Kazumasa Miki

Usefulness of gastric cancer screening using the serum pepsinogen test method

OBJECTIVE:The measurement of serum pepsinogen has recently gained attention as a candidate for a new screening test for gastric cancer. This method is particularly attractive given its lower cost and simplicity to administer relative to photofluorography. To compare the accuracy between the two screening methods, and to elucidate the usefulness of the serum pepsinogen test method, we performed this study.METHODS:Mass screening for gastric cancer was performed using both the x-ray and pepsinogen test methods simultaneously on 286 company employees. The number of tests conducted was 5567 in total. The mean age was 48 yr in both men and women. Informed consent was taken individually. Fasting blood samples were collected, and measurement of the serum pepsinogen concentration was carried out by immunoradiometric assay.RESULTS:The percentage of those screened, who needed further examination was 11.7% for the x-ray method and 23.6% for the pepsinogen test method. The percentage of those who required further investigation, as the second step of screening, using endoscopy, was 55.4% for the x-ray method and 51.9% for the pepsinogen test method, respectively. Ten gastric cancers were detected in total. The incidence was 0.05% in the x-ray method and 0.18% in the pepsinogen test method. The rate of early gastric cancer to advanced gastric cancer was 9 to 1, that is, 90% were in the early stages. The positive predictive value was 0.8% in the x-ray method and 1.4% in the pepsinogen test method.CONCLUSIONS:The pepsinogen test method can be used as a screening test for high-risk subjects with atrophic gastritis, rather than as a tool for cancer itself. Systemic endoscopic surveillance of this group is also useful.

Relationship between Helicobacter pylori infection and smoking and drinking habits

Background : Helicobacter pylori is a major cause of various gastroduodenal diseases. Some risk factors related to H. pylori infection have been reported; however, studies on the relationship between H. pylori infection and smoking or drinking habits have given conflicting results. In the present study, these relationships were investigated by collecting sera and information from 8837 subjects.

Prescreening of a High-Risk Group for Gastric Cancer by Serologically Determined Helicobacter pylori Infection and Atrophic Gastritis

BackgroundThough gastric cancer screening by X-ray examination has been confirmed to be effective for reducing gastric cancer mortality, decreases in efficiency have been pointed out. Establishment of an effective screening system, focusing on high-risk status such as Helicobacter pylori infection and atrophic gastritis, is desirable. To date, combined use of serum anti-Helicobacter pylori antibodies and pepsinogen measurement has been assessed prospectively in participants in opportunistic and workplace health check-ups; however, there are no reports of population-based cohort study.AimsTo clarify the population-based risk of Helicobacter pylori infection and atrophic gastritis for gastric cancer, a cohort study was conducted in rural towns in Kyoto Prefecture.MethodsSubjects were 1,011 males and 1,848 females recruited in a health check-up in 1987. Their serum was examined for anti-Helicobacter pylori antibodies and pepsinogenxa0I and II. Gastric cancer cases were assessed from the cancer registry of those towns.ResultsUp to the end of 1996, 33 males and 28 females developed gastric cancer. A sex- and age-adjusted hazard ratio was calculated by Cox’s proportional model. Helicobacter pylori infection increased the risk of gastric cancer even when the subjects had no atrophy (hazard ratioxa0=xa04.20; 95% confidence interval, 0.96–18.40). The risk increased further when they had both Helicobacter pylori infection and atrophy (hazard ratioxa0=xa011.23; 95% confidence interval, 2.71–46.51). Subjects with atrophy but negative for anti-Helicobacter pylori antibodies had the highest risk (hazard ratioxa0=xa014.81; 95% confidence interval, 2.47–88.80).ConclusionsA high-risk group for gastric cancer can be selected by serological prescreening.

Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography

With the aim of developing more efficient gastric cancer screening programs for use in Japan, we studied a new screening program that combines serum pepsinogen (PG) testing and barium digital radiography (DR). A total of 17 647 middle‐aged male subjects underwent workplace screening over a 7‐year period using a combination of PG testing and DR. This programs effectiveness, as well as other characteristics of the program, was analyzed. Forty‐nine cases of gastric cancer were detected (comprising 88% early cancer cases). The detection rate was 0.28%, and the positive predictive value was 0.85%. The PG test detected 63.3% of cases, DR detected 69.4% of cases, and both tests were positive in 32.7% of cancer cases. The two methods were almost equally effective, and were considerably more effective than conventional screening using photofluorography. Each screening method detected a distinct gastric cancer subgroup; the PG test efficiently detected asymptomatic small early cancer with intestinal type histology, while DR was efficient at detecting cancers with depressed or ulcerated morphology and diffuse type histology. The cost for the detection of a single cancer was much less than that for conventional screening. In fact, it is possible to further reduce the cost of detecting a single cancer to a cost comparable to that of surgically resecting a single gastric cancer. Thus, it is probable that a highly efficient gastric cancer screening system can be implemented by combining the two screening methods. Such a screening program would be beneficial in a population at high risk for gastric cancer. (Cancer Sci 2005; 96: 713u2003–u2003720)

Using serum pepsinogens wisely in a clinical practice

Serum pepsinogen (PG) has been used as biomarkers of gastric inflammation and mucosal status, including atrophic change, before the discovery of Helicobacter pylori (H. pylori). Serum pepsinogen I (PG I) and pepsinogen II (PG II) levels are known to increase in the presence of H. pylori‐related nonatrophic chronic gastritis. The measurement of serum PG provides much information on the presence of intestinal metaplasia as well as atrophic gastritis. The eradication of H. pylori provokes a significant change in serum PG values: it reduces both PG I and PG II and elevates the PG I to PG II ratio. Recently, the serum PG test method has been the first screening step in Japan, as well as photofluorography. Serum PG tests are used to screen for high risk subjects with atrophic gastritis, rather than as a test for cancer itself. Unlike photofluorography or endoscopy, serum PG screening can identify non‐ulcerated differentiated asymptomatic cancer, irrespective of the size and location of the lesion. Most cases detected by the PG method are asymptomatic early gastric cancers and are limited to the mucosa, which are particularly well suited for endoscopic treatment. The PG method can contribute greatly to the patients’ quality of life.

Helicobacter pylori, pepsinogen, and gastric adenocarcinoma in Hawaii

BACKGROUNDnThe objective was to investigate the association of Helicobacter pylori and serum pepsinogen (PG) levels with gastric adenocarcinoma.nnnMETHODSnSerum obtained from 299 patients at the time of cancer diagnosis and from 336 population-based control subjects was tested for PG I, PG II, and antibodies to H. pylori and to CagA.nnnRESULTSnSubjects with low PG I levels or low PG I/II ratios were at increased risk for cardia and noncardia gastric cancer, whereas those with H. pylori or CagA seropositivity had an elevated risk for noncardia cancer only. Subjects seropositive for either H. pylori or CagA who had low PG I levels had the highest odds ratio (OR) (9.21 [95% confidence interval {CI}, 4.95-17.13]) for noncardia cancer, compared with subjects with neither factor. Elevated risks were also found among subjects with only 1 factor (OR, 5.40 [95% CI, 2.61-11.20] for low PG I level only; OR, 4.86 [95% CI, 5.90-8.13] for H. pylori or CagA seropositivity only). This pattern persisted when PG I/II ratio replaced PG I level and when CagA seropositivity alone replaced H. pylori immunoglobulin G or CagA seropositivity.nnnCONCLUSIONSnThe results suggest that persons with both H. pylori or CagA seropositivity and a low PG I level or PG I/II ratio are highly susceptible to development of noncardia gastric cancer.

Trends in the incidence of gastric cancer in Japan and their associations with Helicobacter pylori infection and gastric mucosal atrophy

BackgroundAlthough age-adjusted mortality from gastric cancer has been decreasing in Japan, the crude incidence of gastric cancer shows a slight increase.MethodsWe have observed trends in the incidence of gastric cancer by sex and 20-year age groups over the past two decades (1976–1996). Source data were obtained from the cancer statistics materials provided by the Research Group for Population-Based Cancer Registration in Japan. Simultaneously, we observed changes in the prevalence of Helicobacter pylori infection and in serological atrophy of the gastric mucosa, and compared the results with those involving changes in the incidence of gastric cancer.ResultsA slight decline was observed in all age groups over 40 years old, in both men and women, between 1986 and 1996. However, a marked decline in incidence was observed for those aged 20–39 years. The prevalence of H. pylori infection declined in both sexes between 1989 and 1998. The frequency of serological atrophy of the gastric mucosa significantly declined in all age groups between 1989 and 1996, with young age groups experiencing a more marked decrease.ConclusionThe marked decline in gastric cancer incidence observed in the young population will also begin to occur in the elderly population in the future.

