Radiological findings Others

953 40 24.4 7.5 6.6 3.3 1.8 4 3.6 4.1 2.5 2.8

1245 42.8 33.6 6.3 3.8 3.5 1.3 3.6 4 3.5 1.5 1.3

2350 19.7 54.3 7.6 1.9 3.3 5.1 3.9 1.3 4.3 4.3 1.8

2528 14.3 51.3 8.8 1.5 1.5 10.8 3.4 3.9 1.7 4.9 1.3

⬍0.001 0.002 NS NS NS 0.005 NS NS NS NS NS

1.5 6.0

1.6 4.1

2.8 4.9

0.9 3.1

NS NS

Peptic ulcer declined as an endoscopic finding in patients that underwent endoscopy over the 15 years. The endoscopic findings of duodenal ulcer (39.1%, 22.5%, 20.5%, 9.3%, P ⬍ 0.001), gastric ulcer (15.9%, 8.3%, 5.7%, 4.6%, P ⫽ 0.036), as well as erosive gastroduodenitis (35.6%, 22.2%, 15.3%, 4.7%, P ⬍ 0.001) decreased. On the other side, the prevalence of reflux esophagitis increased significantly (3.1%, 10.1%, 12%, 16%, P ⫽ 0.034) (Table 3, Figure 3). Moreover, the percentage of patients with negative endoscopy or minimal endoscopic findings (eg, nonerosive gastritis) increased (12.8%, 33.7%, 54.1%, 64.4%, P ⬍ 0.001). The rates of gastric and esophageal cancer remained very low (2.6%, 1.8%, 1.2%, 0.2%) and (1.3%, 1.2%, 0.7%, 0.2%) in the 4 periods, respectively.

Figure 2. Trends in indications for upper GI tract endoscopy during the last 15 years: Acute upper GI bleeding has been decreased as an indication for upper endoscopy, while dyspepsia and reflux have been increased, with dyspepsia being the most frequent indication for upper endoscopy nowadays.

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Discussion The present study demonstrates changes in indications for upper GI tract endoscopy and endoscopic findings over the last 15 years in south-western Greece. Among patients that underwent upper endoscopy in our referral center, the finding of peptic ulcer disease has decreased significantly from 55% in 1990 to 13.9% in 2005. Endoscopic findings of both gastric and duodenal ulcers, as well as erosive gastroduodenitis have decreased. Moreover, peptic ulcer bleeding has also declined significantly. On the other side, the endoscopic finding of gastroesophageal reflux disease has been increasing since 1990. These changes in endoscopic findings in patients referred for upper GI tract endoscopy might be the result of a reduction in the prevalence of peptic ulcer disease in the general population in our area and/or may reflect the increased usage of endoscopy in patients with dyspeptic symptoms over these years. The reduction in the endoscopic finding of peptic ulcer disease could be attributed to the reduction of new cases of duodenal ulcer patients, the better management of patients with chronic duodenal ulcers, and the prevention of NSAIDs related ulcers. Several epidemiological studies worldwide have shown that the incidence of uncomplicated duodenal ulcers has been reduced in the last years.16 –21 This reduction has been attributed to the decline in the prevalence of HP infection, the main agent responsible for duodenal ulcer formation.18,20,21 A low acquisition rate of the organism because of an improvement in the socio-sanitary conditions is responsible for this change. Also, almost inevitable exposure to antibiotics during childhood and adolescence may be another contributing factor, as well as, the widespread use of HP eradication therapy at the present time.22 Nowadays, the trend is to eradicate HP right 23

Changes in Indications and Findings at Upper GI Tract Endoscopy

Table 3. Major Endoscopic Findings in Upper Gastrointestinal Endoscopy Year Endoscopic Findings (%)

1990

1995

2000

2005

Statistics

Total number of endoscopies per year Nothing or non erosive gastritis Duodenal ulcer Gastric ulcer Erosive gastroduodenitis Esophagitis Hiatus hernia Esophageal and/or fundic varices Gastric cancer Esophageal cancer Angiodysplasia Polyps Others

