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Sasakabe T, Obata Y, Kawai S, Lin Y, Kikuchi S. Comparison of Gastric Cancer Risk Classifications Using Conventional and New Pepsinogen Criteria. Gastroenterol Res Pract 2023; 2023:7646536. [PMID: 37287936 PMCID: PMC10243942 DOI: 10.1155/2023/7646536] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 03/06/2023] [Accepted: 05/11/2023] [Indexed: 06/09/2023] Open
Abstract
Background New serum pepsinogen (PG) criteria have been shown to indicate more accurately infection with Helicobacter pylori (H. pylori). We sought to improve risk classification for gastric cancer by adopting the new PG criteria with the addition of an H. pylori antibody test. Methods The study participants were 275 patients with gastric cancer and 275 apparently healthy controls from case-control study data. We cross-sectionally compared the results of gastric cancer risk classifications that were based on a combination of the new PG criteria (PG II ≥ 10 ng/mL or PG I/II ≤ 5) and an H. pylori antibody test with those that were based on a combination of the conventional criteria (PG I ≤ 70 ng/mL and PG I/PG II ≤ 3) and an H. pylori antibody test. Results Applying the conventional criteria resulted in 89 controls being classified as low risk. Applying the new criteria resulted in 23 controls (bootstrapped 95% confidence intervals [CI]: 14, 32) being additionally classified as high risk. Eight patients with gastric cancer were classified as low risk using the conventional criteria; however, six of these patients were classified as high risk by the new criteria (bootstrapped 95% CI: 2, 11). Conclusions Compared with the conventional criteria, the new PG criteria with H. pylori antibody reduced instances of gastric cancer cases being misclassified as low risk. These findings suggest that the new PG criteria may help identify individuals at high risk of developing gastric cancer.
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Affiliation(s)
- Tae Sasakabe
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Yuki Obata
- College of Pharmacy, Kinjo Gakuin University, Nagoya, Aichi, Japan
| | - Sayo Kawai
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Yingsong Lin
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Shogo Kikuchi
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
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Januszewicz W, Turkot MH, Malfertheiner P, Regula J. A Global Perspective on Gastric Cancer Screening: Which Concepts Are Feasible, and When? Cancers (Basel) 2023; 15:664. [PMID: 36765621 PMCID: PMC9913879 DOI: 10.3390/cancers15030664] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/12/2023] [Accepted: 01/16/2023] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) remains the fifth most common cancer and the third most common cause of cancer-related death globally. In 2022, GC fell into the scope of the updated EU recommendations for targeted cancer screening. Given the growing awareness of the GC burden, we aimed to review the existing screening strategies for GC in high-risk regions and discuss potentially applicable modalities in countries with low-to-intermediate incidence. METHODS The references for this Review article were identified through searches of PubMed with the search terms "gastric cancer", "stomach cancer", "Helicobacter pylori", and "screening" over the period from 1995 until August 2022. RESULTS As Helicobacter pylori (H. pylori)-induced gastritis is the primary step in the development of GC, the focus on GC prevention may be directed toward testing for and treating this infection. Such a strategy may be appealing in countries with low- and intermediate- GC incidence. Other biomarker-based approaches to identify at-risk individuals in such regions are being evaluated. Within high-incidence areas, both primary endoscopic screening and population-based H. pylori "test-and-treat" strategies represent cost-effective models. CONCLUSIONS Given the significant variations in GC incidence and healthcare resources around the globe, screening strategies for GC should be adjusted to the actual conditions in each region. While several proven tools exist for accurate GC diagnosis, a universal modality for the screening of GC populations remains elusive.
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Affiliation(s)
- Wladyslaw Januszewicz
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland
| | - Maryla Helena Turkot
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Jaroslaw Regula
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland
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Shida A, Fukuyama T, Futawatari N, Ohmiya H, Ichiki Y, Yamashita T, Nishi Y, Kobayashi N, Yamazaki H, Watanabe M, Takahashi Y. Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers. World J Gastroenterol 2020; 26:424-432. [PMID: 32063691 PMCID: PMC7002902 DOI: 10.3748/wjg.v26.i4.424] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Revised: 12/23/2019] [Accepted: 01/11/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The ABCD stratification [(combination of serum pepsinogen (PG) levels and titers of antibody (immunoglobulin G, IgG) against Helicobacter pylori (H. pylori)] is effective for the classification of individuals at risk of developing gastric cancer (GC). The Kita–Kyushu lung cancer antigen-1 (KK-LC-1) is a Cancer/Testis antigen frequently expressed in GC.
AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.
METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors. The levels of serum PG I/PG II and IgG against H. pylori were measured. According to their serological status, the patients were classified into the four groups of the ABCD stratification.
RESULTS Of the 77 examined patients, 63 (81.8%) expressed KK-LC-1. The IgG titers of H. pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1 (P = 0.0289 and P = 0.0041, respectively). The expression of KK-LC-1 in group C [PG method (+)/H. pylori infection (+)] was as high as 93.9% high. KK-LC-1 was also detected in group A [-/-].
CONCLUSION The KK-LC-1 expression in GC was associated with H. pylori infection and atrophic status, so that, KK-LC-1 may be a useful marker for the diagnosis of GC.
