Serological parameters in assessment of degree of gastritis in healthy volunteers.

This study was undertaken in healthy volunteers to determine the relation between serum levels of pepsinogen A, pepsinogen C, pepsinogen A:C ratio, and gastrin on the one hand and histology of the gastric mucosa on the other. The grade of gastritis was scored separately for antral and fundic mucosa by three different classifications: Whitehead, activity, and the Sydney score. Among 48 healthy volunteers studied, 17 were found to have gastritis according to the criteria of Whitehead. Fourteen of these 17 subjects with gastritis had H. pylori in gastric biopsies. In all 48 subjects serum pepsinogen A (r = 0.298-0.506; P < 0.01-P < 0.05), pepsinogen A:C ratio (r between -0.377 and -0.495; P < 0.001-P < 0.05) and gastrin (r = 0.38-0.695; P = 0.007-P < 0.01) were significantly correlated to the severity of both antral and body gastritis as assessed by all three classifications. In contrast, there was no significant correlation between serum pepsinogen C and any of the gastritis scores. When the 17 subjects with gastritis were analyzed separately, there were no correlations between the parameters studied and gastritis of the antrum. Regarding the corpus mucosa, serum PgA correlated significantly with the activity score (r = 0.520; P = 0.03), weakly with the Sydney score (r = 0.465; P = 0.06), but not with the Whitehead score. Serum PgC correlated with the Whitehead (r = 0.555; P = 0.02) and Sydney score (r = 0.523; P = 0.03), but only weakly with the activity score (r = 0.441; P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between IgG and IgA antibody titres against Helicobacter pylori in serum and severity of gastritis in asymptomatic subjects.

AIMS: To investigate whether the absorbance index of IgG and IgA antibodies against Helicobacter pylori is related to a semiquantitative assessment of the density of H pylori colonisation in gastric biopsy specimens and to the severity of gastritis. METHODS: The grade of gastritis was scored separately for antral and fundic mucosa using three different classifications. Serum IgA and IgG antibodies against H pylori were measured by ELISA. The density of gastric H pylori colonisation was graded semiquantitatively from 0 to 3. RESULTS: Among 48 healthy volunteers studied, 17 were found to have gastritis according to Whitehead's criteria. H pylori was present in the biopsy specimens of 14 of 17 subjects with gastritis. The IgG H pylori antibody absorbance index was significantly (p < 0.05) correlated not only with the density of antral H pylori colonisation, but also with the degree of gastritis of the antrum, as assessed by the Whitehead score, activity, and the Sydney system (p < 0.05). The IgA H pylori antibody absorbance index was significantly correlated with the Whitehead score and Sydney system, but not with the activity score of the antrum or with the density of antral gastric H pylori infection. There were no significant correlations between the IgG H pylori antibody absorbance index and the gastritis scores of the fundus mucosa and the density of H pylori infection of the gastric body. The IgA H pylori antibody absorbance index was only significantly (p < 0.05) correlated with the density of H pylori colonisation and the Sydney system gastritis score of the corpus. CONCLUSIONS: The serological absorbance index of IgG antibodies against H pylori is related to the severity of antral gastritis and the density of antral H pylori colonisation. Thus a high absorbance index of IgG antibodies against H pylori points to severe antral gastritis and dense H pylori colonisation of the antrum.

Serum pepsinogens in patients with gastric diseases or after gastric surgery.

As no comparative study is available on the categorized serum pepsinogen A and C concentrations, we have measured serum pepsinogens in patients with gastric diseases and after gastric surgery. Hyperpepsinogenemia A (> 120 micrograms/l) occurred frequently in patients with the Zollinger-Ellison syndrome (71%) and hypertrophic gastropathy (100%), whereas hypopepsinogenemia A (< 17 micrograms/l) was found mostly in patients with achlorhydria (87%) and after total gastrectomy (100%). Patients with the Zollinger-Ellison syndrome frequently (58%) had hyperpepsinogenemia C (> 40 micrograms/l), which was also the case in all patients with hypertrophic gastropathy who had in addition a low pepsinogen A:C ratio (< 1.6). Patients with achlorhydria, hypertrophic gastropathy, or after total gastrectomy fell into an aberrant category. From this study we conclude that measurement of serum pepsinogen A and C and calculation of their ratio yield information useful for differentiation of gastric abnormalities.

Diagnostic value of serum pepsinogen C in patients with raised serum concentrations of pepsinogen A.

