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Sun HT. Helicobacter pylori-related serum indicators: Cutting-edge advances to enhance the efficacy of gastric cancer screening. World J Gastrointest Oncol 2025; 17:100739. [PMID: 40092953 PMCID: PMC11866254 DOI: 10.4251/wjgo.v17.i3.100739] [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: 08/30/2024] [Revised: 12/08/2024] [Accepted: 01/03/2025] [Indexed: 02/14/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection induces pathological changes via chronic inflammation and virulence factors, thereby increasing the risk of gastric cancer development. Compared with invasive examination methods, H. pylori-related serum indicators are cost-effective and valuable for the early detection of gastric cancer (GC); however, large-scale clinical validation and sufficient understanding of the specific molecular mechanisms involved are lacking. Therefore, a comprehensive review and analysis of recent advances in this field is necessary. In this review, we systematically analyze the relationship between H. pylori and GC and discuss the application of new molecular biomarkers in GC screening. We also summarize the screening potential and application of anti-H. pylori immunoglobulin G and virulence factor-related serum antibodies for identifying GC risk. These indicators provide early warning of infection and enhance screening accuracy. Additionally, we discuss the potential combination of multiple screening indicators for the comprehensive analysis and development of emerging testing methods to improve the accuracy and efficiency of GC screening. Although this review may lack sufficient evidence due to limitations in existing studies, including small sample sizes, regional variations, and inconsistent testing methods, it contributes to advancing personalized precision medicine in high-risk populations and developing GC screening strategies.
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Affiliation(s)
- Hao-Tian Sun
- Cancer Institute, University College London, London WC1E 6BT, United Kingdom
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2
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Lim JH, Han A, Cho SJ, Hahn S, Kim SG. Nomogram Prediction for Gastric Cancer Development. Clin Transl Gastroenterol 2025:01720094-990000000-00380. [PMID: 40062861 DOI: 10.14309/ctg.0000000000000833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 02/18/2025] [Indexed: 04/17/2025] Open
Abstract
INTRODUCTION Helicobacter pylori ( Hp ) and gastric atrophy represent significant risk factors for gastric cancer (GC). Nevertheless, to date, no nomogram has been developed to predict GC based on the specific combination of risk factors present in individual cases. METHODS A retrospective cohort study was conducted using health screening data collected between 2003 and 2018. Subjects with positive results for anti- Hp antibody were enrolled. Individuals were classified into 4 groups: low-B (low titer without atrophy), high-B (high titer without atrophy), high-C (high titer with atrophy), and low-C (low titer with atrophy). Nomogram prediction models were developed for overall GCs as well as intestinal and diffuse cancers, with each type considered a competing event, by using both Cox proportional and subdistribution hazard models. Prediction performance was evaluated using the concordance index (c-index) and the area under the curve through 10-fold cross-validation. RESULTS During a median follow-up period of 5.7 years, 231 new GC cases developed among the total cohort of 28,311 subjects, including 159 intestinal type, 68 diffuse type, and 4 cases of unknown type. Multivariable analyses indicated that age, body mass index, family history, smoking, and classification into the high-C or low-C group were significant predictors of GC. The nomograms for intestinal type, diffuse type, and total GC demonstrated area under the curve values of 0.82, 0.62, and 0.75, respectively, and c-indices of 0.85, 0.54, and 0.76, respectively. DISCUSSION The nomograms for GC prediction would be useful in identifying high-risk individuals, particularly for intestinal type. This would facilitate the implementation of personalized eradication and intensive screening strategies to target those at higher risk for GC.
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Affiliation(s)
- Joo Hyun Lim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, South Korea
| | - Areum Han
- Interdisciplinary Program of Medical Informatics, Seoul National University College of Medicine, Seoul, South Korea
- Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, South Korea
| | - Soo-Jeong Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Seokyung Hahn
- Department of Human Systems Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Institute of Health Policy and Management, Medical Research Center, Seoul, South Korea
- Medical Big Data Research Center, Seoul National University, Seoul, South Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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3
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Huang Y, Shao Y, Yu X, Chen C, Guo J, Ye G. Global progress and future prospects of early gastric cancer screening. J Cancer 2024; 15:3045-3064. [PMID: 38706913 PMCID: PMC11064266 DOI: 10.7150/jca.95311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 03/21/2024] [Indexed: 05/07/2024] Open
Abstract
Gastric cancer is a prevalent malignancy that poses a serious threat to global health. Despite advances in medical technologies, screening methods, and public awareness, gastric cancer remains a significant cause of morbidity and mortality worldwide. Early gastric cancer frequently does not present with characteristic symptoms, while advanced stage disease is characterized by a dismal prognosis. As such, early screening in gastric cancer is of great importance. In recent years, advances have been made globally in both clinical and basic research for the screening of early gastric cancer. The current predominant screening methods for early gastric cancer include imaging screening, endoscopic screening and serum biomarker screening. Imaging screening encompasses upper gastrointestinal barium meal, multidimensional spiral computed tomography (MDCT), Magnetic resonance imaging (MRI), and ultrasonography. Endoscopic screening methods include white light endoscopy, chromoendoscopy, computed virtual chromoendoscopy, and other endoscopic techniques like endocytoscopy, confocal laser endomicroscopy, optical coherence tomography and so on. Biomarkers screening involves the assessment of conventional biomarkers such as CEA, CA19-9 and CA72-4 as well as more emerging biomarkers such as peptides (PG, G-17, GCAA, TAAs and others), DNA (cfDNA, DNA methylation, MSI), noncoding RNA (miRNA, lncRNA, circRNA, and tsRNA) and others. Each screening method has its strengths and limitations. This article systematically summarizes worldwide progress and future development of early gastric cancer screening methods to provide new perspectives and approaches for early diagnostic and treatment advancements in gastric cancer worldwide.
