Yoshihisa Urita

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.

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.

Comparison between gastric scintigraphy and the [13C]-acetate breath test with Wagner-Nelson analysis in humans.

1 The [13C]‐acetate breath test (ABT) quantifies gastric emptying as the half [13CO2]‐excretion time (T1/2b), but T1/2b differs from the scintigraphic half‐emptying time (T1/2s). The aims of the present study were to accurately determine the half‐emptying time by ABT with Wagner–Nelson analysis (T1/2WN), to compare T1/2WN with T1/2s and to validate the Wagner–Nelson strategy in ABT. 2 For a comparative study, eight volunteers simultaneously underwent ABT and scintigraphy. Anterior images were acquired and breath samples were collected every 15 min for 4.0 h after ingestion of a 200 kcal liquid meal labelled with 37 MBq [99mTc]‐colloidal sulphur and 100 mg [13C]‐acetate. For the validation experiment, another six volunteers underwent ABT, on two randomized occasions, using the 200 kcal liquid meal with 100 mg [13C]‐acetate. On either of the two occasions, a gel‐forming agent was stirred into the meal to intentionally delay gastric emptying by increasing meal viscosity. Breath samples were collected at regular 15 min intervals for 4 h post ingestion. 3 The Wagner–Nelson equation for ABT is F(t) = (Abreath(t) + C(t)/0.65)/Abreath(∞), where F(t) is a fractional dose of the [13C] label emptied, C(t) is the [13CO2] excretion (% dose/h), Abreath(t) is the area under the C(t) curve (% dose) and Abreath(∞) is the ultimate [13CO2] recovery in breath (% dose). The percentage gastric retention was estimated as 100 × (1 − F(t)). The time plots of scintigraphic activity and 100 × (1 − F(t)) were fitted to y(t) = 100 × e−K×t, K values were estimated mathematically for each plot by regression analysis and T1/2s and T1/2WN were calculated as (ln2)/K. The time versus pulmonary [13CO2] excretion plots were fitted to z(t) = m × k × β × e−kt(1 − e−k×t)β−1, where m, k and β are constants; T1/2b was calculated as –(ln(1 − 2−1/β)]/k. 4 Values of T1/2WN were closer to T1/2s than T1/2b, although T1/2WN and T1/2b yielded significant under‐ and overestimation of T1/2s, respectively. The high viscosity meal significantly prolonged T1/2WN and T1/2b; T1/2WN could detect the delayed transit of the viscous meal more sensitively than T1/2b. 5 The Wagner–Nelson method improves the accuracy of the ABT.

Role of infected grandmothers in transmission of Helicobacter pylori to children in a Japanese rural town.

Although the prevalence of Helicobacter pylori (H. pylori) increases with age and the main period of acquisition is childhood, the route of transmission of H. pylori infection remains unclear. This study aims to evaluate the relationship between prevalence of children and grandparents.

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.

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 100 mg of 13C-acetate and 12 g of lactulose, while they were in the sitting position after an overnight fast. Breath samples were collected at 10-min intervals of 120 min and both 13CO2 and hydrogen (H2) levels were measured. Subsequently, H2 concentrations were measured at 30-min intervals, for a total of 240 min. 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 5 ppm above the baseline value. The onset of H2 enrichment in the breath began at 90–110 min, whereas 13CO2 levels increased from the beginning, with peak enrichment values being reached after 60–80 min. OCTT was related to 13CO2 peak time. In 5 of the 25 patients, H2 breath enrichment in the 10-min sample was more than 5 ppm 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.

Studies on absorption and metabolism of palatinose (isomaltulose) in rats.

We evaluated the absorption and metabolism of palatinose in rats by the carbohydrate load test and the 13C- and H2-breath tests. We compared the results of these tests with those of sucrose, since sucrose is an isomer of palatinose and generally known to be degraded and absorbed from the small intestine. In the carbohydrate load test, blood glucose and plasma insulin levels after oral administration of palatinose rose more gradually and reached a maximum that was lower than that after sucrose administration. In the 13C-breath test, rats were orally administrated [1-13C]sucrose or [1-13C]palatinose and housed in a chamber. The expired air in the chamber was collected, and the level of 13CO2 in the expired air was measured at appropriate intervals for 360 min. The value of time taken to reach the maximum concentration for expired 13CO2 from [1-13Cglucose] ([1-13Cglc]) and [1-13Cfructose] ([1-13Cfru]) palatinose was significantly longer than that from [1-13Cglc] and [1-13Cfru]sucrose, respectively. The value of area under the curve (AUC) for [1-13Cglc]palatinose was larger than that for [1-13Cglc]sucrose, but AUC for [1-13Cfru] showed no difference between palatinose and sucrose. In the H2-breath test, the concentration of H2 in the expired air was measured for 420 min. H2 was hardly detected with both palatinose and sucrose and no significant difference was observed between the two groups. These results suggest that palatinose is utilised in vivo at a rate equal to that of sucrose.

Continuous consumption of fermented milk containing Bifidobacterium bifidum YIT 10347 improves gastrointestinal and psychological symptoms in patients with functional gastrointestinal disorders

The aim of this study was to investigate whether consumption of probiotic fermented milk containing Bifidobacterium bifidum YIT 10347 improves symptoms in patients with functional gastrointestinal disorders (FGID). Thirty-seven FGID patients (18 male, 19 female) aged 12–80 years (mean ± SD, 52.6 ± 17.5 years) whose condition had not improved despite being seen at several medical institutions consumed 100 mL/day of B. bifidum YIT 10347 fermented milk for 4 weeks. Symptoms were evaluated after the enrollment period (BL: baseline), sample consumption period (CP) and 4 weeks after the CP (FP: follow-up period). Gastrointestinal symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) and the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG); psychological symptoms were evaluated using the Profile of Mood States (POMS) short form. Concentrations of salivary stress markers and the oxidative stress marker urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) were measured. GSRS subscale scores for abdominal pain, diarrhea, and constipation significantly improved relative to BL after consumption of the fermented milk, as did FSSG subscale scores for symptoms of acid-related dyspepsia. Some subjective psychological symptoms improved. POMS scores significantly improved, and “Anger-Hostility” subscale scores significantly decreased after the consumption period, while “Vigor” subscale scores marginally increased during the consumption period. The concentrations of urinary 8-OHdG and the stress marker salivary cortisol were significantly lower at CP but returned to baseline levels at FP. Continuous consumption of B. bifidum YIT 10347 fermented milk is expected to improve gastrointestinal symptoms and reduce psychological stress in FGID patients.

Effect of acotiamide on gastric emptying in healthy adult humans

Acotiamide is a first‐in‐class drug that is used to treat functional dyspepsia (FD). It is considered that acotiamide acts as an antagonist on muscarinic autoreceptors in the enteric nervous system and inhibits acetylcholinesterase activity. We examined the effect of acotiamide on gastric emptying in healthy adult humans.

Influence of urease activity in the intestinal tract on the results of 13C-urea breath test

Background and Aim:  A late rise in 13CO2 excretion in the 13C‐urea breath test (UBT) should be found when the substrate passes rapidly through the stomach and makes contact with the colonic bacteria. The aim of this study was to evaluate the influence of intestinal urease activity on the results of the UBT.