Peptic Ulcer Disease

Background

Peptic ulcer disease are usually solitary lesions that can occur anywhere in the gastrointestinal tract. The most common site is in the first portion of the duodenum followed by the stomach antrum, then Barrett's mucosa. Gastric acid is necessary for the production but the discovery of Helicobacter pylori as an important agent to break down the protective mucus.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/Immunohistochemistry/Electron Microscopy

Differential Diagnosis

Prognosis and Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS PUD

GEOGRAPHY

ICELAND

Trends in peptic ulcer morbidity and mortality in Iceland.

Thors H, Svanes C, Thjodleifsson B.

Department of Gastroenterology, National University Hospital, 101 Reykjavik, Iceland.
J Clin Epidemiol 2002 Jul;55(7):681-6 Abstract quote
A cohort pattern has been demonstrated for ulcer mortality and perforation, pointing to a role of early life factors, while only a period-related decrease has been observed in elective ulcer surgery, which reflects uncomplicated ulcer.

The aim of this article was to study whether the susceptibility to peptic ulcer disease is determined early in life, as reflected in a cohort pattern consistent for all ulcer manifestations. The subjects were all patients treated surgically for peptic ulcer (perforations 1962-1990; bleedings 1971-1990; elective surgery 1971-1990) and all deaths from peptic ulcer (perforations and other ulcer deaths 1951-1989) in Iceland. Age-specific incidence and mortality were analyzed graphically by year of birth (cohort) and by year of event (period).

The effects of cohort and period on incidence and mortality were analyzed by Poisson regression. Ulcer perforation and bleeding, operative incidence, and mortality, showed a rise and subsequent fall in successive generations, with the highest risks observed in the subjects born after the turn of the 20(th) century. This was confirmed by statistical analyses showing highly significant cohort effects (P <.001) and no period effects. A cohort pattern was similarly found for elective ulcer surgery (P <.001), as well as a period-related decrease across age groups (P <.001).

Ulcer complications, ulcer deaths, and uncomplicated ulcer were particularly common in specific generations carrying a high risk of peptic ulcer throughout their lives. These were the generations with the highest prevalence of H. pylori antibodies, the subjects born after the turn of the century at a time of maximum crowding and poor hygiene in Iceland due to the industrial revolution.

KOREANS

High prevalence of duodenal ulcer and gastric cancer in dyspeptic patients in Korea.

Malaty HM, Kim JG, El-Zimaity HM, Graham DY.

Dept. of Medicine, Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Scand J Gastroenterol 1997 Aug;32(8):751-4 Abstract quote
BACKGROUND: Although gastric cancer and duodenal ulcer are both related to Helicobacter pylori infection, they are mutually exclusive diseases such that patients with a history of duodenal ulcer have a markedly reduced risk of developing gastric cancer. It has been hypothesized that different strains of H. pylori may be related to the different diseases. Our aim was to study the prevalence of duodenal ulcer disease and gastric cancer in dyspeptic patients in South Korea, a country with a high incidence of gastric cancer.

METHODS: The study population consisted of consecutive patients between the ages of 20 and 81 years referred to Guro Hospital's Endoscopic Unit for evaluation of dyspepsia. Patients with a history of peptic ulcer or gastric cancer were excluded. Each patient underwent endoscopy and completed a detailed questionnaire. Peptic ulcer was defined as the presence of an active ulcer, red scar, or white scar.

RESULTS: One thousand patients were evaluated, and 867 (43% men and 57% women) met the entry criteria. The prevalence of peptic ulcer and gastric cancer were 24% and 7%, respectively. Among peptic ulcer patients, duodenal ulcer was commoner (75%) than gastric ulcer or coexistent duodenal and gastric ulcer (21% and 4%, respectively). The mean age of duodenal and gastric ulcer patients (45 +/- 14 and 48 +/- 12 years, respectively) was significantly lower than that of gastric cancer patients (59 +/- 11 years) (P < 0.01). Only 44 (7%) of the 597 remaining patients had definite endoscopic abnormalities (for example, erosive esophagitis, duodenitis, or pyloric deformity).

CONCLUSION: Gastric cancer and duodenal ulcer were prevalent diagnoses among Korean patients undergoing endoscopy for evaluation of dyspepsia. Korea may be the ideal country to investigate the relation between specific H. pylori strains and different H. pylori diseases.

DISEASE ASSOCIATIONS CHARACTERIZATION

ANXIETY

Generalized anxiety disorder and peptic ulcer disease among adults in the United States.

Goodwin RD, Stein MB.

Department of Epidemiology (R.D.G.), Mailman School of Public Health, Columbia University, New York, New York.

Psychosom Med 2002 Nov-Dec;64(6):862-6 Abstract quote
OBJECTIVE: Previous research has suggested a link between chronic anxiety and peptic ulcer disease, though recent evidence documenting an infectious cause (Helicobacter pylori) for ulcer has led to doubt about this association. The goal of the current study was to determine the relationship between generalized anxiety disorder (GAD) and self-reported peptic ulcer disease (PUD) among adults in the community.

METHODS: Data were drawn from the National Comorbidity Survey, a representative household survey of the adult population of the United States (N = 8098). Multivariate logistic regression analyses were used to determine the relationship between GAD and self-reported ulcer, controlling for differences in sociodemographic characteristics and psychiatric and medical comorbidity.

RESULTS: GAD was associated with a significantly increased risk of self-reported PUD (odds ratio = 2.8, 95% confidence interval = 1.4-5.7; p =.0002) after adjusting for differences in sociodemographic characteristics, comorbid mental disorders, and physical morbidity. Further analyses revealed a dose-response relationship between number of GAD symptoms (odds ratio = 1.2, 95% confidence interval = 1.1-1.4; p =.001) and increased risk of self-reported PUD.

CONCLUSIONS: These findings are consistent with and extend previous clinical and epidemiologic data, providing evidence of a dose-response relationship between GAD and self-reported PUD among adults in the general population. The mechanism of this association remains unknown. Future work investigating the relationship between onset of GAD and development of PUD in prospective, longitudinal, epidemiologic data with objective measures of physical health status and mental health may be useful in improving our understanding of this link.

ULCERATIVE COLITIS

The long-term time trends of peptic ulcer and ulcerative colitis are interrelated.

Cucino C, Sonnenberg A.

New Mexico VA Health Care System, Albuquerque 87108, USA.
Am J Gastroenterol 2002 Oct;97(10):2657-62 Abstract quote
OBJECTIVE: A birth-cohort phenomenon in the time trends of a disease indicates that exposure to relevant risk factors must have occurred during an early period of life. The aim of this study was to determine whether birth-cohort patterns are common features of ulcerative colitis, gastric ulcer, and duodenal ulcer in different countries.

METHODS: The number of deaths from ulcerative colitis, gastric, and duodenal ulcer in England, Netherlands, Italy, Switzerland, United States, and Scotland were retrieved from the respective national statistics offices. The death rates from the six countries were plotted against the period of birth. Age-standardized cohort mortality ratios were calculated as a summary of the overall mortality associated with each consecutive birth-cohort.

RESULTS: In all countries alike, mortality from ulcerative colitis, gastric, and duodenal ulcer increased among successive generations born during the 19th century and, after reaching a sharp peak around the turn of the 20th century, declined among generations born subsequently. The rise in mortality from gastric ulcer preceded a similar rise in mortality from duodenal ulcer by 10-20 yr, and the temporal changes of duodenal ulcer coincided with those of ulcerative colitis.

CONCLUSIONS: The sudden rise of peptic ulcer disease during the 19th century and the 10-20-yr time lag between gastric and duodenal ulcer are difficult to explain based on changing infection rates with Helicobacterpylori alone. The similarity between the time trends of duodenal ulcer and ulcerative colitis suggests the influence of one or more shared risk factors.

PATHOGENESIS CHARACTERIZATION

GENERAL

Bleeding peptic ulcers and presence of Helicobacter pylori by various tests: a case-control study.

Castillo-Rojas G, Ballesteros MA, Ponce de Leon S, Morales-Espinosa R, Cravioto A, Lopez-Vidal Y.

Universidad Nacional Autonoma de Mexico, Facultad de Medicina, Programa de Inmunologia Molecular Microbiana, Edif. de investigacion, 4to piso, Mexico DF, CP 04510, Mexico.

Eur J Gastroenterol Hepatol 2002 Oct;14(10):1113-8 Abstract quote.
BACKGROUND: Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with bleeding peptic ulcers (BPU). AIM: To determine whether H. pylori and/or the cytotoxin-associated gene (cagA) can increase the risk of bleeding in peptic ulcers.

PATIENTS: Sixty-seven patients were studied. Thirty had BPU, 20 had non-bleeding peptic ulcers (NBPU), and 17 were control subjects (NPU).

METHODS: The prevalence of H. pylori was assessed by the urease fast test, histological examination, serology, and 16S ribosomal RNA and cagA gene amplification by polymerase chain reaction (PCR).

