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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Competing interests
  9. Acknowledgement
  10. References

Summary

Background

Despite reports of decreasing hospitalizations and mortality due to peptic ulcer, it is unclear whether the incidence has truly declined over time.

Aim

To investigate time trends in the incidence of and in hospital admission rates for peptic ulcer in the Netherlands.

Methods

The nationwide registry of pathology reports (PALGA) and the national registry of hospital admissions (Landelijke Medische Registratie) were used. Standardized morbidity ratios were calculated to assess the magnitude of the changes.

Results

The age-adjusted incidence of gastric ulcer halved for both men (standardized morbidity ratio 0.48; CI 0.46–0.49) and women (standardized morbidity ratio 0.49; CI 0.47–0.51). Although the number of gastric biopsies obtained at endoscopy increased, the proportion with a diagnosis of peptic ulcer decreased by more than 50% (standardized morbidity ratio 0.47; CI 0.46–0.49). The admission rate for peptic ulcer more than halved between 1980 and 2003. In contrast, admission rates for complicated ulcers barely changed and slightly increased among women.

Conclusions

The incidence of histopathologically confirmed gastric ulcer halved between 1992 and 2003 in the Netherlands. As the number of gastric biopsies increased in this period, a true decrease is likely. Hospital admissions for peptic ulcer declined dramatically between 1980 and 2003, but remained unchanged or slightly increased for complicated ulcers.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Competing interests
  9. Acknowledgement
  10. References

Over the past two decades, important changes have occurred in the epidemiology of ulcer disease. The identification of Helicobacter pylori infection as a major cause of ulcer disease led to the development of H. pylori eradication therapy, which cured patients with previous chronic recurrent ulcer disease.1 Furthermore, a decrease in the prevalence of H. pylori has occurred in industrialized countries since the second world war, presumably as a result of improving living conditions.2, 3

In the 1960s, Susser and Stein already had suggested a decline in the incidence of peptic ulcer on the basis of a cohort analysis. Mortality due to peptic ulcer decreased in successive birth cohorts following the peak among those born at the end of the 19th century.4 Decreasing hospitalization rates for peptic ulcer over the past decades in the United States of America (USA) support this hypothesis.5 However, because a considerable, and probably increasing proportion of uncomplicated peptic ulcers is treated on an out-patient basis, trends in the number of hospital admissions may differ from changes in the incidence of this disease. Moreover, increased use of non-steroidal anti-inflammatory drugs (NSAIDs) may have increased the incidence of NSAID-associated ulcer disease, and aggravated the risk of bleeding from a peptic ulcer.6

Although log-linear modelling of morbidity and mortality data suggest a decrease in the incidence of peptic ulcer,7 a decline in the incidence has never been shown directly. The availability of a national pathology database allows to confirm the existence of a decline in incidence, at least for gastric ulcer disease. Routinely, a biopsy is taken during endoscopy from virtually all patients with a clinically diagnosed gastric ulcer, to exclude gastric carcinoma. Therefore, the trend in histopathologically confirmed gastric ulcer would reflect the incidence of this disease. In contrast, duodenal ulcers are biopsied to a lesser extent because these ulcers do not carry an increased risk of cancer.8 For this reason, we studied trends in the incidence of histopathologically confirmed gastric ulcer between 1992 and 2003. In order to asses the consequences of changes in incidence, diagnosis and treatment, we studied trends in the number of hospital admissions for both gastric and duodenal ulcer over a longer period, i.e. 1980–2003.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Competing interests
  9. Acknowledgement
  10. References

The PALGA registry

The PALGA database is a national archive containing the abstracts of all histopathology and cytopathology reports in the Netherlands since 1991. Our country nowadays consists of 16 million inhabitants. Every record in the database contains a summary of the report and diagnostic codes similar to the Systematized Nomenclature of Medicine (SNOMED) classification of the College of American Pathologists.9 After a report has been coded, it is submitted online to the central database. Today, the PALGA database contains up to 38 million records from approximately 10 million individuals. The present study was based on the data recorded in the PALGA database between 1992 and 2003.

Analysis of PALGA data

Hisopathologically confirmed diagnoses of peptic ulcer were included if one of the following diagnoses was assigned to biopsies taken from the stomach to evaluate the presence of malignant ulcer disease and of H. pylori infection: ‘ulcer’, ‘peptic ulcer’, ‘acute peptic ulcer’ or ‘chronic peptic ulcer’. In order to assess the impact of possible changes in the frequency of biopsies during upper gastrointestinal (GI) endoscopy, we also studied the trend in the total number of first-time biopsies of the stomach. We were interested in the ratio of the number of new patients with a positive biopsy for peptic ulcer to the number of new ‘patients’ with a first time biopsy from the stomach. In this way, we were able to estimate accurately the population that underwent a diagnostic investigation, i.e. endoscopy with a biopsy taken.