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Affiliation(s)
- Yixiao Huang
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo 315020, China
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Yongfu Shao
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo 315020, China
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Xuan Yu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Chujia Chen
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Junming Guo
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo 315211, China
| | - Guoliang Ye
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo 315020, China
- Institute of Digestive Disease of Ningbo University, Ningbo 315020, China
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Takayama T, Suzuki H, Okada K, Akiyama S, Narasaka T, Maruo K, Sakamoto T, Seo E, Tsuchiya K. A novel predictive formula for highly accurate discrimination between truly Helicobacter pylori-uninfected and currently infected/spontaneously eradicated individuals for gastric cancer screening. Medicine (Baltimore) 2024; 103:e36335. [PMID: 38428882 PMCID: PMC10906593 DOI: 10.1097/md.0000000000036335] [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: 08/08/2023] [Accepted: 11/06/2023] [Indexed: 03/03/2024] Open
Abstract
The ABC classification, which categorizes gastric cancer risk based on serum Helicobacter pylori (H pylori) antibody and pepsinogen levels, has a limitation of potentially misclassifying high-risk individuals as low risk. To overcome the problem, we previously developed a 4-parameter predictive formula (age, serum H pylori antibody, PGI, and PGII) using logistic regression analysis to accurately identify low-risk truly H pylori-uninfected status. Our predictive formula demonstrated superior sensitivity and specificity in distinguishing between low-risk truly uninfected individuals and high-risk currently/spontaneously eradicated status individuals, compared to the modified ABC classification based on latex immunoassay kits (traditional 3-parameter model). This study aimed to revalidate the diagnostic accuracy of the predictive formula in a new and different study population. We applied the predictive formula to the target population and compared the sensitivity and specificity with those of the traditional 3-parameter model. A total of 788 enrollees were analyzed: 703 were classified as truly uninfected, 45 as currently infected, and 40 as spontaneously eradicated according to the results of stool antigen testing and endoscopic findings. The sensitivities and specificities of the predictive formula and the traditional 3-parameter model were 89.5% and 87.1% versus 89.8% and 80.0%, respectively. The specificity of the predictive formula was superior in the 70 to 89 age range and H pylori antibody < 3 U/mL groups. The predictive formula had higher specificity than the traditional 3-parameter model. The results should contribute to efficient gastric cancer screening by predicting H pylori infection status.
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Affiliation(s)
- Takako Takayama
- Tsukuba Preventive Medical Research Center, University of Tsukuba Hospital, Tsukuba, Japan
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Hideo Suzuki
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kosuke Okada
- Tsukuba Preventive Medical Research Center, University of Tsukuba Hospital, Tsukuba, Japan
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Shintaro Akiyama
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Toshiaki Narasaka
- Tsukuba Preventive Medical Research Center, University of Tsukuba Hospital, Tsukuba, Japan
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kazushi Maruo
- Department of Biostatistics, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Taku Sakamoto
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Emiko Seo
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan
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Fujihata S, Sakuramoto S, Morimoto Y, Matsui K, Nishibeppu K, Ebara G, Fujita S, Oya S, Sugita H, Lee S, Miyawaki Y, Sato H, Takiguchi S, Yamashita K. Remnant gastritis in gastric cancer patients causes loss of muscle mass 6 months after gastrectomy: a retrospective cohort study of Helicobacter pylori infection. Surg Today 2024; 54:152-161. [PMID: 37351638 DOI: 10.1007/s00595-023-02712-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 05/17/2023] [Indexed: 06/24/2023]
Abstract
PURPOSE In this study, we assessed the relationship between remnant gastritis and muscle mass loss and then investigated the potential relationship between Helicobacter pylori (HP) infection and remnant gastritis and muscle loss. METHODS We reviewed the medical records of 463 patients who underwent distal gastrectomy between January 2017 and March 2020. Of these patients, 100 with pStage I after laparoscopic surgery were included in this analysis. RESULTS A multivariate analysis showed that the total Residue, