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Kotelevets SM, Chukov SZ. Gastric cancer diagnosis and prevention: Detecting precancerous at community level. World J Gastrointest Oncol 2025; 17:100521. [PMID: 40092955 PMCID: PMC11866251 DOI: 10.4251/wjgo.v17.i3.100521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 12/18/2024] [Accepted: 01/02/2025] [Indexed: 02/14/2025] Open
Abstract
The problem of gastric cancer (GC) prevention remains relevant for a long time. Various methods of population serological screening of atrophic gastritis and precancerous changes in the gastric mucosa have been created at present. Modern endoscopic and morphological methods of verification of the diagnosis of precancerous diseases and changes in the gastric mucosa have been introduced into the practice of gastroenterologists and oncologists. GC risk stratification systems allow the formation of risk groups that require population screening. Practical hints for population serological screening of atrophic gastritis, endoscopic and morphological verification of precancerous changes and diseases of the stomach recommend using it: When developing state programs for the prevention of stomach cancer; when implementing preventive measures for stomach cancer by doctors of all specialties; the authors also offer the possibility of use by anyone over the age of 40, provided that they seek methodological help from their doctor; in the work of health schools in any medical and preventive institutions. The use of an assessment system of certain risk factor signatures with prognostic value would add significant assistance to preventive measures against GC.
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Affiliation(s)
- Sergey M Kotelevets
- Department of Propaedeutics of Internal Medicine, North Caucasus State Academy, Cherkessk 369000, Russia
| | - Sergey Z Chukov
- Department of Pathological Anatomy, Stavropol State Medical University, Stavropol 355017, Russia
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Karhunen P, Tuomisto S, Goebeler S, Martiskainen M, Kok E. Common occurrence of atrophic gastritis in an ageing non-hospitalised population: an autopsy study. Age Ageing 2025; 54:afaf047. [PMID: 40037561 PMCID: PMC11879357 DOI: 10.1093/ageing/afaf047] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 02/12/2025] [Indexed: 03/06/2025] Open
Abstract
BACKGROUND Atrophic gastritis-the end stage of chronic gastritis-is an asymptomatic disease due to Helicobacter pylori infection causing decreased vitamin B12 and folate absorption, which may lead to severe haematological and neuropsychological disorders including Alzheimer's disease. The diagnosis requires endoscopy and biopsies from symptomatic patients, explaining why its true prevalence in the population is not well-known. OBJECTIVE We aimed to evaluate the prevalence of various stages of chronic gastritis in an autopsy series most closely representing the general population. SUBJECTS AND METHODS Gastric mucosa samples were collected prospectively from out-of-hospital deaths included in the Tampere Sudden Death Study (n = 70, mean age 63, age range 22-91 years). Antrum and corpus samples were stained with a H. pylori antibody and staged histopathologically. RESULTS Chronic gastritis with or without atrophic changes was detected in 40% of the cases. The proportion of healthy mucosa decreased age-dependently from 71.4% among individuals aged <50 years to 43.5% among the oldest individuals (>70 years), and that of chronic non-atrophic gastritis from 21.4% to 8.7%. In contrast, the prevalence of atrophic gastritis was 27.1% and increased in the age groups from 7.1% to 47.8% (P = .019) among the oldest individuals, showing a strong association (P < .0001) with H. pylori immunopositivity. CONCLUSIONS Atrophic gastritis is a common feature of the ageing stomach, which is observed in every second individual aged 70+ years, showing a strong association with H. pylori immunopositivity. Atrophic gastritis may be a more common risk factor in old age for diseases associated with low serum B12 and folate levels than has been previously known.
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Affiliation(s)
- Pekka Karhunen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Fimlab Laboratories Ltd, Tampere, Pirkanmaa, Finland
| | - Sari Tuomisto
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Fimlab Laboratories Ltd, Tampere, Pirkanmaa, Finland
| | - Sirkka Goebeler
- Finnish Institute for Health and Welfare, Helsinki, Uusimaa, Finland
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Pirkanmaa, Finland
| | - Mika Martiskainen
- Finnish Institute for Health and Welfare, Helsinki, Uusimaa, Finland
- Department of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Eloise Kok
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Pirkanmaa, Finland
- Faculty of Medicine, Department of Pathology, University of Helsinki, Helsinki, Uusimaa, Finland
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Xia R, Jiang Z, Zhou Y, Pan L, Wang Y, Ma Y, Fan L, Yuan L, Cheng X. Oral microbiota and gastric cancer: recent highlights and knowledge gaps. J Oral Microbiol 2024; 16:2391640. [PMID: 39161727 PMCID: PMC11332296 DOI: 10.1080/20002297.2024.2391640] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 07/19/2024] [Accepted: 08/08/2024] [Indexed: 08/21/2024] Open
Abstract
Gastric cancer is one of the most common malignant tumors worldwide and has a high mortality rate. However, tests for the early screening and diagnosis of gastric cancer are limited and invasive. Certain oral microorganisms are over-expressed in gastric cancer, but there is heterogeneity among different studies. Notably, each oral ecological niche harbors specific microorganisms. Among them, tongue coating, saliva, and dental plaque are important and unique ecological niches in the oral cavity. The colonization environment in different oral niches may be a source of heterogeneity. In this paper, we systematically discuss the latest developments in the field of the oral microbiota and gastric cancer and elucidate the enrichment of microorganisms in the oral ecological niches of the tongue coatings, saliva, and dental plaque in gastric cancer patients. The various potential mechanisms by which the oral microbiota induces gastric cancer (activation of an excessive inflammatory response; promotion of proliferation, migration, invasion, and metastasis; and secretion of carcinogens, leading to imbalance in gastric microbial communities) are explored. In this paper, we also highlight the applications of the rapeutics targeting the oral microbiota in gastric cancer and suggests future research directions related to the relationship between the oral microbiota and gastric cancer.
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Affiliation(s)
- Ruihong Xia
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhengchen Jiang
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Ying Zhou
- Department of Pharmacy, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Libin Pan
- Department of Pharmacy, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
| | - Yanan Wang
- School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yubo Ma
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Lili Fan
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
| | - Li Yuan
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Department of Integrated Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Xiangdong Cheng
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China
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Kotelevets SM, Chekh SA, Chukov SZ. Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention. World J Gastrointest Endosc 2024; 16:462-471. [PMID: 39155993 PMCID: PMC11325870 DOI: 10.4253/wjge.v16.i8.462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 06/30/2024] [Accepted: 07/25/2024] [Indexed: 08/01/2024] Open
Abstract
BACKGROUND New markers are needed to improve the effectiveness of serological screening for atrophic gastritis. AIM To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity. METHODS Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. All 169 patients were examined for postprandial levels of gastrin-17 (G17) and pepsinogen-1 (PG1) using GastroPanel® (Biohit Plc, Helsinki, Finland). RESULTS We used the histological standard of five biopsies of the gastric mucosa, in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy. We also compared the morpho-functional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1, as the markers of atrophic gastritis. The sensitivity of postprandial G17 was 62.2% for serological levels of G17 (range: 0-4 pmol/L) and 100% for serological G17 (range: 0-10 pmol/L) for the detection of monofocal severe atrophic gastritis. No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus. In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis, there is a pronounced positive long-term dynamics of the serological marker of atrophy - postprandial G17, after five months of rennet replacement therapy. CONCLUSION Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity. Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system. Therefore, postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.
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Affiliation(s)
- Sergey M Kotelevets
- Department of Therapy, North Caucasus State Academy, Cherkessk 369000, Karachay-Cherkess Republic, Russia
| | - Sergey A Chekh
- Department of Mathematics, North Caucasus State Academy, Cherkessk 369000, Karachay-Cherkess Republic, Russia
| | - Sergey Z Chukov
- Department of Pathological Anatomy, Stavropol State Medical University, Stavropol 355017, Russia
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Sipponen P, Sarna S, Seppä K. Risk of gastric carcinoma will be low in generations born at turn of the 20 th and 21 st centuries in Finland. Modelling NORDCAN data of the age group specific incidence rates of gastric cancer with PLS-regression and with attention to age ('age effect') and year of the birth ('cohort effect'). Scand J Gastroenterol 2023; 58:1271-1279. [PMID: 37291889 DOI: 10.1080/00365521.2023.2220858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 05/29/2023] [Accepted: 05/29/2023] [Indexed: 06/10/2023]
Abstract
BACKGROUND AND METHODS We examined in NORDCAN database how the annual age group-specific incidence rates (IR) of gastric cancer (GCA), and correspondingly the GCA risk, have declined in Finland during the twentieth century, and whether this decline corresponds to a decrease in the cohort-specific prevalence rate of Helicobacter pylori (Hp) gastritis that is considered an important precancerous risk condition for GCA. RESULTS In modelling with partial least squares regression (PLSR), the logarithmically transformed IRs (ln(IR) of GCA were well explained with age and birth cohort as explanatory model variables. By considering the observed (actual) and the PLSR-modelled IRs, the IR of GCA (and the risk of GCA) has decreased gradually in Finland from 1900 onward, cohort by cohort. By prediction of the future with PLSR, the IRs of GCA will be markedly lower in all cohorts during the twenty-first century than in the twentieth century. By PLSR modelling, less than 10 GCA cases per 100,000 people are predicted to appear annually in cohorts (generations) born at the turn of the 20th and 21st centuries, even when these people will be 60-80 years old in the years 2060-2070. CONCLUSIONS The IR of GCA and GCA risk progressively declined by cohort in Finland during the whole twentieth century. This decline corresponds in extent and time window to earlier observations in the decline of the prevalence rate of Hp gastritis in the same birth cohorts and supports the hypothesis of the role of Hp gastritis as an important risk condition of GCA.
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Affiliation(s)
| | - Seppo Sarna
- Department of Public Health, University of Helsinki, Helsinki, Finland
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Development of amplified luminescent proximity homogeneous assay for quantitation of gastrin-17. Anal Biochem 2023; 662:115016. [PMID: 36502889 DOI: 10.1016/j.ab.2022.115016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 12/07/2022] [Indexed: 12/14/2022]
Abstract
A highly sensitive and convenient amplified luminescent proximity homogeneous assay (AlphaLISA) method with high throughput and automation potential was developed for quantitation of serum Gastrin-17 (G-17) levels, which can facilitate the early diagnosis of atrophic gastritis in people at high risk of gastric cancer using a non-invasive approach. In this study, donor and acceptor beads with modified carboxyl groups on the surface were directly coupled to anti-G-17 antibodies through activation was proposed for application in the development of the new AlphaLISA, which can effectively simplify the steps and shorten the reaction time to achieve faster detection. Therefore, the G-17-AlphaLISA only needs to react for 15 min to obtain good analysis results. The proposed method has a wider detection range than commercial enzyme-linked immunosorbent assay (ELISA) kits (0.12-112.8 pmol/L > 0.5-40 pmol/L). In addition, results of G-17-AlphaLISA and ELISA had good correlation and agreement (ρ = 0.936). Importantly, the developed method may be more suitable for the large-scale screening of people at high risk for gastric cancer than traditional ELISA and provides a novel solution for other biomarkers that require accurate, highly sensitive, and high throughput detection.
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Otsu H, Nambara S, Hu Q, Hisamatsu Y, Toshima T, Takeishi K, Yonemura Y, Masuda T, Oki E, Mimori K. Identification of serum microRNAs as potential diagnostic biomarkers for detecting precancerous lesions of gastric cancer. Ann Gastroenterol Surg 2023; 7:63-70. [PMID: 36643367 PMCID: PMC9831904 DOI: 10.1002/ags3.12610] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 07/16/2022] [Indexed: 01/18/2023] Open
Abstract
Aim Gastric mucosal changes associated with chronic gastritis are known to be precancerous lesions of gastric cancer. We aimed to identify individuals with a high risk of gastric cancer by detection of microRNAs (miRNA) in the blood as biomarkers. Methods Of 1206 individuals screened, 144 who were positive for Helicobacter pylori (H. pylori) by the serum antibody test and who underwent endoscopy were the subjects of this study. For the gross assessment of mucosal inflammation, we applied the Kimura-Takemoto classification, in which normal mucosa was defined as grade 0, and atrophy was categorized as grade 1 (C-1 and C-2), grade 2 (C-3 and O-1), and grade 3 (O-2 and O-3). Serum samples were divided into two phases and used for miRNA microarray profiling. We compared the expression of miRNAs in grade 3 mucosa and other grades. Expression in gastric cancer was confirmed with TCGA data. Results miR-196b-3p was significantly upregulated, and miR-92a-2-5p was downregulated (P < .05 and q < 0.2). TCGA data showed a high expression of miR-196b-3p in gastric cancer cases (P < .001). Comparing grade 3 and the others, the area under the receiver operating characteristic curve using the detected miRNAs was as high as about 0.7. Furthermore, the combination of miRNAs resulted in higher accuracy. In terms of the significance of the combinatory mRNAs, the combination of three miRNAs (miR-196b-3p, miR-92a-2-5p, and miR-6791-3p) revealed high sensitivity and specificity, with the area under the curve exceeding 0.8. Conclusion The identified combinatory miRNAs may represent promising biomarkers of precancerous lesions in gastric cancer.
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Affiliation(s)
- Hajime Otsu
- Department of SurgeryKyushu University Beppu HospitalBeppuJapan
| | - Sho Nambara
- Department of SurgeryKyushu University Beppu HospitalBeppuJapan
| | - Qingjiang Hu
- Department of SurgeryKyushu University Beppu HospitalBeppuJapan
| | | | - Takeo Toshima
- Department of SurgeryKyushu University Beppu HospitalBeppuJapan
| | - Kazuki Takeishi
- Department of SurgeryKyushu University Beppu HospitalBeppuJapan
| | - Yusuke Yonemura
- Department of SurgeryKyushu University Beppu HospitalBeppuJapan
| | - Takaaki Masuda
- Department of SurgeryKyushu University Beppu HospitalBeppuJapan
| | - Eiji Oki
- Department of Surgery and Science Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Koshi Mimori
- Department of SurgeryKyushu University Beppu HospitalBeppuJapan
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Di Mario F, Rodriguez-Castro KI, Franceschi M, Landi S, Grillo S, Franzoni L, Russo M, Brandimarte G, Tursi A, Crafa P. Improvement of Symptoms in Patients Affected by Chronic Atrophic Gastritis Using L-Cysteine (Acetium®). Dig Dis 2022; 41:198-205. [PMID: 36423587 DOI: 10.1159/000528168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 11/08/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Chronic atrophic gastritis (CAG) alone is a precancerous condition for gastric cancer. Achlorhydria plays an important role in the formation of a class I carcinogen, acetaldehyde. L-cysteine has been claimed to bind acetaldehyde covalently. Symptoms are present in 55% of CAG patients, of whom 70% have upper gastrointestinal complaints. The aim of this study was to investigate the properties of L-cysteine in the modification of symptom patterns in CAG patients. METHODS Consecutive patients with histological diagnosis of CAG (OLGA ≥1 with gastric corpus involvement) were evaluated with serological determination of gastric function, clinical assessment of symptoms using the visual analog score (VAS) and the global symptomatic score (GSS), and considered for therapy with L-cysteine, 300 mg daily. Data regarding symptoms were collected at enrollment and after 3, 6, 12, 18, and 24 months, with an ultimate follow-up of 2 years. RESULTS A total of 330 patients with CAG were divided in group 1 (77 patients treated with L-cysteine) and group 2 (50 patients who received no specific treatment - control group). A statistically significant improvement in the VAS score (7.8 at baseline vs. 4.5 after 24 months; p < 0.01) was observed in patients treated with L-cysteine, while no significant changes in symptom pattern/intensity were recorded in the 2-year follow-up of untreated patients with CAG. CONCLUSIONS Long-term treatment with L-cysteine provides symptom improvement in CAG patients and might be proposed as maintenance therapy in such patients.
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Affiliation(s)
| | | | - Marilisia Franceschi
- Endoscopy Unit, Department of Medicine, ULSS7 Pedemontana, AltoVicentino Hospital, Santorso, Italy
| | - Stefano Landi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Simone Grillo
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Lorella Franzoni
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Michele Russo
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Giovanni Brandimarte
- Division of Internal Medicine and Gastroenterology, Cristo Re Hospital, Rome, Italy
| | - Antonio Tursi
- Territorial Gastroenterology Service, Azienda Sanitaria Locale Barletta-Andria-Trani, Andria, Italy
| | - Pellegrino Crafa
- Department of Medicine and Surgery, University of Parma, Parma, Italy
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Hamashima C. Forthcoming Step in Gastric Cancer Prevention: How Can Risk Stratification Be Combined with Endoscopic Screening for Gastric Cancer? Gut Liver 2022; 16:811-824. [PMID: 35314519 PMCID: PMC9668507 DOI: 10.5009/gnl210313] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 10/29/2021] [Accepted: 11/12/2021] [Indexed: 11/04/2022] Open
Abstract
Although the concern for gastric cancer prevention has increased, gastric cancer has remained a heavy burden worldwide and is not just a local issue in East Asian countries. However, as several screening programs (listed below) have shown some success, it is important to determine whether the situation is changing in some other countries and whether similar methods should be recommended. Endoscopic screening has been performed as a national program in South Korea and Japan, and the results have shown a reduction in gastric cancer mortality. Although the efficacy of Helicobacter pylori eradication has been established, the efficacy of the screen-and-treat strategy is presently being evaluated in randomized controlled trials. The serum pepsinogen test and endoscopic examination can divide high-risk subjects with severe gastric atrophy from average-risk subjects. Risk stratification is anticipated to contribute to an efficient method of prediction of gastric cancer development when combined with endoscopic screening. Countries with a high incidence rate should realize the immediate need to reduce gastric cancer death directly by endoscopic screening and should recognize screen-and-treat as a second option to reduce future risk. However, all forms of gastric cancer prevention programs have some harms and potential to increase unnecessary examinations. A balance of the benefits and harms should be always considered. Although further study is needed to obtain sufficient evidence for gastric cancer prevention, the best available method should be examined in the context of each country.
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Affiliation(s)
- Chisato Hamashima
- Health Policy Section, Department of Nursing, Faculty of Medical Technology, Teikyo University, Tokyo, Japan
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Grad C, Pop A, Gaborean E, Grad S, Dumitrascu D. Value of GastroPanel in the diagnosis of atrophic gastritis. Exp Ther Med 2021; 22:1347. [PMID: 34630701 PMCID: PMC8495588 DOI: 10.3892/etm.2021.10782] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 06/15/2021] [Indexed: 01/10/2023] Open
Abstract
Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as precursor of the intestinal type of gastric cancer, is of growing interest. The combination of pepsinogen (PG), gastrin-17 (G17) and anti-Helicobacter pylori (H. pylori) antibody serological assays (panel test) is a non-invasive tool for the diagnosis of atrophic gastritis. However, the diagnostic reliability of this test remains uncertain. The aim of our study was to assess the diagnostic performance of the serum panel test (GastroPanel) for the diagnosis of atrophic gastritis. From dyspeptic patients, endoscopic biopsy samples (two from the gastric corpus and two from the antrum) and blood samples were collected. The determination of sPGI, sPGII, sG17 and IgG antibodies to H. pylori (H.p IgG) was performed using an enzyme-linked immunosorbent assay (GastroPanel; Biohit Oyj). Histopathology results were compared with GastroPanel values. Sixty patients were included: 35 (58.3%) females and 25 (41.66%) males; mean age 67.63±9.36 years; 45% H. pylori-positive. A total of 65% of patients had atrophic gastritis. There were no significant differences between the levels of biomarkers and localization of atrophy. The ratio PG1/PG2 was lower in patients with multifocal atrophy; the difference being close to the threshold of statistical significance. In cases of intestinal metaplasia the values of G17, PG1, PG2, H.p IgG were not statistically altered compared to those without intestinal metaplasia; only the ratio PG1/PG2 was lower in intestinal metaplasia; the difference being almost of statistical significance. Our results revealed that, GastroPanel values did not differ depending on the severity of the atrophy. Biomarkers used by GastroPanel do not have enough accuracy for use in the diagnosis of atrophy in the population studied. A low accuracy only for the ratio PG1/PG2 in patients with multifocal atrophy was found. However, our data revealed a correlation in detecting intestinal metaplasia.
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Affiliation(s)
- Cosmin Grad
- Second Medical Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Andrei Pop
- Second Medical Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Emil Gaborean
- Second Medical Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Simona Grad
- Second Medical Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Dan Dumitrascu
- Second Medical Department, 'Iuliu Hatieganu' University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
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Helicobacter pylori-Induced Inflammation: Possible Factors Modulating the Risk of Gastric Cancer. Pathogens 2021; 10:pathogens10091099. [PMID: 34578132 PMCID: PMC8467880 DOI: 10.3390/pathogens10091099] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/21/2021] [Accepted: 08/25/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic inflammation and long-term tissue injury are related to many malignancies, including gastric cancer (GC). Helicobacter pylori (H. pylori), classified as a class I carcinogen, induces chronic superficial gastritis followed by gastric carcinogenesis. Despite a high prevalence of H. pylori infection, only about 1–3% of people infected with this bacterium develop GC worldwide. Furthermore, the development of chronic gastritis in some, but not all, H. pylori-infected subjects remains unexplained. These conflicting findings indicate that clinical outcomes of aggressive inflammation (atrophic gastritis) to gastric carcinogenesis are influenced by several other factors (in addition to H. pylori infection), such as gut microbiota, co-existence of intestinal helminths, dietary habits, and host genetic factors. This review has five goals: (1) to assess our current understanding of the process of H. pylori-triggered inflammation and gastric precursor lesions; (2) to present a hypothesis on risk modulation by the gut microbiota and infestation with intestinal helminths; (3) to identify the dietary behavior of the people at risk of GC; (4) to check the inflammation-related genetic polymorphisms and role of exosomes together with other factors as initiators of precancerous lesions and gastric carcinoma; and (5) finally, to conclude and suggest a new direction for future research.
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Kotelevets SM, Chekh SA, Chukov SZ. Updated Kimura-Takemoto classification of atrophic gastritis. World J Clin Cases 2021; 9:3014-3023. [PMID: 33969087 PMCID: PMC8080746 DOI: 10.12998/wjcc.v9.i13.3014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 02/01/2021] [Accepted: 03/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The Updated Sydney system for visual evaluation of gastric mucosal atrophy via endoscopic observation is subject to sampling error and interobserver variability. The Kimura-Takemoto classification system was developed to overcome these limitations.
AIM To compare the morphological classification of atrophic gastritis between the Kimura-Takemoto system and the Updated Sydney system.
METHODS A total of 169 patients with atrophic gastritis were selected according to diagnosis by the visual endoscopic Kimura-Takemoto method. Following the Updated Kimura-Takemoto classification system, one antrum biopsy and five gastric corpus biopsies were taken according to the visual stages of the Kimura-Takemoto system. The Updated Kimura-Takemoto classification system was then applied to each and showed 165 to have histological mucosal atrophy; the remaining 4 patients had no histological evidence of atrophy in any biopsy. The Updated Kimura-Takemoto classification was verified as a reference morphological method and applied for the diagnosis of atrophic gastritis. Adding one more biopsy from the antrum to the six biopsies according to the Updated Kimura-Takemoto classification, constitutes the updated combined Kimura-Takemoto classification and Sydney system.
RESULTS The sensitivity for degree of mucosal atrophy assessed by the Updated Sydney system was 25% for mild, 36% for moderate, and 42% for severe, when compared with the Updated Kimura-Takemoto classification of atrophic gastritis for morphological diagnosis. Four types of multifocal atrophic gastritis were identified: sequential uniform (type 1; in 28%), sequential non-uniform (type 2; in 7%), diffuse uniform (type 3; in 23%), diffuse non-uniform (type 4; in 24%), and "alternating atrophic – non-atrophic" (type 5; in 18%). The pattern of the spread of atrophy, sequentially from the antrum to the cardiac segment of the stomach, which was described by the Updated Kimura-Takemoto system, was histologically confirmed in 82% of cases evaluated.
CONCLUSION The Updated Sydney system is significantly inferior to the Updated Kimura-Takemoto classification for morphological verification of atrophic gastritis.
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Affiliation(s)
- Sergey M Kotelevets
- Department of Therapy, Medical Institute, North Caucasus State Academy for Humanities and Technologies, Cherkessk 369000, Russia
| | - Sergey A Chekh
- Department of Software Development, Institute of Applied Mathematics and Information Technology, North Caucasus State Academy of Humanities and Technologies, Cherkessk 369000, Russia
- Department of Mathematics, Institute of Applied Mathematics and Information Technology, North Caucasus State Academy of Humanities and Technologies, Cherkessk 369000, Russia
| | - Sergey Z Chukov
- Department of Pathological Anatomy, Stavropol State Medical University, Stavropol 355017, Russia
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Coelho MCF, Ribeiro HG, Gomes CGDO, Marinho FP, Barbosa AJA, Coelho LGV. HELICOBACTER PYLORI CHRONIC GASTRITIS ON PATIENTS WITH PREMALIGNANT CONDITIONS: OLGA AND OLGIM EVALUATION AND SERUM BIOMARKERS PERFORMANCE. ARQUIVOS DE GASTROENTEROLOGIA 2021; 58:39-47. [PMID: 33909795 DOI: 10.1590/s0004-2803.202100000-08] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 10/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND H. pylori chronic atrophic gastritis is a premalignant lesion, and its staging, according to OLGA and OLGIM systems aims to identify patients at increased risk of developing gastric cancer and optimize their follow-up. GastroPanel®, serum biomarkers panel including pepsinogen I (PGI), pepsinogen II (PGII), Gastrin 17 (G17) and anti- H. pylori antibodies is a noninvasive test for adenocarcinoma risk assessment in chronic H. pylori gastritis patients. OBJECTIVE Prospective study to evaluate the concordance between OLGA and OLGIM grading systems, as well as to evaluate GastroPanel´s performance in patients with premalignant lesions secondary to H. pylori chronic gastritis in Brazil. METHODS Patients with H. pylori chronic gastritis with premalignant lesions confirmed by histology were recruited from the gastrointestinal clinic of a University Hospital. All participants underwent endoscopic examination with biopsies which were reported according to updated Sydney system and premalignant lesions grading systems (OLGA and OLGIM). Blood samples were collected for biomarkers serological analysis (GastroPanel®, Biohit, Helsinki, Finland). The cut off values used to define high risk patients were those recommended by the manufacturer: PGI ≤30 µm/L and PGI/PGII ≤3. RESULTS 41 patients were recruited: 28 women, 13 men, mean age 67.3 (47-89, SD: 9.6) years. By OLGA system, were obtained: OLGA 0 (n=1), OLGA I (n=7), OLGA II (n=17), OLGA III (n=9), and OLGA IV (n=7). By OLGIM system, were obtained: OLGIM 0 (n=14), OLGIM I (n=5), OLGIM II (n=10), OLGIM III (n=10), and OLGIM IV (n=2). Regarding histological staging among patients staged as low risk (OLGA/OLGIM 0, I and II) and high risk (OLGA/OLGIM III and IV) for gastric cancer development, the concordance rate found between both classifications was 85.4%. Considering high risk patients, those patients thus included in at least one of the systems the final distribution of our sample considered 24 low-risk and 17 high-risk patients for the development of gastric cancer. To determine by GastroPanel® whether the patient would be at low or high risk of developing gastric cancer, PGI showed a sensitivity, specificity and accuracy of 0.47 (95%CI: 0.26-0.69), 0.67 (95%CI: 0.47-0.82), and 0.58 (95%CI: 0.43-0.72), respectively, while PGI/PGII showed sensitivity, specificity and accuracy of 0.06 (95%CI: 0.01-0.27), 0.83 (95%CI: 0.64-0.93) and 0.51 (95%CI: 0.36-0.66), respectively. CONCLUSION The histological classifications OLGA and OLGIM presented a substantial concordance rate among themselves. Simultaneous use of both histological classification systems increased the identification's rate of high-risk patients. Biomarker analysis was not effective to distinguish low to high risk patients in the studied population. Further studies are needed to validate its use in clinical practice in Brazil.
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Affiliation(s)
- Maria Clara Freitas Coelho
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Belo Horizonte, MG, Brasil.,Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, MG, Brasil
| | - Henrique Gomes Ribeiro
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Belo Horizonte, MG, Brasil
| | - Celio Geraldo de Oliveira Gomes
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Belo Horizonte, MG, Brasil
| | - Frederico Passos Marinho
- Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Belo Horizonte, MG, Brasil
| | - Alfredo J A Barbosa
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Belo Horizonte, MG, Brasil.,Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Belo Horizonte, MG, Brasil
| | - Luiz Gonzaga Vaz Coelho
- Universidade Federal de Minas Gerais, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Aplicadas à Saúde do Adulto, Belo Horizonte, MG, Brasil.,Universidade Federal de Minas Gerais, Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Belo Horizonte, MG, Brasil
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Watari J, Tomita T, Tozawa K, Oshima T, Fukui H, Miwa H. Preventing Metachronous Gastric Cancer after the Endoscopic Resection of Gastric Epithelial Neoplasia: Roles of Helicobacter pylori Eradication and Aspirin. Gut Liver 2021; 14:281-290. [PMID: 31547640 PMCID: PMC7234884 DOI: 10.5009/gnl19079] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Revised: 05/11/2019] [Accepted: 06/06/2019] [Indexed: 12/13/2022] Open
Abstract
Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.
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Affiliation(s)
- Jiro Watari
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Toshihiko Tomita
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Katsuyuki Tozawa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hirokazu Fukui
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
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15
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Incidence of Multiple Metachronous Gastric Cancers After Pyloric-Preserving Gastrectomy. World J Surg 2021; 44:2719-2727. [PMID: 32266453 DOI: 10.1007/s00268-020-05492-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
AIM Pylorus-preserving gastrectomy (PPG) is widely used for early gastric cancer located in the middle third of the stomach. The minimization of the extent of gastrectomy may increase the risk of metachronous multiple gastric cancer (MGC). We report the findings of a study that was conducted to evaluate the prevalence of MGC after PPG. METHODS The clinical data of 533 patients who underwent PPG for gastric cancer between 1993 and 2018 were reviewed. The clinicopathological characteristics at the time of the primary treatment that were predictive of the development of MGC were explored. The median (range) observation period was 112.4 (8.1-290.7) months. RESULTS Metachronous MGC was diagnosed in 33 of the 533 patients. The cumulative 5-year and 10-year event rates were 3.3% and 6.2%, respectively. The patient gender, presence/absence of synchronous MGC and the macroscopic type of the primary gastric cancer were significantly associated with the risk of development of metachronous MGC. Multivariate analysis identified the presence of synchronous MGC (hazard ratio [HR]: 4.828, 95% confidence interval [CI]; 1.611-12.30, p = 0.004) and Type 0-IIa primary gastric cancer (HR 2.810, 95% CI; 1.113-7.090, p = 0.029) as independent factors associated with the risk of development of MGC. All the patients could be treated by surgical or endoscopic resection for the metachronous MGC. Recurrence was observed in one patient. CONCLUSIONS There was quite a few incidence of development of metachronous MGC after PPG. Nevertheless, PPG remains reasonable treatment option, if adequate postoperative surveillance can be ensured.
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16
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-196 to -174del, rs4696480, rs3804099 polymorphisms of Toll-like receptor 2 gene impact the susceptibility of cancers: evidence from 37053 subjects. Biosci Rep 2020; 39:221065. [PMID: 31710083 PMCID: PMC6900473 DOI: 10.1042/bsr20191698] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 10/22/2019] [Accepted: 11/06/2019] [Indexed: 02/06/2023] Open
Abstract
Relationship between Toll-like receptor-2 (TLR2) and cancer risk has been illustrated in some studies, but their conclusions are inconsistent. Therefore, we designed this meta-analysis to explore a more accurate conclusion of whether TLR2 affects cancer risks. Articles were retrieved from various literature databases according to the criteria. We used STATA to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to evaluate the relationship between certain polymorphism of TLR2 and cancer risk. Finally, 47 case-control studies met the criteria, comprising 15851 cases and 21182 controls. In the overall analysis, people are more likely to get cancer because of -196 to -174del in TLR2 in all five genetic models, B vs. A (OR = 1.468, 95% Cl = 1.129-1.91, P=0.005); BB vs. AA (OR = 1.716, 95% Cl = 1.178-2.5, P=0.005); BA vs. AA (OR = 1.408, 95% Cl = 1.092-1.816, P=0.008); BB+BA vs. AA (OR = 1.449, 95% Cl = 1.107-1.897, P=0.007); BB vs. BA+AA (OR = 1.517, 95% Cl = 1.092-2.107, P=0.013). Meanwhile, rs4696480 could significantly increase the risk of cancer in Caucasians, furthermore, rs3804099 significantly decreased cancer risk in overall analysis, but more subjects are necessary to confirm the results. All in all, this meta-analysis revealed that not only -196 to -174del increased the risk of among overall cancers, Caucasians are more likely to get cancer because of rs4696480, while rs3804099 polymorphism could reduce the risk of cancer in some genetic models. There is no direct evidence showing that rs5743708, rs3804100 and rs1898830 are related to cancer.
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17
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Crafa P, Franceschi M, Rodriguez Castro KI, Barchi A, Russo M, Franzoni L, Antico A, Baldassarre G, Panozzo MP, Di Mario F. Functional Dyspesia. ACTA BIO-MEDICA : ATENEI PARMENSIS 2020; 91:e2020069. [PMID: 32921764 PMCID: PMC7716988 DOI: 10.23750/abm.v91i3.10150] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 07/06/2020] [Indexed: 12/26/2022]
Abstract
Dyspepsia is a functional GI disorder consisting in a wide range of symptoms. The main diagnostic challenge has been whether to perform an EGD or an abdominal US in order not to miss organic lesions, but to avoid unnecessary and sometimes invasive tests. Pepsinogen serology has been proposed as an useful non-invasive test to explore the status of the gastric mucosa, suggesting this strategy as an adequate approach in management of dyspepsia. In a primary care setting, 266 dyspeptic patients were investigated to establish the proper diagnosis. The workup included upper GI endoscopy with biopsies, a structured questionnaire including type and severity of symptoms, serological determination of serum pepsinogens, gastrin 17 and IgG against Hp. Inclusion criteria were dyspeptic symptoms (epigastric pain, nausea and/or vomiting, post prandial fullness, early satiation) lasting more than 1 year and the association between symptoms and food ingestion.. Helicobacter pylori infection was present in 114 subjects, characterized by high levels of pepsinogen II and IgG against Hp. Twenty subjects were classified according with the diagnosis of chronic body atrophic gastritis. Nausea and post prandial fullness were the most frequent symptoms (48% and 41%, respectively) in the studied population, followed by epigastric pain and early satiation (37% and 26% respectively). A diagnosis of normality by serological diagnosis was found in half of patients experiencing epigastric pain and in about 60% of subjects with the three other symptoms (nausea, post prandial fullness, and early satiation). In conclusion, this experience confirms the clinical usefulness of serology in dyspepsia, contributing to correctly diagnosing CAG and H.p. infection in such patients and providing a good correlation with the clinical picture.