RESULTS: Histology and PCR showed greater sensitivity for diagnosis of H. pylori under bleeding circumstances when compared with other tests. Association of H. pylori was greater in the NBPU group (odds ratio [OR] 4.91, P = 0.06) than in the BPU group (OR 1.27, P = NS) when compared with the control group. When the BPU and NBPU groups were compared, H. pylori was found more often in the NBPU group (OR 0.26, P < 0.10 ). The cagA-positive gene showed a similar distribution in the three groups. The titres for anti-CagA immunoglobulin A (IgA) antibodies were higher in NBPU patients (83%) than in BPU or control patients. Furthermore, anti-urease immunoglobulin G (IgG) was detected more frequently among BPU and NBPU patients.

CONCLUSIONS: NBPU patients had the highest prevalence of H. pylori by PCR. It seems unlikely that either H. pylori or the cagA-positive gene act as significant risk factors for bleeding in peptic ulcers. The lower prevalence of the microorganism among patients who bleed cannot be explained as an artificial finding.

Helicobacter pylori genotypes, host factors, and gastric mucosal histopathology in peptic ulcer disease

Kyi T. Tham, etal.

Hum Pathol 2001 Mar;32(3):264-73. (Abstract quote)

From 183 patients undergoing upper gastrointestinal endoscopy, we used antral and corpus gastric biopsies for bacterial culture and histopathologic examination, blood samples to detect immunoglobulin G antibodies against Helicobacter pylori, and H pylori genomic DNA to analyze cytotoxin-associated gene A (cagA) and vacuolating cytotoxin (vacA) genotypes.

As expected, among H pylori biopsy-positive patients, those with duodenal ulcer (DU) (n = 34) had significantly more severe chronic and acute inflammation (P < .001) and epithelial degeneration (P = .004) in the gastric antrum than in the gastric corpus. Each of those 3 parameters and H pylori density were significantly higher in the antrum of patients with DU than in patients with gastric ulcer (GU) or no ulcer. Colonization with vacA s1/cagA-positive strains of H pylori was associated with inflammation and epithelial degeneration in gastric mucosa and increased risk for peptic ulcer disease (PUD), whereas colonization with vacA s2m2/cagA-negative strains was associated with mild gastric histopathology and was not associated with any significant risk for PUD. The predominant H pylori strains in African Americans were vacA s1bm1/cagA-positive, whereas all genotypes were well represented in non�Hispanic-Caucasians.

By multivariate analysis, H pylori colonization was significantly associated with DU (Adjusted odds ratio [AdjOR] = 3.2 [1.4-7.2]) and nonsteroidal anti-inflammatory drugs (NSAID) use was inversely associated (AdjOR = 0.3 [0.2-0.7]). NSAID use (AdjOR = 4.3 [1.02-18.5]) and African-American ethnicity (AdjOR = 10.9 [2.6-50]) were significantly associated with GU. Smoking and age were not significantly associated with either DU or GU.

These data indicate that DU is associated with an antral-dominant gastritis, and H pylori genotype and NSAID use independently contribute to the pathogenesis of PUD.

HELICOBACTER PYLORI

NSAIDS

Prevention of complicated ulcer disease among chronic users of nonsteroidal anti-inflammatory drugs: the use of a nomogram in cost-effectiveness analysis.

El-Serag HB, Graham DY, Richardson P, Inadomi JM.

Health Services Research Sections, Houston Center for Quality of Care & Utilization Studies, Department of Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.
Arch Intern Med 2002 Oct 14;162(18):2105-10 Abstract quote
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of clinical upper gastrointestinal tract (UGI) events, namely, symptomatic ulcer, perforation, bleeding, and obstruction. Our objective in this study was to compare the cost-effectiveness of several strategies aimed at reducing the risk of clinical UGI events in NSAID users.

METHODS: A decision tree model was used for patients requiring long-term treatment with NSAIDs to compare conventional NSAID therapy alone with 7 other treatment strategies to reduce the risk of NSAID-related clinical UGI events (cotherapy with proton-pump inhibitor, cotherapy with misoprostol, cyclooxygenase [COX]-2-selective NSAID therapy, or Helicobacter pylori treatment followed by each of the previous strategies, including conventional NSAID treatment, respectively). The outcome measure is the incremental cost per clinical UGI event prevented compared with conventional NSAID treatment over 1 year.

RESULTS: The use of a COX-2-selective NSAID and cotherapy with proton-pump inhibitors were the 2 most cost-effective strategies. However, the incremental cost associated with these strategies was high (>$35 000) in persons with a low risk of clinical UGI event with conventional NSAIDs (eg, 2.5% per year). If the baseline risk of clinical UGI events is moderately high (eg, 6.5%), using a COX-2-selective NSAID becomes the most effective and least costly (dominant) treatment strategy, followed closely by cotherapy with a daily proton-pump inhibitor. Because small changes in costs or assumed efficacy of these drugs could change the conclusions, the incremental cost-effectiveness ratios between any 2 strategies were presented in a nomogram that allows the flexible use of a wide range of values for costs and rates of clinical UGI events.

CONCLUSIONS: The risk of clinical UGI events in NSAID users depends on their baseline risk, the added risk associated with the individual NSAID, and the protection conferred by cotherapy. A nomogram can be used to incorporate these factors and derive estimates regarding cost-effectiveness of competing strategies aimed at reducing the risk of clinical UGI events.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

LABORATORY MARKERS

ENDOSCOPY

Diagnostic yield of upper endoscopy in Asian patients presenting with dyspepsia.

Wai CT, Yeoh KG, Ho KY, Kang JY, Lim SG.

Division of Gastroenterology, Department of Medicine, National University Hospital, Singapore.

Gastrointest Endosc 2002 Oct;56(4):548-51 Abstract quote
BACKGROUND: The aim of this study was to determine the frequency of diagnosis of significant disease by EGD in Asian patients of various ages with simple dyspepsia.

METHODS: Database records of 10,488 consecutive patients undergoing EGD between 1992 and 1998 were analyzed. The frequency of significant upper GI disease (defined as esophagitis, peptic ulcer, and cancer) in patients presenting with simple dyspepsia was determined for various age groups.

RESULTS: For the indication simple dyspepsia, 5066 (48.3%) EGDs were performed. At 988 (19.5%) EGDs, significant disease was noted (peptic ulcer 14.9%, esophagitis 5.0%, stomach cancer 0.47%, esophageal cancer 0.06%). There was a positive correlation between disease frequency and increasing age. The cumulative percentages of significant disease by age group were as follows: 10.8% in patients less than 35 years of age, 11.9% for those less than 40 years old, 13.7% for patients less than 45 years of age, and 19.5% overall. The cumulative frequencies of gastric cancer by age group were as follows: 0.68 of 1000 EGDs in patients less than 35 years of age, 1.15 of 1000 EGDs in patients less than 45 years old, and 9.60 of 1000 EGDs in patients greater than 45 years of age.

CONCLUSION: The present study provides data to assist decision-making regarding the use of EGD in the patient population of Singapore. For patients with simple dyspepsia residing in Singapore, an age threshold of 45 years is reasonable inasmuch as gastric cancer is rarely found at endoscopy in younger patients. The age threshold for EGD for simple dyspepsia for Asians residing in other parts of the world would have to be determined based on the local prevalence of gastric cancer.

Accuracy of the initial endoscopic diagnosis in the discrimination of gastric ulcers: is endoscopic follow-up study always needed?

Bustamante M, Devesa F, Borghol A, Ortuno J, Ferrando MJ.

Francesc de Borja Hospital, Valencia, Spain.
J Clin Gastroenterol 2002 Jul;35(1):25-8 Abstract quote
BACKGROUND: Endoscopic follow-up study of gastric ulcers has been recommended routinely because of the possibility that a gastric neoplasm will be missed in the initial endoscopy. Some authors, most of them reporting data from areas of low gastric carcinoma incidence, have questioned this policy because of the low numbers of curable cancers detected and the high cost of such a program.

GOALS: To assess the accuracy of endoscopy diagnosis of gastric ulcers, and to evaluate the efficacy and cost of a gastric ulcer follow-up endoscopic program in an area with an intermediate incidence rate of gastric cancer.

STUDY: A retrospective study was used to identify all the gastroscopies in which a gastric ulcer had been diagnosed during a 6-year period. The endoscopic impression was compared with the histologic diagnosis, sensitivity, specificity, positive and negative predictive values, and the likelihood ratio. Patients who completed a follow-up program also were reviewed. For each neoplasm discovered, the number of endoscopies and global cost were calculated.

RESULTS: In the 741 gastroscopies performed, 547 gastric ulcers were diagnosed in 529 patients. Biopsies were taken in 330 patients, in whom 341 gastric ulcers were found. At the index endoscopy, 41 gastric neoplasms (12.4%) were diagnosed. The accuracy of endoscopic malignancy diagnosis was as follows: positive predictive value of 0.68, negative predictive value of 0.98, sensitivity of 0.82, and specificity of 0.95. The likelihood ratio was 16. A total of 117 patients completed the follow-up program. Three new cases of gastric cancer (2.6%) were identified. In these three cases, the initial opinion of the endoscopist was uncertain. In the authors' experience, the cost of each gastric cancer diagnosed has been $4.653 (U.S. dollars).