Serum Pepsinogens as a Predicator of the Topography of Intestinal Metaplasia in Patients with Atrophic Gastritis

The importance of atrophic gastritis with intestinal metaplasia is related to the fact that it increases the risk of gastric cancer development. The aim of this study is to evaluate the diagnostic potential of serum pepsinogens in predicting the topography of intestinal metaplasia. Both dye endoscopy and 13C-urea breath test were carried out in 878 subjects. Serum pepsinogen I, pepsinogen II, and IgG antibody to Helicobacter pylori were measured. The overall prevalence of intestinal metaplasia was higher in subjects with lower PG I/II ratios and lower PG I values. Based on ROC curves, a cutoff value for pepsinogen I/II ratio of less than 3.0 would have identified intestinal metaplasia with a sensitivity of 71.7% and a specificity of 66.7% in Helicobacter pylori-positive subjects. It is possible that serum pepsinogens could be used as a screening test for high-risk subjects with intestinal metaplasia.

Significance of lymphatic invasion on regional lymph node metastasis in early gastric cancer using LYVE-1 immunohistochemical analysis

It has been reported that lymphatic invasion is a predictor for lymph node metastasis in early gastric cancer (EGC); however, it has been impossible to differentiate between lymphatic invasion and blood vessel invasion using current staining techniques. We studied the significance of lymphatic invasion on regional lymph node metastasis in EGC by using human lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) antibody, specific to lymphatic vessels, and von Willebrand factor (vWF) antibody, specific to the blood vessels, to clearly distinguish these vascular tissues.EGC tissues were obtained from 66 node-positive and 66 node-negative subjects and were matched by age and sex. These tissues were immunostained with antibodies against LYVE-1 and vWF. Multivariate logistic regression analysis demonstrated that lymphatic invasion was a significant independent predictor for regional lymph node metastasis (odds ratio, 4.667; P = .0094), whereas blood vessel invasion was not. Thus, lymphatic invasion identified by LYVE-1 antibody could predict the existence of regional lymph node metastasis in EGC.

Efficacy of lactulose plus 13C-acetate breath test in the diagnosis of gastrointestinal motility disorders.

Background:Background: We designed a new method of measuring gastric emptying and orocecal transit time (OCTT) at the same time to assess the influence of gastric emptying upon OCTT. Methods: Twenty-five dyspeptic patients (6 men, 19 women) with a mean age of 64.8 years (range, 25–80 years) were studied. The patients received a liquid test meal, containing 100u2009mg of 13C-acetate and 12u2009g of lactulose, while they were in the sitting position after an overnight fast. Breath samples were collected at 10-min intervals of 120u2009min and both 13CO2 and hydrogen (H2) levels were measured. Subsequently, H2 concentrations were measured at 30-min intervals, for a total of 240u2009min. Results: The results of gastric emptying were expressed as the time of peak 13CO2 excretion. OCTT was defined as the period between the ingestion of lactulose and a H2 peak rise of 5u2009ppm above the baseline value. The onset of H2 enrichment in the breath began at 90–110u2009min, whereas 13CO2 levels increased from the beginning, with peak enrichment values being reached after 60–80u2009min. OCTT was related to 13CO2 peak time. In 5 of the 25 patients, H2 breath enrichment in the 10-min sample was more than 5u2009ppm over the baseline value. All these 5 patients had double or triple peaks in serial breath H2 concentrations. Conclusions: The combination of the lactulose hydrogen breath test (LHBT) with the 13C-acetate breath test, which requires only breath samples, provides us with much information on the gastrointestinal tract; gastric emptying, OCTT, bacterial overgrowth in the small intestine, colonic fermentation, and oropharyngeal flora. The 13C-acetate breath test can be useful as an adjuvant test when LHBT is performed for measuring OCTT.