Age-specific (for 15-year age groups) and age-standardized (World Standardized Rate, WSR10) incidence rates of histopathologically confirmed peptic ulcers were calculated for the years 1992–2003. To assess the magnitude of the observed changes, the incidence rates were standardized indirectly by calculating standardized morbidity ratios (SMR) for three consecutive 4-year periods, i.e. 1992–1995, 1996–1999 and 2000–2003. Ninety-five per cent confidence intervals (CI) were calculated, assuming a Poisson distribution. To assess the influence of possible changes in the frequency of biopsies during upper GI endoscopy, we calculated the SMR of the change in the age-adjusted proportion of biopsies from the stomach that contained histological evidence of gastric ulcer. In that way, we were able to assess the magnitude of a possible change in the incidence of ulcer disease, corrected for the possible change in the use of upper GI endoscopy and for changes in the age distributions.

National hospital admission database

Hospital discharge diagnoses were obtained from the national registry of hospital admissions, the Landelijke Medische Registratie, which contains information on all admissions in general and academic hospitals throughout the Netherlands. The ICD-9 classification has been used to classify admissions in the Netherlands during the whole study period, 1980–2003. All admissions for the discharge diagnoses starting with the ICD-9 codes 531, 532 and 533 (admissions for gastric ulcer, duodenal ulcer and for unspecified peptic ulcer, respectively) were included for the years 1980–2003. Each of these categories were studied in more detail. Admissions for ulcer bleeding, ulcer perforation and uncomplicated ulcers were studied separately. Ulcers presenting with both bleeding and perforation were included in the ‘ulcer perforation’ group. Population data (population on 1 January of each year) were obtained from Statistics Netherlands (accessed through http://www.cbs.nl).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Competing interests
  9. Acknowledgement
  10. References

Incidence of histopathologically confirmed gastric ulcers

Between 1992 and 2003, 28 802 cases of histopathologically confirmed gastric ulcer were recorded. Of these, 2868 (10%) were diagnosed with a malignant ulcer. The age-adjusted incidence of gastric ulcer disease decreased from 18.3 per 100 000 in 1992 to 6.8 per 100 000 in 2003 among men and from 13.0 to 5.1 per 100 000 among women (Figure 1) The SMR indicated a 52% decrease among men (SMR 48%; CI 46–49%) in 2000–2003, compared with the reference period 1992–1995. The decrease amounted to 51% (SMR 49%; CI 47–51%) among women (Table 1).

image

Figure 1.  Trends in the incidence of histopathologically confirmed gastric ulcer (WSR, world standardized rate).

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Table 1.   Trend in the number of cases of gastric ulcer and its incidence relative to the reference period, 1992–1995
 CasesSMR95% CI
  1. * Reference.

  2. SMR, standardized morbidity ratio.

Males
 1992–199564181*
 1996–199944930.650.63–0.67
 2000–200335250.480.46–0.49
Females
 1992–199563451*
 1996–199944340.650.63–0.67
 2000–200334730.490.47–0.51

The decrease in the incidence was similar in all age groups (data not shown).

The total number of gastric biopsies increased by 19% among men and by 30% among women from 1992–1995 to 2000–2003. Of these, the proportion indicating peptic ulcer decreased by more than 50% among both men (SMR 47%; CI 46–49%) and women (SMR 46%; CI 45–48%) (Table 2).

Table 2.   Trend in the number of gastric biopsies and in the age-adjusted incidence of gastric ulcer relative to the reference period, corrected for changes in the number of gastric biopsies
 BiopsiesGastric ulcers% UlcersSMR 95% CI
  1. * Reference.

  2. SMR, standardized morbidity ratio.

Males
 1992–199574 90464189%1*
 1996–1999101 50644934%0.540.52–0.55
 2000–200388 79135254%0.470.46–0.49
 % Change19%−45%   
Females
 1992–199573 33263459%1*
 1996–1999103 83544344%0.540.52–0.55
 2000–200395 15734734%0.460.45–0.48
 % Change30%−45%   

Trends in hospital admissions

Between 1980 and 2003, 78 025 admissions for gastric ulcer, 69 803 admissions for duodenal ulcer, and 2529 admissions for unspecified peptic ulcer were recorded. The male/female ratio decreased from 1.5 in 1980 to 1.0 in 2003 for gastric ulcer and from 2.6 to 1.6 for duodenal ulcer.

The admission rate for gastric ulcer disease decreased among men from 32.4 to 16.2 per 100 000 between 1980 and 2003. Among women, it decreased from 21.2 to 15.7 per 100 000. These decreases were due mainly to a decrease in the admission rate for uncomplicated ulcer disease, which declined among men from 19.6 in 1980 to 4.2 per 100 000 in 2003. The decline was smaller among women, from 13.8 to 4.7 per 100 000 (Figure 2). The admission rate for bleeding ulcer increased among men from 7.6 per 100 000 in 1980 to 10.5 per 100 000 in 1989, but subsequently returned to its original level in the late 1990s. Among women, it increased to a larger extent from 4.8 to 9.1 per 100 000 in 1994 and remained 6.5 per 100 000 in 2003. The admission rates for perforating ulcer remained relatively stable among men. Among women, the admission rate increased from 2.7 in 1980 to 4.4 per 100 000 in 1990 and remained at this higher level up to 2003.

image

Figure 2.  Trends in hospital admission rates for gastric ulcer in the Netherlands.

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The admission rate for duodenal ulcer more than halved. It decreased among men from 52.0 in 1980 to 13.8 per 100 000 in 2003 (Figure 3). Among women, it decreased from 20.1 to 8.8 per 100 000. This was also due mainly to a dramatic decrease in admissions for uncomplicated duodenal ulcers. The admission rate for bleeding ulcer decreased among men from 11.6 in 1980 to 8.6 per 100 000 in 2003. In contrast, it slightly increased among women from 4.0 to 4.3 per 100 000.

image

Figure 3.  Trends in hospital admission rates for duodenal ulcer in the Netherlands.

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The admission rate for ‘peptic ulcer’ (without a specific location) more than halved during the study period. This group continued to represent <1–2% of all admissions for ulcer disease.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Competing interests
  9. Acknowledgement
  10. References

Dramatic changes in the diagnosis and treatment of peptic ulcer have occurred over the past two decades. Yet, data on trends in the incidence of peptic ulcer are scarce. Using our nation-wide registry of pathology reports, we observed a 50% decline in the incidence of gastric ulcer for both men and women between 1992 and 2003 in the Netherlands. A dramatic decrease in hospital admissions for ulcer disease paralleled this decrease. The admission rate for uncomplicated duodenal and gastric ulcers declined in particular (more than fourfold for men). In contrast, admissions for complicated ulcer disease did not decrease and even increased in the 1980s, in particular among women, to remain relatively stable since then.

Methodological considerations

We based our incidence figures of gastric ulcer on histopathologically confirmed diagnoses. This means that the reported incidence is influenced by the extent to which patients with symptoms suggestive for ulcer disease undergo endoscopy and histopathological confirmation. Successive guidelines on the diagnosis and treatment of dyspeptic symptoms have maintained the advice to perform diagnostic endoscopy in patients with recurrent dyspepsia, and immediate endoscopy in case of alarm symptoms such as bleeding.11 Moreover, it is generally recommended to obtain biopsy samples in case of gastric ulcer disease to exclude malignancy. We do however realize that in case of simple gastritis or H. pylori gastritis, biopsies are often not taken. Nonetheless, we consider it likely that the vast majority of gastric ulcers observed during endoscopy have over the years consistently been histopathologically confirmed. Moreover, in spite of an increase in the number of gastric biopsies obtained every year, the incidence of gastric ulcer declined. For these reasons, we believe that the observed trends with respect to gastric ulcer disease are realistic, and our main conclusions justified.

Hospital admissions for ulcer disease have been recorded in the Netherlands according to ICD-9 criteria and were distinguished in admissions for gastric ulcer, duodenal ulcer and for unspecified peptic ulcer. We realize that misclassification of gastric as duodenal ulcer and vice versa may have taken place to some extent. However, there is no reason to assume systematic misclassification.

Explanations for the decrease in incidence

The observed decrease in the incidence of gastric ulcer may have been caused by two main factors. As a result of improved living conditions, the prevalence of H. pylori infection has decreased since World War II.2, 3 This is thought to have caused a decreasing incidence of peptic ulcer disease. In the 1960s, Susser and Stein4 were the first to suggest a decline in the incidence of peptic ulcer on the basis of a cohort analysis of mortality. More recent analyses supported their conclusion that cohort effects, caused by changes in risk factors, were responsible for the decline.12 The introduction of H. pylori eradication therapy has presumably further reduced the incidence of ulcer disease, both by minimizing the risk for ulcer relapse in patients with previous ulcer disease, and by primary prevention in patients with non-ulcer dyspepsia.

A further contribution to the decreasing incidence of ulcer disease likely came from the introduction and widespread increasing use of proton pump inhibitors (PPIs). In a recent cohort study including 600 000 primary care patients, we recently found that the prevalence of PPI use increased from 2.5/100 person years (95% CI 2.4–2.7) in 1996 to 5.8/100 person years (95% CI 5.6–5.9) in 2003 (E.M. van Soest, P.D. Siersema, J.P. Dieleman, M.C.J.M. Sturkenboom, E.J. Kuipers; unpublished data).

In spite of various studies suggesting a decrease in the incidence of peptic ulcer on the basis of birth cohort analyses,4, 7, 12 our study is the first to show directly that the incidence of gastric ulcer has decreased over the past decades.

Trends in admission rates

The overall decrease in hospital admissions for peptic ulcer was in particular due to a decline in admissions for uncomplicated ulcer disease. In contrast, the number of admissions for complicated ulcer disease changed very little over time. The admission rate for perforating ulcer disease remained stable, and the number of admissions for bleeding ulcer even increased, in particular among women. The literature on hospital discharge rates for ulcer disease yields a variable picture. In the USA, hospital admissions declined since the 1970s for both gastric and duodenal ulcer,5 but not for hospitalizations for upper GI bleeding.13 Moreover, mortality rates because of peptic ulcer or upper GI bleeding remained relatively stable.13 In England, admission rates for gastric ulcer increased between 1989 and 1999, in particular admissions for bleeding gastric ulcers and admissions of older people (≥65 years). The admission rates for duodenal ulcer barely changed overall, but the admission rate for bleeding duodenal ulcers also increased in the elderly.14 In Denmark, admissions for peptic ulcer slightly decreased for men, but increased for women. In particular, admissions for bleeding and perforated duodenal ulcers increased by 77% and 54% respectively over the periods 1981–1983 to 1991–1993.15 In a recent study in the Amsterdam area in the Netherlands, the overall incidence rate of peptic ulcer bleeding did not decrease between 1993/1994 and 2000. The proportion of NSAID-related ulcer bleedings increased, while the number of presumed H. pylori-related ulcer disease had decreased.16

Explanations for the stable admission rates for complicated ulcer disease

The increase in admissions for peptic ulcer in the elderly has been attributed to an increased use of NSAIDs and selective serotonin reuptake inhibitors.14, 16 Whereas H. pylori infection is the main risk factor for peptic ulcer in general,17 NSAIDs incur a fourfold increase in risk of peptic ulcer bleeding.18 Increased use of NSAIDs probably plays an important role. Indeed, 70% of the long-term users of NSAIDs in the Netherlands between 2001 and 2002 were women.19 Use of NSAIDs increases the risk of peptic ulcer, and can also mask ulcer symptoms by its analgesic effect.20 As a consequence, ulcer complications, requiring hospital admission, may be the first sign of peptic ulcer in these patients. Therefore, prescription of a PPI or H2-receptor antagonist is advocated for patients requiring treatment with a NSAID, especially for those with a history of peptic ulcer.21 Although an increasing number of NSAID users has received PPI prophylaxis since 1993, this guideline was still incompletely followed in the Netherlands in 2000–2002.16, 19 Only 43% of long-term NSAID users in the Netherlands between 2001 and 2002 had received GI protective treatment such as PPIs and (double dose) H2-receptor antagonists or were treated with selective Cox-2-inhibitors.19 This persistently high incidence of complicated ulcer disease is remarkable in a period of a decreasing prevalence of H. pylori, the advocacy to consider H. pylori eradication in chronic NSAID users to reduce ulcer risk, and the availability of gastro-protective agents such as PPIs and Cox-2-inhibitors. Our findings contrast with a recent report from the USA, which showed that NSAID gastropathy is disappearing in the USA as a result of preventive measures.22 This suggests that adherence to guidelines and use of preventive resources are still inadequate in patients using NSAIDs in the Netherlands.

Conclusions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Competing interests
  9. Acknowledgement
  10. References

The incidence of gastric ulcer decreased substantially between 1991 and 2003 in the Netherlands, most likely caused by the declining prevalence of H. Pylori. Hospital admissions for both gastric and duodenal ulcer also decreased. However, the admission rates for complicated ulcers barely changed and even increased among women. Whether NSAIDs are responsible for this increase deserves further study.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Conclusions
  8. Competing interests
  9. Acknowledgement
  10. References
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