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Affiliation(s)
- Pellegrino Crafa
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Marilisa Franceschi
- Endoscopy Unit, Department of Medicine, ULSS7 Pedemontana, Hospital AltoVicentino, Santorso (VI), Italy.
| | | | - Alberto Barchi
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Michele Russo
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Lorella Franzoni
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
| | - Antonio Antico
- Laboratory of Clinical Pathology, ULSS7 Pedemontana, Hospital AltoVicentino, Santorso (VI), Italy.
| | - Gianluca Baldassarre
- Endoscopy Unit, Department of Medicine, ULSS7 Pedemontana, Hospital AltoVicentino, Santorso (VI), Italy.
| | - Maria Piera Panozzo
- Laboratory of Clinical Pathology, ULSS7 Pedemontana, Hospital AltoVicentino, Santorso (VI), Italy.
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18
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Cha JH, Jang JS. Clinical correlation between serum pepsinogen level and gastric atrophy in gastric neoplasm. Korean J Intern Med 2020; 35:550-558. [PMID: 30400679 PMCID: PMC7214368 DOI: 10.3904/kjim.2018.282] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Accepted: 10/01/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS The relationship between the serum pepsinogen (sPG) level and changes in gastric mucosa has been well studied. Here, we evaluated the usefulness of sPG (I, II, I/II ratio) and intragastric pH as a biomarker of severe gastric atrophy in gastric neoplastic lesions. METHODS A total of 186 consecutive Korean patients with gastric neoplastic lesions underwent endoscopic submucosal dissection (ESD) in this study. The serologic atrophy group had sPG I level ≤ 70 ng/mL and an sPG I/II ratio ≤ 3.0. Before ESD, overnight fasting venous blood and gastric juice samples were collected to measure the sPG level and intragastric pH. The degree of gastric atrophy was estimated by endoscopy, and the rapid urease test was performed to investigate Helicobacter pylori infection. RESULTS Patients who met the criteria of serologic atrophy showed more severe endoscopic atrophic changes (61% vs. 18%, p = 0.000). Older patients and those with more atrophic changes at the gastric upper body demonstrated both a lower sPG I level and a lower PG I/II ratio and more severe endoscopic atrophy. The sPG I/II ratio was the lowest in low grade dysplasia than in high grade dysplasia and early gastric cancer (EGC) (p = 0.015). In addition, patients who tested negative for serologic atrophy and H. pylori showed the lowest intragastric pH (p = 0.000). CONCLUSION A low sPG I level and a low I/II ratio were correlated with the severity of gastric atrophy in gastric neoplastic lesions, thus indicating it to be a sensitive biomarker of gastric precancerous lesions or EGC.
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Affiliation(s)
- Jae Hwang Cha
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Jin Seok Jang
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
- Correspondence to Jin Seok Jang, M.D. Department of Internal Medicine, Dong-A University Medical Center, 26 Daesingongwon-ro, Seo-gu, Busan 49201, Korea Tel: +82-51-240-2609 Fax: +82-51-253-2087 E-mail:
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19
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Qian S, Golubnitschaja O, Zhan X. Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles. EPMA J 2019; 10:365-381. [PMID: 31832112 PMCID: PMC6882964 DOI: 10.1007/s13167-019-00194-x] [Citation(s) in RCA: 136] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 11/06/2019] [Indexed: 12/24/2022]
Abstract
A strong relationship exists between tumor and inflammation, which is the hot point in cancer research. Inflammation can promote the occurrence and development of cancer by promoting blood vessel growth, cancer cell proliferation, and tumor invasiveness, negatively regulating immune response, and changing the efficacy of certain anti-tumor drugs. It has been demonstrated that there are a large number of inflammatory factors and inflammatory cells in the tumor microenvironment, and tumor-promoting immunity and anti-tumor immunity exist simultaneously in the tumor microenvironment. The typical relationship between chronic inflammation and tumor has been presented by the relationships between Helicobacter pylori, chronic gastritis, and gastric cancer; between smoking, development of chronic pneumonia, and lung cancer; and between hepatitis virus (mainly hepatitis virus B and C), development of chronic hepatitis, and liver cancer. The prevention of chronic inflammation is a factor that can prevent cancer, so it effectively inhibits or blocks the occurrence, development, and progression of the chronic inflammation process playing important roles in the prevention of cancer. Monitoring of the causes and inflammatory factors in chronic inflammation processes is a useful way to predict cancer and assess the efficiency of cancer prevention. Chronic inflammation-based biomarkers are useful tools to predict and prevent cancer.
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Affiliation(s)
- Shehua Qian
- 1Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 2Hunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 3State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
| | - Olga Golubnitschaja
- 4Radiological Clinic, UKB, Excellence Rheinische Friedrich-Wilhelms-University of Bonn, Sigmund-Freud-Str 25, 53105 Bonn, Germany
- 5Breast Cancer Research Centre, UKB, Excellence Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany
- 6Centre for Integrated Oncology, Cologne-Bonn, Excellence Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany
| | - Xianquan Zhan
- 1Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 2Hunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 3State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China
- 7Department of Oncology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan People's Republic of China
- 8National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan People's Republic of China
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Cui J, Cui H, Yang M, Du S, Li J, Li Y, Liu L, Zhang X, Li S. Tongue coating microbiome as a potential biomarker for gastritis including precancerous cascade. Protein Cell 2019; 10:496-509. [PMID: 30478535 PMCID: PMC6588651 DOI: 10.1007/s13238-018-0596-6] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 10/23/2018] [Indexed: 02/06/2023] Open
Abstract
The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progress. In this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrence and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.
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Affiliation(s)
- Jiaxing Cui
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Hongfei Cui
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
- Institute for Artificial Intelligence and Department of Computer Science and Technology, Tsinghua University, Beijing, 100084, China
| | - Mingran Yang
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Shiyu Du
- China-Japan Friendship Hospital, Beijing, 100029, China
| | - Junfeng Li
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Yingxue Li
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Liyang Liu
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China
| | - Xuegong Zhang
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China.
- School of Life Sciences and Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084, China.
| | - Shao Li
- MOE Key Laboratory of Bioinformatics and TCM-X center/Bioinformatics Division, BNRist/Department of Automation, Tsinghua University, Beijing, 100084, China.
- School of Life Sciences and Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084, China.
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Tepes B, Seruga M, Vujasinovic M, Urlep D, Ljepovic L, Brglez JN, Forte A, Anita Kek L, Skvarc M. Premalignant Gastric Lesions in Patients Included in National Colorectal Cancer Screening. Radiol Oncol 2018; 52:7-13. [PMID: 29520200 PMCID: PMC5839076 DOI: 10.1515/raon-2017-0054] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Accepted: 10/10/2017] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Gastric cancer is the fifth most common malignancy in the world with almost one million new cases annually. Helicobacter pylori infection causes 89% of all gastric cancers. Premalignant lesions (atrophy and intestinal metaplasia) develop after several decades of inflammation. Secondary prevention with gastroscopy is possible, but it is costly and has a low compliance rate. Alternative procedures like serology testing for pepsinogen I and II and pepsinogen I/II ratio are available to select patients for surveillance gastroscopies. PATIENTS AND METHODS In seven outpatient endoscopic units, 288 patients (154 men; 53.5%), average age 60.68 years, tested positive in National colorectal cancer screening programme SVIT, were included in the study. Gastropanel (BioHit, Finland) was used as a serologic biopsy method. RESULTS We found 24 patients (12 men, mean age 63.7 years) with pepsinogen (pepsinogen I/II < 3 and/or pepsinogen I < 30 μg/L). Premalignant changes were found on gastric biopsies in 21 patients (7.3% incidence). Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) ≥ 1 was found in 20 patients; Operative Link for Gastritis Assessment (OLGA) ≥ 1 was found in 19 patients. Combined accuracy for preneoplastic lesions in Gastropanel positive patients was 87.5%. H. pylori seropositivity was found in 219 patients (76%). Only 24% of our population had normal results. CONCLUSIONS Gastropanel test has proven to be a reliable non-invasive test for advanced gastric preneoplastic lesions that can select patients for further gastroscopy. We found high H. pylori seropositivity in older age groups in Slovenia.
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Affiliation(s)
- Bojan Tepes
- Abacus Medico, Diagnostic Center Rogaška, Rogaška Slatina, Slovenia
| | - Maja Seruga
- General Hospital Murska Sobota, Murska Sobota, Slovenia
| | | | | | | | | | | | | | - Miha Skvarc
- IMI, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Nieminen MT, Salaspuro M. Local Acetaldehyde-An Essential Role in Alcohol-Related Upper Gastrointestinal Tract Carcinogenesis. Cancers (Basel) 2018; 10:E11. [PMID: 29303995 PMCID: PMC5789361 DOI: 10.3390/cancers10010011] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 12/20/2017] [Accepted: 12/20/2017] [Indexed: 02/07/2023] Open
Abstract
The resident microbiome plays a key role in exposure of the upper gastrointestinal (GI) tract mucosa to acetaldehyde (ACH), a carcinogenic metabolite of ethanol. Poor oral health is a significant risk factor for oral and esophageal carcinogenesis and is characterized by a dysbiotic microbiome. Dysbiosis leads to increased growth of opportunistic pathogens (such as Candida yeasts) and may cause an up to 100% increase in the local ACH production, which is further modified by organ-specific expression and gene polymorphisms of ethanol-metabolizing and ACH-metabolizing enzymes. A point mutation in the aldehyde dehydrogenase 2 gene has randomized millions of alcohol consumers to markedly increased local ACH exposure via saliva and gastric juice, which is associated with a manifold risk for upper GI tract cancers. This human cancer model proves conclusively the causal relationship between ACH and upper GI tract carcinogenesis and provides novel possibilities for the quantitative assessment of ACH carcinogenicity in the human oropharynx. ACH formed from ethanol present in "non-alcoholic" beverages, fermented food, or added during food preparation forms a significant epidemiologic bias in cancer epidemiology. The same also concerns "free" ACH present in mutagenic concentrations in multiple beverages and foodstuffs. Local exposure to ACH is cumulative and can be reduced markedly both at the population and individual level. At best, a person would never consume tobacco, alcohol, or both. However, even smoking cessation and moderation of alcohol consumption are associated with a marked decrease in local ACH exposure and cancer risk, especially among established risk groups.
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Affiliation(s)
- Mikko T Nieminen
- Department of Oral and Maxillofacial Diseases, University of Helsinki, and Helsinki University Central Hospital, University of Helsinki, Biomedicum Helsinki P.O. Box 63, 00014 Helsinki, Finland.
- Research Unit on Acetaldehyde and Cancer, University of Helsinki, Biomedicum Helsinki P.O. Box 63, 00014 Helsinki, Finland.
| | - Mikko Salaspuro
- Research Unit on Acetaldehyde and Cancer, University of Helsinki, Biomedicum Helsinki P.O. Box 63, 00014 Helsinki, Finland.
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Sepulveda AR, J. Del Portillo A. Molecular Basis of Diseases of the Gastrointestinal Tract. MOLECULAR PATHOLOGY 2018:387-415. [DOI: 10.1016/b978-0-12-802761-5.00019-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Cvetkovska K, Bauer B. Ethnopharmacological and toxicological review of Cydonia oblonga M. MAKEDONSKO FARMACEVTSKI BILTEN 2018. [DOI: 10.33320/maced.pharm.bull.2018.64.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Abstract
Cydonia oblonga M. is a medicinal plant of family Rosaceae which is used to prevent or treat several ailments such as cancer, diabetes, hepatitis, ulcer, respiratory, and urinary infections, etc. Cydonia oblonga commonly known as quince is rich in useful secondary metabolites such as phenolics, steroids, flavonoids, terpenoids, tannins, organic acids, and glycosides. It shows a wide range of pharmacological effects like antioxidant, antibacterial, antifungal, anti-inflammatory, hepatoprotective, cardiovascular, antidepressant, hypolipidemic, diuretic, etc. The polysaccharide mucus, glucuronoxylane located in the seeds of the quince, is used in the dermatology, for the production of wound patches.
The aim of this paper focuses on detailed research on the value of phytochemicals, as pharmacological and attributes of phytomedicine herbs.
Keywords: Cydonia oblonga, phytomedicine, pharmacological attributes, folk medicinal uses, quince
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Affiliation(s)
- Katerina Cvetkovska
- Faculty of Pharmacy, Ss. Cyril and Methodius University, Majka Tereza 47, 1000 Skopje, Republic of Macedonia
| | - Biljana Bauer
- Faculty of Pharmacy, Ss. Cyril and Methodius University, Majka Tereza 47, 1000 Skopje, Republic of Macedonia
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Key role of local acetaldehyde in upper GI tract carcinogenesis. Best Pract Res Clin Gastroenterol 2017; 31:491-499. [PMID: 29195668 DOI: 10.1016/j.bpg.2017.09.016] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Revised: 09/11/2017] [Accepted: 09/22/2017] [Indexed: 01/31/2023]
Abstract
Ethanol is neither genotoxic nor mutagenic. Its first metabolite acetaldehyde, however, is a powerful local carcinogen. Point mutation in ALDH2 gene proves the causal relationship between acetaldehyde and upper digestive tract cancer in humans. Salivary acetaldehyde concentration and exposure time are the two major and quantifiable factors regulating the degree of local acetaldehyde exposure in the ideal target organ, oropharynx. Instant microbial acetaldehyde formation from alcohol represents >70% of total ethanol associated acetaldehyde exposure in the mouth. In the oropharynx and achlorhydric stomach acetaldehyde is not metabolized to safe products, instead in the presence of alcohol it accumulates in saliva and gastric juice in mutagenic concentrations. A common denominator in alcohol, tobacco and food associated upper digestive tract carcinogenesis is acetaldehyde. Epidemiological studies on upper GI tract cancer are biased, since they miss information on acetaldehyde exposure derived from alcohol and acetaldehyde present in 'non-alcoholic' beverages and food.
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Magnifying NBI Patterns of Gastric Mucosa After Helicobacter pylori Eradication and Its Potential Link to the Gastric Cancer Risk. Dig Dis Sci 2017; 62:2421-2427. [PMID: 28702753 DOI: 10.1007/s10620-017-4676-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2017] [Accepted: 07/06/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gastric cancer develops after successful H. pylori eradication in patients with severe atrophic gastritis. We classified atrophic and non-atrophic mucosa of gastric body using magnifying NBI endoscopy in patients after successful H. pylori eradication. MATERIALS AND METHODS One hundred and twenty-five patients after successful H. pylori eradication (median period after eradication: 36 months) were enrolled. Magnifying NBI patterns in the uninvolved gastric body were divided into the following: restored-small, round pits, accompanied with honeycomb-like subepithelial capillary networks; atrophic-well-demarcated oval or tubulovillous pits with clearly visible coiled or wavy vessels. The subjects were also classified into the three types: Grade 0-restored pattern is shown in all or almost the entire area of gastric body; Grade 1-mixture of restored and atrophic pattern, there is a considerable portion of the atrophic area in the lesser curvature; Grade 2-atrophic pattern is shown in all or almost the entire area of the gastric body. RESULTS Sensitivity and specificity for atrophic type for detection of histological intestinal metaplasia were 95.9 and 98.3%, respectively. No association was observed between the prevalence of Grades 0, 1 and 2 and duration after eradication, while grades 1 and 2 were significantly frequent in gastric cancer patients diagnosed both before (27/35: 77%) and after (23/31: 74%) eradication, compared to the cancer-free subjects (15/59: 25%) (P < 0.001). The grades 1 and 2 were also common in patients who underwent H. pylori eradication for gastric ulcer. CONCLUSIONS Magnifying the NBI pattern well correlates with pathological status of gastric mucosa after H. pylori eradication and may predict gastric cancer occurrence.
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Vohlonen I, Härkönen M, Malila N, Pukkala E, Sipponen P, Koistinen V, Hakama M. Challenges in evaluation of screening for gastric cancer among men based on nonrandomized design. Acta Oncol 2017; 56:917-922. [PMID: 28514928 DOI: 10.1080/0284186x.2016.1278304] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Objective was to quantify biases in screening for gastric cancer when comparing attenders to nonattenders using serum pepsinogen I (SPGI) level as primary test. METHODS In mid 1990s, all men aged 51-65 years from two Finnish cities were invited to SPGI screening. Mortality and premature mortality in attenders were compared to nonattenders. Efficacy of screening was studied by 15 years' follow-up of standardized mortality ratio (SMR) and potential years of life lost (PYLL) due to gastric cancer. Bias due to selective attendance was quantified using corrective coefficients based on total cancer incidence and mortality, and gastric cancer-specific incidence and mortality for total population and nonattenders. RESULTS In 1994-1996, men aged 51-65 years (16,872) were invited to SPGI assay and 12,175 men (72%) attended. SPGI was 25 microg/l or less in 610 (5%) men, indicating severe atrophic gastritis (AG). Post-screening gastroscopy was performed to 435 men with low SPGI. Of these, 168 men were referred for treatment due to abnormal focal lesions. Attributable proportions in reductions of SMR and PYLL from gastric cancer due to screening were 59% and 67%. After correcting for selective participation, attributable proportions were reduced to 23% and 39%. CONCLUSIONS Biomarker screening by low SPGI among middle-aged men followed by upper gastrointestinal endoscopy decreased long-term and premature mortality due to gastric cancer. However, in spite of methodological corrections done, the results do not justify any firm conclusions or recommend general screening programs. Randomized trials are warranted for this purpose.
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Affiliation(s)
- Ilkka Vohlonen
- Department of Public Health, Health Policy, University of Eastern Finland, Kuopio, Finland
| | - Matti Härkönen
- Department of Clinical Chemistry, Clinical Chemistry, University of Helsinki, Helsinki, Finland
| | - Nea Malila
- Cancer Epidemiology, Finnish Cancer Registry, Helsinki, Finland
- School of Health Sciences, University of Tampere, Tampere, Finland
| | - Eero Pukkala
- Epidemiology, Finnish Cancer Registry, Helsinki, Finland
- School of Health Sciences, University of Tampere, Tampere, Finland
| | | | - Veli Koistinen
- Department of Biostatistics, Finnish Consulting Group, Helsinki, Finland
| | - Matti Hakama
- Department of Epidemiology, Finnish Cancer Registry, Helsinki, Finland
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Hellström PM, Hendolin P, Kaihovaara P, Kronberg L, Meierjohann A, Millerhovf A, Paloheimo L, Sundelin H, Syrjänen K, Webb DL, Salaspuro M. Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis. Scand J Gastroenterol 2017; 52:230-237. [PMID: 27806647 DOI: 10.1080/00365521.2016.1249403] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. OBJECTIVE To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. METHODS Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. RESULTS Administration of L-cysteine increased MTCA (p < .0004) and decreased gastric acetaldehyde concentrations by 68% (p < .0001). The peak L-cysteine level was 7552 ± 2687 μmol/L at 40 min and peak MTCA level 196 ± 98 μmol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. CONCLUSIONS After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.
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Affiliation(s)
- Per M Hellström
- a Department of Medical Sciences, Gastroenterology and Hepatology Unit , Uppsala University Hospital, Uppsala University , Uppsala , Sweden
| | - Panu Hendolin
- b Clinical Sciences , Biohit Oyj , Helsinki , Finland
| | - Pertti Kaihovaara
- b Clinical Sciences , Biohit Oyj , Helsinki , Finland.,c Research Unit on Acetaldehyde and Cancer, University of Helsinki , Helsinki , Finland
| | - Leif Kronberg
- d Laboratory of Organic Chemistry , Johan Gadolin Process Chemistry Centre, Åbo Akademi University , Turku , Finland
| | - Axel Meierjohann
- d Laboratory of Organic Chemistry , Johan Gadolin Process Chemistry Centre, Åbo Akademi University , Turku , Finland
| | - Anders Millerhovf
- e Clinical Trial Consultants , Uppsala University Hospital , Uppsala , Sweden
| | - Lea Paloheimo
- b Clinical Sciences , Biohit Oyj , Helsinki , Finland
| | - Heidi Sundelin
- d Laboratory of Organic Chemistry , Johan Gadolin Process Chemistry Centre, Åbo Akademi University , Turku , Finland
| | - Kari Syrjänen
- b Clinical Sciences , Biohit Oyj , Helsinki , Finland
| | - Dominic-Luc Webb
- a Department of Medical Sciences, Gastroenterology and Hepatology Unit , Uppsala University Hospital, Uppsala University , Uppsala , Sweden
| | - Mikko Salaspuro
- c Research Unit on Acetaldehyde and Cancer, University of Helsinki , Helsinki , Finland
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Rabben HL, Zhao CM, Hayakawa Y, Wang TC, Chen D. Vagotomy and Gastric Tumorigenesis. Curr Neuropharmacol 2017; 14:967-972. [PMID: 26791481 PMCID: PMC5333586 DOI: 10.2174/1570159x14666160121114854] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 11/20/2015] [Accepted: 01/20/2016] [Indexed: 01/17/2023] Open
Abstract
Vagotomy reduces gastric acid secretion and was therefore introduced as a surgical treatment for peptic ulcers in the 1970s. Later, it was replaced by acid reducing medication, such as histamine type 2 (H2) receptor antagonists and proton pump inhibitors (PPIs). A large body of evidence has indicated that drug-induced hypochlorhydria per se does not increase the risk of gastric cancer. Early studies on the effects of vagotomy in chemically-induced rodent models of gastric cancer reported an increased risk of developing gastric cancer. This was most likely due to a delayed gastric emptying, which later has been accounted for by including an additional drainage procedure, e.g. pyloroplasty. In a recent study using three different mouse models of gastric cancer (including genetically engineered, chemically-induced and Helicobacter pylori-infected mice), either unilateral vagotomy or bilateral truncal vagotomy with pyloroplasty was found to significantly attenuate tumorigenesis in the denervated side of the stomach at early preneoplastic stages as well as at later stages of tumorigenesis. Consistently, pharmacological denervation using botulinum toxin A or muscarinic acetylcholine receptor 3 (M3R) blockade inhibited tumorigenesis. Moreover, it was found that recurrence of gastric cancer was reduced in patients following vagotomy. Thus, these new findings suggest the potential treatment strategies to target the nerve, neurotransmitters, corresponding receptors and their downstream signaling pathways for the malignancy.
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Affiliation(s)
| | | | | | | | - Duan Chen
- Department of Cancer Research and Molecular Medicine, The Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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Vohlonen I, Pukkala E, Malila N, Härkönen M, Hakama M, Koistinen V, Sipponen P. Risk of gastric cancer in Helicobacter pylori infection in a 15-year follow-up. Scand J Gastroenterol 2016; 51:1159-64. [PMID: 27338132 PMCID: PMC4960513 DOI: 10.1080/00365521.2016.1183225] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE We investigated the risk of gastric cancer among men with Helicobacter pylori (H. pylori) infection or atrophic gastritis (AG) in a 15-year follow-up. MATERIALS AND METHODS Study population consists of 12,016 men aged 50-65 years at the beginning of the follow-up in 1994-1996. Serum levels of pepsinogen I (SPGI) and antibodies (IgG) to H. pylori (HpAb) were assayed from serums collected in 1994-1996. Incidence of gastric cancer in the study population was assessed in follow-up from 1994 to 2011 by data from the nationwide cancer registry. Based on SPGI and HpAb values, standardized incidence ratios (SIRs) of gastric cancer were calculated in three subgroups, that is, in those with a healthy stomach, those with H. pylori infection but without AG and those with AG. Risk ratios (RR) of gastric cancer were calculated using SIR of subgroups. RESULTS During 15 years, seven gastric cancers appeared per 79,928 person years among men with healthy stomachs, 50 cancers per 92,533 person years in men with H. pylori infection but without AG, and 8 per 8658 person years in men with AG. Risk ratio (RR) of stomach cancer in men with H. pylori infection was 5.8 (95%CI: 2.7-15.3) compared to men with healthy stomachs, and 9.1 (95%CI: 2.9-30.0) in men with AG. There were no differences in cancer risk between cardia and distal stomach. CONCLUSIONS Risk of gastric cancer is low in men with healthy stomachs. It is significantly increased in those with H. pylori infection and more in those with AG.
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Affiliation(s)
- Ilkka Vohlonen
- Department of Public Health, University of Eastern Finland,
Kuopio,
Finland,CONTACT Ilkka Vohlonen University of Eastern Finland, Public Health, BOX 1627,
Kuopio70100,
Finland
| | | | - Nea Malila
- Department of Epidemiology, Finnish Cancer Registry,
Helsinki,
Finland
| | - Matti Härkönen
- Department of Clinical Chemistry, University of Helsinki,
Helsinki,
Finland
| | - Matti Hakama
- Department of Epidemiology, Finnish Cancer Registry,
Helsinki,
Finland
| | - Veli Koistinen
- Department of Biostatistics, Finnish Consulting Group,
Helsinki,
Finland
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Ashraf MU, Muhammad G, Hussain MA, Bukhari SNA. Cydonia oblonga M., A Medicinal Plant Rich in Phytonutrients for Pharmaceuticals. Front Pharmacol 2016; 7:163. [PMID: 27445806 PMCID: PMC4914572 DOI: 10.3389/fphar.2016.00163] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 06/01/2016] [Indexed: 01/06/2023] Open
Abstract
Cydonia oblonga M. is a medicinal plant of family Rosaceae which is used to prevent or treat several ailments such as cancer, diabetes, hepatitis, ulcer, respiratory, and urinary infections, etc. Cydonia oblonga commonly known as Quince is rich in useful secondary metabolites such as phenolics, steroids, flavonoids, terpenoids, tannins, sugars, organic acids, and glycosides. A wide range of pharmacological activities like antioxidant, antibacterial, antifungal, anti-inflammatory, hepatoprotective, cardiovascular, antidepressant, antidiarrheal, hypolipidemic, diuretic, and hypoglycemic have been ascribed to various parts of C. oblonga. The polysaccharide mucilage, glucuronoxylan extruded from seeds of C. oblonga is used in dermal patches to heal wounds. This review focuses on detailed investigations of high-valued phytochemicals as well as pharmacological and phytomedicinal attributes of the plant.
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Affiliation(s)
| | - Gulzar Muhammad
- Department of Chemistry, University of SargodhaSargodha, Pakistan
| | | | - Syed N. A. Bukhari
- Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan MalaysiaKuala Lumpur, Malaysia
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Khatoon J, Rai RP, Prasad KN. Role of Helicobacter pylori in gastric cancer: Updates. World J Gastrointest Oncol 2016; 8:147-158. [PMID: 26909129 PMCID: PMC4753165 DOI: 10.4251/wjgo.v8.i2.147] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/14/2015] [Accepted: 12/15/2015] [Indexed: 02/05/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is highly prevalent in human, affecting nearly half of the world’s population; however, infection remains asymptomatic in majority of population. During its co-existence with humans, H. pylori has evolved various strategies to maintain a mild gastritis and limit the immune response of host. On the other side, presence of H. pylori is also associated with increased risk for the development of various gastric pathologies including gastric cancer (GC). A complex combination of host genetics, environmental agents, and bacterial virulence factors are considered to determine the susceptibility as well as the severity of outcome in a subset of individuals. GC is one of the most common cancers and considered as the third most common cause of cancer related death worldwide. Many studies had proved H. pylori as an important risk factor in the development of non-cardia GC. Although both H. pylori infection and GC are showing decreasing trends in the developed world, they still remain a major threat to human population in the developing countries. The current review attempts to highlight recent progress in the field of research on H. pylori induced GC and aims to provide brief insight into H. pylori pathogenesis, the role of major virulence factors of H. pylori that modulates the host environment and transform the normal gastric epithelium to neoplastic one. This review also emphasizes on the mechanistic understanding of how colonization and various virulence attributes of H. pylori as well as the host innate and adaptive immune responses modulate the diverse signaling pathways that leads to different disease outcomes including GC.
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Abstract
Prevalence of chronic gastritis has markedly declined in developed populations during the past decades. However, chronic gastritis is still one of the most common serious pandemic infections with such severe killing sequelae as peptic ulcer or gastric cancer. Globally, on average, even more than half of people may have a chronic gastritis at present. Helicobacter pylori infection in childhood is the main cause of chronic gastritis, which microbial origin is the key for the understanding of the bizarre epidemiology and course of the disease. A life-long and aggressive inflammation in gastritis results in destruction (atrophic gastritis) of stomach mucosa with time (years and decades). The progressive worsening of atrophic gastritis results subsequently in dysfunctions of stomach mucosa. Atrophic gastritis will finally end up in a permanently acid-free stomach in the most extreme cases. Severe atrophic gastritis and acid-free stomach are the highest independent risk conditions for gastric cancer known so far. In addition to the risks of malignancy and peptic ulcer, acid-free stomach and severe forms of atrophic gastritis may associate with failures in absorption of essential vitamins, like vitamin B12, micronutrients (like iron, calcium, magnesium and zinc), diet and medicines.
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Affiliation(s)
- Pentti Sipponen
- Patolab Oy, Espoo, Finland and Tartu State University, Tartu, Estonia,Correspondence: Professor Pentti Sipponen, Käärmesaarentie 4A2, 02160, Espoo, Finland.
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Maejima R, Iijima K, Kaihovaara P, Hatta W, Koike T, Imatani A, Shimosegawa T, Salaspuro M. Effects of ALDH2 genotype, PPI treatment and L-cysteine on carcinogenic acetaldehyde in gastric juice and saliva after intragastric alcohol administration. PLoS One 2015; 10:e0120397. [PMID: 25831092 PMCID: PMC4382225 DOI: 10.1371/journal.pone.0120397] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 01/21/2015] [Indexed: 12/12/2022] Open
Abstract
Acetaldehyde (ACH) associated with alcoholic beverages is Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30-50% of Eastern Asians. In alcohol drinkers, ALDH2-deficiency is a well-known risk factor for upper aerodigestive tract cancers, i.e., head and neck cancer and esophageal cancer. However, there is only a limited evidence for stomach cancer. In this study we demonstrated for the first time that ALDH2 deficiency results in markedly increased exposure of the gastric mucosa to acetaldehyde after intragastric administration of alcohol. Our finding provides concrete evidence for a causal relationship between acetaldehyde and gastric carcinogenesis. A plausible explanation is the gastric first pass metabolism of ethanol. The gastric mucosa expresses alcohol dehydrogenase (ADH) enzymes catalyzing the oxidation of ethanol to acetaldehyde, especially at the high ethanol concentrations prevailing in the stomach after the consumption of alcoholic beverages. The gastric mucosa also possesses the acetaldehyde-eliminating ALDH2 enzyme. Due to decreased mucosal ALDH2 activity, the elimination of ethanol-derived acetaldehyde is decreased, which results in its accumulation in the gastric juice. We also demonstrate that ALDH2 deficiency, proton pump inhibitor (PPI) treatment, and L-cysteine cause independent changes in gastric juice and salivary acetaldehyde levels, indicating that intragastric acetaldehyde is locally regulated by gastric mucosal ADH and ALDH2 enzymes, and by oral microbes colonizing an achlorhydric stomach. Markedly elevated acetaldehyde levels were also found at low intragastric ethanol concentrations corresponding to the ethanol levels of many foodstuffs, beverages, and dairy products produced by fermentation. A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These results provide entirely novel perspectives for the prevention of gastric cancer, especially in established risk groups.
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Affiliation(s)
- Ryuhei Maejima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Katsunori Iijima
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Pertti Kaihovaara
- Research Unit on Acetaldehyde and Cancer, University of Helsinki, Helsinki, Finland
| | - Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Akira Imatani
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Mikko Salaspuro
- Research Unit on Acetaldehyde and Cancer, University of Helsinki, Helsinki, Finland
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Mansour-Ghanaei F, Joukar F, Mojtahedi K, Sokhanvar H, Askari K, Shafaeizadeh A. Does treatment of Helicobacter pylori infection reduce gastric precancerous lesions? Asian Pac J Cancer Prev 2015; 16:1571-1574. [PMID: 25743833 DOI: 10.7314/apjcp.2015.16.4.1571] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Treatment of Helicobacter pylori (H. pylori) decreases the prevalence of gastric cancer, and may inhibit gastric precancerous lesions progression into gastric cancer. The aim of this study was to determine the effect of treatment on subsequent gastric precancerous lesion development. MATERIALS AND METHODS We prospectively studied 27 patients who had low grade dysplasia at the time of enrollment, in addition to dysplasia atrophic gastritis and intestinal metaplasia observed in all patients. All were prescribed quadruple therapy to treat H. Pylori infection for 10 days. Patients underwent endoscopy with biopsy at enrollment and then at follow up two years later. Biopsy samples included five biopsies from the antrum of lesser curvature, antrum of greater curvature, angularis, body of stomach and fundus. RESULTS of these biopsies were compared before and after treatment. RESULTS Overall, the successful eradication rate after two years was 15/27 (55.6%). After antibiotic therapy, the number of patients with low grade dysplasia decreased significantly (p=0.03), also with reduction of the atrophic lesions (p=0.01), but not metaplasia. CONCLUSIONS Treatment of H. pylori likely is an effective therapy in preventing the development of subsequent gastric premalignant lesions.
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Affiliation(s)
- Fariborz Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences (GUMS), Rasht, Iran E-mail : ,
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Sakakibara M, Ando T, Ishiguro K, Maeda O, Watanabe O, Hirayama Y, Morise K, Maeda K, Matsushita M, Furukawa K, Funasaka K, Nakamura M, Miyahara R, Goto H. Usefulness of Helicobacter pylori eradication for precancerous lesions of the gastric remnant. J Gastroenterol Hepatol 2014; 29 Suppl 4:60-4. [PMID: 25521735 DOI: 10.1111/jgh.12772] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIM Secondary stomach cancer in lesions of the remnant stomach occurs relatively soon after distal gastrectomy using the Billroth I reconstruction procedure. Prophylactic eradication of Helicobacter pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma. However, the effect of H. pylori eradication on the gastric remnant has not been clearly determined. METHODS Eight patients who were H. pylori-positive after distal gastrectomy for primary gastric cancer underwent eradication therapy and were followed by endoscopy for 9 years. Upper gastroenteroscopy series were done before and at 1, 3, 5, 7 and 9 years after eradication, and biopsy specimens were taken from the lesser and greater curvatures, respectively. Histological changes, including chronic inflammation, activity, atrophy, and intestinal metaplasia, were evaluated using the updated Sydney system. RESULTS Successful eradication was confirmed using the urea breath test in all eight patients. Chronic inflammation scores were improved after eradication at both the lesser (mean scores ± SD: before eradication, 2.9±0.5; 1 year after, 2.3±0.4; 3 years, 1.8±0.3; 5 years, 1.5±0.3; 7 years, 1.3±0.3; and 9 years, 1.0±0.3) and greater curvatures (before, 2.9±0.4; 1 year after, 1.9±0.3; 3 years, 1.4±0.4; 5 years, 1.3±0.3; 7 years, 1.1±0.2; and 9 years, 0.6±0.3). Atrophy scores improved more quickly after eradication than chronic inflammation scores at both the lesser (before, 2.4±0.5; 1 year after, 1.8±0.4; 3 years, 0.8±0.3; 5 years, 0.3±0.1; 7 years, 0.0; and 9 years, 0.0) and greater curvatures (before, 2.2±0.4; 1 year after, 1.3±0.3; 3 years, 0.5±0.3; 5 years, 0.0; 7 years, 0.0; and 9 years, 0.0). No secondary stomach cancers were found on endoscopy. CONCLUSIONS Undergoing H. pylori eradication improved possible precancerous lesions of the gastric remnant among patients who had undergone distal gastrectomy. Prophylactic H. pylori eradication in the gastric remnant may be useful in preventing the development of metachronous gastric carcinoma.
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Affiliation(s)
- Masatoshi Sakakibara
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Gastroenterology, Aichi Cancer Center Aichi Hospital, Okazaki, Japan
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Xie XQ, Zheng KC, Wu BS, Chen TH, Lai SR, Lin ZS, Aoki K. Differences in the levels of gastric cancer risk factors between Nanjing and Minqing counties, China. J Prev Med Public Health 2014; 47:281-7. [PMID: 25284200 PMCID: PMC4186548 DOI: 10.3961/jpmph.14.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 09/04/2014] [Indexed: 01/26/2023] Open
Abstract
OBJECTIVES In Fujian Province, China, gastric cancer is one of the leading causes of mortality among all malignant tumors. Nanjing county and Minqing county are located in inland Fujian and have similar general demographics. However, the adjusted mortality rate of gastric cancer in Minqing was found to be much higher than that in Nanjing. We sought to explore factors associated with this increased risk of gastric cancer between the two counties. METHODS We recruited 231 and 224 residents from Nanjing and Minqing, respectively, and analyzed differences between their dietary habits, Helicobacter pylori infection rates, and concentrations of serum pepsinogen I, pepsinogen II, gastrin-17, and ratio of pepsinogen I:II. RESULTS Subjects in Minqing had more first-degree relatives who had been diagnosed with upper gastrointestinal tumor, more unhealthy dietary habits, a higher Helicobacter pylori positive rate, and greater proportion of abnormal serum gastrin-17 than those in Nanjing did. CONCLUSIONS The factors that differed between these two counties might indicate that residents in Minqing have a higher risk for developing gastric cancer than those in Nanjing do.
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Affiliation(s)
- Xiang-Quan Xie
- Fujian Center for Disease Control and Prevention, Fuzhou, China
- Fujian Medical University School of Public Health, Fuzhou, China
| | - Kui-Cheng Zheng
- Fujian Center for Disease Control and Prevention, Fuzhou, China
- Fujian Medical University School of Public Health, Fuzhou, China
- Fujian Key Laboratory for Zoonoses Research, Fuzhou,China
| | - Bing-Shan Wu
- Fujian Center for Disease Control and Prevention, Fuzhou, China
| | - Tie-Hui Chen
- Fujian Center for Disease Control and Prevention, Fuzhou, China
| | - Shan-Rong Lai
- Fujian Center for Disease Control and Prevention, Fuzhou, China
| | - Zai-Sheng Lin
- Fujian Center for Disease Control and Prevention, Fuzhou, China
| | - Kazuo Aoki
- Department of Public Health and Hygiene, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
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Roy B, Chattopadhyay G, Mishra D, Das T, Chakraborty S, Maiti TK. On-chip lectin microarray for glycoprofiling of different gastritis types and gastric cancer. BIOMICROFLUIDICS 2014; 8:034107. [PMID: 24959308 PMCID: PMC4048441 DOI: 10.1063/1.4882778] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2014] [Accepted: 05/29/2014] [Indexed: 05/30/2023]
Abstract
An on-chip lectin microarray based glycomic approach is employed to identify glyco markers for different gastritis and gastric cancer. Changes in protein glycosylation have impact on biological function and carcinogenesis. These altered glycosylation patterns in serum proteins and membrane proteins of tumor cells can be unique markers of cancer progression and hence have been exploited to diagnose various stages of cancer through lectin microarray technology. In the present work, we aimed to study the alteration of glycan structure itself in different stages of gastritis and gastric cancer thoroughly. In order to perform the study from both serum and tissue glycoproteins in an efficient and high-throughput manner, we indigenously developed and employed lectin microarray integrated on a microfluidic lab-on-a-chip platform. We analyzed serum and gastric biopsy samples from 8 normal, 15 chronic Type-B gastritis, 10 chronic Type-C gastritis, and 6 gastric adenocarcinoma patients and found that the glycoprofile obtained from tissue samples was more distinctive than that of the sera samples. We were able to establish signature glycoprofile for the three disease groups, that were absent in healthy normal individuals. In addition, our findings elucidated certain novel signature glycan expression in chronic gastritis and gastric cancer. In silico analysis showed that glycoprofile of chronic gastritis and gastric adenocarcinoma formed close clusters, confirming the previously hypothesized linkage between them. This signature can be explored further as gastric cancer marker to develop novel analytical tools and obtain in-depth understanding of the disease prognosis.
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Affiliation(s)
- Bibhas Roy
- Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
| | - Gautam Chattopadhyay
- Department of Surgical Gastroenterology, Kolkata Medical College, Kolkata, India
| | - Debasish Mishra
- Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
| | - Tamal Das
- Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
| | - Suman Chakraborty
- Department of Mechanical Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
| | - Tapas K Maiti
- Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India
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Abstract
Helicobacter pylori-associated gastric cancer is a major cause of morbidity and mortality worldwide, and is predicted to become even more common in developing countries as the population ages. Since gastric cancer develops slowly over years to decades, and typically progresses though a series of well-defined histologic stages, cancer biomarkers have potential to identify asymptomatic individuals in whom surgery might be curative, or even those for whom antibiotics to eradicate H. pylori could prevent neoplastic transformation. Here we describe some of the challenges of biomarker discovery, summarize current approaches to biomarkers of gastric cancer, and explore some recent novel strategies.
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Affiliation(s)
- Cara L Cooke
- Departments of Medicine and Microbiology & Immunology; University of California; Davis School of Medicine; Davis, CA USA,Center for Comparative Medicine; University of California; Davis School of Medicine; Davis, CA USA
| | - Javier Torres
- Infectious Diseases Research Unit; Instituto Mexicano del Seguro Social; Mexico City, Mexico
| | - Jay V Solnick
- Departments of Medicine and Microbiology & Immunology; University of California; Davis School of Medicine; Davis, CA USA,Center for Comparative Medicine; University of California; Davis School of Medicine; Davis, CA USA,California National Primate Research Center; University of California; Davis School of Medicine; Davis, CA USA,Correspondence to: Jay V Solnick,
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Shiotani A, Cen P, Graham DY. Eradication of gastric cancer is now both possible and practical. Semin Cancer Biol 2013; 23:492-501. [PMID: 23876852 DOI: 10.1016/j.semcancer.2013.07.004] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Accepted: 07/12/2013] [Indexed: 01/06/2023]
Abstract
In 1994, Helicobacter pylori was declared a human carcinogen. Evidence has now accumulated to show that at least 95% of gastric cancers are etiologically related to H. pylori. An extensive literature regarding atrophic gastritis and its effects on acid secretion, gastric microflora, and its tight association with gastric cancer has been rediscovered, confirmed, and expanded. Methods to stratify cancer risk based on endoscopic and histologic findings or serologic testing of pepsinogen levels and H. pylori testing have been developed producing practical primary and secondary gastric cancer prevention strategies. H. pylori eradication halts progressive mucosal damage. Cure of the infection in those with non-atrophic gastritis will essentially prevent subsequent development of gastric cancer. For all, the age-related progression in cancer risk is halted and likely reduced as eradication reduces or eliminates mucosal inflammation and reverses or reduces H. pylori-associated molecular events such aberrant activation-induced cytidine deaminase expression, double strand DNA breaks, impaired DNA mismatch repair and aberrant DNA methylation. Those who have developed atrophic gastritis/gastric atrophy however retain some residual risk for gastric cancer which is proportional to the extent and severity of atrophic gastritis. Primary and secondary cancer prevention starts with H. pylori eradication and cancer risk stratification to identify those at higher risk who should also be considered for secondary cancer prevention programs. Japan has embarked on population-wide H. pylori eradication coupled with surveillance targeted to those with significant remaining risk. We anticipate that countries with high gastric cancer burdens will follow their lead. We provide specific recommendations on instituting practical primary and secondary gastric cancer prevention programs as well identifying research needed to make elimination of gastric cancer both efficient and cost effective.
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Affiliation(s)
- Akiko Shiotani
- Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan
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Interobserver variation in assessment of gastric premalignant lesions: higher agreement for intestinal metaplasia than for atrophy. Eur J Gastroenterol Hepatol 2013; 25:694-9. [PMID: 23337173 DOI: 10.1097/meg.0b013e32835e3397] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Either atrophy or intestinal metaplasia of the gastric mucosa are considered premalignant lesions. The new operative link for gastritis assessment staging system is based on the detection of atrophy, and the operative link for assessment of intestinal metaplasia staging system is based on the detection of intestinal metaplasia. Good interobserver agreement is necessary for identification of any premalignant condition. AIMS The aim of this study was to compare the agreement between findings of gastric atrophy and intestinal metaplasia by expert and general pathologists and to analyze the possible reasons behind any possible disagreement. METHODS Patients with dyspeptic symptoms, aged 55 years and above, without previous Helicobacter pylori eradication were enrolled and analyzed according to the updated Sydney Classification by two expert pathologists and an experienced general pathologist; the results were compared with the consensus driven by the two experts. RESULTS Gastric biopsy specimens from 121 patients (91 women) were included in the analysis; the mean age of the patients was 67.4 years. H. pylori infection was present in 61.2% of patients. The level of agreement between the general pathologist and the two experts (κ-value) was 0.12, 0.46, and 0.87, respectively, for detecting atrophy in the corpus; 0.77, 0.77, and 0.65, respectively, for detecting intestinal metaplasia in the corpus; 0.06, 0.51, and 0.54, respectively, for detecting atrophy in the antrum; and 0.69, 0.85, and 0.79, respectively, for detecting metaplasia in the antrum. CONCLUSION The agreement was substantially higher for intestinal metaplasia than for atrophy. This could result in discrepancies when the operative link for gastritis assessment and operative link for assessment of intestinal metaplasia staging systems are applied and can be caused by differences in the criteria used to define atrophy.
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Joo YE, Park HK, Myung DS, Baik GH, Shin JE, Seo GS, Kim GH, Kim HU, Kim HY, Cho SI, Kim N. Prevalence and risk factors of atrophic gastritis and intestinal metaplasia: a nationwide multicenter prospective study in Korea. Gut Liver 2013; 7:303-310. [PMID: 23710311 PMCID: PMC3661962 DOI: 10.5009/gnl.2013.7.3.303] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2012] [Revised: 09/05/2012] [Accepted: 09/24/2012] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND/AIMS Atrophic gastritis (AG) and intestinal metaplasia (IM) are premalignant gastric lesions. The aims of this study were to evaluate the prevalence of endoscopic AG and IM and to document the risk factors for these lesions. METHODS In total, 4,023 subjects were enrolled at eight hospitals in Korea. AG and IM were diagnosed by endoscopy. Helicobacter pylori immunoglobulin G antibodies were measured. RESULTS The prevalences of endoscopic AG and IM were 40.7% and 12.5%. In a multivariate analysis, the risk factors for AG were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, IM, and education below the college level (odds ratio [OR], 2.55, 5.00, 1.38, 1.41, 4.29, and 1.35, respectively). The risk factors for IM were age groups of 40 to 59 years and >60 years, male sex, positive H. pylori serology, AG, having relatives with gastric cancer, education below the college level and consumption of dairy products (OR, 3.16, 3.25, 1.88, 2.17, 3.68, 1.48, 1.47, and 1.40, respectively). CONCLUSIONS A nationwide survey regarding the prevalence of endoscopic AG and IM and their risk factors in Korea supports the hypothesis that endoscopic diagnosis of these premalignant lesions could be helpful to describe a group at high risk for gastric cancer.
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Affiliation(s)
- Young-Eun Joo
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun-Kyung Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Dae-Seong Myung
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Gwang-Ho Baik
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Jeong-Eun Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Geom-Seog Seo
- Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea
| | - Heung Up Kim
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Hyun Young Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Sung-Il Cho
- School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Kim TH, Han SW. Atrophic Gastritis: Reversible after Treatment? THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2013. [DOI: 10.7704/kjhugr.2013.13.1.25] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Tae Ho Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sok Won Han
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Abadir A, Streutker C, Brezden-Masley C, Grin A, Kim YI. Intestinal metaplasia and the risk of gastric cancer in an immigrant asian population. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2012; 5:43-50. [PMID: 24833933 PMCID: PMC3987763 DOI: 10.4137/cgast.s10070] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The development of intestinal metaplasia (IM) has been purported to be a critical step in the pathogenesis of gastric cancer. However, the natural history of IM in migrant human populations has not been well elucidated. The purpose of this study was to determine the risk of gastric cancer posed by IM in Asian immigrants undergoing gastric cancer screening. A retrospective review of Asian immigrants found to have IM during screening was conducted over an 18-month period. In total, 222 patients were found to have IM. Altogether, 24% had a history of smoking, 48% had a family history of gastric cancer, and 52% had a history of Helicobacter pylori (H. pylori) infection with a 96% eradication rate. Patients with stable IM (SIM) were then compared with those who developed high risk pathology (HRP), specifically dysplasia and/or adenocarcinoma. Thirty-five patients (16%) were included in the HRP group, 31 with dysplasia (14%) and 4 with adenocarcinoma (2%). Of those with dysplasia, 55% demonstrated regression to IM over the course of follow-up. Patients in the SIM group were more likely to be female (60% vs. 31%, P = 0.002) and more likely to have had a normal biopsy during follow-up (32% vs. 9%, P = 0.005). Odds ratios for IM stability were 3.3 (95% CI 1.5-7.0) and 5.0 (95% CI 1.5-17.1) for female gender and presence of a normal biopsy, respectively. Intestinal metaplasia in immigrant Asian populations is predominantly a stable histologic finding associated with a low rate of persistent dysplasia and adenocarcinoma.
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Affiliation(s)
- Amir Abadir
- Division of Gastroenterology, Department of Medicine, University of Toronto
| | - Catherine Streutker
- Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto
| | | | - Andrea Grin
- Department of Laboratory Medicine, St. Michael's Hospital, University of Toronto
| | - Young-In Kim
- Division of Gastroenterology, Department of Medicine, University of Toronto. ; Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
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Theodoropoulos GE, Saridakis V, Karantanos T, Michalopoulos NV, Zagouri F, Kontogianni P, Lymperi M, Gazouli M, Zografos GC. Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development. Breast 2012; 21:534-538. [PMID: 22560646 DOI: 10.1016/j.breast.2012.04.001] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Revised: 03/20/2012] [Accepted: 04/11/2012] [Indexed: 12/16/2022] Open
Abstract
Toll-like receptor (TLR) activation may be an important event in tumor cell immune evasion. TLR2 and TLR4 gene polymorphisms have been related to increased susceptibility to cancer development in various organs. 261 patients and 480 health individuals were investigated for genotype and allelic frequencies of a 22-bp nucleotide deletion (-196 to -174del) in the promoter of TLR2 gene as well as two polymorphisms causing amino acid substitutions (Asp299Gly and Thr399Ile) in TLR4 gene. As far as (-196 to -174del) in TLR2 gene is concerned ins/del and del/del genotypes and del allele were significantly more frequent in breast cancer patients compared to healthy controls. Considering Asp299Gly replacement of TLR4 gene, Gly carriers (Asp/Gly & Gly/Gly genotype) and Gly allele were overrepresented among the breast cancer cases. The -174 to -196del of TLR2 gene and Asp299Gly of TLR4 gene polymorphisms may confer an increased susceptibility to breast cancer development.
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Affiliation(s)
- George E Theodoropoulos
- First Propaedeutic Surgical Dept, School of Medicine, Hippocratio General Hospital, Athens, Greece
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Kang JM, Kim N, Shin CM, Lee HS, Lee DH, Jung HC, Song IS. Predictive factors for improvement of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication: a three-year follow-up study in Korea. Helicobacter 2012; 17:86-95. [PMID: 22404438 DOI: 10.1111/j.1523-5378.2011.00918.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS To date, data on the effects of anti-Helicobacter therapy on the improvement of atrophic gastritis (AG) and intestinal metaplasia (IM) have been conflicting. This study was performed to investigate whether eradication of H. pylori could lead to the improvement of AG and IM, and the prognostic factors associated with the improvement of AG and IM. METHODS Four hundred patients consisting of H. pylori-negative (n = 116) and H. pylori-positive (n = 284) groups were followed up 1 and 3 years after initial H. pylori tests. Serum levels of pepsinogen (PG), bacteria, environmental factors, and genetic polymorphisms were determined. RESULTS The grade of corpus atrophy decreased at 1 and 3 years after successful eradication (p < .001 and p = .033, respectively). However, there was no significant change in the IM in the antrum and in the corpus. Prediction factors for the improvement of corpus AG by H. pylori eradication were baseline low PG I/II ratio (≤3), high salt intake, and corpus-predominant gastritis. IM improvement was also associated with spicy food intake and high baseline grade of IM, in addition to these factors. In addition, IL-1B-511 C/T and IL-6-572 C/G alleles were found to inhibit IM improvement. However, H. pylori-negative and noneradicated group did not show any significant change in AG or IM. CONCLUSION Corpus AG was reversed by H. pylori eradication, and improvement of IM by H. pylori eradiation was more definite in patients with severe IM, low PG I/II ratio, and corpus-predominant gastritis, suggesting that H. pylori eradication is valuable even in severe cases.
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Affiliation(s)
- Jung Mook Kang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Watanabe M, Kato J, Inoue I, Yoshimura N, Yoshida T, Mukoubayashi C, Deguchi H, Enomoto S, Ueda K, Maekita T, Iguchi M, Tamai H, Utsunomiya H, Yamamichi N, Fujishiro M, Iwane M, Tekeshita T, Mohara O, Ushijima T, Ichinose M. Development of gastric cancer in nonatrophic stomach with highly active inflammation identified by serum levels of pepsinogen and Helicobacter pylori antibody together with endoscopic rugal hyperplastic gastritis. Int J Cancer 2012; 131:2632-42. [PMID: 22383377 DOI: 10.1002/ijc.27514] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2011] [Accepted: 02/14/2012] [Indexed: 12/14/2022]
Abstract
This study aimed to elucidate groups at high risk of developing cancer among patients with serologically identified Helicobacter pylori infection and nonatrophic stomach. Annual endoscopy was performed for a mean of 5.4 years in 496 asymptomatic middle-aged men who were H. pylori antibody-positive and pepsinogen (PG) test-negative. Subjects were stratified according to the activity of H. pylori-associated gastritis measured by serum levels of PG and H. pylori antibody, and/or by endoscopic findings of rugal hyperplastic gastritis (RHG), and cancer development was investigated. During the study period, seven cases of cancer developed in the cohort (incidence rate, 261/100,000 person-years), with 85.7% developing in the group showing a PGI/II ratio ≤ 3.0, reflecting active inflammation-based high PGII levels. Cancer incidence was significantly higher in this group (750/100,000 person-years) than in groups with less active gastritis. Furthermore, cancer incidence for this group was significantly higher in the subgroup with high H. pylori antibody titers than in the low-titer subgroup. Meanwhile, endoscopic findings revealed that 11.7% of subjects showed RHG reflecting localized highly active inflammation, and cancer risk was significantly higher in patients with RHG than in patients without. Combining the two serum tests and endoscopic examination for RHG allowed identification of subjects with more active gastritis and higher cancer risk. No cancer development was observed in these high-risk subjects after H. pylori eradication. Subjects with highly active gastritis identified by the two serological tests and endoscopic RHG constitute a group at high risk of cancer development with H. pylori-infected nonatrophic stomach.
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Affiliation(s)
- Mika Watanabe
- Second Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama City, Wakayama, Japan
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Toyoda K, Furusyo N, Ihara T, Ikezaki H, Urita Y, Hayashi J. Serum pepsinogen and Helicobacter pylori infection--a Japanese population study. Eur J Clin Microbiol Infect Dis 2012; 31:2117-24. [PMID: 22354521 DOI: 10.1007/s10096-011-1543-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2011] [Accepted: 12/29/2011] [Indexed: 12/11/2022]
Abstract
The decreased ratio of serum pepsinogen (PG) I and II has good correlation with the presence of atrophic gastritis. A total of 1,540 residents aged 30-89 years were enrolled into this study to investigate which serum PG level of residents with Helicobacter pylori infection would represent an adjunct to the diagnosis and progression of atrophic gastritis. All participants received esophagogastroduodenoscopy. Serum antibody to H. pylori (anti-H. pylori) was measured by an enzyme-linked immunosorbent assay (ELISA). Serological atrophic gastritis was defined as serum PG I isozyme level ≤70 ng/ml and a PG I/II ratio of ≤3.0. Of the 1,540 participants, 923 (59.9%) were positive for anti-H. pylori. Serological atrophic gastritis was found significantly more often in anti-H. pylori-positive participants (40.8%) than in anti-H. pylori-negative participants (7.9%) (p ≤ 0.0001). The endoscopic findings of anti-H. pylori-positive participants with serological atrophic gastritis were significantly more frequent by 4.06 times for atrophic gastritis (p ≤ 0.0001) than anti-H. pylori-negative participants without serological atrophic gastritis. Eight anti-H. pylori-positive participants were diagnosed with gastric cancer, but no cancer was found in anti-H. pylori-negative participants without serological atrophic gastritis. Serum PG testing is clinically useful for the prediction of gastric lesions in H. pylori-infected persons.
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Affiliation(s)
- K Toyoda
- Department of Environmental Medicine and Infectious Diseases, Kyushu University, Fukuoka, Japan
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Agréus L, Kuipers EJ, Kupcinskas L, Malfertheiner P, Di Mario F, Leja M, Mahachai V, Yaron N, Van Oijen M, Perez GP, Rugge M, Ronkainen J, Salaspuro M, Sipponen P, Sugano K, Sung J. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers. Scand J Gastroenterol 2012; 47:136-147. [PMID: 22242613 PMCID: PMC3279132 DOI: 10.3109/00365521.2011.645501] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2011] [Revised: 11/22/2011] [Accepted: 11/22/2011] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. METHODS The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. RESULTS In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria. CONCLUSIONS Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach.
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Affiliation(s)
- Lars Agréus
- Karolinska Institute, Center for Family and Community Medicine, Stockholm, Sweden
| | - Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Limas Kupcinskas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Peter Malfertheiner
- University, Department of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg, Germany
| | - Francesco Di Mario
- Department of Clinical Sciences, University of Parma, Section of Gastroenterology, Parma, Italy
| | - Marcis Leja
- Riga East University Hospital, Digestive Diseases Centre, Riga, Latvia
| | - Varocha Mahachai
- Department of Medicine, Division of Gastroenterology, Chulalongkorn University, Thailand
| | - Niv Yaron
- Department of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
| | - Martijn Van Oijen
- Dept. Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Massimo Rugge
- Department of Pathology, University of Padova, Padova, Italy
| | | | - Mikko Salaspuro
- University of Helsinki, Research Unit on Acetaldehyde and Cancer, Helsinki, Finland
| | | | - Kentaro Sugano
- Department of Internal Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi, Japan
| | - Joseph Sung
- Institute of Digestive Disease, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
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Ryu CB, Chen YK. Endoscopic Therapy for Gastric Neoplasms. CLINICAL GASTROINTESTINAL ENDOSCOPY 2012:425-447. [DOI: 10.1016/b978-1-4377-1529-3.00033-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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