953 12.8 39.1 15.9 35.6 3.1 4.1 1.8 2.6 1.3 0.1 0.3 3

1245 33.7 22.5 8.3 22.2 10.1 3.8 3.8 1.8 1.2 0.4 0.1 3.3

2350 54.1 20.5 5.7 15.3 12 4 7 1.2 0.7 0.5 0.4 2.9

2528 64.4 9.3 4.6 4.7 16 4.2 6.8 0.2 0.2 0.4 0.6 2.2

⬍0.001 ⬍0.001 0.036 ⬍0.001 0.034 NS NS NS NS NS NS NS

at its detection, even in the absence of a peptic ulcer, in a positive Campylobacter-like organism (CLO) test or in biopsies taken in a gastroscopy or even after the measurement of antibodies against Helicobacter or in a breath test examination. The reduction of peptic ulcer recurrences is an additional factor. Eradication of HP, which can be achieved in over 90% of patients with peptic ulcer, reduces ulcer recurrences as well as ulcer bleeding and rebleeding rates in these patients.23,24 Also prevention of peptic ulcer formation and bleeding in patients taking NSAIDs adds to this reduction. Although the population is aging and the range of indications for aspirin or NSAIDs is increasing, NSAIDs are more carefully prescribed according to current guidelines.25 In our study, there were no differences in the proportion of patients referred for endoscopy who had received aspirin or other NSAIDs over the last 15 years, whereas there was a significant increase in the use of proton pump inhibitors (PPIs). Widespread gastroprophylaxis with

Figure 3. Trends in findings of upper GI tract endoscopy during the last 15 years: The findings of duodenal ulcer, gastric ulcer and erosive gastroduodenitis have been significantly decreased, while reflux esophagitis and minimal endoscopic findings (nothing or nonerosive gastritis) have been increased, with the later being the most frequent endoscopic finding nowadays.

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PPIs in current doses especially in high risk patients and treatment with the minimum effective dose of indicated NSAIDs (such as prophylaxis for ischemic disease) seems to have been used more often during the last years. More recently, the increased use of safer COX-2 selective inhibitors, which have been associated with significantly fewer gastroduodenal lesions and complications, may be an additional factor in decreasing the chance of peptic ulcer disease,26 but the current study did not gather data concerning this issue. In our study, we observed an almost threefold increase in the number of endoscopies performed over the last 15 years, attributed mainly to increased number of patients with dyspeptic symptoms referred for upper endoscopy. Dyspepsia is a common disorder with reported prevalence ranging from 13% to 40% in Western countries.27 Approximately 60% of patients with dyspeptic symptoms have functional dyspepsia in which no organic cause of upper GI tract symptoms can be found in previous studies.28,29 The best initial work up in patients with dyspeptic symptoms who have no alarm symptoms, such as weight loss and anemia, vomiting, or evidence of bleeding, remains to be established.30,31 Endoscopy can reliably exclude malignancy and identify other relevant causes of dyspepsia, but is an invasive procedure. During the past decades, 2 different approaches have been proposed in patients with dyspepsia; empirical antisecretory therapy with a proton pump inhibitor or test and treat method to avoid endoscopy initially in these patients. The test and treat approach involves noninvasive testing for HP infection followed by eradication therapy if positive. The decreasing rates of finding peptic ulcers and increasing rates of finding gastroesophageal reflux disease at endoscopy in our study, point out that test and treat should not be the initial management strategy for uninvestigated dyspepsia. HP eradication has negligible if any benefiJuly 2008 Volume 336 Number 1

