血清胃蛋白酶原检测在胃癌及其癌前病变筛查中的价值

目的:探讨血清胃蛋白酶原(PG)检测在胃癌及其癌前病变筛查中的价值.方法:在胃癌高发区对35岁以上无症状、有胃病史及胃癌家族史者进行内镜筛查.同时采用免疫比浊法测定受检者血清PG水平,结合内镜活检和病理检查结果,对比分析接受受检者血清PGⅠ、PGⅡ水平和PGⅠ/Ⅱ值与胃癌及其癌前病变的关系.结果:内镜筛查共计918例,其中PG阴性718例(78.21%);阳性200例(21.79%),阳性人群中以40-60岁最多139例(69.50%);总体胃癌检出率7/918(0.76%),早期胃癌检出率为5/7(71.43%),进展期为2/7(28.57%);PG阳性癌检出率3/200(1.50%),高级别上皮内瘤变检出率2/200(1.00%),低级别上皮内瘤变检出率23/200(11.50%);PG阴性癌检出率4/718(0.56%),高级别上皮内瘤变检出率0/718(00.00%),低级别上皮内瘤变检出率54/718(7.52%);PG阳性与PG阴性之间胃癌及其癌前病变检出率有显著性差异(P<0.01).PG阳性中早期胃癌检出率为2/3(66.67%),胃癌诊断的敏感性42.86%,特异性78.38%.结论:以血清...     

胃癌与十二指肠溃疡患者血清胃蛋白酶原比较

目的 比较胃癌患者与十二指肠溃疡患者血清胃蛋白酶原水平的差异及探讨其与H．pylori感染的关系。方法 采用时间分辨荧光免疫分析方法检测108例胃癌和96例十二指肠溃疡患者血清胃蛋白酶原Ⅰ、Ⅱ（PGⅠ，PGⅡ），ELISA方法检测血清H．pylori抗体。结果 胃癌和十二指肠溃疡患者之间PGⅠ水平有显著性差异，胃癌组和十二指肠溃疡组中H．pylori阳性和阴性间PGⅠ、PGⅡ、PGⅠ，PGⅡ水平等无显著性差异。结论 胃癌患者血清PGⅠ水平显著低于十二指肠溃疡患者，H．pylori感染对胃癌和十二指肠溃疡患者血清胃蛋白酶原水平和PGⅠ，PGⅡ比值均无影响。     

The role of serum pepsinogen in the detection of gastric cancer

The incidence of gastric cancer is very high in Japan, Korea, and China. Reducing the morbidity and mortality associated with gastric cancer requires early diagnosis, which can be facilitated by applying gastroscopy more frequently in high-risk groups. A strategy of population screening for gastric cancer is currently being adopted in Korea, Japan, and the Matsu region of Taiwan, but using different screening methods. In addition, the history of pepsinogen (PG) in research as a gastric cancer biomarker has varied, in that the use of serum levels of PGI and PGII and the PGI/PGII ratio as gastric cancer screening tools was introduced in Japan before 1990, but in Korea the first research results were only reported in 2008. This review first evaluates the physiology of PG, followed by the usefulness or limitations of serum PG testing with regard to the detection of gastric cancer. Finally, the factors affecting the efficacy of PG tests as a gastric cancer biomarker (i.e., Helicobacter pylori infection status, gender, histopathologic features, and cancer location and depth) are evaluated. It was found that the strategies used to increase the efficacy of PG tests should be individualized in each country according to the seroprevalence of H. pylori.     

Basal and stimulated gastrin and pepsinogen levels after eradication of Helicobacter pylori: a 1-year follow-up study

