Is Age a Good Discriminator When Deciding Whether to Perform Gastroscopy?

How to select patients for upper gastrointestinal endoscopy is a question of paramount clinical importance given the high prevalence of upper gastrointestinal symptoms (in particular of dyspepsia) and the relapsing nature of these complaints. Indeed, about 1 % [1] [2] to 1.8 % [3] of the population undergo gastroscopy each year. The decision to perform a diagnostic procedure such as gastroscopy must take into account the probability and net benefit of identifying disease; in contrast, the decision not to perform it must take into account the risk of missing significant disease [4] for which early, appropriate treatment can improve outcome.

In this issue of Endoscopy, two original papers examine the use of upper gastrointestinal endoscopy with regard to patient age. Patient age has traditionally been an important factor for the clinician in deciding whether or not endoscopy should be done. Indeed, the probability of discovering a clinically relevant lesion, including cancer, at gastroscopy increases with age [5] [6] [7] [8] [9] [10] [11]. A gradual increase in diagnostic yield for gastroscopy from 30 % at under 25 years to 61 % at over 65 years [12] has been reported.

The paper by Boldys et al. [13] focuses on the relationship between gastric cancer, patient age, and the presence of alarm symptoms. The authors considered 860 patients who underwent a first gastroscopy at a secondary referral center for symptoms compatible with possible gastric cancer. Gastric cancers, most of which were advanced, were found in 83 patients (9.7 %). Of the patients with gastric cancer, 27 % did not have alarm symptoms, and as many as 24 % of them were younger than 45 years. Gastric cancer patients had more symptoms over a shorter period of time than patients without cancer. This paper reports a rate of gastric cancer which is 4 - 8 times greater than the prevalence of this disease in Europe as a whole [14]. The main explanation for this provocative and unexpectedly high cancer rate is patient selection, as the prevalence of gastric cancer in Poland seems to be comparable to that in other European countries. Patient selection is significant in this paper for the following reasons. First, the patient sample under consideration represents only 1.3 % of all patients who had undergone gastroscopy at this center over the 10-year period of the study. The results relate to one among eight centers participating in a national gastric cancer program in Poland. Secondly, the centers were allowed to include no more than 100 consecutive patients per year. Thirdly, patient symptoms were already suggestive of possible gastric cancer. Nevertheless, at least in this highly selected population, one out of four patients with gastric cancer was under 45 years old or did not have any alarm symptoms. The authors therefore emphasize the need for endoscopy even in young patients with no alarm symptoms. This is in contrast to current guidelines [15] [16] [17], and certainly cannot be translated into clinical practice as the patient sample in this study is overselected.

The paper by Boulton-Jones et al. [18] reviews the appropriateness and diagnostic yield of 1000 consecutive open-access referrals for upper gastrointestinal endoscopy in a UK district hospital. One-third of the procedures were found to be inappropriate according to the guidelines of the British Society of Gastroenterology (BSG). These guidelines [17] state that dyspeptic patients should undergo gastroscopy only if they test positive for Helicobacter pylori (“test-and-scope” strategy) or present with alarm symptoms or recurrent or persistent dyspepsia; furthermore, any patient over 45 years with recent-onset dyspepsia should be referred for endoscopy. The good news to be drawn from this study is that none of the 17 cases of gastric or esophageal malignancy would have been missed if BSG guidelines had been followed, as 16 of these patients were over 45 years old and the single patient under 45 years presented with alarm symptoms. However, all these patients died, thus demonstrating that open-access endoscopy was a poor tool for diagnosing gastroesophageal cancer at a curable stage. The bad news from this study is that these guidelines were unable to discriminate organic pathology other than malignancy (with the exception of esophagitis in severe reflux disease), as the detection rates for endoscopic pathology were comparable between patients under 45 years and those over 45 years of age, or in patients presenting with alarm symptoms.