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cial effect on functional dyspepsia32 and may result in worsening of reflux symptoms in some patients.33 Moreover, widespread H. pylori eradication has not been proven to have chemopreventive benefits for gastric cancer. Empiric antisecretory therapy has long been used as an initial management option in dyspeptic patients. Despite its effectiveness in reducing the application of diagnostic endoscopy initially, endoscopy may be ultimately avoided in only a minority of patients. In a previous Danish randomized trial, patients suffering from dyspepsia had no difference in their symptoms a year after initial endoscopy or acid suppression therapy, but early endoscopy led to greater patient satisfaction and reduction in the number of consultations and prescriptions.34 In our country, the cost of endoscopy is yet low, so endoscopists prefer to view the upper GI tract as the initial method of managing patients with dyspepsia. The percentage of patients with major pathology at endoscopy that had direct therapeutic and/or prognostic consequences has been decreasing in our study over the past 15 years. Over 64% of patients had negative endoscopy or minimal findings in 2005 compared with 12.8% of patients in 1990. This is probably due to the combination of decrease in the finding of peptic ulcer disease and increase in the percentage of patients with functional dyspepsia submitted to endoscopy. Although the finding of reflux disease has been increasing, in more than 50% of these patients endoscopy is negative. An empiric course of PPI treatment may mask upper GI track pathology, particularly esophagitis. In a previous study fewer endoscopic findings were observed in patients with dyspepsia being treated with a PPI for at least 4 weeks compared with those taking an H2 receptor antagonist or no therapy.35 Although in our study population a percentage of patients were treated with PPIs, this percentage was less than 20%, the duration of treatment was usually shorter than 4 weeks and treatment was not continuous in all patients, as in our country diagnostic endoscopy is performed more easily in patients with dyspeptic symptoms. Similar findings were reported in a recent multicenter study from Italy. A relevant endoscopic finding was detected in only 2929 out of 6270 examinations (46.7%), and the diagnostic yield was significantly higher for “generally indicated” endoscopies compared with those judged “generally not indicated” according to the American society of GI tract endoscopy criteria.36 On the other side, use of alarm symptoms to select dyspeptic patients for endoscopy, in order to avoid a large number of negative endoscopies, may lead to overlook the small number of patients with curable esophagogastric cancer.37 A strategy based on the selection of candidates for endoscopy by using a predictive model based not only on H. pylori status but also on clinical characteristics and symptoms THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES

would be more cost effective.34,38 In the present study, despite the increased usage of upper endoscopy, over the last 15 years, mainly for the evaluation of patients with dyspeptic symptoms, we did not demonstrate a benefit in the endoscopic detection of gastric and esophageal cancers (37 patients with gastroesophageal cancer were detected in 1990 and 10 patients were detected in 2005, Table 3). On the other hand, the proportion of patients with negative endoscopy is rapidly increasing over these years. In addition, endoscopy hardly ever alters therapy: most patients with dyspeptic symptoms will receive acidinhibiting treatment after endoscopy anyway.36,39 Therefore, we suggest that patients with dyspepsia but without alarm symptoms, should not be initially evaluated by upper GI tract endoscopy, but the therapeutic trial of PPIs for 1 month might be a more justified approach, even for our country where endoscopy is relatively cheap. In conclusion, in the area of south-western Greece, dyspepsia and reflux as an indication for upper endoscopy have been increasing, whereas acute upper GI bleeding has been decreasing. The finding of peptic ulcers at upper endoscopy has become significantly less frequent, while the percentage of patients with negative endoscopy seems to have been increasing rapidly. Stratification of patients by a predictive model and submit to endoscopy only those at higher risk of organic dyspepsia would be more cost effective in the future. References 1. Talley NJ, Axon A, Bytzer P, et al. Management of uninvestigated and functional dyspepsia: a Working Party report for the World Congresses of Gastroenterology 1998. Aliment Pharmacol Ther 1999;13:1135– 48. 2. Chey WD, Moayyedi P. Review article: uninvestigated dyspepsia and non-ulcer dyspepsia-the use of endoscopy and the roles of Helicobacter pylori eradication and antisecretory therapy. Aliment Pharmacol Ther 2004;19(suppl 1):1– 8. 3. Axon AT. Chronic dyspepsia: who needs endoscopy? Gastroenterology 1997;112:1376 – 80. 4. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984;1:1311–5. 5. NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease. JAMA 1994;272:65–9. 6. Metz DC, Kroser JA. Helicobacter pylori and gastroesophageal reflux disease. Gastroenterol Clin North Am 1999;28: 971– 85. 7. Dent J, Jones R, Kahrilas P, et al. Management of gastrooesophageal reflux disease in general practice. BMJ 2001; 322:344 –7. 8. McLoughlin RM, O’Morain CA, O’Connor HJ. Eradication of Helicobacter pylori: recent advances in treatment. Fundam Clin Pharmacol 2005;19:421–7. 9. Grace ND, Bhattacharya K. Pharmacologic therapy of portal hypertension and variceal hemorrhage. Clin Liver Dis 1997;1:59 –75. 10. Pilotto A. Aging and upper gastrointestinal disorders. Best Pract Res Clin Gastroenterol 2004;18(Suppl):73– 81. 11. Weil J, Langman MJ, Wainwright P, et al. Peptic ulcer

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