Hypopepsinogenaemia A is often found in patients with gastric atrophy and gastric surgery. In these conditions serum pepsinogen C provides additional diagnostic information, especially when expressed as pepsinogen A:C ratio. Hyperpepsinogenaemia A has been shown in patients with duodenal ulcer disease, Zollinger-Ellison syndrome, hypertrophic gastropathy, chronic renal failure, and during omeprazole treatment. As patients with hyperpepsinogenaemia A often overlap in symptoms, endoscopical findings, and serum gastrin values, this study has evaluated whether measurement of serum pepsinogen C in subjects with hyperpepsinogenaemia A can help in differentiating clinical conditions. Serum concentrations of pepsinogen A and C were measured in serologically Helicobacter pylori negative blood transfusion donors (127) as reference population, and in patients with Zollinger-Ellison syndrome (24), duodenal ulcer (50), hypertrophic gastropathy (5), and chronic renal failure (50), and also in reflux oesophagitis patients on longterm omeprazole treatment (28). A low pepsinogen A:C ratio was found in all patients with hypertrophic gastropathy. A pepsinogen A:C ratio above the critical value of 4.7 was found in 14 (70.0%) of the Zollinger-Ellison patients, two (9.5%) of the duodenal ulcer patients, 11 (25.6%) of the patients with chronic renal failure, and in one (7.1%) of the patients receiving longterm omeprazole treatment. In fact, all but three hyperpepsinogenaemia A patients with a pepsinogen A:C ratio greater than 4.7 and normal renal function had the Zollinger-Ellison syndrome. In patients with hyperpepsinogenaemia A, a low pepsinogen A:C ratio may point to hypertrophic gastropathy, while a pepsinogen A:C ratio greater than 4.7 is suggestive for the Zollinger-Ellison syndrome.

Pneumatosis cystoides intestinalis in intestinal pseudoobstruction. Resolution after therapy with metronidazole.

A 66-year-old man with chronic idiopathic intestinal pseudoobstruction was admitted for pneumatosis cystoides intestinalis, complicated by pneumoperitoneum. The latter conditions resolved after treatment with metronidazole. There was no favorable effect of the prokinetic agents cisapride and erythromycin. To the authors' knowledge, this is the first reported case of successful treatment of pneumatosis cystoides intestinalis with metronidazole in primary chronic intestinal pseudoobstruction.

Influence of age and Helicobacter pylori infection on serum pepsinogens in healthy blood transfusion donors.

In a healthy population pepsinogen A and pepsinogen C increase with advancing age. As pepsinogen A and C are raised in chronic superficial gastritis which is caused by H pylori infection, we investigated whether H pylori is responsible for the age related increase of pepsinogen A and C. In H pylori positive blood transfusion donors serum pepsinogen A (mean (SD) 73 (35) micrograms/ml v 52 (19) micrograms/ml, p much less than 0.01) and C (mean (SD) 24 (13) micrograms/ml v 10 (7) micrograms/ml, p much less than 0.01) concentrations were significantly higher than in H pylori negative blood transfusion donors, while the serum pepsinogen A:C ratio mean (SD) 3.5 (1.4) v 6.2 (3.4), p much less than 0.01) was significantly decreased because of a relative greater increase in serum pepsinogen C in H pylori positive blood transfusion donors. Analysis of variance showed that pepsinogen A and C concentrations differed significantly in the different age groups (p much less than 0.01) when we considered all blood transfusion donors and H pylori positive blood transfusion donors, the mean pepsinogen levels being highest in the older age categories. In H pylori negative blood transfusion donors no such age related difference in pepsinogen A and C could be shown. In H pylori positive blood transfusion donors a weak positive but significant correlation between pepsinogen A and C and age could be shown (r = 0.30; p = 0.01 and r = 0.31; p = 0.01 respectively). In H pylori negative blood transfusion donors no correlation between serum pepsinogens and age was found. We conclude that the age related increase in serum pepsinogen A and C described in healthy control populations is caused by an increasing prevalence of H pylori infection. Serum pepsinogen A and C concentrations in patients should therefore be related to the presence or absence of H pylori infection.

Long term serological surveillance after treatment of Helicobacter pylori infection.