AIM: A decrease in gastrin and pepsinogen (PG) levels 1 month after Helicobacter pylori eradication has been described repeatedly, but the long-term progression of such a decrease has been scarcely studied. We therefore studied the effect of H. pylori eradication on basal and stimulated gastrin and PG levels for 1 year. Initially, the usefulness of measuring these parameters for the noninvasive diagnosis of H. pylori eradication was validated. Furthermore, an assessment was made of the association between H. pylori reinfection and a re-increase in gastrin and PG values. Finally, an evaluation was made of the variables influencing gastrin and PG concentration, with particular attention to H. pylori infection and histological lesions of gastric mucosa. METHODS: Two-hundred and twenty-two patients with duodenal ulcer were studied prospectively. Exclusion criteria were the administration of antibiotics, H2 antagonists, omeprazole or bismuth prior to endoscopy. In all patients serum basal levels of gastrin, PGI, and PGII were measured before and 1 month after completing eradication therapy. In the successfully eradicated patients, gastrin, PGI, and PGII were also measured at 6 and 12 months. In 80 patients stimulated measurements of gastrin (after ingestion of two beef cubes) and PGI (after injection of pentagastrin) were also performed. H. pylori-negative patients after therapy underwent a urea breath test at 6 and 12 months, and patients who had stimulated gastrin and PG concentration measured had also an endoscopy performed at 6 months. RESULTS: H. pylori was eradicated in 73% of patients. A histological improvement was observed 1 month after completing H. pylori eradication therapy, both at gastric antrum and body (P < 0.001), while a further improvement at antrum was demonstrated at 6 months (P < 0.01). With regard to the different cut-off points for decreased basal and stimulated measurements for diagnosing H. pylori eradication, the best results were obtained, respectively, with PGII (sensitivity of 90% and specificity of 76%) and PGI 30 min after stimulation (sensitivity and specificity of 82%), with an area under the ROC curve of 0.87 in both cases. In the multiple regressions analysis H. pylori status correlated with gastrin, PGI and PGII after therapy (P < 0.001), while histological lesions correlated only with gastrin levels (P < 0.05). A decrease in basal and stimulated serum parameters was demonstrated immediately after eradication (Wilcoxon test, P < 0.001), and an additional decrease (at 6 months) was observed just in PGI (Friedman test, P < 0.01). However, gastrin and PGII values remained unchanged after the first month post-eradication. Seven patients were reinfected with H. pylori during follow-up. Quantitation of basal and stimulated gastrin and PGI levels was not reliable as a reinfection marker. Regarding basal PGII, the parallelism was strong at 6 months (re-increase in all four reinfected patients), although only in one out of three with reinfection at 1 year did PGII rise at that stage. CONCLUSIONS: (1) Measurement of gastrin and PG levels (especially basal PGII values) is a useful non-invasive method to confirm H. pylori eradication after therapy. (2) H. pylori eradication is associated with a significant decrease in basal and stimulated gastrin levels and in basal PGII levels that is detected immediately (1 month) after finishing treatment, and remains unchanged for 1 year. However, the decrease in basal and stimulated PGI levels occurs progressively for 6 months, although such levels remain also unchanged afterwards. (3) Measurement of gastrin and PGI concentrations has a limited usefulness in the diagnosis of H. pylori reinfections after successful eradication, although PGII determination could be more useful in this situation.     

The correlation between histological gastritis staging- ‘OLGA/OLGIM’ and serum pepsinogen test in assessment of gastric atrophy/intestinal metaplasia in China

Background: Serum pepsinogen (PG) test, as an indicator of gastric mucosal atrophy, reflects the functional and morphologic status of gastric mucosal and it is suggested to serve as a useful predictive marker for patients with gastric cancer (GC). The available classifications of gastritis, known as the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal Metaplasia (OLGIM), integrating the severity and topography of atrophy/intestinal metaplasia (IM), have been gradually accepted and used in screening for GC in recent years.

Goals: To assess whether serum pepsinogen test, including PGI, PGII, PGI/PGII and gastrin-17 (G-17) could reflect the extent and topography of gastric mucosal atrophy/IM. Furthermore, to discuss the relationship between OLGA/OLGIM staging system and serum pepsinogen test in assessment of gastric atrophy/IM.

Methods: The OLGA/OLGIM ranks the gastric staging according to both the topography and the severity of gastric atrophy/IM. A retrospective study was conducted with 331 patients who underwent endoscopy with consecutive biopsy sampling and reassessed according to OLGA/OLGIM staging system. Serum pepsinogen test, including PGI, PGII, PGI/PGII and G-17, as well as serological Helicobacter pylori (Hp) antibody were also measured. Results were presented as gastritis stage, serum pepsinogen level and Hp status. Baseline characteristics were compared using analysis of variance (ANOVA) test for continuous data and Pearson’s χ² test for categorical data. A logistic regression model was used for the correlation analysis between OLGA/OLGIM and serological pepsinogen test.