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Affiliation(s)
- Akiko Shida
- Division of Pathology, Kitasato University, Sagamihara, Kanagawa 252-0374, Japan
| | - Takashi Fukuyama
- Division of Biomedical Research, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
| | - Nobue Futawatari
- Division of Surgery, Toho University, Ohashi Medical Center, Meguroku, Tokyo 153-8515, Japan
| | - Haruki Ohmiya
- Department of Biological Chemistry and Food Sciences, Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8505, Japan
| | - Yoshinobu Ichiki
- Department of General Thoracic Surgery, National Hospital Organization Saitama Hospital, Wako, Saitama 364-8501, Japan
| | - Tetsuro Yamashita
- Department of Biological Chemistry and Food Sciences, Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8505, Japan
| | - Yatsushi Nishi
- Division of Surgery, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
| | - Noritada Kobayashi
- Division of Biomedical Research, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
| | - Hitoshi Yamazaki
- Division of Pathology, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
| | - Masahiko Watanabe
- Division of Surgery, Kitasato University, Sagamihara, Kanagawa 252-0374, Japan
| | - Yoshihito Takahashi
- Division of Surgery, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
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Hishida A, Ugai T, Fujii R, Nakatochi M, Wu MC, Ito H, Oze I, Tajika M, Niwa Y, Nishiyama T, Nakagawa-Senda H, Suzuki S, Koyama T, Matsui D, Watanabe Y, Kawaguchi T, Matsuda F, Momozawa Y, Kubo M, Naito M, Matsuo K, Wakai K. GWAS analysis reveals a significant contribution of PSCA to the risk of Heliobacter pylori-induced gastric atrophy. Carcinogenesis 2019; 40:661-668. [DOI: 10.1093/carcin/bgz016] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
Abstract
Abstract
Although recent genome-wide association studies (GWASs) have identified genetic variants associated with Helicobacter pylori (HP)-induced gastric cancer, few studies have examined the genetic traits associated with the risk of HP-induced gastric precancerous conditions. This study aimed to elucidate genetic variants associated with these conditions using a genome-wide approach. Data from four sites of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study were used in the discovery phase (Stage I); two datasets from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center 2 (HERPACC2) study were used in the replication phases (Stages II and III) and SKAT (SNP-set Kernel Association Test) and single variant-based GWASs were conducted for the risks of gastric atrophy (GA) and severe GA defined by serum pepsinogen (PG) levels, and PG1 and PG1/2 ratios. In the gene-based SKAT in Stage I, prostate stem cell antigen (PSCA) was significantly associated with the risks of GA and severe GA, and serum PG1/2 level by linear kernel [false discovery rate (FDR) = 0.011, 0.230 and 7.2 × 10−7, respectively]. The single variant-based GWAS revealed that nine PSCA single nucleotide polymorphisms (SNPs) fulfilled the genome-wide significance level (P < 5 × 10−8) for the risks of both GA and severe GA in the combined study, although most of these associations did not reach genome-wide significance in the discovery or validation cohort on their own. GWAS for serum PG1 levels and PG1/2 ratios revealed that the PSCA rs2920283 SNP had a striking P-value of 4.31 × 10−27 for PG1/2 ratios. The present GWAS revealed the genetic locus of PSCA as the most significant locus for the risk of HP-induced GA, which confirmed the recently reported association in Europeans.
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Affiliation(s)
- Asahi Hishida
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Tomotaka Ugai
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Ryosuke Fujii
- Department of Preventive Medical Sciences, Fujita Medical University School of Health Sciences, Toyoake, Japan
| | - Masahiro Nakatochi
- Data Coordinating Center, Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan
| | - Michael C Wu
- Biostatistics and Biomathematics Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Hidemi Ito
- Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Isao Oze
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
| | | | | | - Takeshi Nishiyama
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hiroko Nakagawa-Senda
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Sadao Suzuki
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Teruhide Koyama
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Daisuke Matsui
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshiyuki Watanabe
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takahisa Kawaguchi
- Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Fumihiko Matsuda
- Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yukihide Momozawa
- Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Michiaki Kubo
- Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Mariko Naito
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Keitaro Matsuo
- Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
- Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenji Wakai
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Predicting the Development of Gastric Neoplasms in a Healthcare Cohort by Combining Helicobacter pylori Antibodies and Serum Pepsinogen: A 5-Year Longitudinal Study. Gastroenterol Res Pract 2018; 2018:8796165. [PMID: 30140281 PMCID: PMC6081561 DOI: 10.1155/2018/8796165] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 06/25/2018] [Indexed: 02/07/2023] Open
Abstract
Background Helicobacter pylori (HP) and gastric atrophy are risk factors for gastric cancer. We evaluated whether the combination of serum HP antibody and pepsinogen (PG), which is indicative of gastric atrophy, could serve as a predictive marker for the development of gastric neoplasms in a Korean population. Methods The subjects who had undergone health-screening examination with endoscopic follow-ups were classified into the following 4 groups according to serum PG status and HP antibody at baseline: group A (HP (-), normal PG), group B (HP (+), normal PG), group C (HP (+), atrophic PG), and group D (HP (-), atrophic PG). We compared the development of gastric neoplasms among the groups. Results Of the 3297 subjects, 1239 (37.6%) were categorized as group A, 1484 (45.0%) as group B, 536 (16.3%) as group C, and 38 (1.2%) as group D. During the 5.6 years of mean follow-up period, the annual incidence of gastric neoplasms increased gradually by 0.06% in group A, 0.16% in group B, 0.38% in group C, and 0.49% in group D. A Cox proportional hazard model showed increased development of gastric neoplasms according to group (P for trend = 0.025). Compared to group A, the hazard ratio was 8.25 for group D (95% confidence interval 0.2-74.24), 5.35 for group C (1.68-17.05), and 2.65 for group B (0.86-8.14). Conclusion The combination of serum PG and HP antibody is useful for predicting the development of gastric neoplasms, including cancer and adenoma, in a Korean population using endoscopic surveillance.