The aim of guidelines related to gastroscopy is to ensure a rapid diagnosis of gastroesophageal malignancy and to provide a cost-effective way of managing patients with nonmalignant conditions, such as ulcer disease or Barrett’s esophagus. Boulton-Jones et al. found that application of BSG guidelines [17] did not enhance the diagnostic yield of non-neoplastic lesions, while cancer was readily predicted. Similarly disappointing results have previously been reported when the guidelines of the American Society for Gastrointestinal Endoscopy (ASGE) were applied in consecutive patients undergoing gastroscopy [19]. In contrast, the use of more detailed and explicit appropriateness criteria, such as those developed by a multidisciplinary panel process (RAND Corporation), gives better results in clinical practice: in a series of 2088 patients, gastroscopies judged appropriate (or uncertain) yielded significantly more relevant lesions (60 %) than did those judged to be inappropriate (37 %; odds ratio 2.6; 95 % CI 2.2 - 3.2) [12]. The diagnostic yield of gastroscopy was higher in inpatients and in men, and increased with age. The RAND panel process [20] is based on a multi-step approach, including a structured literature review, the development of specific clinical indications (scenarios) for the procedure, a first individual rating round performed by each expert panelist on a 9-point scale (1 = very inappropriate, 5 = uncertain, 9 = very appropriate), an extensive discussion of all scenarios, and a second rating round (panel meeting). This technique allows the simultaneous development of appropriateness criteria (to assess inappropriateness or overuse of a procedure) and necessity criteria (to assess underuse of a procedure) [4] [21] [22]. Appropriateness criteria based on a RAND panel held in the fall of 1998 in Lausanne are currently available on the internet (http://www.epage.ch). These EPAGE criteria (European Panel on the Appropriateness of Gastrointestinal Endoscopy) cover indications for gastroscopy and colonoscopy, and will be updated regularly in the light of current knowledge. In order to determine the appropriateness of gastroscopy in dyspepsia, the EPAGE criteria are based on the following parameters: patient age (< 45 or ≥ 45 years); presence of H. pylori; use of nonsteroidal anti-inflammatory drugs (NSAIDs); results of previous investigations; and the presence of and response to empirical acid-lowering treatment [23]. With the advent of computer technology and the internet, even complex sets of criteria containing several hundred scenarios (e. g. 1998 EPAGE criteria feature 264 indications related to gastroscopy, 192 of which were for dyspepsia alone) do not preclude feasibility in clinical practice.

Although the EPAGE criteria are detailed and specific, endoscopies labeled as inappropriate still yield a high number (37 %) of significant lesions [12]. In practice, the evaluation of appropriateness criteria must be based on clinical parameters that are clinically relevant and readily available: patient symptoms and signs, and laboratory tests. The problem is that the relationship between the clinical presentation and the endoscopic diagnosis is far from perfect, thus explaining the noteworthy number of significant diagnoses resulting from inappropriate endoscopies. This seems to be an inherent limitation of clinical judgment, at least in terms of diagnostic yield. Thus, even gastroscopies performed on account of alarm symptoms (e. g. dysphagia, hematemesis) did not show a pathological finding in 42 % of patients [24].

The paper by Boulton-Jones et al. [18] indicates that one-third of gastroscopies were inappropriate according to the criteria issued by the British Society of Gastroenterology. The reported rate of inappropriate gastroscopy varies widely, from 5 % [25] to 49 % [21]; direct comparisons between studies are, however, difficult due to differences in the type of patients (inpatients vs. outpatients, patient age), in the type of criteria used, and the particular health care system under investigation.

