Generation and characterization of nanobodies targeting human pepsinogens.

Human pepsinogens (mainly pepsinogen I and pepsinogen II) are the major inactive precursor forms of the digestive enzyme pepsin which play a crucial role in protein digestion. The levels and ratios of human pepsinogens have demonstrated potential as diagnostic biomarkers for gastrointestinal diseases, particularly gastric cancer. Nanobodies are promising tools for the treatment and diagnosis of diseases, owing to their unique recognition properties. In this study, recombinant human pepsinogens proteins were expressed and purified as immunized antigens. We constructed a VHH phage library and identified several nanobodies via phage display bio-panning. We determined the binding potency and cross-reactivity of these nanobodies. Our study provides technical support for developing immunodiagnostic reagents targeting human pepsinogens.

Value of serum gastrin and pepsinogen examination combined with narrow-band imaging endoscopy in the diagnosis of early gastric cancer / 中国基层医药

Objective:To investigate the value of serum gastrin-17 (G-17), pepsinogen (PG) I and II, and narrow-band imaging endoscopy in combination for identifying early gastric cancer.Methods:A total of 86 patients with suspected gastric cancer admitted to Zhoushan Hospital from January to September 2021 were included in this study. These patients underwent serum G-17, PG I, and PG II examination and narrow-band imaging endoscopy. PG I/PG II ratio (PGR) was calculated. Taking pathological results as a gold standard, the sensitivity, specificity, and accuracy of serum G-17, PG I, PG II, and narrow-band imaging endoscopy in combination for identifying early gastric cancer were calculated.Results:Serum G-17 level and PGR in the gastric cancer group were (20.14 ± 4.59) pmol/L and (20.21 ± 4.50) μg/L, respectively, which were significantly higher than (17.06 ± 4.05) pmol/L and (17.15 ± 4.08) μg/L in the atrophic gastritis group ( q = 4.12, 3.77, both P < 0.05) and (12.35 ± 3.31) pmol/L and (10.82 ± 5.26) μg/L in the non-atrophic gastritis group ( q = 9.34, 10.39, both P < 0.05). PG I and PGR in the gastric cancer group were (63.90 ± 14.41) μg/L and (3.17 ± 2.08), respectively, which were significantly lower than (79.34 ± 16.25) μg/L and (5.04 ± 3.61) in the atrophic gastritis group ( q = 5.33, 3.44, both P < 0.05) and (106.42 ± 20.18) μg/L and (9.22 ± 4.06) in the non-atrophic gastritis group ( q = 13.16, 9.97, both P < 0.05). Among the 86 patients included, gastric cancer was determined by biopsy in 43 patients. Pathological results showed that 37 patients had early gastric cancer and 6 patients had gastric cancer involving the muscle layer or serous layer. Narrow-band imaging endoscopy results showed that 83.78% (31/37) of patients had early gastric cancer. Serum G-17, PG, and narrow-band imaging endoscopy in combination showed that 91.89% (34/37) of patients had early gastric cancer. Taking pathological results as a gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of serum G-17 combined with PG for screening early gastric cancer were 72.97% (27/37), 77.55% (38/49), 71.05% (27/38), and 79.17% (38/48), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of narrow-band imaging endoscopy for screening early gastric cancer were 83.78% (31/37), 85.71% (42/49), 83.10% (31/38), and 87.50% (42/48). The sensitivity and specificity of serum G-17, PG, and narrow-band imaging endoscopy in combination for screening early gastric cancer were 91.89% (34/37) and 91.84% (45/49), respectively. Conclusion:Serum G-17, pepsinogen, and narrow-band imaging endoscopy in combination can improve the diagnostic accuracy of early gastric cancer and is an effective method for screening early gastric cancer.

A comparative study of three primary screening methods for gastric cancer among healthy people / 中华消化内镜杂志

Objective:To compare the role and efficacy of serum Helicobacter pylori ( HP) antibody combined with pepsinogen (PG) (ABC method), serum PG combined with gastrin-17 (G-17) (new ABC method) and a new gastric cancer screening scoring system for early gastric cancer screening in healthy people. Methods:Serological examinations were performed on healthy people who underwent physical examination and gastroscopy at the Physical Examination Center of Shanghai Songjiang District Central Hospital from January 2019 to December 2021. The population were divided into low-risk population, medium-risk population and high-risk population based on the above three primary screening methods for gastric cancer. Using gastroscopy and biopsy pathology as the gold standard, the ratio of each risk stratification and the detection rate of gastric cancer of the three screening methods were calculated. Advantages and disadvantages of the three methods were evaluated.Results:A total of 3 199 people who completed physical examination and gastroscopy were included in the study. Ten cases (0.31%) of esophageal cancer were detected by endoscopy, all of whom were early esophageal cancer. Thirty-seven cases (1.16%) of gastric cancer were detected,and the detection rate of early gastric cancer was 86.49%(32/37). The three gastric cancer screening methods were used to evaluate the risk of gastric cancer. According to ABC method, there were 1 853 cases (7.92%) in the low-risk group, 1 339 cases (41.86%) in the medium-risk group, and 7 cases (0.22%) in the high-risk group. The detection rates of gastric cancer were 0.97% (18/1 853), 1.42% (19/1 339), and 0.00%, respectively. According to the new ABC method, there were 2 362 cases (73.84%) in the low-risk group, 804 cases (25.13%) in the medium-risk group, and 33 cases (1.03%) in the high-risk group. The detection rates of gastric cancer were 1.14% (27/2 362), 1.24% (10/804), and 0.00%, respectively. According to the new gastric cancer screening scoring system, there were 1 448 cases (45.26%) in the low-risk group, 1 213 cases (37.92%) in the medium-risk group and 538 cases (16.82%) in the high-risk group. The detection rates of gastric cancer were 0.28% (4/1 448), 1.32% (16/1 213) and 3.16% (17/538), respectively. The detection rate of gastric cancer in the medium- and high-risk groups in total was significantly higher than that in the low-risk group with significant difference ( χ 2=17.935, P<0.001). The ROC curve showed that the AUC of the ABC method, the new ABC method and the new gastric cancer screening scoring system were 0.546, 0.503 and 0.760, respectively. The AUC of the new gastric cancer screening scoring system was significantly higher than those of the ABC method and the new ABC method, and the differences were statistically significant ( P<0.001). Conclusion:The detection rate of gastric cancer in the medium- and high-risk groups of the new gastric cancer screening scoring system is higher than that of the low-risk group, and the missed diagnosis rate of the new gastric cancer screening scoring system is lower than those of the ABC method and the new ABC method. The screening score is of high value for early gastric cancer screening in the healthy population.