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Screening Biomarker as an Alternative to Endoscopy for the Detection of Early Gastric Cancer: The Combination of Serum Trefoil Factor Family 3 and Pepsinogen. Gastroenterol Res Pract 2018; 2018:1024074. [PMID: 29977284 PMCID: PMC5994275 DOI: 10.1155/2018/1024074] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2017] [Accepted: 04/03/2018] [Indexed: 12/12/2022] Open
Abstract
Objective The serum pepsinogen test has limitation in its predictive power as a noninvasive biomarker for gastric cancer screening. We aimed to investigate whether the combination of TFF3 and pepsinogen could be an effective biomarker for the detection of gastric cancer even in the early stages. Methods In total, 281 patients with early gastric cancer (EGC), who underwent endoscopic submucosal dissection in Korea, and 708 healthy individuals from Japan were enrolled in the derivation cohort. The validation cohort included 30 Korean patients with EGC and 30 Korean healthy control blood donors. Serum TFF3 levels were examined using enzyme-linked immunosorbent assay. Results Using a cutoff of 6.73 ng/mL in the derivation cohort, the sensitivity of the combination of tests for EGC detection was superior (87.5%) to that of TFF3 (80.4%) or pepsinogen test alone (39.5%). Similarly, in the validation cohort, the sensitivity of TFF3 plus pepsinogen was higher (90.4%) than that of TFF3 (80.0%) or pepsinogen test alone (33.3%). Conclusion The combination of serum TFF3 and pepsinogen is a more effective noninvasive biomarker for gastric cancer detection compared with pepsinogen or TFF3 alone, even in EGC. This trial is registered with NCT03046745.
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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 2017. [PMID: 29520200 PMCID: PMC5839076 DOI: 10.1515/raon-2017-0054] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [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
- Prof. Bojan Tepeš, M.D., Ph.D., FEBGH FSMA, AM DC Rogaška, Prvomajska 29 A, 3250 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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Kaise M. Advanced endoscopic imaging for early gastric cancer. Best Pract Res Clin Gastroenterol 2015; 29:575-87. [PMID: 26381303 DOI: 10.1016/j.bpg.2015.05.010] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Revised: 04/22/2015] [Accepted: 05/21/2015] [Indexed: 01/31/2023]
Abstract
Considerable numbers of early gastric cancers can be missed or misdiagnosed with conventional white light imaging endoscopy (WLI), thus advanced endoscopic imaging modalities have been applied to overcome the issue. High definition endoscopy can improve diagnostic accuracy, but still misses 20-25% of early gastric cancer. Magnifying endoscopy combined with narrow band imaging (NBI) allows for very high accuracy, with sensitivity and specificity of over 95%. The algorithm for magnifying endoscopy diagnosis of gastric cancer is composed of 1) presence of demarcation line, and 2) presence of irregular microsurface and/or microvascular pattern. Ultra-high magnification of 400 times with endocytoscopy (ECS) can produce images reflecting structural and cellular atypia. Using high grade ECS atypia as the diagnostic criteria for gastric cancer, ECS achieves a high diagnostic accuracy (86% of sensitivity, 100% of specificity) although approximately 10% of target lesions are not assessable because of poor dye staining.
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Affiliation(s)
- Mitsuru Kaise
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.
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Randomized controlled trial comparing gastric cancer screening by gastrointestinal X-ray with serology for Helicobacter pylori and pepsinogens followed by gastrointestinal endoscopy. Gastric Cancer 2015; 18:605-11. [PMID: 25118857 DOI: 10.1007/s10120-014-0408-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Accepted: 07/13/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Based on the results of several case-control and cohort studies gastrointestinal X-ray (GI X-ray) has been recommended for use in the nationwide screening program for gastric cancer.. Although this was the only effective screening program when almost all of the Japanese population were Helicobacter pylori (H. pylori) positive, there has been concern whether an alternative effective screening system should be established for the future H. pylori-negative generation. We therefore conducted the first randomized controlled trial (RCT) comparing GI X-ray and gastrointestinal endoscopy (GIE) scheduled according to results of serological testing (ST); this was done to determine the potential for an alternative screening method. METHODS Subjects who fulfilled the inclusion criteria were residents between the ages of 30 and 74 and who were able to receive gastric cancer screening in the Yurihonjo area. Participants were assigned to the GI X-ray group or the GIE-ST group by computer randomization. Subjects in each group were further subdivided into 4 categories according to their different risks for gastric cancer. The feasibility of stratified randomization was serologically assessed and detection rates of gastric cancer at entry by the different screening methods were also compared. RESULTS Of the 2,962 subjects invited, 1,206 individuals (41 percent) were included in the first stage of this stratified RCT, and 604 and 602 individuals were assigned to the GI X-ray group and the GIE-ST group, respectively. There were no statistically significant differences in sex, age, height, body weight, smoking, alcohol intake and family history of cancer between the 2 groups. During ST the GI X-ray group showed a distribution that was not statistically different from that of the GIE-ST group. Although 3 cases of gastric cancer were detected in the GIE-ST group, there was no statistically significant difference between the 2 groups. One complication found was barium aspiration during the examination in the X-ray group. CONCLUSION We confirmed that baseline demographic features of the 2 groups were well balanced. We are now organizing the first RCT to compare the existing screening method and the alternative method (Clinical trial registration number: UMIN000005962).