The possibility of missing a gastric cancer is of the greatest concern to the clinician contemplating the option of not performing gastroscopy in a given clinical situation, with empirical therapy being provided instead. Fortunately, in nonselected series, few patients undergoing gastroscopy (1 - 2 %) turn out to have gastric cancer [8] [9] [10]. Furthermore, gastric cancer is exceedingly rare in those younger than 40 years (0.8 per 1000 vs. 1.8 per 1000 in those over 40 years) [8] [9] [10]. On the other hand, superficial and surgically curable gastric carcinoma typically produces no symptoms [26] and is thus not likely to be discovered by strategies based on the assessment of clinical symptoms and signs. Unlike the case in Europe and the US, mass screening may be worthwhile in high-prevalence areas for gastric cancer such as Japan, Russia, or China. Many physicians may experience in their practice some tragic and striking instances of gastric cancer discovered in patients younger than 45 years without alarm symptoms, but this will remain the exception [27]. Recommendations should, however, be based on evidence where available and not on anecdotal cases. Due to a selection bias, the paper by Boldys et al. [13] clearly overemphasizes the issue of young and asymptomatic patients with gastric cancer. The observational study by Boulton et al. [18] seems to come closer to the real situation, as one out of 17 patients with gastric cancer (and with alarm symptoms) was less than 45 years old. In 2088 consecutive patients studied prospectively, we found 26 gastroesophageal cancers, two of which (7.6 %) indeed occurred in patients younger than 45 [12]. Caution is thus necessary, and the decision to perform endoscopy should not be based solely on age.

Two important questions, at each extreme of the diagnostic spectrum, remain unanswered by these papers: the issue of patients undergoing gastroscopy who have normal results (“negative endoscopy”), and the outcome of symptomatic patients who do not undergo endoscopy. The clinician has a tendency to limit the utility of endoscopy to the discovery of relevant lesions resulting in specific therapeutic approaches. However, an endoscopic finding is beneficial in patient management only if it represents the cause of patient symptoms and if there is effective treatment. Moreover, there is now evidence that a “negative endoscopy” has a favorable impact on work-loss and the use of medical consultations and drugs [28] [29] [30] [31]. A randomized trial comparing prompt endoscopy and usual care in symptomatic patients older than 50 reported a significant improvement in quality of life and symptoms, and an important reduction in the use of proton-pump inhibitors (PPIs) in the endoscopy arm [32]. Complex outcomes such as health care consumption and quality of life are more difficult to assess than the pick-up rate of endoscopy. The outcome for symptomatic patients who do not undergo gastroscopy is not well known. As outlined in the discussion by Boldys et al., the literature on this matter is controversial and so far it remains unclear how best to manage these patients.

Guidelines are intended to help the clinician in everyday decision-making, in particular when randomized controlled trials are lacking. Different management strategies have been proposed in dyspepsia, ranging from prompt endoscopy or symptomatic antisecretory treatment, to H. pylori testing and treatment. None of these strategies has convincingly and consistently proven superior to another [16], not even a “test-and-treat” strategy, the value of which has been questioned by a recent decision analysis in patients younger than 45 years [33]. A substantial number of situations are considered equivocal indications for gastroscopy when explicit and detailed criteria such as EPAGE are used, leaving room for individualized clinical judgment. Clinical expertise, common sense, and a profound knowledge of the literature are particularly important in these equivocal situations. Ideally, for a routine procedure such as gastroscopy to be performed at the right moment in the right patient, the clinician (general practitioners and specialists) should be assisted by appropriateness criteria to avoid overuse [12] [21], but also by necessity criteria to identify and avoid underuse [22]. In fact, if quality of care is to be improved, we have to redirect increasingly restricted resources from inappropriate care to necessary care [4] in all medical domains.

Finally then, is age a valid discriminator for deciding whether gastroscopy should be performed? The answer based on the Polish paper [13] would be “No, but…”, as the surprising results are mainly explained by selection bias. The answer to be drawn from the UK report [18] would be “Yes”, as no cancer would be missed by relying on the criteria of age over 45 years and/or the presence of alarm symptoms. Increasing age is correlated with an increasing frequency of esophageal and gastric pathology, including cancer. In clinical practice, age (the cutoff being traditionally 45 years) will remain an important parameter for selecting patients for gastroscopy. However, the age criterion should not be used in a rigid manner and must be combined with parameters such as alarm symptoms, results of previous gastroscopies, medication (e. g. NSAIDs), H. pylori status, and patient setting (inpatients vs. outpatients), to improve quality of care and the endeavor to discover any gastric cancer as early as possible in more patients.

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