Application of serum gastrin 17, pepsinogen I, pepsinogen II, and programmed cell death protein 5 protein in the identification of gastric precancerous state and diagnosis of early gastric cancer / 中国基层医药

Objective:To investigate the value of serum gastrin 17 (G-17), pepsinogen I (PG I), pepsinogen II (PG II), and programmed cell death protein 5 (PDCD5) in the identification of gastric precancerous state and the diagnosis of early gastric cancer.Methods:A total of 86 patients with early gastric cancer who received treatment at the Marine Police Corps Hospital of Chinese People's Armed Police Force from July 2018 to June 2022 were included in the gastric cancer group. Eighty patients with gastric precancerous states who concurrently received treatment in the same hospital were included in the precancerous state group. An additional 80 partiapants who concurrently received physical examination in the same hospital were included in the healthy group.The value of G-17, PG I, PG II, and PDCD5 in the diagnosis of early gastric cancer was analyzed.Results:The levels of G-17 and PG II in the precancerous state group [(10.87 ± 3.23) pmol/L, (15.78 ± 3.33) μg/L] and gastric cancer group [(18.78 ± 4.10) pmol/L, (21.25 ± 4.48) μg/L] were significantly higher compared with the healthy group [(5.56 ± 1.43) pmol/L, (13.52 ± 3.02) μg/L, F = 362.65, 94.12, all P < 0.05]. The levels of PG I and PDCD5 in the precancerous state group [(79.52 ± 16.62) μg/L, (1.35 ± 0.15) μg/L] and gastric cancer group [(50.06 ± 15.58) μg/L, (0.85 ± 0.13) μg/L] were significantly lower than those in the healthy group [(110.12 ± 30.23) μg/L, (1.60 ± 0.12) μg/L, F = 151.07, 650.56, all P < 0.05)].There were significant differences between the precancerous state and the gastric cancer groups in terms of family history of gastric cancer, consumption of high salt fried foods, alcohol consumption history, and Helicobacter pylori (Hp) infection ( χ2 = 10.39, 4.68, 11.47, 36.49, all P < 0.05). Family history of gastric cancer ( OR = 1.42, 95% CI = 1.03-1.96) and Hp infection ( OR = 3.76, 95% CI = 1.30-10.85) were identified as risk factors for gastric cancer ( P < 0.05). The combination of G-17, PG I, PG II, and PDCD5 had the highest predictive efficiency for early gastric cancer ( P < 0.05), with the area under the receiver operating characteristic curve being 0.982, sensitivity and specificity of 98.84% and 90.00%, respectively. Conclusion:Family history of gastric cancer and Hp infection are risk factors for gastric cancer. Patients with precancerous state and early gastric cancer have elevated serum levels of G-17 and PG II and reduced serum levels of PG I and PDCD5 protein. Combined detection of these four indicators has a high diagnostic value for early gastric cancer.

Value of serum pepsinogen Ⅰ, Ⅱ and gastrin-17 in screening precancerous lesions of gastric cancer in physical examination population / 中国医师进修杂志

Objective:To evaluate the value of serum pepsinogen Ⅰ and Ⅱ combined with gastrin-17 in screening precancerous lesions of gastric cancer in physical examination population.Methods:Serum pepsinogen, gastrin-17 and Helicobacter pylori (Hp) antibody were detected in 18 354 physical examination people from July to December 2017 in Wenrong Hospital, Hengdian, Dongyang. The patients were divided into youth group (18 to 39 years old), middle-aged group (40 to 59 years old) and elderly group (≥60 years old) according to their ages. The correlation between the serological level of the above indexes and age was analyzed; according to the new ABC method, the test results were divided into groups A, B, C and D. The patients in group C and D were examined by gastroscopy. The differences of gastric mucosal atrophy or intestinal metaplasia and other precancerous lesions detected by gastroscopy in different age groups were compared.Results:Finally, 18 354 cases were enrolled, including 9 614 males and 8 740 females. With the increase of age, the proportion of group C and D increased gradually. In group C, 181 cases underwent gastroscopy, including 39 cases of atrophic gastritis, 29 cases of intestinal metaplasia and 3 cases of dysplasia/intraepithelial neoplasia, the detection rate of precancerous lesions was 39.23%; in group D, 94 cases underwent gastroscopy, including 22 cases of atrophic gastritis and 13 cases of intestinal metaplasia, the detection rate of precancerous lesions was 37.23%. The proportion of gastric precancerous lesions in group C and D was 29.63% in the young group, 69.70% in the middle-aged group and 71.58% in the old group, respectively. There was significant difference compared with the young group ( P<0.01); atypical hyperplasia occurred in 2.02% and 9.47% of the middle-aged group and the elderly group. Conclusions:The combined detection of serum pepsinogen Ⅰ and Ⅱ and gastrin-17 levels is of great value in the screening of precancerous lesions of gastric cancer; when this method used for early gastric cancer screening in healthy population, it is necessary to consider the influence of age for the risk stratification of gastric cancer.

Helicobacter pylori infection and serum pepsinogen concentrations in an elderly population representative of Costa Rica / Infección por helicobacter pylori y concentraciones séricas de pepsinógenos en una población representativa de adultos de Costa Rica

Abstract Introduction: Costa Rica has among the highest mortality rates from gastric cancer in the world, largely due to late detection. It is therefore important that economically and logistically sustainable screening is implemented in order to detect risk of developing cancer. We have previously shown that low pepsinogen (PG) values and infection with Helicobacter pylori-CagA+ are associated with risk of gastric atrophy and cancer in Costa Rican populations. OBJECTIVES: To determine how markers for gastric cancer risk are distributed in an elderly population representative of Costa Rica in order to design a screening strategy. METHODS: The population studied consists of 2,652 participants in a nationally representative survey of ageing. Information concerning epidemiologic, demographic, nutritional and life style factors is available. Serum PG concentrations as well as H. pylori and CagA status were determined by serology. Possible associations were determined by regression analyses. RESULTS: Antibodies to H. pylori were present in 72% of the population and of those, 58% were CagA positive. Infection with H. pylori was associated with higher PGI concentrations (p=0.000) and infection with H. pylori-CagA. with lower PGI concentrations (p=0.025). Both showed association with lower PGI/PGII (p=0.006 and p=0.000). Higher age was associated with lower prevalence of H. pylori infection (OR=0.98; p=0.000) and CagA. (OR=0.98; p=0.000) but not with PG values. Regions with high risk of gastric cancer showed lower PGI (p=0.004) and PGI/PGII values (p=0.021) as well as higher prevalence of H. pylori infection (OR=1.39; p=0.013) but not CagA.. Using cut-off values of PGI<100 µg/L and PGI/PGII<2.0, 2.5 and 3.0, 7-15% of the population would be considered at risk. CONCLUSIONS: H. pylorialone is not a useful marker for risk of gastric cancer. Screening using serum pepsinogen concentrations and infection with H. pylori-CagA. is feasible in the general elderly population of Costa Rica but appropriate cut-off values have to be determined based on more clinical data and follow up capacity.

Resumen Introducción: Costa Rica tiene una de las tasas de mortalidad por cáncer gástrico más altas del mundo, en gran parte debido a la detección tardía. Por lo tanto, es importante que se implemente un tamizaje económico y logísticamente sostenible para detectar el riesgo de desarrollar cáncer. En estudios anteriores demostramos, que valores bajos de pepsinógeno (PG) y la infección por Helicobacter pylori-CagA+ están asociados con el riesgo de atrofia gástrica y cáncer en poblaciones costarricenses. OBJETIVO: Determinar cómo se distribuyen los marcadores de riesgo de cáncer gástrico en una población representativa de adultos de Costa Rica para diseñar una estrategia de tamizaje. MÉTODOS: Se estudió una población representativa a nivel nacional de 2.652 adultos, que formaron parte de un estudio longitudinal sobre envejecimiento. Se dispone de información sobre factores epidemiológicos, demográficos, nutricionales y de estilo de vida. Las concentraciones séricas de PG, así como el estado de H. pylori y CagA se determinaron mediante serología. Las posibles asociaciones se determinaron mediante modelos de regresión (logística y lineal múltiple). RESULTADOS: El 72% de la población presenta anticuerpos contra H. pylori, de ellos, el 58% fueron positivos para CagA. La infección por H. pylori se asoció con altas concentraciones de PGI (p = 0,000) y la infección por H. pylori-CagA+ con bajas concentraciones de PGI (p = 0,025). Ambas pruebas mostraron asociación con una baja razón PGI/PGII (p = 0,006 y p = 0,000). El rango de mayor edad se asoció con una menor prevalencia de la infección por H. pylori (OR = 0,98; p = 0,000) y de CagA+ (OR = 0,98; p = 0,000) pero no se asoció con los valores de PG. Las regiones con alto riesgo de CG mostraron valores bajos de PGI (p = 0,004) y de PGI/PGII (p = 0,021) así como una alta prevalencia de la infección por H. pylori (OR = 1,39; p = 0,013), no así con CagA+. Utilizando valores de corte de PGI<100 µg/L y de PGI/PGII <2,0, 2,5 y 3,0, se consideraría en riesgo de cáncer entre 7-15% de la población. CONCLUSIONES: La infección por H. pylori, por sí sola, no es un marcador de riesgo de CG útil. Es factible realizar el tamizaje de adultos de la población general de Costa Rica, utilizando como marcadores las concentraciones séricas de pepsinógenos y la infección por H. pylori-CagA+, sin embargo, los valores de corte apropiados deben determinarse con base en una mayor cantidad de datos clínicos y la capacidad de seguimiento.

Exploratory multigroup structural equation modeling approach to analyzing H. pylori infection, serological pepsinogen levels, and life style factors in an elderly population in Costa Rica / Enfoque exploratorio del modelo de ecuaciones estructurales multigrupo para el análisis de la infección con H. pylori, niveles de pepsinógenos séricos y factores asociados a estilo de vida en una población de adultos mayores en Costa Rica

Abstract The aim of this work is to describe and analyze the association of PGI/PGII ratio (indicator of gastric atrophy) with H. pylori-CagA and life style factors such as caloric intake, obesity, and harmful habits amongst H. pylori-positive elderly people infected in Costa Rica using an exploratory multigroup structural equations model (SEM). Using a sample of 1748 H. pylori-positive elderly people from CRELES first wave study, a SEM was employed analyze if the relationships between PGI/PGII ratio with levels of H. pylori-CagA, caloric intake, obesity, and harmful habits, differs by sex, age and risk areas subgroups. The proposed SEMs exhibited a good fit in males (RMSEA = 0.039), females (RMSEA = 0.000), low-risk area (RMSEA = 0.038), middle-risk area (RMSEA = 0.042), individuals under 80 years (RMSEA = 0.038) and individuals aged 80 and over (RMSEA = 0.042), while an acceptable fit was observed for the high-risk area (RMSEA = 0.061). Fitted SEMs showed that CagA predicted PG-ratio as expected, with effects increasing with the risk area, but similar between sex and age groups. All indicators measuring obesity (BMI, arms, and waist) showed significant standardized coefficients, with similar effects between sex, age and risk area groups. No other significant effects or differences between groups were identified. We propose a good-fitted SEM model for the possible relationships between CagA and PG ratio and the geographical risk area level for elderly people. No differences were observed on measured parameters between male and female population, or between under 80 years and older individuals.