Results: A total of 177 non-atrophic gastritis and 154 atrophic gastritis were analyzed, among which 40 were antrum atrophy, 32 were corpus atrophy and 82 were pan-atrophy. All patients were assessed applying the OLGA/OLGIM criteria with a mean age of 54.7?±?10.8 years. Patients among OLGA/OLGIM Stage III–IV were presented with a lower level of serum PGI and PGI/PGII (p?<?.05), especially for Stage IV (p?=?.01). For both Hp-positive patients and Hp-negative patients according to OLGA system, PGI/PGII level correlated inversely with the rising stage (p?=?.022; p?=?.028). As for OLGIM system, similar difference can be seen in PGI/PGII level in either Hp-positive patients, or Hp-negative patients (p?=?.036; p?=?.013). In addition, the percentage of G-17 <1?pmol/L combined with PG-negative in antrum atrophy group was much higher than that of non-atrophy group and corpus atrophy group (25 versus 15.8 versus 6.3%) (p?=?.029). The proportion of G-17?>?15?pmol/L combined with PG-positive was apparently higher in corpus atrophy group, compared with other two groups (25 versus 11.3 versus 8.1%) (p?=?.023). Logistic regression modeling showed there exist significant connections between OLGA/OLGIM stages and serum pepsinogen test in patient stratification for gastric mucosal atrophy assessment (p?<?.001, p?<?.001).

Conclusions: Serum pepsinogen test has a strong correlation with OLGA/OLGIM gastritis stage and could provide important information in assessment of atrophy/intestinal metaplasia.     

Follow-up study on a high risk population of gastric cancer in north China by serum pepsinogen assay

OBJECTIVE: To explore the features and clinical significance of serum pepsinogen (PG) assay in a follow-up study on a high-risk gastric cancer (GC) population. METHODS: A total of 444 participants from a high-risk area of GC in north China were enrolled in this follow-up study from April 1997 to December 1999. Serum PG was measured by enzyme-linked immunosorbent assay (ELISA), and the percentage changes in PG were calculated with 'PG( follow-up)/PG (first test)' thrice from the beginning to the end of these 30 months. Stomach diseases were diagnosed by a gastroscopy with biopsy examination. Helicobacter pylori (H. pylori) status was assessed by histopathological examination and serum H. pylori-immunoglobulin (Ig)G antibody assay with ELISA. RESULTS: In all groups except for the 51-60-year olds no significant differences of percentage changes in PGII and the PGI/II ratio were observed during 30-month follow-up period. In the superficial gastritis (SG) group the percentage change in PGI of group A (after 6 months' follow up) was significantly lower than that of group B (after 12 months' follow up) (0.69 vs 0.97, P = 0.002) in SG-->SG; while in SG-->normal (NOR), it was significantly higher than that in SG-->atrophic gastritis (AG) (0.94 vs 0.79, P = 0.022). In the AG group the percentage change in the PGI/II ratio of group A was significantly higher than that of group C (after 30 months' follow up) (1.13 vs 0.75, P = 0.042) in AG-->AG; and the percentage changes in PGI and PGII in AG-->NOR were significantly lower than those in AG-->SG (0.43 vs 0.87, P = 0.000; 0.60 vs 1.11, P = 0.010, respectively). In the H. pylori(-) (Hp(-)) group, the percentage change in PG of Hp(-)-->Hp(+) was significantly higher than that of Hp(-)-->Hp(-) (0.94 vs 0.81, P = 0.026). Percentage changes in PGI and PGII of Hp(+)-->Hp(-) were significantly lower than those of Hp(+)-->Hp(+) (0.74 vs 0.93, P = 0.000; 0.86 vs 1.15, P = 0.000, respectively), while the percentage change in the PGI/II ratio was higher than that the group of Hp(+)-->Hp(-) (0.90 vs 0.70, P = 0.022). CONCLUSION: The serum PG levels were influenced by the physiopathologic status of gastric mucosa and H. pylori infection, but they altered during the period of follow up. Serum PG assay might be a feasible and appropriate procedure to use in following up on a high-risk GC population.     

血清胃蛋白酶原检测在胃癌筛查中的价值

背景:我国在亚太地区属于胃癌高危地区。亚太地区胃癌预防共识指出,低血清胃蛋白酶原(PG)Ⅰ水平和低PGⅠ/PGⅡ比值可作为筛查胃癌高危人群的标记物。目的:明确血清PG检测在胃癌筛查中的价值。方法:纳入1880例2010年3月～2011年12月南京市市级机关医院的健康体检人员以及有上腹部不适症状的门诊患者,行血清PGⅠ、PGⅡ检测,其中1028例(包括所有血清PG筛查结果阳性者和部分筛查结果阴性但有上腹部不适症状或胃癌家族史者)接受胃镜和活检组织病理检查。结果:各年龄段受检者血清PGⅠ、PGⅡ水平差异均无统计学意义,≥70岁年龄段组PGⅠ/PGⅡ比值显著低于其他各年龄段组(P<0.05)。萎缩性胃炎组、上皮内瘤变组和胃癌组血清PGⅠ水平和PGⅠ/PGⅡ比值显著低于正常/非萎缩性胃炎组(P<0.01)。以PGⅠ<70 ng/mL+PGⅠ/PGⅡ<3.0为界值,血清PG检测筛查胃癌的敏感性为74.1%,特异性为84.9%,阳性似然比为4.93,阴性似然比为0.30。结论:血清PG检测用于胃癌初筛具有敏感性高、易于接受、成本低等优势,适用于大面积人群普查,结果阳性者应进一步行胃镜筛查。     

血清胃蛋白酶原对胃癌的诊断价值

目的探讨血清胃蛋白酶原对胃癌的诊断价值。方法收集我院2011年6月-2011年11月经胃镜活检病理诊断浅表性胃炎27例,癌前状态51例,癌前病变8例,胃癌17例,晨起空腹采静脉血3 mL,收集血清,以酶联免疫吸附测定(ELISA)定量检测血清胃蛋白酶原Ⅰ(PGⅠ)、PGⅡ水平,计算PGⅠ/PGⅡ(PGR)值。结果在浅表性胃炎、癌前状态、癌前病变、胃癌中血清PGⅠ水平及PGR逐渐降低,而血清PGⅡ水平逐渐升高;血清PGⅠ、PGR在胃癌与浅表性胃炎、癌前状态比较差异有统计学意义,与癌前病变比较差异无统计学意义;血清PGⅡ在胃癌与浅表性胃炎、癌前状态、癌前病变比较差异均有统计学意义;胃癌与癌前疾病ROC曲线下面积PGⅠAUCROC=0.782,PGⅡAUCROC=0.919,PGR AUCROC=0.989,PGⅠ为93.53 g/L时诊断胃癌的敏感性76.47%,特异性76.27%;PGⅡ为58.85 g/L时诊断胃癌的敏感性82.35%,特异性89.83%;PGR为1.88时诊断胃癌的敏感性94.12%,特异性89.83%。结论血清PGⅠ、PGⅡ水平及PGR值对诊断胃癌有较高的敏感性和特异性,可用于胃癌筛查和早期诊断。     

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.     

Serum pepsinogen II levels are doubled with Helicobacter pylori infection in an asymptomatic population of 40,383 Chinese subjects

Pepsinogen (PG) I and II are crucial in the gastric digestive processes. This study is to examine the relationship of serum PGI, PGII, and PGI/PGII ratio with Helicobacter pylori (Hp) infection, age, sex, and body mass index (BMI) in subjects in Beijing, China.A total of 40,383 asymptomatic subjects, who underwent medical examination in Beijing Rehabilitation Hospital, were included in this study. Serum PG levels were measured using chemoluminescence techniques. The age, sex, and BMI data were collected, and Hp infection was identified with ¹³C-urea breath test. Statistical analysis was conducted with Python, Pandas and Seaborn software.Asymptomatic subjects with Hp infection (Hp+) had a significantly higher level of PGI in the serum (111 ng/mL [median]) than those without Hp infection (Hp−) (94 ng/mL, P < .001). The asymptomatic Hp+ subjects had 2-fold higher PGII levels (7.2 ng/mL) than Hp− subjects (3.2 ng/mL, P < .001). These changes produced significantly lower PGI/II ratio in Hp+ patients than in Hp− subjects (16:30, P < .001). The serum PGI and PGII levels were higher in males than in females (PGI: 104 ng/mL vs 95 ng/mL, PGII: 4.3 ng/mL vs 3.7 ng/mL, both P < .001), PGI/II ratio of males is at 95% of that in females (P < .001). PGI and PGII levels gradually increased in older people (P < .001), whereas the PGI/II ratio decreased significantly with age (P < .001). The levels of the two serum PGs were decreased and the ratio increased when BMI were higher than 28 kg/cm² (P < .05).The levels of serum PGI, especial PGII, were increased by Hp infection, and also influenced by age, sex, and BMI. Therefore, these influencing factors should be considered during clinical practice.     

Serum pepsinogen levels in the Japanese population: prospective study of 9 years of follow-up

BACKGROUND/AIMS: Natural alterations of serum pepsinogen (PG) levels are still unclear. We investigated the natural course of pepsinogen levels by prospective study over a period of 9 years. METHODOLOGY: Out of 18,676 participants of a cancer screening program, 262 individuals (79 males, mean age 58.6 years) were enrolled. Sera were obtained from all participants in 1989 and again in 1998 to screen for gastric cancer. PG concentrations were determined by radioimmunoassay. Subjects with a PGI concentration of > 50 or a PGI/II ratio of > 3 were considered PG-negative. RESULTS: Initially, 207 and 55 subjects were considered to be PG-negative and positive, respectively. Of the 207 PG-negative subjects, 25 (12.1%) had seroconverted to a PG-positive status. All of the 41 subjects with a PGI/II ratio > 6.5, in whom H. pylori should be negative, remained PG-negative. Seroconversion to a PG-positive status was more frequently found in subjects with PGII > 15ng/mL, in whom active gastritis is more likely to be present. Of the 55 with PG-positive subjects, as assessed in 1989, 18 (32.7%) had seroconversion to a PG-negative status. Conclusions: PG-seroconversion occurred in 16% of people over a 9-year period. Seroconversion to a PG-positive status may be induced by active gastritis.     

Relationship among serum pepsinogens, serum gastrin, gastric mucosal histology and H. pylori virulence factors in a paediatric population

OBJECTIVE: Serum pepsinogens and gastrin have been proposed as markers of gastritis, but have seldom been studied in children. In this study the aim was to identify host- and Helicobacter pylori-related factors linked to variations in serum gastrin, PGI, PGII, and to evaluate the potential of these biomarkers for diagnosing gastritis, whether H. pylori-associated or not. MATERIAL AND METHODS: Ninety-two dyspeptic children referred for endoscopy (peptic ulcer exclusion) were included in the study. H. pylori status (urease, culture, histology) was assessed, and genotype determined (PCR) in H. pylori-positive subjects. Serum gastrin, PGI and PGII levels were measured by standard radioimmunoassay (RIA). RESULTS: PGI and PGII levels were significantly higher in H. pylori-positive subjects (p=0.007; p=0.012, respectively). Gastrin levels were significantly higher in H. pylori-negative subjects (p=0.035). PGI and PGII were associated significantly with higher antrum inflammation scores (p=0.002; p=0.016, respectively); only PGI was associated with age, after controlling for inflammation (p=0.033) and for activity (p=0.037). The contribution of virulence factors could not be assessed owing to the low number of virulent strains. After multivariate analysis, only antrum inflammation was independently associated with PGI level (p=0.012). Receiver operating characteristic (ROC) analysis showed a low PGI and PGII discriminant power for predicting antrum inflammation. CONCLUSIONS: Pepsinogen levels as measured in this study seem predominantly to reflect antral inflammation, but they are not an effective screening test for gastritis (H. pylori-positive or -negative) in dyspeptic children.     

Plasma ghrelin concentration correlates with the levels of serum pepsinogen I and pepsinogen I/II ratio--a possible novel and non-invasive marker for gastric atrophy

BACKGROUND/AIMS: Ghrelin, a novel growth-hormone-releasing peptide, has been reported to be localized mainly in the A-like cells in the gastric fundic mucosa. With the extension of gastric inflammation caused by H. pylori infection, gastric mucosal atrophy extends from the antrum to the corpus, which is the predominant site of localization of the ghrelin-producing A-like cells. The present study was designed to investigate the correlation between the plasma ghrelin levels and the extent of gastric mucosal atrophy in patients with chronic gastritis caused by H. pylori infection. METHODOLOGY: Sixty-nine patients with dyspeptic symptoms were enrolled for the study. Of these, 41 patients were confirmed to become negative for H. pylori after therapy to eradicate the infection. The other 28 patients were diagnosed as positive for H. pylori infection. Blood samples were collected from all the patients after 12 hours of fasting, before upper gastrointestinal endoscopy was performed. The plasma levels of total and active ghrelin, as well as the serum levels of pepsinogen I (PGI) and pepsinogen II (PGII) were measured by radioimmunoassay. Based on endoscopic assessment, the atrophic changes in the gastric mucosa were classified as open-type atrophy or closed-type atrophy. RESULTS: There were no significant differences in the plasma total and active ghrelin levels between H. pylori-positive and H. pylori-eradicated (negative) patients. The serum levels of PGI correlated well with the plasma levels of total ghrelin (p<0.01, r=0.38) and active ghrelin (p<0.05, r=0.29). The ratio of serum PGI to PGII level (PG I/II ratio) also correlated well with the plasma level of total ghrelin (p<0.05. r=0.31) and active ghrelin (p<0.05, r=0.27). The plasma levels of total as well as active ghrelin were significantly decreased in patients with low PG levels as compared with those in patients with high PG levels (PGI > 70 ng/mL or PGI/II >3.0). The plasma levels of total as well as active ghrelin were also significantly decreased in patients with endoscopically diagnosed open-type atrophy as compared with those in patients with endoscopically diagnosed closed-type atrophy (p < 0.01), especially in the H. pylori-eradicated cohorts. CONCLUSIONS: The plasma levels of ghrelin, which correlated well with the serum levels of PGI as well as the PGI/II ratio, decreased with increasing extent of gastric mucosal atrophy, suggesting that it could be a potentially useful non-invasive marker for chronic atrophic gastritis.     

Screening of atrophic gastritis and gastric cancer by serum pepsinogen, gastrin-17 and Helicobacter pylori immunoglobulin G antibodies

OBJECTIVE: Currently the screening and diagnosis of gastric cancer and atrophic gastritis are mainly made by endoscopy and biopsy. The aim of this study was to evaluate the use of serum tests: serum pepsinogen I (PGI pepsinogen I/II ratio (PGR), gastrin‐17 (G‐17) and H. pylori‐immunoglobulin G (IgG) antibodies to screen atrophic gastritis and gastric cancer. METHODS: A total of 458 patients were recruited, and each underwent endoscopy with biopsies before the serum tests were performed. These patients were divided into five groups based on the endoscopic and histological findings: 92 patients in the atrophic gastritis group, 58 in the gastric ulcer group, 90 in the duodenal ulcer group, 141 in the gastric cancer group (40 early gastric cancer and 101 advanced gastric cancer) and 77 (including mild non‐atrophic gastritis) served as a control group. Serum samples for PGI and II, G‐17, and H. pylori‐IgG antibodies estimation were analyzed by ELISA. RESULTS: PGI and PGR values decreased significantly both in atrophic gastritis and gastric cancer groups (P < 0.01). For the best discrimination of atrophic gastritis, the cut‐off values of PGI and PGR were 82.3 µg/L and 6.05, respectively. The PGI, PGR and G‐17 values were related significantly with the grades and/or sites of atrophic gastritis (P < 0.01). Patients with atrophic corpus gastritis had low PGI and PGR values and high G‐17 level, and patients with atrophic antral gastritis had low G‐17 level. G‐17 increased significantly in the gastric cancer group (P < 0.01). PGI and PGR values were significantly lower in patients with advanced gastric cancer than in patients with early gastric cancer, while there was no difference in G‐17 level between them. The positivity rate of H. pylori‐IgG antibodies was 54.55% in the control group. The PGI level was higher in H. pylori positive patients than in H. pylori negative ones (P < 0.001), while there was no difference in G‐17 level between them. The positivity rates of H. pylori‐IgG antibodies were over 85% in all other four groups. CONCLUSIONS: Low serum PGI, PGR and G‐17 values are biomarkers of atrophic antral gastritis. Atrophic corpus gastritis can be screened by lower serum PGI, PGR and high G‐17 values. [Correction added after online publication on 2 February 2007: the preceding sentence has replaced one that read ‘Atrophic be screened by serum PGI and PGR values’]. Gastric cancer can be screened on the basis of increased serum G‐17 and remarkedly low serum PGI and PGR values. The H. pylori infection is related to the change of PG level.     

Serum pepsinogen concentration as a marker of <Emphasis Type="Italic">Helicobacter pylori </Emphasis>infection and the histologic grade of gastritis; evaluation of gastric mucosa by serum pepsinogen levels

Background: Helicobacter pylori infection and associated gastritis are well-known significant factors in many gastrointestinal diseases, and evaluation of these conditions is important for health evaluation. We investigated the utility of serum pepsinogen (PG) concentrations for the diagnosis of H. pylori infection and evaluation of the grade of histologic gastritis. Methods: The subjects consisted of 283 individuals (147 men and 136 women; mean age, 44.0 years). Biopsy specimens were obtained from the gastric antrum and body to assess grade of inflammation and atrophy and histologic evidence of H. pylori infection. H. pylori infection was judged by Giemsa staining and serum IgG antibodies against H. pylori. PG concentrations were determined by radioimmunoassay. Results: In subjects with H. pylori infection, serum PGII concentrations were increased, and the PGI/PGII ratio (I/II ratio) was decreased. In patients with marked atrophy or intestinal metaplasia, both serum PGI and the I/II ratio were decreased. When PGII concentrations of 12 ng/ml or more, or a I/II ratio of 4.0 or less were used as the cutoff points for the diagnosis of H. pylori infection, the sensitivity and specificity of diagnosis were 90.0% and 93.5%, respectively. All subjects with serum PGI concentrations of 85 or more ng/ml, or serum PGII concentrations of 15 or more ng/ml were H. pylori-positive and all subjects with a I/II ratio of more than 6.5 were H. pylori-negative. Conclusions: These results suggest that H. pylori infection, gastritis, and glandular atrophy of the stomach can be evaluated via serum PG concentrations, allowing the evaluation of gastric mucosal integrity. Received: April 1, 2002 / Accepted: September 6, 2002 Acknowledgments. The authors thank Goro Kajiyama, M.D., Ph.D., and Koji Sumii, MD., PhD. (First Department of Internal Medicine, Hiroshima University School of Medicine) for helpful advice and supervision. This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan. Reprint requests to: M. Yoshihara     

Serum pepsinogen I and pepsinogen II, and the ratio of pepsinogen I pepsinogen II in peptic ulcer diseases: With special emphasis on the influence of the location of the ulcer crater

To investigate the effect of the location of the ulcer crater on the serum levels of pepsinogen I (PGI), pepsinogen II (PGII) and the ratio of PGI/PGII, these parameters were determined in 161 healthy controls, 29 patients with gastric ulcer in the gastric body (GU-I), 65 with coexistent gastroduodenal ulcer (GU-II), 104 with gastric ulcer in the prepyloric region (GU-III), and 116 with duodenal ulcer (DU). Serum PGI levels were significantly higher (P<0.01) in patients with GU-III (110.6 ± 65.1 ng/mL), GU-II (100.0 ± 46.6 ng/mL), and DU (92.2 ± 35.2 ng/mL) than in the controls (77.4 ± 31.4 ng/mL), while there were no significant differencs between GU-I (82.5 ± 36.3 ng/mL) and the controls. Patients with gastric ulcer in any region had significantly higher (P<0.01) serum PGII levels (GU-I, 20.0 ± 15.7 ng/mL; GU-II, 15.5 ± 10.9 ng/mL; GU-III, 14.3 ± 10.0 ng/mL) than the controls (10.6 ± 6.0 ng/mL) and the patients with DU (10.0 ± 5.5 ng/mL), whereas no significant differences existed between the latter two. The ratio of PGI/PGII in GU-I (5.86 ± 3.90) was significantly lower (P<0.01) than any other group (controls, 8.83 ± 4.70; GU-II, 8.33 ± 4.99; GU-III; 9.64 ± 6.13; DU, 10.45 ± 4.49), while patients with DU it was significantly higher (P<0.01) than any other groups. These findings indicate that peptic ulcer is comprised of a heterogeneous group of diseases. A normal level of serum PGI, an increased level of PGII, and a decreased ratio of PGI/PGII in GU-I patients reflected extensive atrophic gastritis, while an elevated level of PGI, a normal level of PGII, and an increased ratio of PGI/PGII in DU patients implicated hypersecretory status coexistent with superficial fundic gastritis. These findings suggest functional heterogeneity of the gastric mucosa according to the different locations of the ulcer crater.     

血清胃蛋白酶原比值和CA724对胃癌的诊断价值及相关性分析

目的探讨血清胃蛋白酶原比值与CA724对胃癌的诊断价值及相关性分析。方法收集上海交通大学附属第六人民医院南院2011年7月-2012年6月经胃镜活检病理诊断非萎缩性胃炎的患者187例,萎缩性胃炎伴肠化108例,胃癌91例,空腹采静脉血,酶联免疫吸附(ELISA)定量测定血清胃蛋白酶原Ⅰ(PGⅠ)、PGⅡ,计算PGⅠ/PGⅡ(PGR)值,电化学发光免疫分析法(ECLIA)检测血清糖类抗原724(CA724)。结果血清PGR=2.78时诊断胃癌敏感性为72.7%,特异性为77.2%,CA724=15.77u/ml时诊断胃癌敏感性为88.9%,特异性为97.2%;PGR联合CA724诊断胃癌阳性率为89%,与PGR(61.5%)、CA724(73.6%)单独诊断胃癌的阳性率比较,差异有统计学意义(P0.05);胃癌组中血清PGR与CA724无明显相关性(R=0.078,P=0.462)。结论胃癌组血清PGR与CA724无相关性,但二者联合检测可提高胃癌诊断阳性率,可用于胃癌筛查。     

Non-invasive tests in gastric diseases

Although the gastric cancer incidence is decreasing, this neoplasia remains one of the major causes of oncological mortality. Because of an insidious development, gastric cancer is often diagnosed in an advanced stage and consequently with a poor prognosis. Accurate non-invasive tests should be extremely useful in order to detect gastric neoplasm in an early phase. In clinical practice, there is no reliable bio-marker for detecting this malignant disease. However, intestinal as well as diffuse types of gastric cancer are preceded by gastric mucosa inflammation. Furthermore, the intestinal type of the neoplasia is, generally, related to chronic atrophic gastritis, especially if associated with intestinal metaplasia. In particular, the risk of the neoplasm is linked to both extension and severity of gastric atrophy. Serological parameters such as serum pepsinogens I (PGI) and II (PGII), gastrin-17 (G-17) cytokines (e.g. IL-8), antiparietal cells, IgG anti-Hp and CagA antibodies and lastly ghrelin supply information about either atrophic or inflammatory conditions characterising gastric mucosa. Low PGI and PGI/PGII ratio levels, especially if combined with high G-17 levels, are recognised bio-markers of corpus atrophic gastritis. Low G-17 levels could be, also, suggestive of antral atrophic gastritis. Furthermore, plasmatic ghrelin levels seem to be also a bio-marker of corpus atrophy. Anti-Hp IgG and CagA antibodies as well as PGII levels are able to detect gastric inflammation. Serological parameters could select subjects at risk for gastric mucosa alterations such as inflammation or atrophy, rather than gastric cancer itself. This review analyses the information derived from serological bio-markers as well as the involved clinical studies.     

Noninvasive evaluation of Helicobacter pylori therapy: role of fasting or postprandial gastrin, Pepsinogen I, Pepsinogen II, or serum IgG antibodies

OBJECTIVE: We evaluated the potential value of a change in serum IgG antibodies, fasting or meal-stimulated gastrin levels, and pepsinogen I (PGI) or pepsinogen II (PGII) levels for identifying Helicobacter pylori (H. pylori) status after antibiotic therapy. METHODS: A total of 32 men and one woman with peptic ulcer disease and documented H. pylori infection were enrolled. Fasting and 30-min postprandial blood samples were obtained at 0, 2, 7, 11, 17, 23, 27, and 39 wk of the study and were analyzed for the factors evaluated. RESULTS: Treatment was successful in 25 patients and failed in seven. Serum IgG antibodies, meal-stimulated gastrin, and both fasting and meal-stimulated pepsinogen I and II levels fell throughout the study, and pepsinogen I:II ratios increased in those whose infection was cured. The mean levels at wk 0 versus wk 7 were: fasting gastrin (fmol/ml) 12.4 and 11, meal-stimulated gastrin 26.5 and 15.4, PGI (ng/ml) 83.7 and 59, PGII (ng/ml) 24.5 and 13.6, PGI/PGII 3.5 and 4.7, and enzyme-linked immunosorbent assay value 4.8 and 4.55. The sensitivity, specificity, and positive and negative predictive values for the data analyzed using different percent changes (e.g., 80%, 50%, and 20%) were calculated. The specificity and sensitivity remained <80% at all time points. CONCLUSIONS: Despite a significant fall in serum markers of H. pylori infection in groups of individuals, no marker tested could be used to reliably determine posttherapy H. pylori status for individual patients.     

Helicobacter pylori infection, but not mucosal atrophy, significantly affects serum pepsinogen level after gastric cancer surgery

BACKGROUND/AIMS: Helicobacter pylori (Hp) infection is frequently observed in the remnant stomach after gastric cancer surgery, and is considered to play one of the important roles in chronic mucosal inflammation and cancer development. METHODOLOGY: Serum pepsinogen (PG) levels were measured in one hundred and eight patients after gastrectomy performed because of gastric cancer. The correlation between PG levels and the grade of mucosal inflammation in the remnant stomach was investigated together with the status of Hp infection. RESULTS: No statistical difference in serum PG level was found according to the severity of reflux gastritis, or grade of mucosal atrophy. Significantly higher serum PG II level and lower PG I/II ratio were found in cases with histologically severe mucosal inflammation than in those without inflammation. In Hp positive cases, PG I level stayed constant while PG II level scored a significantly higher value than those of negative cases. As a result, PG I/II ratio became significantly lower in cases with Hp infection than in those without infection. CONCLUSIONS: Hp infection and active mucosal inflammation, but not bile reflux or mucosal atrophy, significantly affect on the serum PG level in patients with remnant stomach after gastric cancer surgery. Serum PG level was suggested to indicate the grade of acute and chronic Hp-related inflammation in those patients.