CONCLUSIONS: The endoscopic impression correlates with the histologic diagnosis even in a area of intermediate gastric cancer incidence. Endoscopic follow-up study may be restricted to cases of uncertain or malignant endoscopic impression.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

DUODENAL ULCERS

Non-Helicobacter pylori related duodenal ulcer disease in children.

Elitsur Y, Lawrence Z.

Department of Pediatrics, Division of Gastroenterology, Marshall University School of Medicine, Huntington, WV 25701-0195, USA.

Helicobacter 2001 Sep;6(3):239-43 Abstract quote
BACKGROUND: In spite of the worldwide distribution of Helicobacter pylori infection, recent data have reported an increased rate of non-H. pylori, non-NSAIDs-duodenal ulcer disease in adults. The estimated rate of these ulcers in children is unknown. We aimed to investigate the prevalence of non-H. pylori, non-NSAIDs-peptic ulcer disease in our pediatric patients who undergo upper endoscopic procedures.

METHODS: A retrospective analysis of 622 upper endoscopic reports was performed. Reports that documented mucosal ulcerations were included in our study. The demographic, clinical, endoscopic, and histological data were retrieved. The H. pylori-negative, duodenal/gastric ulcer-positive patients were compared with H. pylori-positive, duodenal/gastric ulcer-positive patients.

RESULTS: Out of the 622 upper endoscopy reports, a total of 11 (1.8%) children with mucosal ulceration were studied. Mucosal ulceration was distributed in the following locations: stomach-3 (27%), and duodenal bulb-10 (91%) (two children had ulcers in both the stomach and duodenal bulb). Helicobacter pylori infection was only detected in three (27%) children with duodenal ulcer. Gastritis was more severe in patients with H. pylori infection/duodenal ulcer compared with H. pylori-negative/duodenal ulcer group. No statistical difference in clinical symptoms or endoscopic appearance was observed between the H. pylori-negative and H. pylori-positive groups.

CONCLUSION: 'Idiopathic' (H. pylori-negative, NSAIDs-negative) duodenal/gastric ulcers are present in symptomatic children. Clinical or endoscopic characteristics are insufficient markers to identify those 'idiopathic' ulcers. Investigating the 'risk factors' for those ulcers will be helpful in reducing the morbidity in these children.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL

VARIANTS

FUNDIC GLAND POLYPS

Fundic Gland Polyps Are Not Induced by Proton Pump Inhibitor Therapy

Michael Vieth, MD, PhD, and Manfred Stolte, MD, PhD

Am J Clin Pathol 116:716-720 Abstract quote

It is still unclear whether proton pump inhibitors (PPIs) could cause fundic gland polyps (FGPs) in patients without Helicobacter pylori infection. The frequency of FGPs in patients during PPI therapy has not been compared, however, with a control group of patients who did not have H pylori infection and were not undergoing PPI treatment.

In a retrospective 12-month study, the frequency of FGPs in 2,251 patients without H pylori infection receiving PPI therapy (duration of treatment at least 4 weeks) was compared with a control group of 28,096 patients who did not have H pylori infection and were not receiving PPI therapy. FGPs were identified with an identical frequency in both groups (5.0% in the control and 5.2% in the PPI group).

No significant differences were present between the groups with respect to the presence of gastritis or age or sex. Our study shows that a causal pathogenetic relationship between PPI therapy and FGPs is unlikely.

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

IMMUNOPEROXIDASE

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

MORTALITY

Hospitalization and mortality rates from peptic ulcer disease and GI bleeding in the 1990s: relationship to sales of nonsteroidal anti-inflammatory drugs and acid suppression medications.

Lewis JD, Bilker WB, Brensinger C, Farrar JT, Strom BL.

Center for Clinical Epidemiology and Biostatistics, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA.

Am J Gastroenterol 2002 Oct;97(10):2540-9 Abstract quote
OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause peptic ulcer disease and upper GI bleeding. Acid suppression medications effectively treat NSAID-induced ulcers. However, it is unknown what effect the availability of proton pump inhibitors and over-the-counter preparations of NSAIDs and histamine type 2 receptor antagonists have had on population rates of hospitalization and mortality from GI toxicity. This study examines trends in hospitalization and mortality rates from GI toxicity during the 1990s.

METHODS: We performed an analysis of secular trends of hospitalization and mortality rates from peptic ulcer disease, upper GI bleeding, and any GI bleeding using data from the National Hospital Discharge Survey, comparing them with sales of NSAIDs, aspirin, and acid suppression medications from 1992 to 1999.

RESULTS: From 1992 to 1999, annual rates of hospitalization and mortality per 100,000 population for peptic ulcer disease declined from 205 to 165 and 7.7 to 6.0, respectively; calendar year was negatively correlated with both peptic ulcer disease hospitalization rates (p = -0.88, p = 0.007) and mortality rates (p = -0.71, p = 0.058). In contrast, these correlations did not reach statistical significance for upper or any GI bleeding (p > 0.1 for all comparisons). Sales of acid suppression medications were negatively correlated with peptic ulcer disease hospitalization rates (p = -0.76, p = 0.037) and mortality rates (p = -0.83, p = 0.015). Sales of NSAIDs were not positively correlated with hospitalization or mortality rates from peptic ulcer disease or GI bleeding (p > 0.2 for all comparisons).

CONCLUSIONS: Despite changing patterns of use of NSAIDs and acid suppression medications during the 1990s, mortality rates from GI bleeding and peptic ulcer disease have been relatively stable, with an apparent decline in hospitalization rates and mortality from peptic ulcer disease. Changing rates of peptic ulcer disease morbidity and mortality were temporally related to increasing sales of antiulcerants but not to change in sales of NSAIDs.

Hospitalization for peptic ulcer bleeding: evaluation of a risk scoring system in clinical practice.

Garripoli A, Mondardini A, Turco D, Martinoglio P, Secreto P, Ferrari A.

Gastrointestinal Unit, Maria Vittoria Hospital, Torino, Italy.
Dig Liver Dis 2000 Oct;32(7):577-82 Abstract quote
BACKGROUND: Upper gastrointestinal tract haemorrhage is a common cause of hospitalization: resource utilization in management of peptic ulcer bleeding varies considerably with no apparent effect on patient outcome. Several risk score systems based on endoscopic and clinical data have been proposed and validated in order to aid patient management. AIM: To assess clinical reliability of a scoring system and to define guidelines to improve efficiency of patient management without reducing efficacy

METHODS: We considered all patients admitted to our unit for bleeding peptic ulcer over a one-year period. Every patient had an early endoscopy (within 12 hours) and therapy according to the appearance of the ulcer defined by Forrest classification. All subjects were classified into low-, intermediate- and high-risk patients on basis of clinical and endoscopic features according to "Cedar Sinai Medical Center predictive index" which was applied retrospectively in first six months then perspectively for the last period using the results obtained from first semester. For each risk group, we compared Length of Hospital Stay number of blood units used in transfusion, rebleeding rate, need for surgery as well as mortality in the two periods, using Student t test. We correlated Length of Hospital Stay and every score parameter by applying analysis of variance to results over the one-year period.

RESULTS: Study population consists of 91 patients. Recurrent bleeding was observed in only three entering the high-risk group, only one of whom needed surgery Overall mortality was 9.8% (9 patients, only one for rebleeding). Variance analysis showed that the only parameter of the "Cedar Sinai Medical Center predictive index" which correlated with Length of Hospital Stay was comorbidity (p < or =0.05). Comparing the two periods, a close application of the score in the last six months allowed Length of Hospital Stay to be reduced in low-risk patients (t test with p=0.004) resulting in early discharge of 33% of cases without affecting patient outcome.

CONCLUSIONS: This study confirms the reliability of the "Cedar Sinai Medical Center predictive index" in clinical practice improving the strategy of applying economic resources. Longer Length of Hospital Stay of intermediate- and high-risk groups is influenced more by comorbidities than by endoscopic findings. Early discharge was possible in one third of low risk patients. An accurate evaluation clinical para meters on admission together with early endoscopy may achieve the goal of reducing costs with a correct patient management.

REBLEEDING AFTER TREATMENT

Effect of programmed endoscopic follow-up examinations on the rebleeding rate of gastric or duodenal peptic ulcers treated by injection therapy: a prospective, randomized controlled trial.

Messmann H, Schaller P, Andus T, Lock G, Vogt W, Gross V, Zirngibl H, Wiedmann KH, Lingenfelser T, Bauch K, Leser HG, Scholmerich J, Holstege A.

Dept. of Internal Medicine, University of Regensburg, Germany.

Endoscopy 1998 Sep;30(7):583-9 Abstract quote
BACKGROUND AND STUDY AIMS: A second-look endoscopy is often performed to evaluate the efficacy of a prior injection therapy in patients with bleeding peptic gastric or duodenal ulcers. Although this strategy is widely established, it does not rely on unequivocal data from controlled studies. In a prospective, randomized, controlled multicenter trial we assessed the effect of programmed endoscopic follow-up examinations with eventual retreatment on the outcome of bleeding ulcers in these patients.