Resumen El objetivo de este trabajo es describir y analizar la asociación entre PGI/PGII (indicador de atrofia gástrica con H. pylori-CagA y factores asociados a estilo de vida como ingesta calórica, obesidad y hábitos nocivos entre adultos mayores positivos por H. pylori en Costa Rica utilizando modelos de ecuaciones estructurales multigrupo (SEM). Con una muestra de 1748 adultos mayores del estudio CRELES, se utilizó un SEM para analizar las relaciones entre PGI/PGII, CagA, ingesta calórica, obesidad y hábitos nocivos difieren por sexo, edad y áreas de riesgo. Los SEMs propuestos exhibieron un buen ajuste en hombres (RMSEA = 0.039), mujeres (RMSEA = 0.000), área de bajo riesgo (RMSEA = 0.038), áreas de riesgo medio (RMSEA = 0.042), individuos menores de 80 años (RMSEA = 0.038) e individuos de 80 años o más (RMSEA = 0.042), mientras que hubo un ajuste aceptable en áreas de alto riesgo (RMSEA = 0.061). Los SEMs ajustados mostraron que CagA predice la relación PGI/II en la dirección esperada con efectos proporcionales al área de riesgo, pero no por sexo y edad. Todos los indicadores medibles de obesidad (IMC, brazos y cintura) mostraron coeficientes estandarizados significativos con efectos similares entre los grupos por sexo, edad y área de riesgo. No se encontraron otros efectos o diferencias significativas. Proponemos un modelo SEM bien ajustado para las posibles relaciones entre CagA y PGI/II y el nivel de riesgo del área geográfica en adultos mayores. No se encontraron diferencias en las variables analizadas entre hombres y mujeres ni entre los grupos de edad.

Clinical significance of standardized screening of early gastric cancer in Qinghai Province / 中华消化内镜杂志

Objective:To explore the clinical significance of standardized screening for diagnosis and treatment of early gastric cancer in Qinghai Province.Methods:Opportunistic early gastric cancer screening was conducted in outpatients of Digestive Department, Physical Examination Center and inpatients of Qinghai Provincial People′s Hospital from January 2016 to December 2020, according to the optimal cut-off values of serum pepsinogen (PG)Ⅰ, PGⅠ/PGⅡ ratio (PGR) and serum gastrin 17 (G17) obtained from the previous screening study of gastric cancer and precancerous diseases in different areas of Qinghai Province. At the same time, the standardized early gastric cancer screening program was applied in 10 municipal (county-level) hospitals in Qinghai Province. The detection rate, early diagnosis rate and endoscopic treatment rate of early gastric cancer in Qinghai Provincial People′s Hospital and the above 10 hospitals in the past five years were analyzed respectively.Results:In the five years, the total detection rate, early diagnosis rate and endoscopic treatment rate of early gastric cancer in Qinghai Provincial People′s Hospital were 0.214% (407/190 178), 17.54% (407/2 321) and 81.82% (333/407), respectively. The above indices in 10 other hospitals were 0.085% (264/309 217), 12.94% (264/2 040) and 37.12% (98/264), respectively. The overall detection rate of early gastric cancer was higher than 0.024% reported previously.Conclusion:The standardized early gastric cancer screening program can not only improve the diagnosis rate of early gastric cancer in Qinghai Province, but also save medical resources. It is an economical, efficient and feasible program, suitable for the highin-cidence area of gastric cancer in Qinghai Province.

Clinical and Histological Characteristics of Esophageal Heterotopic Gastric Mucosa: Analysis of 1 229 Cases / 胃肠病学

Background: There is still controversy whether the existence of esophageal heterotopic gastric mucosa (EHGM) and its histological type are related to the laryngopharyngeal symptoms. Aims: To analyze the clinical and histological characteristics of EHGM and its correlation with gastroesophageal reflux. Methods: A retrospective study was conducted in consecutive gastroscopy-proved EHGM cases from September 2018 to January 2020 at the Second Affiliated Hospital of Baotou Medical College. Besides clinical data review and questionnaire survey on reflux symptoms, histological typing of EHGM and immunohistochemistry were also performed in some cases. Results: A total of 1 229 cases of EHGM were recruited. The male-to-female ratio was 1.67:1, and middle-aged people were predominant. Most of the heterotopic mucosa were located 15-18 cm away from the incisors, and were mainly single. Two hundred and ninety-four cases (23.9%) were complicated with reflux esophagitis (RE), of which Los Angeles grade A and B accounted for 96.6%. Regurgitation/acid reflux (15.5 %) and heartburn (12.3%) were the most common esophageal symptoms, while extraesophageal symptoms were rare. Histological typing was obtained in 57 cases, of which, 37 (64.9%) were cardia-type, 18 (31.6%) were fundic-type, and 2 (3.5%) were mixed type. There were no significant differences in gender, age, location and number of EHGM, expression levels of H

Correlations of OLGIM Stage With Gastric Mucosal Serology and Helicobacter pylori Infection in Patients With Chronic Gastritis / 胃肠病学

Background: The OLGIM (operative link on gastric intestinal metaplasia assessment) staging system is important for the prediction of gastric cancer risk in patients with chronic gastritis. However, there are few studies focusing on the correlations of OLGIM stage with gastric mucosal serology and Helicobacter pylori ( Hp) infection. Aims: To investigate the correlations between OLGIM stage and serum pepsinogens (PGs) , gastrin-17 (G-17) , and Hp infection in patients with chronic gastritis. Methods: Individuals undergoing health examination and upper GI endoscopy in the Affiliated Provincial Hospital of Anhui Medical University from May 2015 to December 2017 were enrolled consecutively in this retrospective study. Information on demography, gastric mucosal serology, endoscopy, biopsy pathology and Hp infection was collected. The severity, topography and extension of intestinal metaplasia were assessed by OLGIM staging system. The clinical features of chronic gastritis patients with different OLGIM stages were compared; the risk factors for OLGIM stage HI-IV and the predictive performance of PG I to PG II ratio (PGR) for OLGIM stage HI -TV were analyzed. Results: A total of 1 112 health examination subjects were included in this study. The Hp infection rate was 49. 1%. The serum levels of PG I , PGII , and G-17 were higher, whereas the PGR was lower in Hp-positive subjects than those in Hp-negative ones (all P <0. 05). With the increasing of OLGIM stage, the serum levels of PG II and G-17 were increased, and the PGR was decreased ( all P < 0. 05 ). Meanwhile, the Hp infection rate and the proportion of family history of GI tumors were increased in patients with higher OLGIM stages (all P < 0. 05). In multivariate Logistic regression analysis, age was identified as the independent risk factor for OLGIM stage IH -IV ( OR = 1. 032 , 95% CI: 1. 002-1. 063 , P = 0. 035 ) , while higher PGR was a protective factor ( OR = 0. 837, 95% CI: 0. 754-0. 928 , P = 0. 001) . The optimal cut-off value of PGR for predicting OLGIM stage HI -IV was 8. 065 , with the sensitivity and specificity of 73. 8% and 69. 4% , respectively. Conclusions: Older age and lower PGR are independent risk factors for OLGIM stage HI-IV- PGR can be used as an indicator for screening OLGIM stage HI -IV individuals.

Application of New Gastric Cancer Screening Scoring System in Early Gastric Cancer Screening: A Preliminary Community-based Study / 胃肠病学

Background: Gastric cancer is one of the common gastrointestinal malignancies. Early diagnosis can reduce the mortality rate significantly. In the Chinese consensus published in 2017, the New Gastric Cancer Screening Scoring System was recommended to be used for risk stratification of gastric cancer. Aims: To preliminarily explore the value of the New Gastric Cancer Screening Scoring System in early gastric cancer screening in asymptomatic community population. Methods: At several communities in Suzhou City Xiangcheng District, a questionnaire survey was conducted in asymptomatic community residents willing to accept voluntary serum tests to collect information on high risk factors of gastric cancer. Serum pepsinogen (PG), PGⅡ, gastrin 17 (G-17) and Helicobacter pylori (Hp) IgG were tested simultaneously. Risk stratification of gastric cancer was carried out in accordance with the New Gastric Cancer Screening Scoring System. Gastroscopy was recommended for moderate to high risk individuals. Results: A total of 540 asymptomatic individuals completed the study, of which 11 were categorized as high risk (2.0%), 168 as moderate risk (31.1%), and 361 as low risk (66.9%). Sixty-four moderate to high risk individuals completed the gastroscopy with a response rate of 35.8%. Four precancerous lesions were detected (6.2%), including 3 gastric low-grade intraepithelial neoplasia and 1 duodenal adenoma. No gastric cancer was detected. Conclusions: The New Gastric Cancer Screening Scoring System is useful for risk stratification of gastric cancer in asymptomatic population and may provide a basis for further endoscopic examination. However, the value of this scoring system in low risk areas of gastric cancer needs to be further verified.

Feasibility analysis of pepsin strip test in diagnosis of laryngopharyngeal reflux disease / 中华耳鼻咽喉头颈外科杂志

Objective@#To evaluate the feasibility of pepsin strip test in the diagnosis of laryngopharyngeal reflux.@*Methods@#From August 2017 to September 2018,80 patients in Department of Otorhniolaryngology Head and Neck Surgery,Chinese People′s Liberation Army General Hospital-Six Medical Centre, underwent pepsin strip test and 24-hour multichannel intraluminal impedance(MII)-pH monitoring. The results of the two methods were analyzed for consistency,and 24-hour MII-pH monitoring was used as a statistical reference for the sensitivity and specificity of pepsin strip test in the diagnosis of laryngopharyngeal reflux. Data were analyzed by SPSS 19.0 software.@*Results@#There were 57 patients with positive pepsin test strip and 23 patients with negative pepsin test strip. The score of reflux symptoms and signs, and the positive rate of laryngopharyngeal reflux events in patients with positive pepsin strip test were significantly higher than those in patients with negative pepsin test strip. If there was one or more throat reflux events (including acid reflux,weak acid reflux and alkali reflux) as the positive results of 24-hour MII-pH monitoring,the consistency between the results of pepsin strip and 24-hour MII-pH was moderate (Kappa=0.614). The sensitivity and specificity of pepsin strip were 86.9% (53/61) and 78.9% (15/19) respectively.@*Conclusions@#Pepsin strip detection has the advantages of non-invasive,cheap and easy to operate.As an objective method for early diagnosis of laryngopharyngeal reflux, pepsin strip detectionis feasible,but can not be the final diagnosis for laryngopharyngeal reflux disease.

Diagnostic value of gastric cancer risk assessment systems for patients with early gastric cancer / 中国实用内科杂志

OBJECTIVE: To evaluate the predictive value of various gastric cancer risk scoring systems based on the detection of pepsinogen and gastrin 17 for the risk of developing gastric cancer. METHODS: One hundred and forty-four patients were enrolled into the study from the First Affiliated Hospital of Anhui Medical University between April 2018 and October 2018.Among them, seventyfour patients were diagnosed with early gastric cancer while seventy patients didn't have gastric cancer(control group). The levels of serum pepsinogen I(PGI)/pepsinogen II(PGII), gastrin-17(G-17) and H.pylori antibody were measured. Patients were scored according to the Japanese ABC method, the modified ABC method, and the Chinese new gastric cancer risk scoring system. Compare the accuracy of the three methods for predicting the risk of developing gastric cancer. RESULTS: Compared with the control group, there was no significant difference in PG levels between the two groups, the serum G-17 levels were lower in gastric cancer patients than those in control group(P<0.05). According to the ABC method, the incidence rates of gastric cancer in the four groups of ABCD were 48.6%,59.4%, 0.0% and 100% respectively; the incidence rates of gastric cancer in the three groups of modified ABC method were 57.6%, 35.9% and 50% respectively. The cut-off value of new gastric cancer risk scoring system to diagnose gastric cancer was 11. The sensitivity,specificity, accuracy, positive predictive value and negative predictive value were 64.8%, 71.4%, 68.1%, 70.6 and 65.8% respectively. But in the low risk group, there were 26 cases(35.1%) of gastric cancer. Comparing the low-risk with the middle-high-risk population of gastric cancer, there were more females in the low risk group. CONCLUSION: The Japanese ABC method and the modified ABC method have value for limited screening gastric cancer and are not suitable for China's national conditions. The screening efficacy of the new gastric cancer scoring system for gastric cancer is significantly higher than the other two methods; however we should be vigilant when it is used in women with low risk.

Changes in Helicobacter pylori Immunoglobulin G Levels and Gastric Mucosal Atrophy after Successful Eradication of Helicobacter pylori

BACKGROUND/AIMS: Limited information is available about the relationship between Helicobacter pylori (H. pylori) immunoglobulin (Ig) G and serum pepsinogen (pepsinogen [PG], a marker of gastric mucosal atrophy) concentrations after H. pylori eradication. MATERIALS AND METHODS: Eligible patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer from August 2007 to March 2013 in a tertiary-referral center, and whose serum H. pylori IgG and PG concentrations were measured at the time of performing ESD and one year post-ESD, were selected. Successful H. pylori eradication was achieved after ESD in all the patients. According to the decrease in serum H. pylori IgG concentration after bacterial eradication, the patients were categorized as group 1 (IgG concentration decreased by <50%), and group 2 (IgG concentration decreased by ≥50%). RESULTS: Of the 106 patients, 25 (23.6%) were classified into group 1 and 81 (76.4%) into group 2. One year after H. pylori eradication, the serum PG II concentration was significantly decreased in group 2 (12.46±8.18 vs. 8.28±6.11, P=0.024). Although the serum PG I/II ratio of group 2 was higher than that of group 1 (8.32±4.52 ng/mL vs. 6.39±4.04 ng/mL), the difference was not significant (P=0.058). One year after successful eradication, elevated serum PG I/II ratio was observed in 21 patients (84%) in group 1 and in 77 patients (95.1%) in group 2 (P=0.087). The mean serum PG I/II ratio was also elevated in both groups. Serum PG II concentration was significantly decreased in group 2. CONCLUSIONS: A notable decrease in the concentration of H. pylori IgG antibody after bacterial eradication might reflect gastric mucosal atrophy. However, our study showed no statistically significant difference.

Value of New Screening Scoring System of Gastric Cancer for Detecting Early Gastric Cancer Patients in Local Region / 胃肠病学

Background: The prognosis of early gastric cancer is significantly better than that of advanced gastric cancer. Because of the lacking of rational screening means, the detection rate of early gastric cancer is low. Serum pepsinogen Ⅰ (PGⅠ), PGⅡ, gastrin-17 (G-17) can be used for the screening of early gastric cancer. Aims: To investigate the value of new screening scoring system of gastric cancer for detecting patients with early gastric cancer in local region. Methods: A total of 393 patients from April 2017 to December 2018 were enrolled. According to pathological findings, patients were divided into control group, gastric ulcer group, dysplasia group and early gastric cancer group. Levels of PGⅠ, PGⅡ, G-17, Hp antibody were detected, and PGR was calculated. ROC curve was used to analyze the value of parameters for detecting early gastric cancer. Detection rates of early gastric cancer via serum ABC method, new ABC method and new screening scoring system were compared. Results: Compared with control group, serum PGⅠ and PGⅡ in gastric ulcer group were significantly increased, PGR was significantly decreased (P12.80 pmol/L and ≤6.90, respectively, the combination of these three indices for screening early gastric cancer had a sensitivity of 90.6%, specificity of 91.1%, and AUC of 0.965. The detection rate of early gastric cancer via new screening scoring system was significantly increased than that of serum ABC method, however, no significant difference was found between new screening scoring system and new ABC method (P>0.05). Conclusions: Decreased serum PGⅠ, PGR and increased G-17 may suggest the occurrence of early gastric cancer. New screening scoring system of gastric cancer is an efficient method for screening early gastric cancer.

Clinical value of serum pepsinogen, carcinoembryonic antigen and carbohydrate antigen 19-9 in diagnosis and prognosis evaluation of gastric cancer / 肿瘤研究与临床

Objective To investigate the clinical value of serum pepsinogen (PG), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) in diagnosis, prognosis evaluation and postoperative monitoring of gastric cancer. Methods A total of 100 patients diagnosed by the gastroscope in the Third People's Hospital of Hefei from January 2016 to October 2018 were selected. The patients were divided into the non-atrophic gastritis group (50 cases) and the gastric cancer group (50 cases) according to histopathological results. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum PGI and PGII. The ratio of PGI and PGII ratio (PGR) was calculated. Radioimmunoassay was used to detect CEA and CA19-9 levels. Results Serum PGI and PGR in the gastric cancer group were lower than those in the non-atrophic gastritis group [PGI: (96±35) μg/L vs. (144±44) μg/L; PGR: 7±3 vs. 11±5], and there was a significant difference (t=3.861, P<0.01; t=3.043, P=0.003]. Serum CEA and CA19-9 in the gastric cancer group were higher than those in the non-atrophic gastritis group [(7.5 ±4.8) ng/ml vs. (1.5 ±0.6) ng/ml, (49.7±29.4) U/ml vs. (8.7±2.6) U/ml], and there were statistical differences (t= 3.100, P= 0.003; t= 3.139, P= 0.002). Serum PGR of the gastric cancer group was decreased in TNM Ⅲ-Ⅳ stage, poorly differentiated adenocarcinoma and lymph node metastasis (t= 2.185, P= 0.034; t= 2.197, P= 0.033; t= 2.130, P=0.038); CA19-9 of the gastric cancer group was increased in TNM stage (Ⅲ-Ⅳ stage) and lymph node metastasis (t= 2.405, P= 0.020;t= 2.076, P= 0.043). There were no statistical differences in PGⅠ, PGⅡand CEA of gastric cancer patients with different clinicopathological characteristics (all P> 0.05). Serum PGⅠ[(46±23)μg/L] and PGⅡ[(8±5)μg/L] were decreased in the postoperative gastric cancer group (t=4.263, P<0.01; t=5.830, P<0.01). Serum CEA and CA19-9 of the postoperative metastatic group were higher than those of the postoperative non-metastatic group [(35.3±14.5) ng/ml vs. (3.6±2.2) ng/ml, (126±57) U/ml vs. (27±12) U/ml]. Conclusion Combined detection of serum PGⅠ, PGⅡ, CEA and CA19-9 could be used for the diagnosis and prognosis evaluation of gastric cancer, and it has a certain clinical value for postoperative metastasis monitoring of gastric cancer.

Comparison of different serological methods in screening early gastric cancer / 中华内科杂志

Objective To compare the consistency and detection rate of early gastric cancer (EGC) of three different methods including anti-Helicobacter pylori (Hp) antibody combined with pepsinogen (PG) (ABC method),serum PG combined with gastrin-17 (G-17) (new ABC method) and the new scoring system.Methods Serological tests were performed in Zhejiang population,which divided the subjects into low risk,intermediate risk and high risk groups.High risk subjects were examined by endoscopic and pathological examination.SPSS19.0 were used to evaluate the consistency of three methods.According to the receiver operating characteristic (ROC) curve,the ratio of G-17 to PG (PGR) was calculated for the optimal diagnostic cut-off value of EGC.Results A total of 30 126 subjects were recruited.Based on the data of ABC method,the proportions of low risk,intermediate risk and high risk group were 15 368 (51.01％),13 246 (43.97％),and 1 512 (5.02％),respectively.These proportions by the new ABC method were 20 584 (68.32％),8 990 (29.84％),552 cases (1.83％),respectively.By new scoring system,these were 20 810 (69.08％),8 059 (26.75％),and 1 257 (4.17％),respectively.Among them,1 263 subjects underwent endoscopy and 22 cases (1.74％) were finally diagnosed as gastric cancer including 19 EGC (86.4％).There were 1 case (0.35％),14 cases (1.84％),and 7 cases (3.21％) with gastric cancer in low risk,intermediate risk,and high risk groups by ABC methods,respectively.Gastric cancer patients were 7 (1.68％),10 (1.38％),and 5 (4.10％) in three groups respectively by new ABC methods.Via new scoring system,gastric cancer were detected in 5 (0.66％),9 (2.22％),and 8 (7.84％) patients of three risk groups respectively.The consistency of three screening methods was poor.The detection rate of gastric cancer in high risk group was higher than that in the other two (P＜0.05).The area under the curve (AUC) for diagnosis of gastric cancer by G-17 and PGR was 0.588 and 0.729,respectively.According to the PGR cut-off value determined by the fitted model,the incidence of gastric cancer in the low,intermediate and high risk groups was 0.94％,1.97％,and 6.31％,respectively.When the cut-off value is PGR＜4.135,the sensitivity is 0.855 and the specificity is 0.545.Conclusion The new scoring system has a better predictive value in EGC screening.The detection rate of EGC in high risk group is higher than that in low and intermediate risk groups.

Clinical value of serum pepsinogen, carcinoembryonic antigen and carbohydrate antigen 19-9 in diagnosis and prognosis evaluation of gastric cancer / 肿瘤研究与临床

Objective@#To investigate the clinical value of serum pepsinogen (PG), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) in diagnosis, prognosis evaluation and postoperative monitoring of gastric cancer.@*Methods@#A total of 100 patients diagnosed by the gastroscope in the Third People's Hospital of Hefei from January 2016 to October 2018 were selected. The patients were divided into the non-atrophic gastritis group (50 cases) and the gastric cancer group (50 cases) according to histopathological results. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum PGI and PGII. The ratio of PGI and PGII ratio (PGR) was calculated. Radioimmunoassay was used to detect CEA and CA19-9 levels.@*Results@#Serum PGI and PGR in the gastric cancer group were lower than those in the non-atrophic gastritis group [PGI: (96±35) μg/L vs. (144±44) μg/L; PGR: 7±3 vs. 11±5], and there was a significant difference (t = 3.861, P < 0.01; t = 3.043, P = 0.003]. Serum CEA and CA19-9 in the gastric cancer group were higher than those in the non-atrophic gastritis group [(7.5±4.8) ng/ml vs. (1.5±0.6) ng/ml, (49.7±29.4) U/ml vs. (8.7±2.6) U/ml], and there were statistical differences (t = 3.100, P = 0.003; t = 3.139, P = 0.002). Serum PGR of the gastric cancer group was decreased in TNM Ⅲ-Ⅳ stage, poorly differentiated adenocarcinoma and lymph node metastasis (t = 2.185, P = 0.034; t = 2.197, P = 0.033; t = 2.130, P = 0.038); CA19-9 of the gastric cancer group was increased in TNM stage (Ⅲ-Ⅳ stage) and lymph node metastasis (t = 2.405, P = 0.020; t = 2.076, P = 0.043). There were no statistical differences in PGⅠ, PGⅡ and CEA of gastric cancer patients with different clinicopathological characteristics (all P > 0.05). Serum PGⅠ [(46±23) μg/L] and PGⅡ [(8±5) μg/L] were decreased in the postoperative gastric cancer group (t = 4.263, P < 0.01; t = 5.830, P < 0.01). Serum CEA and CA19-9 of the postoperative metastatic group were higher than those of the postoperative non-metastatic group [(35.3±14.5) ng/ml vs. (3.6±2.2) ng/ml, (126±57) U/ml vs. (27±12) U/ml].@*Conclusion@#Combined detection of serum PGⅠ, PGⅡ, CEA and CA19-9 could be used for the diagnosis and prognosis evaluation of gastric cancer, and it has a certain clinical value for postoperative metastasis monitoring of gastric cancer.

Combination of Serum Helicobacter pylori Antibody With Pepsinogens and OLGA/OLGIM Staging System for Risk Assessment of Gastric Precancerous Lesions / 胃肠病学

Background: Serum pepsinogens (PGs), as an indicator of gastric mucosal atrophy, reflects the functional and morphological status of gastric mucosa. And OLGA/OLGIM, the staging system of gastritis integrating the severity and topography of gastric mucosal atrophy/intestinal metaplasia, has been gradually accepted and used in gastric cancer screening in recent years. Aims: To investigate the correlation between ABC method [combined assay for serum Helicobacter pylori (Hp) antibody and PGs] and OLGA/OLGIM staging system, as well as the role of PGs test in risk assessment of gastric precancerous lesions. Methods: A total of 331 patients undergoing gastroscopy for upper gastrointestinal symptoms from Jan. 2017 to Jan. 2018 at the First Hospital of Jiaxing were enrolled. According to the results of serum tests and biopsy pathology, these patients were divided into four groups by ABC method and five groups by OLGA/OLGIM staging system, respectively. Hp infection rate, serum levels of PG and PGⅡ, and PG/PGⅡ ratio (PGR) were compared between different OLGA/OLGIM groups, and the correlations between OLGA/OLGIM staging system and ABC method were analyzed. Results: For OLGA/OLGIM staging system, the Hp infection rate was significantly lower in stage-0 and significantly higher in stage- (P<0.05), whereas the PGR decreased with the rising of stage (P<0.05). Only in OLGA groups, the PG level decreased with the rising of stage (P<0.05). Gamma coefficient analysis showed significant correlation between OLGA/OLGIM staging system and ABC method (G=0.589, P<0.05; G=0.440, P<0.05). Conclusions: Serological ABC method and histological OLGA/OLGIM staging system are closely linked in risk assessment of gastric precancerous lesions. Serum PGs test could be applied for screening of gastric precancerous lesions in China, identifying high risk population for further gastroscopy.

Correlation of Serum Pepsinogens and Helicobacter pylori Infection With Aspirin-associated Gastroduodenal Injury / 胃肠病学

Background:It is widely accepted that even low-dose aspirin can cause upper gastrointestinal injury.Studies showed the correlation of serum pepsinogens (PGs) with gastric acid secretion and Helicobacter pylori (Hp) infection is independently associated with peptic ulcer disease.Aims:To study the correlation of serum PGs and Hp infection with gastroduodenal injury induced by aspirin therapy.Methods:Two hundred and forty patients taking aspirin for 1-3 months admitted from Aug.2013 to May 2016 at the East Hospital Affiliated to Tongji University were enrolled.The levels of serum PG Ⅰ,PGⅡ and gastrin 17 (G17) were determined by ELISA.The Hp infection was detected by 14C-urea breath test.The modified Lanza score was used to assess the severity of gastroduodenal mucosal injury endoscopically.Results:The median serum PG Ⅰ level (154.61 ng/mL vs.117.15 ng/mL,P =0.00) and Hp infection rate (75.0％ vs.40.0％,P =0.00) in patients with intensive gastroduodenal injury (IGI) were significantly higher than those in patients with mild gastroduodenal injury (MGI),while no significant differences in serum PG Ⅱ and G17 levels were seen between the two groups (P ＞ 0.05).Univariate and multivariate analyses showed that serum PG Ⅰ and Hp infection were independent risk factors for aspirin-associated gastroduodenal injury.ROC curve analysis revealed that serum PG Ⅰ was the best indicator of aspirin-associated IGI,and the cut-off value,sensitivity and specificity were 125.50 ng/mL,80.15％ and 62.54％,respectively.The risk of IGI was significantly increased in patients with serum PG Ⅰ ≥ 125.50 ng/mL and positive for Hp infection (OR =16.87,95％ CI:2.04-135.44).Conclusions:High serum PG Ⅰ level (≥ 125.50 ng/mL) and Hp infection are risk factors for aspirin-associated gastroduodenal injury.Their combination detection can be used to identify potential patients with high risk of aspirin-associated gastroduodenal injury.