Fifteen patients with type B gastritis caused by Helicobacter pylori infection were treated with 'triple' therapy consisting of colloidal bismuth subcitrate, amoxycillin, and metronidazole. All were followed up as outpatients every three months for at least one year. After 'triple' therapy a significant (p less than 0.01) and persistent reduction in IgA and IgG antibody levels against H pylori was detected. In three patients recurrent active infection with H pylori at nine and 12 months was detected by a rise in IgA (three patients) and IgG (two patients) antibody levels against H pylori and worsening of symptoms, and was confirmed by culture and histology. In 11 patients, the absence of infection at 12 months was confirmed by culture and histology. In a control group of 13 patients with type B gastritis who received no antibacterial treatment, specific IgA and IgG antibody levels against H pylori remained unchanged during 12 months of follow up. Although specific IgG against H pylori is the most widely used serological test for screening, our data indicate that specific IgA is also valuable in monitoring treatment. These serological tests are easy to perform, relatively inexpensive, devoid of radioactivity and are very acceptable to patients. It is concluded that serological testing is the preferred method for follow up after treatment for H pylori infection and will probably replace endoscopy or the urea breath test.

Detection of gastric erosions: comparison of biphasic radiography with fiberoptic endoscopy.

Biphasic radiography was compared with fiberoptic endoscopy in detecting gastric erosions in a prospective, blinded study of 385 patients with dyspepsia. Because no absolute standard was available for the comparison, since histologic confirmation of all erosions was not possible, the kappa statistic was used to compare results from both modalities. Flat (incomplete) erosions were detected with endoscopy only and were considered to be present in 42 patients (11.2%). Varioliform (complete) erosions were identified with both radiography and endoscopy in 12 patients (3.2%). For the detection of varioliform erosions, a substantial agreement beyond chance between both modalities was found (kappa = 0.73; standard error, 0.12). Thus, flat erosions were detected with endoscopy only, whereas state-of-the-art radiography and endoscopy were equally sensitive for detecting varioliform erosions. Histologic confirmation of erosions was obtained in only 75% of the patients. It is unknown whether the demonstration of erosions with radiography and/or endoscopy correlates with dyspepsia.

Duodenal diverticulum complicated by duodenal inflammation and obstruction secondary to the use of the NSAID diclofenac.

In one patient, upper abdominal symptoms developed 6 months after the start of diclofenac. At upper gastrointestinal endoscopy duodenal stenosis was shown next to a large diverticulum containing non-dissolved tablets in the third part of the duodenum. As there was no improvement with medical treatment, resection of the diverticulum and stenosis with primary end-to-end anastomosis was performed. Apart from persistent activity of rheumatoid arthritis the patient has been well since. The possible gastrointestinal side-effects of nonsteroidal antiinflammatory drugs in patients with duodenal diverticula are discussed.

[Comparison of biphasic radiologic stomach and duodenum studies with fiber endoscopy for the diagnosis of peptic ulcer and stomach carcinoma]. / Vergelijking van bifasisch radiologisch maag-en duodenumonderzoek met fiberendoscopie voor de diagnostiek van peptische zweren en maagcarcinomen.

In a prospective, blind study of 385 patients with dyspepsia, the diagnostic value of biphasic radiological examination of stomach and duodenum was compared with endoscopy. The patients were examined for presence of peptic ulcers and gastric carcinomas. No golden standard being available, kappa values were calculated for the comparison. The kappa values were 0.67 and 0.77 for gastric and duodenal ulcers, respectively; for gastric carcinomas the value was 0.91. These values indicate good agreement. The sensitivity and specificity of both methods were high; a lower sensitivity of radiological examination for duodenal ulcers was accounted for by ulcers smaller than 5 mm; for larger ulcers, the sensitivity and specificity of both methods were practically the same. It is concluded that the two methods are of equal value for the diagnosis of peptic ulcers and gastric carcinomas. Endoscopy offers the major advantage that biopsy samples can be taken for histological examination or culturing. The biphasic radiological examination, on the other hand, is cheaper and often better tolerated by the patient.

Campylobacter pylori: prevalence and significance in patients with chronic renal failure.

Since gastric symptoms are frequent in uremic patients, we have studied the prevalence and significance of Campylobacter pylori infection in patients with chronic renal failure. The prevalence of serum IgG antibodies to C. pylori in 50 patients on regular dialysis treatment (44%) was similar to that of a control group of 40 blood donors (45%), but was significantly lower (p = 0.0001) than that in 31 patients with peptic ulcer disease (93%). Furthermore, 11 of the 50 patients with chronic renal failure and a history of documented peptic ulcer disease had a similar prevalence of antibodies to C. pylori (45%) as did the 39 chronic renal failure patients without previous peptic ulcer (44%), which was significantly lower (p less than 0.01) than that in the control group of peptic ulcer patients (93%). Of 10 patients with chronic renal failure (6 with and 4 without gastric complaints) studied by endoscopical biopsies, two had chronic active antral gastritis and were positive for C. pylori by histology, culture and had IgG antibodies in their sera, while one patient with normal antral mucosa had IgG antibodies but was negative by culture and histology. Thus, this study shows that there is no predisposition to C. pylori infection among patients with chronic renal failure, and that C. pylori infection does not play a significant role in the ulcer diathesis in these patients.

Ischemic colitis and acalculous necrotizing cholecystitis as rare manifestations of cholesterol emboli in the same patient.

A case is reported of a patient with ischemic colitis and acalculous necrotizing cholecystitis, rare manifestations of cholesterol emboli in one patient. Cholesterol emboli are often encountered at autopsy, suggesting that such abnormalities frequently are missed during life time, as happened initially in our patient. We conclude that multisystemic disease in elderly patients can be due to cholesterol emboli. The sooner the diagnosis is made, the more beneficial prophylactical measures will be.

Value of serology (ELISA and immunoblotting) for the diagnosis of Campylobacter pylori infection.

Fifty-two unselected patients referred to for upper gastrointestinal endoscopy were evaluated in several ways to determine the presence of Campylobacter pylori. Antibodies against this microorganism were measured to assess the value of serology for the diagnosis of C. pylori infection. Five antral biopsy specimens were taken in each patient for culture and bacteriological determinations, histology [morphology and Warthin-Starry (WS) staining] and the urease test (2, 3 and 24 h). Serum antibodies against a sonicate of 6 strains of microorganisms were assayed by enzyme-linked immunoassay (ELISA) and an immunoblotting technique. In 14 of the 52 patients the histology of the antrum was normal, 18 patients had chronic active gastritis and 20 had chronic gastritis without polymorphonuclear infiltration. In the group with normal histology, only 1 patient was positive for C. pylori with all methods, and 1 other subject was positive for IgG and 2 for IgA only with ELISA. In the group with chronic active gastritis, 14 were positive with all methods, 1 was negative by WS only and another was negative for IgA according to ELISA, WS and antibodies. Among the patients with chronic gastritis, 7 were positive and 7 negative with all tests; in the other 6 patients the results obtained with the various tests were divergent. Four serological tests were studied and validated against culture, WS and urease test which were considered to be the reference methods. The serological tests showed high sensitivity and specificity for the detection C. pylori-associated active chronic gastritis of the antrum, and can therefore serve as noninvasive methods to identify individuals with this condition.

Radioimmunoassay of human pepsinogen A and pepsinogen C.

We describe the development of radioimmunoassays to measure both human pepsinogen A and pepsinogen C concentrations in serum. The antibodies were raised in goats by immunization with purified pepsinogen A or C. The affinity constants of the respective antibodies were 20.10(10) l/mol and 7.10(10) l/mol. Pepsinogens A and C were labeled with Na 125I by the chloramine T method. The binding between labels and antibodies was inhibited by 0.50 at 0.82 ng pepsinogen A per tube and 2.1 ng pepsinogen C per tube. The detection limits of the assay of pepsinogen A and C were 0.12 microgram/l and 1.8 micrograms/l, respectively. Pepsinogen A and C were purified and added to a patient serum, showing a good recovery in the radioimmunoassays. Serial dilution of another patient serum, which contained a high concentration of both antigens, showed curves parallel to the standard curves. The intra- and interassay variations of these radioimmunoassays were evaluated. The intra-assay coefficients of variation for pepsinogen A were found to vary from 0.03 to 0.102 at concentrations in serum in the normal range, while the inter-assay coefficient of variation ranged from 0.118 to 0.194 at the same concentrations in serum. For the pepsinogen C radioimmunoassay we found intra-assay coefficients of variation between 0.126 and 0.147 at concentrations in serum in the normal range, while the inter-assay coefficient of variation ranged from 0.174 to 0.325 for the same sera. In 201 blood donors we found a mean serum concentration of pepsinogen A of 59 micrograms/l and a mean serum concentration of pepsinogen C of 15 micrograms/l. There was a significant relationship between these values (r = 0.779, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic nonspecific duodenitis. A multiple biopsy study of the duodenal bulb in health and disease.

A clinical, endoscopic and histopathologic study on chronic nonspecific duodenitis was performed in 174 subjects, 124 patients (control patients, patients with gastric or duodenal ulcer and nonulcer dyspepsia) and 50 healthy volunteers without clinical history of gastro-intestinal disease. Chronic nonspecific duodenitis was found in 6 healthy volunteers (12%), 5 control patients (7%), one gastric ulcer patient (7%), all duodenal ulcer patients and in 15 patients with nonulcer dyspepsia (83%). Chronic non-specific duodenitis is a focal process affecting the duodenal bulb. It can be missed when only one biopsy is studied. Superficial gastric metaplasia was directly correlated to gastric acid secretion and was found in 32 healthy volunteers (64%), 23 control patients (34%), six gastric ulcer patients (43%), 20 duodenal ulcer patients (20%) and in 17 patients with nonulcer dyspepsia (94%). This study suggests that chronic nonspecific duodenitis is a stage of duodenal ulcer disease.

Generalized peliosis hepatis and cirrhosis after long-term use of oral contraceptives.

Peliosis hepatis, a condition characterized by the presence of blood-filled lacunar spaces in the liver, has been described primarily in patients on androgenic steroid medication and patients with tuberculosis. It has never been reported as a complication of the use of oral contraceptives, except in association with and localized in contraceptive-induced hepatic tumors. The present report concerns a 43-yr-old woman with generalized peliosis hepatis that developed during long-term use of oral contraceptives. Extensive examination did not reveal a hepatic tumor. Liver cirrhosis and portal hypertension developed, although the oral contraceptives had been withdrawn. She finally underwent successfully an orthotopic liver transplantation.

PIP: A case report is presented of a 43-year-old woman with generalized peliosis hepatitis that developed during longterm use of oral contraceptives (OCs). The patient had been in good health until the last 2 years when she began to experience vague epigastric pains and a feeling of abdominal distension. Several months prior to admission, she had started to complain of itching and fatigue. There was no history of dark urine, white stools, or hepatitis. On physical examination, no jaundice or cutaneous stigmata of chronic liver disease were observed. Laboratory studies showed a normal erythrocyte sedimentation rate and hematological blood count. A radionuclide study of the liver showed hepatomegaly; especially the left lobe was enlarged. A computerized tomographic scan of the liver showed multiple areas of decreased density in both of the enlarged lobes. There was no evidence of a tumor. Selective transfemoral angiography of the celiac artery also showed hepatic enlargement but no signs of a space-occupying lesion. At laparoscopy, the liver was grossly enlarged and had a lumpy appearance, but again there were no signs of a tumor. No evidence of veno-occlusive disease or hepatocellular adenoma was found. The diagnosis was peliosis hepatitis. The OCs were withdrawn, and the patient was discharged. Regular follow-up in the outpatient department showed no decrease in the size of the liver. The alkaline phosphatase level rose. The fatigue became worse, and cholestyramine was prescribed for progressive itching. In September 1980, the patient was admitted for reevaluation. A repeated CT scan and angiography of the liver again yielded no evidence of a tumor. Esophagoscopy showed the presence of varices grade 2. The liver at laparoscopy had the same appearance as it had in 1976. Histological examination of a biopsy specimen showed occasional dilated sinusoids and locally marked periportal and intralobular fibrosis. No regeneration nodules were found. The diagnosis was liver fibrosis. The patient's condition deteriorated gradually in the following years. She experienced increasing fatigue. Steatorrhea developed, and the patient lost weight. She needed increasing doses of cholestyramine and oral supplementation of vitamins A, D, and K. She was admitted for a 3rd time in February 1985. Esophagoscopy revealed varices grade 4. A CT scan of the liver showed no change. The patient successfully underwent an orthotopic liver transplantation in January 1987. The diagnosis of peliosis hepatis was well documented in this patient.

Plasma gastrin responses to bombesin and antral gastrin concentrations in patients with the intestinal type of gastric cancer.

Mucosal atrophy of the gastric antrum (type B atrophic gastritis) is generally accepted as predisposing to the development of the intestinal type of gastric cancer. Since bombesin stimulates gastrin release selectively from the antral mucosa, the response can be used as a marker for antral mucosal atrophy. In this study we have investigated bombesin-stimulated plasma gastrin responses in 21 patients with the intestinal type of gastric cancer and we have compared the results with 12 patients with the diffuse type of gastric cancer, 17 patients with benign gastric ulcer, and 30 dyspeptic patients without endoscopical or histological abnormalities. Gastrin concentrations were also measured in extracts of antral biopsies. Basal plasma gastrin concentrations were not significantly different. In contrast, patients with the intestinal type of gastric cancer had a significantly lower plasma gastrin response to bombesin than did the normal subjects (P less than 0.01) and patients with the diffuse type of gastric cancer (P less than 0.05), but the result was not significantly different from that of the gastric ulcer patients. The antral gastrin content of the patients with the intestinal type of gastric cancer was significantly lower than in controls (P less than 0.005), the patients with the diffuse type of gastric cancer (P less than 0.05), and those with gastric ulcer (P less than 0.05). It is concluded that patients with the intestinal type of gastric cancer have, in contrast to those with the diffuse type of gastric cancer, an abnormally low plasma gastrin response to bombesin. This low response is due to a reduced gastrin content of the antral mucosa.

Alpha-1-antitrypsin phenotypes and serum concentrations in duodenal ulcer patients in The Netherlands.

Hereditary alpha 1-antitrypsin (alpha 1-AT) deficiency has been suggested to be associated with peptic ulcer disease. Since the serum concentration of the enzyme is the result of both hereditary and nonhereditary factors, we have studied not only the serum levels but also the alpha 1-AT electrophoretic variants in 177 Dutch patients with duodenal ulcer disease and compared with 357 healthy blood donors. No relation was found between any of the alpha 1-antitrypsin phenotypes and duodenal ulcer disease. Serum levels of alpha 1-AT were significantly higher than in the controls in the patients. This study does not support an association between hereditary alpha 1-AT deficiency and duodenal ulcer disease, and makes therefore a possible role of such a deficiency in the etiology of peptic ulcer disease highly unlikely.

Peptic ulcer and gastric carcinoma: diagnosis with biphasic radiography compared with fiberoptic endoscopy.

The diagnostic value of biphasic radiographic examination of the stomach and duodenum was compared with that of fiberoptic endoscopy in a prospective, blinded study of 385 patients with dyspepsia. This investigation was directed at gastric malignancies and peptic ulcers. Methodologically there is no absolute standard for a study of this kind because histologic examination is useful for detection of cancer but inadequate for ulcers. As an alternative, kappa indexes and the sensitivity and specificity, as derived by Hui and Walter, were calculated and compared. For the detection of gastric carcinoma, radiographic and endoscopic findings had almost perfect agreement beyond chance. For gastric ulcers, radiography and endoscopy had substantial agreement, which became perfect if small ulcers (less than 5 mm) were excluded. For duodenal ulcers, radiography had a lower sensitivity than endoscopy; this disagreement disappeared if small ulcers were excluded. Both methods have equal merit; choice of the initial diagnostic procedure will therefore depend on cost, discomfort to the patient, and risk of complications.

Clinical significance of pepsinogen A isozymogens, serum pepsinogen A and C levels, and serum gastrin levels.

Gastric mucosal pepsinogen A phenotype, serum pepsinogen A level, serum pepsinogen C level, serum pepsinogen A/pepsinogen C ratio, and serum gastrin level were evaluated as potential markers for gastric cancer or its precursors in 19 healthy volunteers and 341 patients from the gastroscopy program. Gastric cancer, atrophic gastritis, and intestinal metaplasia of the stomach were associated with pepsinogen A phenotypes, characterized by an intense fraction 5, and with a low serum pepsinogen A level (less than 25 micrograms/l), a low serum pepsinogen A/pepsinogen C ratio (less than 1.5), and a high serum gastrin level (greater than 79 ng/l). The specificity of pepsinogen A phenotypes with an intense fraction 5 for gastric cancer or its precursors was 95.1% with a sensitivity of 20.4%. The sensitivity and specificity of the noninvasive tests were evaluated with the receiver operating characteristic. For clinical purposes, a serum pepsinogen A/pepsinogen C ratio less than 1.8 is the most suitable test, with a sensitivity of 74% and a specificity of 76% for gastric cancer or its precursors, with a reference population of patients with benign gastric disorders. However, the sensitivity and specificity of the single or combined tests are too low for population screening purposes.