PATIENTS AND METHODS: One hundred and five patients with gastric or duodenal peptic ulcers presenting with active (Forrest type I) or recent (Forrest type IIa and IIb) bleeding upon endoscopy within four hours after admission were included in the study. Emergency treatment consisted of the sequential injection of both epinephrine (1:10,000 v/v) and up to 2 ml of fibrin/thrombin around the ulcer base. Fifty-two patients were randomized to receive programmed endoscopic monitoring with eventual retreatment in cases of Forrest type I, IIa, or IIb ulcers beginning within 16-24 hours after the index bleed. Follow-up endoscopies were continued until the macroscopic appearance revealed a Forrest type IIc or III ulcer. Fifty-three patients in the control group were closely monitored, and only received a second endoscopy when there was clinical or biochemical evidence of recurrent bleeding. The groups did not differ with respect to age, sex, site and severity of bleeding.

RESULTS: The numbers of patients with recurrent bleeding were similar whether they were endoscopically monitored or not (21% versus 17%, P=0.80 chi-squared test). In addition, there was no statistically significant difference between the two groups with respect to the number of blood units transfused, need for surgical intervention, hospital stay or number of deaths (Mann-Whitney U-test). Improving local ulcer stigmata was not related to a better outcome.

CONCLUSIONS: Programmed endoscopic follow-up examinations with eventual retreatment in patients locally injected for an acute or recent hemorrhage from a gastric or duodenal ulcer did not influence their outcome when compared to patients receiving only a second endoscopic intervention upon evidence for recurrent hemorrhage. Scheduled control endoscopies cannot be recommended after an initial successful endoscopic treatment of peptic ulcer bleeding when selection of the patients for second-look endoscopy is directed by the Forrest criteria.

TREATMENT

FIBRIN SEALANT

Endoscopic injection with fibrin sealant versus epinephrine for arrest of peptic ulcer bleeding: a randomized, comparative trial.

Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD.

Division of Gastroenterology, Department of Medicine, VGH-TAIPEI, Taipei, Taiwan, ROC.
J Clin Gastroenterol 2002 Sep;35(3):218-21 Abstract quote
BACKGROUND: endoscopic epinephrine and fibrin injection in the treatment of bleeding peptic ulcer are reported to be safe, effective, and easy to use. However, a wide range of rebleeding rates has been reported with epinephrine injection.

GOALS: to compare the hemostatic effects of endoscopic injection with fibrin sealant versus epinephrine.

STUDY: between December 1998 and July 2000, 51 patients with active bleeding or nonbleeding visible vessels entered this trial. The clinical parameters were comparable between both groups. In the epinephrine group, we injected 5 to 10 mL of 1:10,000 epinephrine, surrounding the bleeder. In the fibrin sealant group, we injected fibrin sealant 4 mL, surrounding the bleeder.

RESULTS: initial hemostasis was obtained in all enrolled patients. Rebleeding was more in the epinephrine group than in the fibrin sealant group (4 [15%] of 26 vs. 14 [56%] of 25, = 0.003 on the intention-to-treat basis, and 4 [16.7%] of 24 vs. 14 [58.3%] of 24, = 0.003 on the per protocol basis, respectively). Volume of blood transfusion, number of surgeries, hospital stay, and number of deaths were similar between both groups.

CONCLUSION: fibrin sealant injection is more effective in preventing rebleeding than epinephrine after endoscopic therapy, but this study showed no difference in outcomes with either therapy.

HELICOBACTER ERADICATION

Helicobacter pylori eradication ameliorates symptoms and improves quality of life in patients on long-term acid suppression. A large prospective study in primary care.

Verma S, Giaffer MH.

Department of Gastroenterology, Hull Royal Infirmary, UK.
Dig Dis Sci 2002 Jul;47(7):1567-74 Abstract quote
Our objective was to determine prescribing patterns for H2 receptor antagonists (H2RA) in primary care and to establish the prevalence and impact of Helicobacter pylori (Hp) eradication in this population of patients. Patients on long-term (6 months or longer) H2RA were identified through a computerized database at the six primary care practices in North England. Hp status was identified by serology, and those positive received standard proton pump-based triple therapy followed by a urea breath test to confirm Hp eradication.

The main outcome measures were the indications for prescribing long-term H2RA in primary care, the prevalence of patients with a positive Hp serology, and the impact of Hp eradication on the subsequent need for acid suppression, severity of dyspepsia, gastrointestinal symptom rating score (GSRS), quality of life (QOL), and overall feeling of well-being. One thousand seven (1.5%) patients were on long-term H2RA. Peptic ulcer disease (PUD) was the most common indication for prescribing (42%), followed by nonulcer dyspepsia (28%) and gastroesophageal reflux disease (23%). In 81% of the patients treatment with H2RA therapy followed a previous endoscopic or radiological investigation. Only 27 (2.5%) patients had had their Hp status checked within the last 6 months. Of the 471 patients who eventually had their Hp serology tested, 297 (63%) were Hp positive. Fifty-eight percent of the Hp-positive patients had PUD. Successful Hp eradication was achieved in 250 (84%) of the patients, of whom 247 (83%) finished the 1-year follow-up.

This was associated with a significant reduction in the amount of H2RA being consumed (P < 0.00001). There was also a significant improvement in the symptom scores and the GSRS after successful Hp eradication (P < 0.00001). Overall 67% of the patients reported an improvement in the QOL and 77% noted a feeling of well-being 1 year after Hp eradication. A significant proportion of patients in primary care is still being maintained on long-term H2RA, imposing a considerable financial drain on the NHS resources.

Approximately two-thirds of these patients will be Hp positive, and among them the largest group will comprise patients with PUD. Hp eradication in such patients results in a significant reduction in usage of acid suppression and an improvement in overall QOL and severity of dyspeptic symptoms.

PROTON PUMP INHIBITORS

Reappraisal of non-invasive management strategies for uninvestigated dyspepsia: a cost-minimization analysis.

Ladabaum U, Chey WD, Scheiman JM, Fendrick AM.

Division of Gastroenterology, Department of Medicine, University of California, San Francisco, Ca 94143-0538, USA.
Aliment Pharmacol Ther 2002 Aug;16(8):1491-501 Abstract quote
BACKGROUND: The benefits of the Helicobacter pylori test-and-treat strategy are attributable largely to the cure of peptic ulcer disease while limiting the use of endoscopy. AIM: To reappraise the test-and-treat strategy and empirical proton pump inhibitor therapy for the management of uninvestigated dyspepsia in the light of the decreasing prevalence of H. pylori infection, peptic ulcer disease and peptic ulcer disease attributable to H. pylori.

METHODS: Using a decision analytical model, we estimated the cost per patient with uninvestigated dyspepsia managed with the test-and-treat strategy ($25/test; H.pylori treatment, $200) or proton pump inhibitor ($90/month). Endoscopy ($550) guided therapy for persistent or recurrent symptoms.

RESULTS: In the base case (25%H. pylori prevalence, 20% likelihood of peptic ulcer disease, 75% of ulcers due to H.pylori), the cost per patient is $545 with the test-and-treat strategy and $529 with proton pump inhibitor, and both strategies yield similar clinical outcomes at 1 year. H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H.pylori are important determinants of the least costly strategy. At an H. pylori prevalence below 20%, proton pump inhibitor is consistently less costly than the test-and-treat strategy.

CONCLUSIONS: As the H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H. pylori decrease, empirical proton pump inhibitor becomes less costly than the test-and-treat strategy for the management of uninvestigated dyspepsia. Given the modest cost differential between the strategies, the test-and-treat strategy may be favoured if patients without peptic ulcer disease derive long-term benefit from H.pylori eradication.

THERMOCOAGULATION

A prospective, randomized trial of endoscopic hemoclip versus heater probe thermocoagulation for peptic ulcer bleeding.

Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD.

Department of Medicine, VGH-Taipei, and School of Medicine, National Yang-Ming University, Taiwan, ROC.

Am J Gastroenterol 2002 Sep;97(9):2250-4 Abstract quote
OBJECTIVES: Endoscopic heater probe thermocoagulation and hemoclip are considered to be safe and very effective in the treatment of bleeding peptic ulcer. So far, there are only few reports concerning hemostasis with endoscopic hemoclip. The aims of this study were to compare the hemostatic effects of both therapeutic modalities in patients with peptic ulcer bleeding.

METHODS: A total of 80 patients with active bleeding or nonbleeding visible vessels were randomized to receive endoscopic hemoclip (n = 40) or heater probe thermocoagulation (n = 40).

RESULTS: Initial hemostasis was achieved in 34 patients (85%) in the hemoclip group and 40 patients (100%) in the heater probe group (p = 0.01277). Rebleeding occurred in three patients (8.8%) in the hemoclip group and two patients (5%) in the heater probe group (p > 0.1). Among patients with difficult-to-approach bleeding, we obtained a better hemostatic rate in the heater probe group (nine of 11 patients vs three of 10, p = 0.02417). The volume of blood transfused after entry into the study, duration of hospital stay, number of patients requiring urgent surgery, and the mortality rate were not statistically significantly different between the two groups.