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Ichikawa H, Sugimoto M, Uotani T, Sahara S, Yamade M, Iwaizumi M, Yamada T, Osawa S, Sugimoto K, Miyajima H, Yamaoka Y, Furuta T. Influence of prostate stem cell antigen gene polymorphisms on susceptibility to Helicobacter pylori-associated diseases: a case-control study. Helicobacter 2015; 20:106-13. [PMID: 25582162 DOI: 10.1111/hel.12183] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients with duodenal ulcer have a reduced risk of developing gastric cancer compared to those without. Recently, the prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with different pathogenesis of duodenal ulcer and gastric cancer developments. However, whether PSCA rs2294008 C>T polymorphism is associated with severity of gastric mucosal atrophy is unclear. We examined the influence of the PSCA rs2294008 C>T polymorphism on susceptibility to H. pylori-related diseases and the relationships between PSCA polymorphism and gastric mucosal atrophy. METHODS PSCA rs2294008 C>T polymorphism was assessed in H. pylori-positive Japanese patients (n = 488) with noncardia gastric cancer (n = 193), gastric ulcer (n = 84), duodenal ulcer (n = 61), and atrophic gastritis (n = 150), as well as in H. pylori-negatives (n = 266). RESULTS Frequency of PSCA rs2294008 C/C genotype in duodenal ulcer was 36.1%, which was significantly higher than those with gastric cancer (12.4%), gastric ulcer (19.0%), gastritis (10.7%), and H. pylori-negatives (19.5%) (p < .001). Compared with duodenal ulcer, having the T allele significantly increased the risk of gastric cancer (OR: 3.97, 95% CI: 2.02-7.80; p < .001), gastric ulcer (2.40, 1.13-5.10; p = .023), and gastritis (4.72, 2.26-9.86; p < .001). Mean pepsinogen (PG) I/PG II ratio in T allele carriers (2.17 ± 0.75) was significantly lower than that in C/C genotype (3.39 ± 1.27, p < .001). CONCLUSIONS The PSCA rs2294008 C>T polymorphism is associated with differing susceptibilities to H. pylori-associated diseases. The PSCA rs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCA rs2294008 T allele carriers, but not duodenal ulcer.
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Affiliation(s)
- Hitomi Ichikawa
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
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Pepsinogen II can be a potential surrogate marker of morphological changes in corpus before and after H. pylori eradication. BIOMED RESEARCH INTERNATIONAL 2014; 2014:481607. [PMID: 25028655 PMCID: PMC4083213 DOI: 10.1155/2014/481607] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Revised: 05/08/2014] [Accepted: 05/20/2014] [Indexed: 12/14/2022]
Abstract
Background. The aim of this investigation is to study the relationship between gastric morphology and serum biomarkers before and after Helicobacter pylori eradication. Methods. First-degree relatives of gastric cancer patients underwent gastroscopy before and 2.5 years after H. pylori eradication. The morphological changes in two categories (normal to mild and moderate to severe) were compared with level of pepsinogens I and II before eradication (n = 369), after eradication (n = 115), and in those with persistent infection (n = 250). Results: After eradication, pepsinogen I decreased to 70% and pepsinogen II to 45% of the previous values. Unlike pepsinogen II and pepsinogen I to II ratio that were affected by the severity of inflammation and atrophy in corpus in all groups, pepsinogen I generally did not change. After eradication, subjects with high mononuclear infiltration in corpus had lower pepsinogen I (54 versus 77.1 μ/mL), higher pepsinogen II (9.4 versus 6.9 μ/mL), and lower ratio (7.9 versus 11.6) than those without (P < 0.05). Conclusion. Pepsinogen II is a good marker of corpus morphological changes before and after H. pylori eradication.
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12
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Yuan Y. A survey and evaluation of population-based screening for gastric cancer. Cancer Biol Med 2013; 10:72-80. [PMID: 23882421 PMCID: PMC3719193 DOI: 10.7497/j.issn.2095-3941.2013.02.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2013] [Accepted: 06/03/2013] [Indexed: 12/24/2022] Open
Abstract
Screening and early diagnosis of gastric cancer play important roles in reducing the mortality of gastric cancer. A vast amount of study data on gastric cancer screening and early diagnosis has been accumulated in and out of China in the past decades. The practice of gastric cancer screening has also been efficiently carried out in different countries and regions. However, no widely accepted principle of population screening for gastric cancer has been developed yet. Screening for gastric cancer requires extensive exploration both theoretically and practically. This article focuses on the method and program of gastric cancer screening based on population. Moreover, the current situation of gastric cancer screening and its evaluation are evaluated.
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Affiliation(s)
- Yuan Yuan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, Shenyang 110001, China
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Influence of Helicobacter pylori status and eradication on the serum levels of trefoil factors and pepsinogen test: serum trefoil factor 3 is a stable biomarker. Gastric Cancer 2013; 16:329-37. [PMID: 22907485 DOI: 10.1007/s10120-012-0185-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2011] [Accepted: 07/31/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM Emerging data indicate that serum trefoil factors (TFFs), especially TFF3, could be potential biomarkers for gastric cancer risk. We aimed to evaluate the influence of Helicobacter pylori (H. pylori) status and eradication on serum TFFs and the pepsinogen test. METHODS Healthy individuals who underwent a thorough medical checkup were enrolled in study 1, and gastric ulcer patients who undertook H. pylori eradication therapy were enrolled in studies 2 and 3. Serum levels of the TFFs (TFF1, TFF2 and TFF3), H. pylori antibody and pepsinogen test were examined in all studies. In study 3, TFF expressions in biopsy samples of the gastric mucosa were additionally examined before and 2 months after eradication. RESULTS In 1,260 healthy individuals enrolled in study 1, serum TFF1 and TFF2 levels were markedly different between H. pylori antibody-positive and -negative participants (P < 0.0001). Differences in serum TFF3 levels between H. pylori antibody-positive (5.85 ± 3.93 ng/ml) and -negative subjects (5.27 ± 2.38 ng/ml) were statistically significant (P = 0.002) but small in absolute value. In 178 gastric ulcer patients enrolled in study 2, serum TFF1, TFF2 and positive rates of the pepsinogen test significantly decreased 2 months after H. pylori eradication therapy (P < 0.001). In contrast, serum TFF3 levels and positive rates of high TFF3 levels (≥7 ng/ml) did not significantly change with H. pylori-eradication until 5 years after eradication. In 18 gastric ulcer patients (study 3), TFF1 and TFF2 were mainly expressed in the foveolar epithelium, and TFF2 was additionally expressed in the pyloric glands. These expressions significantly decreased with H. pylori eradication. TFF3s were scarcely expressed in the gastric mucosa except in goblet cells of intestinal metaplasia, which did not change with H. pylori eradication. CONCLUSION In serum TFFs and pepsinogen tests, only serum TFF3s were not significantly affected by H. pylori eradication, suggesting that serum TFF3 could be a stable biomarker of gastric cancer risk even after H.pylori eradication in contrast with the pepsinogen test.
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Shikata K, Ninomiya T, Yonemoto K, Ikeda F, Hata J, Doi Y, Fukuhara M, Matsumoto T, Iida M, Kitazono T, Kiyohara Y. Optimal cutoff value of the serum pepsinogen level for prediction of gastric cancer incidence: the Hisayama Study. Scand J Gastroenterol 2012; 47:669-75. [PMID: 22428879 DOI: 10.3109/00365521.2012.658855] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Serum pepsinogen (sPG) levels have been established as a good marker of chronic atrophic gastritis and the sequential occurrence of gastric cancer. However, there have been few prospective investigations which investigated the predictive performance of sPG for future gastric cancer incidence. SUBJECTS AND METHODS We prospectively followed-up a total of 2446 community-dwelling Japanese aged ≥ 40 years for 10 years and used the Youden's index to determine the cutoff values of the pepsinogen I level and pepsinogen I/II ratio to accurately discriminate gastric cancer events. Predictive performance of sPG was assessed by ROC curve. RESULTS During the follow-up, 69 subjects developed gastric cancer. The most predictive sPG test criteria were determined to be a pepsinogen I level ≤ 59 ng/ml and pepsinogen I/II ratio ≤ 3.9. The sensitivity and specificity of these criteria to discriminate the actual occurrence of gastric cancer were 71.0% and 69.2%, respectively. The area under the ROC curve for gastric cancer occurrence increased significantly by adding the sPG test to the model that included the status of Helicobater pylori infection and other potential risk factors (from 0.742 to 0.809; p for difference in the area < 0.001). CONCLUSIONS This study determined the optimal sPG test criteria for predicting gastric cancer occurrence over 10 years in a general Japanese population. These criteria would be effective to screen for individuals at high risk of this disease.
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Affiliation(s)
- Kentaro Shikata
- Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Kudo T, Kakizaki S, Sohara N, Onozato Y, Okamura S, Inui Y, Mori M. Analysis of ABC (D) stratification for screening patients with gastric cancer. World J Gastroenterol 2011; 17:4793-8. [PMID: 22147980 PMCID: PMC3229628 DOI: 10.3748/wjg.v17.i43.4793] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2011] [Revised: 06/09/2011] [Accepted: 06/13/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the value of ABC (D) stratification [combination of serum pepsinogen and Helicobacter pylori (H. pylori) antibody] of patients with gastric cancer.
METHODS: Ninety-five consecutive patients with gastric cancer were enrolled into the study. The serum pepsinogen I (PG I)/pepsinogen II (PG II) and H. pylori antibody levels were measured. Patients were classified into five groups of ABC (D) stratification according to their serological status. Endoscopic findings of atrophic gastritis and histological differentiation were also analyzed in relation to the ABC (D) stratification.
RESULTS: The mean patient age was (67.9 ± 8.9) years. Three patients (3.2%) were classified into group A, 7 patients (7.4%) into group A’, 27 patients (28.4%) into group B, 54 patients (56.8%) into group C, and 4 patients (4.2%) into group D, respectively. There were only three cases in group A when the patients taking acid proton pump inhibitors and those who had undergone eradication therapy for H. pylori (group A’) were excluded. These three cases had mucosal atrophy in the grey zone according to the diagnostic manual of ABC (D) stratification. Histologically, the mean age of the patients with well differentiated adenocarcinoma was significantly higher than that of the patients with poorly differentiated adenocarcinoma (P < 0.05). There were no differences in the pattern of atrophy in the endoscopies between the well differentiated and poorly differentiated groups.
CONCLUSION: ABC (D) stratification is a good method for screening patients with gastric cancers. Endoscopy is needed for grey zone cases to check the extent of mucosal atrophy.
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Aikou S, Ohmoto Y, Gunji T, Matsuhashi N, Ohtsu H, Miura H, Kubota K, Yamagata Y, Seto Y, Nakajima A, Goldenring JR, Kaminishi M, Nomura S. Tests for serum levels of trefoil factor family proteins can improve gastric cancer screening. Gastroenterology 2011; 141:837-845.e1-7. [PMID: 21699780 PMCID: PMC3163741 DOI: 10.1053/j.gastro.2011.05.040] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2010] [Revised: 05/12/2011] [Accepted: 05/20/2011] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Improving methods for early detection of gastric cancer could reduce mortality. Measurements of serum pepsinogen levels have been used for screening in Japan without satisfactory levels of sensitivity or specificity. Trefoil factor family (TFF) proteins (TFF1, TFF2, and TFF3) are small and stable molecules secreted by the mammalian gastrointestinal tract. Foveolar hyperplasia, spasmolytic polypeptide (TFF2)-expressing metaplasia, and intestinal metaplasia are histologic changes observed in patients with atrophic gastritis; they express TFF1, TFF2, and TFF3, respectively. We investigated whether serum levels of TFF can be used as markers for gastric cancer screening. METHODS Serum was collected from 183 patients with gastric cancer and 280 healthy individuals without cancer. Serum levels of anti-Helicobacter pylori immunoglobulin G, pepsinogen I, pepsinogen II, TFF1, TFF2, and TFF3 were measured by enzyme-linked immunosorbent assay and associated with gastric cancer. RESULTS Using a cutoff of 3.6 ng/mL, the level of TFF3 was significantly increased in serum samples from patients with cancer (odds ratio, 18.1; 95% confidence interval, 11.2-29.2); using this test, patients with cancer were identified with 80.9% sensitivity and 81.0% specificity. The test for TFF3 had a significantly higher odds ratio than that for pepsinogen. A test for the combination of TFF3 and pepsinogen had better results than the test for only pepsinogen. CONCLUSIONS Serum levels of TFF3 are a better marker of gastric cancer than pepsinogen; a test for the combined levels of serum pepsinogen and TFF3 could improve gastric cancer screening.
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Affiliation(s)
- Susumu Aikou
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo
| | | | | | | | - Hiroshi Ohtsu
- Department of Clinical Trial Data Management, Graduate School of Medicine, University of Tokyo
| | - Hirona Miura
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo
| | - Kensuke Kubota
- Department of Gastroenterology, School of Medicine, Yokohama City University
| | - Yukinori Yamagata
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo
| | - Atsushi Nakajima
- Department of Gastroenterology, School of Medicine, Yokohama City University
| | - James R Goldenring
- Nashville VA Medical Center and the Departments of Surgery and Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine
| | | | - Sachiyo Nomura
- Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo
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The combination of serum trefoil factor 3 and pepsinogen testing is a valid non-endoscopic biomarker for predicting the presence of gastric cancer: a new marker for gastric cancer risk. J Gastroenterol 2011; 46:736-45. [PMID: 21455714 DOI: 10.1007/s00535-011-0396-8] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2011] [Accepted: 03/02/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND A valid biomarker for predicting the presence of gastric cancer may contribute to reducing deaths from this disease. Although pepsinogen (PG) testing has been introduced as a predictor, its predictive power is not satisfactory. We examined whether serum trefoil factor (TFF) could be a non-endoscopic predictor of the presence of gastric cancer. METHODS Gastric cancer patients who underwent preoperative endoscopy were sequentially recruited. Individuals who underwent a thorough medical checkup were enrolled as non-cancer controls. Serum levels of TFF1, TFF2, TFF3, Helicobacter pylori antibody, PG I, and PG II were examined. RESULTS We studied 192 gastric cancer patients aged 64.3 ± 9.7 years and 1254 non-cancer controls aged 52.3 ± 12.4 years. In the age/gender-matched analysis (187 cases and 561 controls), significant relationships were demonstrated between gastric cancer presence and TFF3 (P < 0.0001), the PGI/II ratio (P < 0.0001), H. pylori antibody (P = 0.001), TFF1 (P = 0.012), and TFF2 (P = 0.020). The area under the receiver-operating characteristic curve for predicting gastric cancer presence was comparably high for all factors (0.893) and for the combination of TFF3 and the PG test (0.883), but was significantly (P < 0.0001) lower for the PG test alone (0.823). A positive PG test showed a sensitivity of 67% and specificity of 82%, whereas a combination of TFF3 and PG testing showed a sensitivity of 80% and specificity of 80% in predicting the presence of gastric cancer. CONCLUSION The combination of serum TFF3 and PG testing might be a valid non-endoscopic biomarker for predicting the presence of gastric cancer.
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Abstract
A study conducted by the Japan Gast Study Group showed that eradication of Helicobacter pylori reduced the risk of gastric cancer by about one-third. However, it did not completely prevent the onset of latent gastric cancer among those at high risk (i.e., with atrophic gastritis). To prevent deaths from gastric cancer, it is necessary to eradicate H. pylori infection. We propose a program of risk stratification based on the presence of H. pylori infection with or without atrophic gastritis followed by targeted interventions. Those at no risk for gastric cancer (no H. pylori, no atrophic gastritis) need no therapy or follow-up. Those at low risk (H. pylori infected, nonatrophic gastritis) need only H. pylori eradication therapy. The smaller groups at high or very high risk need eradication and cancer surveillance. We estimated the costs and the benefits of this strategy. Gastric cancer screening by simultaneous measurement of serum pepsinogen and H. pylori antibody combined with eradication of H. pylori in all individuals at risk would initially increase national healthcare expenditure, but this would be offset by markedly reducing the cost of treating gastric cancer. The proposed strategy should prevent about 150,000 deaths from gastric cancer during the 5 years after its adoption. If the loss caused by these deaths is also taken into account, the economic effect of this strategy becomes enormous. It would probably reduce the incidence of gastric cancer by more than 80-90% within 10 years. The Japanese government should take the initiative to implement this strategy as soon as possible.
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Affiliation(s)
- Masahiro Asaka
- Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - David Y. Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, USA
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Kwak MS, Kim N, Lee HS, Lee HE, Jung HC, Song IS. Predictive power of serum pepsinogen tests for the development of gastric cancer in comparison to the histologic risk index. Dig Dis Sci 2010; 55:2275-82. [PMID: 20306133 DOI: 10.1007/s10620-010-1181-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2009] [Accepted: 02/25/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM The selection of a high-risk group of gastric cancer is important. This study was performed to compare the efficacy of non-invasive gastric cancer screening through the measurement of pepsinogen (PG) I/II ratio and endoscopic screening using histologic criteria (Meining's risk index for gastric cancer) in Korean patients. METHODS Included in the study were 460 gastric cancer patients and 460 control cases who underwent upper endoscopy between June 2003 and July 2008 at Seoul National University Bundang Hospital. Serum PG I/II ratio and histologic characteristics were evaluated for each participant. Multivariate logistic regression was performed to compare the predictive power for gastric cancer of both the PG II/I ratio (the inverse form of PG I/II ratio) and the histologic gastric cancer risk index. RESULTS A higher PG II/I ratio was significantly associated with a higher risk for gastric cancer (odds ratio of highest quartile for cancer vs. lowest quartile, 3.51; 95% confidence interval, 2.29-5.36) in the multivariate logistic model. The validity (in terms of calibration and discrimination) of the PG-including multivariate logistic model was comparable to the histologic gastric cancer risk index model. The results were similar regardless of the staging of the cancer, Lauren's histologic classification, and the location of the cancer. CONCLUSIONS These results suggest that non-invasive measurement of serum PG I/II ratio is as effective as Meining's histologic gastric cancer risk index in predicting gastric cancer occurrence.
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Affiliation(s)
- Min Sun Kwak
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
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Comparison of the validity of three biomarkers for gastric cancer screening: carcinoembryonic antigen, pepsinogens, and high sensitive C-reactive protein. J Clin Gastroenterol 2009; 43:19-26. [PMID: 18648315 DOI: 10.1097/mcg.0b013e318135427c] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE To identify a desirable serum marker for screening tools for gastric cancer, we evaluated the validity of 3 biomarkers, namely, carcinoembryonic antigen (CEA), pepsinogens (PGs), and high sensitive C-reactive protein (hsCRP). METHODS We estimated the mean serum levels of CEA, PGs, and hsCRP and compared the sensitivity and specificity of these 3 biomarkers in 378 subjects who were classified into 7 groups: normal, chronic atrophic gastritis, intestinal metaplasia, adenoma, early gastric cancer (EGC), advanced gastric cancer (AGC) without metastasis, and AGC with metastasis (M1). RESULTS There were no significant differences among the normal, high-risk (chronic atrophic gastritis, intestinal metaplasia, and adenoma), and EGC groups for CEA and hsCRP. However, the levels of CEA were relatively higher in the AGC group with intestinal-type cancer (P<0.01). Likewise, hsCRP was relatively higher in the AGC group with diffuse-type cancer (P<0.01). For the PG I/II ratio, there was no significant difference among the normal, high-risk, and cancer groups, including EGC (P<0.01). In addition, there was a negative correlation with grades (gammas=-0.480, P<0.01). However, the PG I/II ratio was relatively less effective in diffuse-type cancer compared with intestinal-type cancer. The combination of serum hsCRP and the PG I/II ratio had a higher sensitivity (77%) than did the PG I/II ratio alone (61%) in diffuse-type cancers. CONCLUSIONS The combination of serum hsCRP and PG I/II ratio would be helpful as a screening tool for gastric cancer in high incidence populations and may help to select high-risk subjects in need of further specific invasive screening tools such as endoscopy.
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Egan BJ, Holmes K, O'Connor HJ, O'Morain CA. Helicobacter pylori gastritis, the unifying concept for gastric diseases. Helicobacter 2007; 12 Suppl 2:39-44. [PMID: 17991175 DOI: 10.1111/j.1523-5378.2007.00575.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Helicobacter pylori infection causes a broad spectrum of clinical diseases and the clinical manifestations of the infection depend on host, environmental, and bacterial factors. These factors have an impact on the pattern and severity of gastritis and ultimately determine the clinical outcome of H. pylori infection. Better staging of gastritis may help to identify patients at risk of gastric cancer. In this article we will examine the complex interaction between host, environmental, and bacterial factors in the pathogenesis of H. pylori infection.
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Affiliation(s)
- Brian J Egan
- Department of Clinical Medicine, Adelaide and Meath Hospital Incorporating the National Children's Hospital, Tallaght, Trinity College, Dublin, Ireland.
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Abstract
The prognosis of early gastric cancer (EGC) is excellent worldwide. Incidence of EGC shows considerable geographic variation, and in high prevalence areas where diagnostic skills are adept, EGCs are not frequently overlooked. In these countries, less invasive, function-preserving treatments such as endoscopic mucosal resection and pylorus-preserving gastrectomy have become standard options. The criteria to apply conservative treatments are being expanded along with the technological improvement. Though its natural history is relatively long, EGC could be a fatal disease and should be carefully treated. Lymph node metastasis is the most important prognostic factor that should be considered in treatment selection and follow-up planning of EGC.
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Affiliation(s)
- T Sano
- Gastric Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
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Miki K. Gastric cancer screening using the serum pepsinogen test method. Gastric Cancer 2007; 9:245-53. [PMID: 17235625 DOI: 10.1007/s10120-006-0397-0] [Citation(s) in RCA: 190] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2006] [Accepted: 08/15/2006] [Indexed: 02/07/2023]
Abstract
The current status of gastric cancer screening, worldwide, as well as in Japan, using the serum pepsinogen test method, was reviewed. We performed a metaanalysis of sensitivity and specificity results from 42 individual studies (27 population-based screening studies: n = 296 553 and 15 selected groups: n = 4 385). Pooled pairs of sensitivity and false-positive rates (FPr) for pepsinogen I level < or = 70 ng/ml; pepsinogen I/II ratio < or = 3, had a sensitivity of 77%/FPr27%. The positive predictive value varied between 0.77% and 1.25%, and the negative predictive value varied between 99.08% and 99.90%. Therefore, we concluded that the definition of the pepsinogen test should include the pepsinogen I/II ratio, as consistency was obtained for both the population-based studies and the selected groups for those studies that used pepsinogen I serum levels together with the pepsinogen I/II ratio for screening for gastric cancer in high-incidence regions other than Japan. Individuals testing positive for extensive atrophic gastritis by serum pepsinogen levels undergo endoscopic examination to test for the presence of gastric cancer. We should increase the efficacy and cost-effectiveness of the gastric cancer screening system, by the identification of groups, at low-risk, as well as those at high-risk, of developing gastric cancer, using a combination of assays of serum Helicobacter pylori antibody titers and the concentration of pepsinogen I and II. In conclusion, the pepsinogen test method can be used as a screening test for high-risk subjects, rather than as a tool for screening for cancer itself. I hope that this pepsinogen test method will become a world standard for gastric cancer prevention in the near future, in other countries, as well as in Japan.
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Affiliation(s)
- Kazumasa Miki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine (Ohmori), School of Medicine, Faculty of Medicine, Toho University, 6-11-1 Ohmori Nishi, Ohta-ku, Tokyo, 143-8541, Japan
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Fujiwara Y, Higuchi K, Shiba M, Yamamori K, Watanabe Y, Sasaki E, Tominaga K, Watanabe T, Oshitani N, Arakawa T. Differences in clinical characteristics between patients with endoscopy-negative reflux disease and erosive esophagitis in Japan. Am J Gastroenterol 2005; 100:754-8. [PMID: 15784015 DOI: 10.1111/j.1572-0241.2005.40966.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Helicobacter pylori infection and atrophic gastritis are inversely related to erosive esophagitis. Whether these factors affect the pathogenesis of endoscopy-negative reflux disease is not clear. We aimed to elucidate the differences in clinical characteristics between endoscopy-negative erosive disease and erosive esophagitis. METHODS 253 subjects (89 with endoscopy-negative reflux disease and 164 with erosive esophagitis) were studied. Gastric atrophy was assessed by measurement of serum pepsinogen. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) of endoscopy-negative reflux disease compared with erosive esophagitis. RESULTS Among GERD patients, female gender (OR = 2.27, 95% CI, 1.25-4.10), smoking (OR = 0.45, 95% CI, 0.22-0.91), and the presence of hiatal hernia (OR = 0.30, 95% CI, 0.17-0.56) were significantly associated with endoscopy-negative reflux disease compared with male gender, not smoking, and absence of hiatal hernia, respectively. Body mass index (BMI) was also significantly associated with a decreased OR for endoscopy-negative reflux disease. Although H. pylori infection and gastric atrophy were significantly more common in patients with endoscopy-negative reflux disease, these associations did not persist in a multiple-adjustment model. After adjustment for gender, BMI, smoking, and hiatal hernia, a decrease in serum pepsinogen I/II ratio was significantly associated with an increased OR for endoscopy-negative reflux disease (p for trend = 0.018). CONCLUSIONS Female gender, low BMI, not smoking, absence of hiatal hernia, and severity of gastric atrophy were positively associated with endoscopy-negative reflux disease compared with erosive esophagitis among Japanese patients.
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Affiliation(s)
- Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Osaka, Japan
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Yamamori K, Fujiwara Y, Shiba M, Watanabe T, Tominaga K, Oshitani N, Matsumoto T, Higuchi K, Arakawa T. Prevalence of symptomatic gastro-oesophageal reflux disease in Japanese patients with peptic ulcer disease after eradication of Helicobacter pylori infection. Aliment Pharmacol Ther 2004; 20 Suppl 1:107-11. [PMID: 15298615 DOI: 10.1111/j.1365-2036.2004.01973.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The association between cure of Helicobacter pylori infection and the development of gastro-oesophageal reflux disease is controversial. AIM To examine the prevalence of symptomatic GERD (sGERD) in Japanese patients with peptic ulcer disease after successful eradication and identify associated factors affecting sGERD development. METHODS We retrospectively examined 72 patients (40 gastric ulcer and 32 duodenal ulcer) with successful eradication. Associated factors such as age, gender, drinking and smoking habits, body mass index, presence of gastric atrophy and hiatal hernia were analysed. RESULTS Seven (9.7%) of 72 peptic ulcer patients newly developed sGERD. There were no differences in mean age, gender, smoking habit, drinking habit, body mass index, or presence of gastric atrophy and hiatal hernia between the sGERD and non-sGERD groups, while the proportion of subjects aged over 70 was significantly higher in the sGERD than the non-sGERD group. Six of 40 patients with gastric ulcer newly developed sGERD while only one of 32 patients with duodenal ulcer developed it. CONCLUSION Approximately 10% of Japanese patients with peptic ulcer disease newly developed sGERD after cure of H. pylori infection. Age > 70 years was associated with development of sGERD. Eradication in patients in this age group should be carefully determined.
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Affiliation(s)
- K Yamamori
- Department of Gastroenterology, Osaka City University, Graduate School of Medicine, Osaka, Japan
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Broutet N, Plebani M, Sakarovitch C, Sipponen P, Mégraud F. Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics. Br J Cancer 2003; 88:1239-47. [PMID: 12698190 PMCID: PMC2747577 DOI: 10.1038/sj.bjc.6600877] [Citation(s) in RCA: 99] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers, that is pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, and gastrin, as screening tests for precancerous lesions: atrophic chronic gastritis (ACG) or Helicobacter pylori-related corpus-predominant or multifocal atrophy. The study population was comprised of a subsample of 284 patients from the 451 included in the Eurohepygast cohort, between 1995 and 1997. The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays. Histological diagnosis was the gold standard. Cut-off points were calculated using receiving operator characteristics (ROC) curves. Factors linked to variation of biomarkers were identified using multivariate linear regression. The mean of each biomarker in the sample was: PGA, 77.4 microg x l(-1); PGC, 13.2 microg x l(-1); PGA/PGC, 6.7; and gastrin, 62.4 ng x l(-1). For ACG patients, the areas under the PGA, PGC, PGA/PGC, and gastrin ROC curves were 0.55, 0.62, 0.73, and 0.58, respectively. The best cut-off point for PGA/PGC was 5.6, with sensitivity 65% and specificity 77.9%. For H. pylori-related corpus-predominant or multifocal atrophy, the areas under the respective ROC curves were 0.57, 0.67, 0.84, and 0.69. The best cut-off point for PGA/PGC was 4.7, with sensitivity 77.1% and specificity 87.4%. The results suggested that only the PGA/PGC ratio can be considered as a biomarker for precancerous lesions of the stomach, and may be useful as a screening test.
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Affiliation(s)
- N Broutet
- Unité d'Epidémiologie des Maladies Digestives, Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux, Cedex, France
| | - M Plebani
- Department of Laboratory Medicine, University Hospital of Padova, Italy
| | - C Sakarovitch
- Unité d'Epidémiologie des Maladies Digestives, Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux, Cedex, France
| | | | - F Mégraud
- Unité d'Epidémiologie des Maladies Digestives, Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux, Cedex, France
- Unité d'Epidémiologie des Maladies Digestives, Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux, Cedex, France. E-mail:
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