CONCLUSIONS: For patients with peptic ulcer bleeding, heater probe thermocoagulation offers an advantage in achieving hemostasis than hemoclip. In difficult-to-approach bleeders, heater probe is a more suitable therapeutic modality.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.

Commonly Used Terms

Stress ulcers -Acutely developing ulcers following severe stress. Often encountered in patients with shock and significant trauma.

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Internet Links

Helicobacter pylori
Pathologists Who Make A Difference

Last Updated 12/6/2002

PATHOGENESIS	CHARACTERIZATION
GENERAL
Bleeding peptic ulcers and presence of Helicobacter pylori by various tests: a case-control study. Castillo-Rojas G, Ballesteros MA, Ponce de Leon S, Morales-Espinosa R, Cravioto A, Lopez-Vidal Y. Universidad Nacional Autonoma de Mexico, Facultad de Medicina, Programa de Inmunologia Molecular Microbiana, Edif. de investigacion, 4to piso, Mexico DF, CP 04510, Mexico.	Eur J Gastroenterol Hepatol 2002 Oct;14(10):1113-8 Abstract quote. BACKGROUND: Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with bleeding peptic ulcers (BPU). AIM: To determine whether H. pylori and/or the cytotoxin-associated gene (cagA) can increase the risk of bleeding in peptic ulcers. PATIENTS: Sixty-seven patients were studied. Thirty had BPU, 20 had non-bleeding peptic ulcers (NBPU), and 17 were control subjects (NPU). METHODS: The prevalence of H. pylori was assessed by the urease fast test, histological examination, serology, and 16S ribosomal RNA and cagA gene amplification by polymerase chain reaction (PCR). RESULTS: Histology and PCR showed greater sensitivity for diagnosis of H. pylori under bleeding circumstances when compared with other tests. Association of H. pylori was greater in the NBPU group (odds ratio [OR] 4.91, P = 0.06) than in the BPU group (OR 1.27, P = NS) when compared with the control group. When the BPU and NBPU groups were compared, H. pylori was found more often in the NBPU group (OR 0.26, P < 0.10 ). The cagA-positive gene showed a similar distribution in the three groups. The titres for anti-CagA immunoglobulin A (IgA) antibodies were higher in NBPU patients (83%) than in BPU or control patients. Furthermore, anti-urease immunoglobulin G (IgG) was detected more frequently among BPU and NBPU patients. CONCLUSIONS: NBPU patients had the highest prevalence of H. pylori by PCR. It seems unlikely that either H. pylori or the cagA-positive gene act as significant risk factors for bleeding in peptic ulcers. The lower prevalence of the microorganism among patients who bleed cannot be explained as an artificial finding.
Helicobacter pylori genotypes, host factors, and gastric mucosal histopathology in peptic ulcer disease Kyi T. Tham, etal.	Hum Pathol 2001 Mar;32(3):264-73. (Abstract quote) From 183 patients undergoing upper gastrointestinal endoscopy, we used antral and corpus gastric biopsies for bacterial culture and histopathologic examination, blood samples to detect immunoglobulin G antibodies against Helicobacter pylori, and H pylori genomic DNA to analyze cytotoxin-associated gene A (cagA) and vacuolating cytotoxin (vacA) genotypes. As expected, among H pylori biopsy-positive patients, those with duodenal ulcer (DU) (n = 34) had significantly more severe chronic and acute inflammation (P < .001) and epithelial degeneration (P = .004) in the gastric antrum than in the gastric corpus. Each of those 3 parameters and H pylori density were significantly higher in the antrum of patients with DU than in patients with gastric ulcer (GU) or no ulcer. Colonization with vacA s1/cagA-positive strains of H pylori was associated with inflammation and epithelial degeneration in gastric mucosa and increased risk for peptic ulcer disease (PUD), whereas colonization with vacA s2m2/cagA-negative strains was associated with mild gastric histopathology and was not associated with any significant risk for PUD. The predominant H pylori strains in African Americans were vacA s1bm1/cagA-positive, whereas all genotypes were well represented in non�Hispanic-Caucasians. By multivariate analysis, H pylori colonization was significantly associated with DU (Adjusted odds ratio [AdjOR] = 3.2 [1.4-7.2]) and nonsteroidal anti-inflammatory drugs (NSAID) use was inversely associated (AdjOR = 0.3 [0.2-0.7]). NSAID use (AdjOR = 4.3 [1.02-18.5]) and African-American ethnicity (AdjOR = 10.9 [2.6-50]) were significantly associated with GU. Smoking and age were not significantly associated with either DU or GU. These data indicate that DU is associated with an antral-dominant gastritis, and H pylori genotype and NSAID use independently contribute to the pathogenesis of PUD.
HELICOBACTER PYLORI
NSAIDS
Prevention of complicated ulcer disease among chronic users of nonsteroidal anti-inflammatory drugs: the use of a nomogram in cost-effectiveness analysis. El-Serag HB, Graham DY, Richardson P, Inadomi JM. Health Services Research Sections, Houston Center for Quality of Care & Utilization Studies, Department of Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.	Arch Intern Med 2002 Oct 14;162(18):2105-10 Abstract quote BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of clinical upper gastrointestinal tract (UGI) events, namely, symptomatic ulcer, perforation, bleeding, and obstruction. Our objective in this study was to compare the cost-effectiveness of several strategies aimed at reducing the risk of clinical UGI events in NSAID users. METHODS: A decision tree model was used for patients requiring long-term treatment with NSAIDs to compare conventional NSAID therapy alone with 7 other treatment strategies to reduce the risk of NSAID-related clinical UGI events (cotherapy with proton-pump inhibitor, cotherapy with misoprostol, cyclooxygenase [COX]-2-selective NSAID therapy, or Helicobacter pylori treatment followed by each of the previous strategies, including conventional NSAID treatment, respectively). The outcome measure is the incremental cost per clinical UGI event prevented compared with conventional NSAID treatment over 1 year. RESULTS: The use of a COX-2-selective NSAID and cotherapy with proton-pump inhibitors were the 2 most cost-effective strategies. However, the incremental cost associated with these strategies was high (>$35 000) in persons with a low risk of clinical UGI event with conventional NSAIDs (eg, 2.5% per year). If the baseline risk of clinical UGI events is moderately high (eg, 6.5%), using a COX-2-selective NSAID becomes the most effective and least costly (dominant) treatment strategy, followed closely by cotherapy with a daily proton-pump inhibitor. Because small changes in costs or assumed efficacy of these drugs could change the conclusions, the incremental cost-effectiveness ratios between any 2 strategies were presented in a nomogram that allows the flexible use of a wide range of values for costs and rates of clinical UGI events. CONCLUSIONS: The risk of clinical UGI events in NSAID users depends on their baseline risk, the added risk associated with the individual NSAID, and the protection conferred by cotherapy. A nomogram can be used to incorporate these factors and derive estimates regarding cost-effectiveness of competing strategies aimed at reducing the risk of clinical UGI events.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
LABORATORY MARKERS
ENDOSCOPY
Diagnostic yield of upper endoscopy in Asian patients presenting with dyspepsia. Wai CT, Yeoh KG, Ho KY, Kang JY, Lim SG. Division of Gastroenterology, Department of Medicine, National University Hospital, Singapore.	Gastrointest Endosc 2002 Oct;56(4):548-51 Abstract quote BACKGROUND: The aim of this study was to determine the frequency of diagnosis of significant disease by EGD in Asian patients of various ages with simple dyspepsia. METHODS: Database records of 10,488 consecutive patients undergoing EGD between 1992 and 1998 were analyzed. The frequency of significant upper GI disease (defined as esophagitis, peptic ulcer, and cancer) in patients presenting with simple dyspepsia was determined for various age groups. RESULTS: For the indication simple dyspepsia, 5066 (48.3%) EGDs were performed. At 988 (19.5%) EGDs, significant disease was noted (peptic ulcer 14.9%, esophagitis 5.0%, stomach cancer 0.47%, esophageal cancer 0.06%). There was a positive correlation between disease frequency and increasing age. The cumulative percentages of significant disease by age group were as follows: 10.8% in patients less than 35 years of age, 11.9% for those less than 40 years old, 13.7% for patients less than 45 years of age, and 19.5% overall. The cumulative frequencies of gastric cancer by age group were as follows: 0.68 of 1000 EGDs in patients less than 35 years of age, 1.15 of 1000 EGDs in patients less than 45 years old, and 9.60 of 1000 EGDs in patients greater than 45 years of age. CONCLUSION: The present study provides data to assist decision-making regarding the use of EGD in the patient population of Singapore. For patients with simple dyspepsia residing in Singapore, an age threshold of 45 years is reasonable inasmuch as gastric cancer is rarely found at endoscopy in younger patients. The age threshold for EGD for simple dyspepsia for Asians residing in other parts of the world would have to be determined based on the local prevalence of gastric cancer.
Accuracy of the initial endoscopic diagnosis in the discrimination of gastric ulcers: is endoscopic follow-up study always needed? Bustamante M, Devesa F, Borghol A, Ortuno J, Ferrando MJ. Francesc de Borja Hospital, Valencia, Spain.	J Clin Gastroenterol 2002 Jul;35(1):25-8 Abstract quote BACKGROUND: Endoscopic follow-up study of gastric ulcers has been recommended routinely because of the possibility that a gastric neoplasm will be missed in the initial endoscopy. Some authors, most of them reporting data from areas of low gastric carcinoma incidence, have questioned this policy because of the low numbers of curable cancers detected and the high cost of such a program. GOALS: To assess the accuracy of endoscopy diagnosis of gastric ulcers, and to evaluate the efficacy and cost of a gastric ulcer follow-up endoscopic program in an area with an intermediate incidence rate of gastric cancer. STUDY: A retrospective study was used to identify all the gastroscopies in which a gastric ulcer had been diagnosed during a 6-year period. The endoscopic impression was compared with the histologic diagnosis, sensitivity, specificity, positive and negative predictive values, and the likelihood ratio. Patients who completed a follow-up program also were reviewed. For each neoplasm discovered, the number of endoscopies and global cost were calculated. RESULTS: In the 741 gastroscopies performed, 547 gastric ulcers were diagnosed in 529 patients. Biopsies were taken in 330 patients, in whom 341 gastric ulcers were found. At the index endoscopy, 41 gastric neoplasms (12.4%) were diagnosed. The accuracy of endoscopic malignancy diagnosis was as follows: positive predictive value of 0.68, negative predictive value of 0.98, sensitivity of 0.82, and specificity of 0.95. The likelihood ratio was 16. A total of 117 patients completed the follow-up program. Three new cases of gastric cancer (2.6%) were identified. In these three cases, the initial opinion of the endoscopist was uncertain. In the authors' experience, the cost of each gastric cancer diagnosed has been $4.653 (U.S. dollars). CONCLUSIONS: The endoscopic impression correlates with the histologic diagnosis even in a area of intermediate gastric cancer incidence. Endoscopic follow-up study may be restricted to cases of uncertain or malignant endoscopic impression.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
MORTALITY
Hospitalization and mortality rates from peptic ulcer disease and GI bleeding in the 1990s: relationship to sales of nonsteroidal anti-inflammatory drugs and acid suppression medications. Lewis JD, Bilker WB, Brensinger C, Farrar JT, Strom BL. Center for Clinical Epidemiology and Biostatistics, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA.	Am J Gastroenterol 2002 Oct;97(10):2540-9 Abstract quote OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause peptic ulcer disease and upper GI bleeding. Acid suppression medications effectively treat NSAID-induced ulcers. However, it is unknown what effect the availability of proton pump inhibitors and over-the-counter preparations of NSAIDs and histamine type 2 receptor antagonists have had on population rates of hospitalization and mortality from GI toxicity. This study examines trends in hospitalization and mortality rates from GI toxicity during the 1990s. METHODS: We performed an analysis of secular trends of hospitalization and mortality rates from peptic ulcer disease, upper GI bleeding, and any GI bleeding using data from the National Hospital Discharge Survey, comparing them with sales of NSAIDs, aspirin, and acid suppression medications from 1992 to 1999. RESULTS: From 1992 to 1999, annual rates of hospitalization and mortality per 100,000 population for peptic ulcer disease declined from 205 to 165 and 7.7 to 6.0, respectively; calendar year was negatively correlated with both peptic ulcer disease hospitalization rates (p = -0.88, p = 0.007) and mortality rates (p = -0.71, p = 0.058). In contrast, these correlations did not reach statistical significance for upper or any GI bleeding (p > 0.1 for all comparisons). Sales of acid suppression medications were negatively correlated with peptic ulcer disease hospitalization rates (p = -0.76, p = 0.037) and mortality rates (p = -0.83, p = 0.015). Sales of NSAIDs were not positively correlated with hospitalization or mortality rates from peptic ulcer disease or GI bleeding (p > 0.2 for all comparisons). CONCLUSIONS: Despite changing patterns of use of NSAIDs and acid suppression medications during the 1990s, mortality rates from GI bleeding and peptic ulcer disease have been relatively stable, with an apparent decline in hospitalization rates and mortality from peptic ulcer disease. Changing rates of peptic ulcer disease morbidity and mortality were temporally related to increasing sales of antiulcerants but not to change in sales of NSAIDs.
Hospitalization for peptic ulcer bleeding: evaluation of a risk scoring system in clinical practice. Garripoli A, Mondardini A, Turco D, Martinoglio P, Secreto P, Ferrari A. Gastrointestinal Unit, Maria Vittoria Hospital, Torino, Italy.	Dig Liver Dis 2000 Oct;32(7):577-82 Abstract quote BACKGROUND: Upper gastrointestinal tract haemorrhage is a common cause of hospitalization: resource utilization in management of peptic ulcer bleeding varies considerably with no apparent effect on patient outcome. Several risk score systems based on endoscopic and clinical data have been proposed and validated in order to aid patient management. AIM: To assess clinical reliability of a scoring system and to define guidelines to improve efficiency of patient management without reducing efficacy METHODS: We considered all patients admitted to our unit for bleeding peptic ulcer over a one-year period. Every patient had an early endoscopy (within 12 hours) and therapy according to the appearance of the ulcer defined by Forrest classification. All subjects were classified into low-, intermediate- and high-risk patients on basis of clinical and endoscopic features according to "Cedar Sinai Medical Center predictive index" which was applied retrospectively in first six months then perspectively for the last period using the results obtained from first semester. For each risk group, we compared Length of Hospital Stay number of blood units used in transfusion, rebleeding rate, need for surgery as well as mortality in the two periods, using Student t test. We correlated Length of Hospital Stay and every score parameter by applying analysis of variance to results over the one-year period. RESULTS: Study population consists of 91 patients. Recurrent bleeding was observed in only three entering the high-risk group, only one of whom needed surgery Overall mortality was 9.8% (9 patients, only one for rebleeding). Variance analysis showed that the only parameter of the "Cedar Sinai Medical Center predictive index" which correlated with Length of Hospital Stay was comorbidity (p < or =0.05). Comparing the two periods, a close application of the score in the last six months allowed Length of Hospital Stay to be reduced in low-risk patients (t test with p=0.004) resulting in early discharge of 33% of cases without affecting patient outcome. CONCLUSIONS: This study confirms the reliability of the "Cedar Sinai Medical Center predictive index" in clinical practice improving the strategy of applying economic resources. Longer Length of Hospital Stay of intermediate- and high-risk groups is influenced more by comorbidities than by endoscopic findings. Early discharge was possible in one third of low risk patients. An accurate evaluation clinical para meters on admission together with early endoscopy may achieve the goal of reducing costs with a correct patient management.
REBLEEDING AFTER TREATMENT
Effect of programmed endoscopic follow-up examinations on the rebleeding rate of gastric or duodenal peptic ulcers treated by injection therapy: a prospective, randomized controlled trial. Messmann H, Schaller P, Andus T, Lock G, Vogt W, Gross V, Zirngibl H, Wiedmann KH, Lingenfelser T, Bauch K, Leser HG, Scholmerich J, Holstege A. Dept. of Internal Medicine, University of Regensburg, Germany.	Endoscopy 1998 Sep;30(7):583-9 Abstract quote BACKGROUND AND STUDY AIMS: A second-look endoscopy is often performed to evaluate the efficacy of a prior injection therapy in patients with bleeding peptic gastric or duodenal ulcers. Although this strategy is widely established, it does not rely on unequivocal data from controlled studies. In a prospective, randomized, controlled multicenter trial we assessed the effect of programmed endoscopic follow-up examinations with eventual retreatment on the outcome of bleeding ulcers in these patients. PATIENTS AND METHODS: One hundred and five patients with gastric or duodenal peptic ulcers presenting with active (Forrest type I) or recent (Forrest type IIa and IIb) bleeding upon endoscopy within four hours after admission were included in the study. Emergency treatment consisted of the sequential injection of both epinephrine (1:10,000 v/v) and up to 2 ml of fibrin/thrombin around the ulcer base. Fifty-two patients were randomized to receive programmed endoscopic monitoring with eventual retreatment in cases of Forrest type I, IIa, or IIb ulcers beginning within 16-24 hours after the index bleed. Follow-up endoscopies were continued until the macroscopic appearance revealed a Forrest type IIc or III ulcer. Fifty-three patients in the control group were closely monitored, and only received a second endoscopy when there was clinical or biochemical evidence of recurrent bleeding. The groups did not differ with respect to age, sex, site and severity of bleeding. RESULTS: The numbers of patients with recurrent bleeding were similar whether they were endoscopically monitored or not (21% versus 17%, P=0.80 chi-squared test). In addition, there was no statistically significant difference between the two groups with respect to the number of blood units transfused, need for surgical intervention, hospital stay or number of deaths (Mann-Whitney U-test). Improving local ulcer stigmata was not related to a better outcome. CONCLUSIONS: Programmed endoscopic follow-up examinations with eventual retreatment in patients locally injected for an acute or recent hemorrhage from a gastric or duodenal ulcer did not influence their outcome when compared to patients receiving only a second endoscopic intervention upon evidence for recurrent hemorrhage. Scheduled control endoscopies cannot be recommended after an initial successful endoscopic treatment of peptic ulcer bleeding when selection of the patients for second-look endoscopy is directed by the Forrest criteria.
TREATMENT
FIBRIN SEALANT
Endoscopic injection with fibrin sealant versus epinephrine for arrest of peptic ulcer bleeding: a randomized, comparative trial. Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD. Division of Gastroenterology, Department of Medicine, VGH-TAIPEI, Taipei, Taiwan, ROC.	J Clin Gastroenterol 2002 Sep;35(3):218-21 Abstract quote BACKGROUND: endoscopic epinephrine and fibrin injection in the treatment of bleeding peptic ulcer are reported to be safe, effective, and easy to use. However, a wide range of rebleeding rates has been reported with epinephrine injection. GOALS: to compare the hemostatic effects of endoscopic injection with fibrin sealant versus epinephrine. STUDY: between December 1998 and July 2000, 51 patients with active bleeding or nonbleeding visible vessels entered this trial. The clinical parameters were comparable between both groups. In the epinephrine group, we injected 5 to 10 mL of 1:10,000 epinephrine, surrounding the bleeder. In the fibrin sealant group, we injected fibrin sealant 4 mL, surrounding the bleeder. RESULTS: initial hemostasis was obtained in all enrolled patients. Rebleeding was more in the epinephrine group than in the fibrin sealant group (4 [15%] of 26 vs. 14 [56%] of 25, = 0.003 on the intention-to-treat basis, and 4 [16.7%] of 24 vs. 14 [58.3%] of 24, = 0.003 on the per protocol basis, respectively). Volume of blood transfusion, number of surgeries, hospital stay, and number of deaths were similar between both groups. CONCLUSION: fibrin sealant injection is more effective in preventing rebleeding than epinephrine after endoscopic therapy, but this study showed no difference in outcomes with either therapy.
HELICOBACTER ERADICATION
Helicobacter pylori eradication ameliorates symptoms and improves quality of life in patients on long-term acid suppression. A large prospective study in primary care. Verma S, Giaffer MH. Department of Gastroenterology, Hull Royal Infirmary, UK.	Dig Dis Sci 2002 Jul;47(7):1567-74 Abstract quote Our objective was to determine prescribing patterns for H2 receptor antagonists (H2RA) in primary care and to establish the prevalence and impact of Helicobacter pylori (Hp) eradication in this population of patients. Patients on long-term (6 months or longer) H2RA were identified through a computerized database at the six primary care practices in North England. Hp status was identified by serology, and those positive received standard proton pump-based triple therapy followed by a urea breath test to confirm Hp eradication. The main outcome measures were the indications for prescribing long-term H2RA in primary care, the prevalence of patients with a positive Hp serology, and the impact of Hp eradication on the subsequent need for acid suppression, severity of dyspepsia, gastrointestinal symptom rating score (GSRS), quality of life (QOL), and overall feeling of well-being. One thousand seven (1.5%) patients were on long-term H2RA. Peptic ulcer disease (PUD) was the most common indication for prescribing (42%), followed by nonulcer dyspepsia (28%) and gastroesophageal reflux disease (23%). In 81% of the patients treatment with H2RA therapy followed a previous endoscopic or radiological investigation. Only 27 (2.5%) patients had had their Hp status checked within the last 6 months. Of the 471 patients who eventually had their Hp serology tested, 297 (63%) were Hp positive. Fifty-eight percent of the Hp-positive patients had PUD. Successful Hp eradication was achieved in 250 (84%) of the patients, of whom 247 (83%) finished the 1-year follow-up. This was associated with a significant reduction in the amount of H2RA being consumed (P < 0.00001). There was also a significant improvement in the symptom scores and the GSRS after successful Hp eradication (P < 0.00001). Overall 67% of the patients reported an improvement in the QOL and 77% noted a feeling of well-being 1 year after Hp eradication. A significant proportion of patients in primary care is still being maintained on long-term H2RA, imposing a considerable financial drain on the NHS resources. Approximately two-thirds of these patients will be Hp positive, and among them the largest group will comprise patients with PUD. Hp eradication in such patients results in a significant reduction in usage of acid suppression and an improvement in overall QOL and severity of dyspeptic symptoms.
PROTON PUMP INHIBITORS
Reappraisal of non-invasive management strategies for uninvestigated dyspepsia: a cost-minimization analysis. Ladabaum U, Chey WD, Scheiman JM, Fendrick AM. Division of Gastroenterology, Department of Medicine, University of California, San Francisco, Ca 94143-0538, USA.	Aliment Pharmacol Ther 2002 Aug;16(8):1491-501 Abstract quote BACKGROUND: The benefits of the Helicobacter pylori test-and-treat strategy are attributable largely to the cure of peptic ulcer disease while limiting the use of endoscopy. AIM: To reappraise the test-and-treat strategy and empirical proton pump inhibitor therapy for the management of uninvestigated dyspepsia in the light of the decreasing prevalence of H. pylori infection, peptic ulcer disease and peptic ulcer disease attributable to H. pylori. METHODS: Using a decision analytical model, we estimated the cost per patient with uninvestigated dyspepsia managed with the test-and-treat strategy ($25/test; H.pylori treatment, $200) or proton pump inhibitor ($90/month). Endoscopy ($550) guided therapy for persistent or recurrent symptoms. RESULTS: In the base case (25%H. pylori prevalence, 20% likelihood of peptic ulcer disease, 75% of ulcers due to H.pylori), the cost per patient is $545 with the test-and-treat strategy and $529 with proton pump inhibitor, and both strategies yield similar clinical outcomes at 1 year. H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H.pylori are important determinants of the least costly strategy. At an H. pylori prevalence below 20%, proton pump inhibitor is consistently less costly than the test-and-treat strategy. CONCLUSIONS: As the H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H. pylori decrease, empirical proton pump inhibitor becomes less costly than the test-and-treat strategy for the management of uninvestigated dyspepsia. Given the modest cost differential between the strategies, the test-and-treat strategy may be favoured if patients without peptic ulcer disease derive long-term benefit from H.pylori eradication.
THERMOCOAGULATION
A prospective, randomized trial of endoscopic hemoclip versus heater probe thermocoagulation for peptic ulcer bleeding. Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD. Department of Medicine, VGH-Taipei, and School of Medicine, National Yang-Ming University, Taiwan, ROC.	Am J Gastroenterol 2002 Sep;97(9):2250-4 Abstract quote OBJECTIVES: Endoscopic heater probe thermocoagulation and hemoclip are considered to be safe and very effective in the treatment of bleeding peptic ulcer. So far, there are only few reports concerning hemostasis with endoscopic hemoclip. The aims of this study were to compare the hemostatic effects of both therapeutic modalities in patients with peptic ulcer bleeding. METHODS: A total of 80 patients with active bleeding or nonbleeding visible vessels were randomized to receive endoscopic hemoclip (n = 40) or heater probe thermocoagulation (n = 40). RESULTS: Initial hemostasis was achieved in 34 patients (85%) in the hemoclip group and 40 patients (100%) in the heater probe group (p = 0.01277). Rebleeding occurred in three patients (8.8%) in the hemoclip group and two patients (5%) in the heater probe group (p > 0.1). Among patients with difficult-to-approach bleeding, we obtained a better hemostatic rate in the heater probe group (nine of 11 patients vs three of 10, p = 0.02417). The volume of blood transfused after entry into the study, duration of hospital stay, number of patients requiring urgent surgery, and the mortality rate were not statistically significantly different between the two groups. CONCLUSIONS: For patients with peptic ulcer bleeding, heater probe thermocoagulation offers an advantage in achieving hemostasis than hemoclip. In difficult-to-approach bleeders, heater probe is a more suitable therapeutic modality.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	PUD
GEOGRAPHY
ICELAND
Trends in peptic ulcer morbidity and mortality in Iceland. Thors H, Svanes C, Thjodleifsson B. Department of Gastroenterology, National University Hospital, 101 Reykjavik, Iceland.	J Clin Epidemiol 2002 Jul;55(7):681-6 Abstract quote A cohort pattern has been demonstrated for ulcer mortality and perforation, pointing to a role of early life factors, while only a period-related decrease has been observed in elective ulcer surgery, which reflects uncomplicated ulcer. The aim of this article was to study whether the susceptibility to peptic ulcer disease is determined early in life, as reflected in a cohort pattern consistent for all ulcer manifestations. The subjects were all patients treated surgically for peptic ulcer (perforations 1962-1990; bleedings 1971-1990; elective surgery 1971-1990) and all deaths from peptic ulcer (perforations and other ulcer deaths 1951-1989) in Iceland. Age-specific incidence and mortality were analyzed graphically by year of birth (cohort) and by year of event (period). The effects of cohort and period on incidence and mortality were analyzed by Poisson regression. Ulcer perforation and bleeding, operative incidence, and mortality, showed a rise and subsequent fall in successive generations, with the highest risks observed in the subjects born after the turn of the 20(th) century. This was confirmed by statistical analyses showing highly significant cohort effects (P <.001) and no period effects. A cohort pattern was similarly found for elective ulcer surgery (P <.001), as well as a period-related decrease across age groups (P <.001). Ulcer complications, ulcer deaths, and uncomplicated ulcer were particularly common in specific generations carrying a high risk of peptic ulcer throughout their lives. These were the generations with the highest prevalence of H. pylori antibodies, the subjects born after the turn of the century at a time of maximum crowding and poor hygiene in Iceland due to the industrial revolution.
KOREANS
High prevalence of duodenal ulcer and gastric cancer in dyspeptic patients in Korea. Malaty HM, Kim JG, El-Zimaity HM, Graham DY. Dept. of Medicine, Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas 77030, USA.	Scand J Gastroenterol 1997 Aug;32(8):751-4 Abstract quote BACKGROUND: Although gastric cancer and duodenal ulcer are both related to Helicobacter pylori infection, they are mutually exclusive diseases such that patients with a history of duodenal ulcer have a markedly reduced risk of developing gastric cancer. It has been hypothesized that different strains of H. pylori may be related to the different diseases. Our aim was to study the prevalence of duodenal ulcer disease and gastric cancer in dyspeptic patients in South Korea, a country with a high incidence of gastric cancer. METHODS: The study population consisted of consecutive patients between the ages of 20 and 81 years referred to Guro Hospital's Endoscopic Unit for evaluation of dyspepsia. Patients with a history of peptic ulcer or gastric cancer were excluded. Each patient underwent endoscopy and completed a detailed questionnaire. Peptic ulcer was defined as the presence of an active ulcer, red scar, or white scar. RESULTS: One thousand patients were evaluated, and 867 (43% men and 57% women) met the entry criteria. The prevalence of peptic ulcer and gastric cancer were 24% and 7%, respectively. Among peptic ulcer patients, duodenal ulcer was commoner (75%) than gastric ulcer or coexistent duodenal and gastric ulcer (21% and 4%, respectively). The mean age of duodenal and gastric ulcer patients (45 +/- 14 and 48 +/- 12 years, respectively) was significantly lower than that of gastric cancer patients (59 +/- 11 years) (P < 0.01). Only 44 (7%) of the 597 remaining patients had definite endoscopic abnormalities (for example, erosive esophagitis, duodenitis, or pyloric deformity). CONCLUSION: Gastric cancer and duodenal ulcer were prevalent diagnoses among Korean patients undergoing endoscopy for evaluation of dyspepsia. Korea may be the ideal country to investigate the relation between specific H. pylori strains and different H. pylori diseases.

DISEASE ASSOCIATIONS	CHARACTERIZATION
ANXIETY
Generalized anxiety disorder and peptic ulcer disease among adults in the United States. Goodwin RD, Stein MB. Department of Epidemiology (R.D.G.), Mailman School of Public Health, Columbia University, New York, New York.	Psychosom Med 2002 Nov-Dec;64(6):862-6 Abstract quote OBJECTIVE: Previous research has suggested a link between chronic anxiety and peptic ulcer disease, though recent evidence documenting an infectious cause (Helicobacter pylori) for ulcer has led to doubt about this association. The goal of the current study was to determine the relationship between generalized anxiety disorder (GAD) and self-reported peptic ulcer disease (PUD) among adults in the community. METHODS: Data were drawn from the National Comorbidity Survey, a representative household survey of the adult population of the United States (N = 8098). Multivariate logistic regression analyses were used to determine the relationship between GAD and self-reported ulcer, controlling for differences in sociodemographic characteristics and psychiatric and medical comorbidity. RESULTS: GAD was associated with a significantly increased risk of self-reported PUD (odds ratio = 2.8, 95% confidence interval = 1.4-5.7; p =.0002) after adjusting for differences in sociodemographic characteristics, comorbid mental disorders, and physical morbidity. Further analyses revealed a dose-response relationship between number of GAD symptoms (odds ratio = 1.2, 95% confidence interval = 1.1-1.4; p =.001) and increased risk of self-reported PUD. CONCLUSIONS: These findings are consistent with and extend previous clinical and epidemiologic data, providing evidence of a dose-response relationship between GAD and self-reported PUD among adults in the general population. The mechanism of this association remains unknown. Future work investigating the relationship between onset of GAD and development of PUD in prospective, longitudinal, epidemiologic data with objective measures of physical health status and mental health may be useful in improving our understanding of this link.
ULCERATIVE COLITIS
The long-term time trends of peptic ulcer and ulcerative colitis are interrelated. Cucino C, Sonnenberg A. New Mexico VA Health Care System, Albuquerque 87108, USA.	Am J Gastroenterol 2002 Oct;97(10):2657-62 Abstract quote OBJECTIVE: A birth-cohort phenomenon in the time trends of a disease indicates that exposure to relevant risk factors must have occurred during an early period of life. The aim of this study was to determine whether birth-cohort patterns are common features of ulcerative colitis, gastric ulcer, and duodenal ulcer in different countries. METHODS: The number of deaths from ulcerative colitis, gastric, and duodenal ulcer in England, Netherlands, Italy, Switzerland, United States, and Scotland were retrieved from the respective national statistics offices. The death rates from the six countries were plotted against the period of birth. Age-standardized cohort mortality ratios were calculated as a summary of the overall mortality associated with each consecutive birth-cohort. RESULTS: In all countries alike, mortality from ulcerative colitis, gastric, and duodenal ulcer increased among successive generations born during the 19th century and, after reaching a sharp peak around the turn of the 20th century, declined among generations born subsequently. The rise in mortality from gastric ulcer preceded a similar rise in mortality from duodenal ulcer by 10-20 yr, and the temporal changes of duodenal ulcer coincided with those of ulcerative colitis. CONCLUSIONS: The sudden rise of peptic ulcer disease during the 19th century and the 10-20-yr time lag between gastric and duodenal ulcer are difficult to explain based on changing infection rates with Helicobacterpylori alone. The similarity between the time trends of duodenal ulcer and ulcerative colitis suggests the influence of one or more shared risk factors.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
DUODENAL ULCERS
Non-Helicobacter pylori related duodenal ulcer disease in children. Elitsur Y, Lawrence Z. Department of Pediatrics, Division of Gastroenterology, Marshall University School of Medicine, Huntington, WV 25701-0195, USA.	Helicobacter 2001 Sep;6(3):239-43 Abstract quote BACKGROUND: In spite of the worldwide distribution of Helicobacter pylori infection, recent data have reported an increased rate of non-H. pylori, non-NSAIDs-duodenal ulcer disease in adults. The estimated rate of these ulcers in children is unknown. We aimed to investigate the prevalence of non-H. pylori, non-NSAIDs-peptic ulcer disease in our pediatric patients who undergo upper endoscopic procedures. METHODS: A retrospective analysis of 622 upper endoscopic reports was performed. Reports that documented mucosal ulcerations were included in our study. The demographic, clinical, endoscopic, and histological data were retrieved. The H. pylori-negative, duodenal/gastric ulcer-positive patients were compared with H. pylori-positive, duodenal/gastric ulcer-positive patients. RESULTS: Out of the 622 upper endoscopy reports, a total of 11 (1.8%) children with mucosal ulceration were studied. Mucosal ulceration was distributed in the following locations: stomach-3 (27%), and duodenal bulb-10 (91%) (two children had ulcers in both the stomach and duodenal bulb). Helicobacter pylori infection was only detected in three (27%) children with duodenal ulcer. Gastritis was more severe in patients with H. pylori infection/duodenal ulcer compared with H. pylori-negative/duodenal ulcer group. No statistical difference in clinical symptoms or endoscopic appearance was observed between the H. pylori-negative and H. pylori-positive groups. CONCLUSION: 'Idiopathic' (H. pylori-negative, NSAIDs-negative) duodenal/gastric ulcers are present in symptomatic children. Clinical or endoscopic characteristics are insufficient markers to identify those 'idiopathic' ulcers. Investigating the 'risk factors' for those ulcers will be helpful in reducing the morbidity in these children.

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
VARIANTS
FUNDIC GLAND POLYPS
Fundic Gland Polyps Are Not Induced by Proton Pump Inhibitor Therapy Michael Vieth, MD, PhD, and Manfred Stolte, MD, PhD	Am J Clin Pathol 116:716-720 Abstract quote It is still unclear whether proton pump inhibitors (PPIs) could cause fundic gland polyps (FGPs) in patients without Helicobacter pylori infection. The frequency of FGPs in patients during PPI therapy has not been compared, however, with a control group of patients who did not have H pylori infection and were not undergoing PPI treatment. In a retrospective 12-month study, the frequency of FGPs in 2,251 patients without H pylori infection receiving PPI therapy (duration of treatment at least 4 weeks) was compared with a control group of 28,096 patients who did not have H pylori infection and were not receiving PPI therapy. FGPs were identified with an identical frequency in both groups (5.0% in the control and 5.2% in the PPI group). No significant differences were present between the groups with respect to the presence of gastritis or age or sex. Our study shows that a causal pathogenetic relationship between PPI therapy and FGPs is unlikely.

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE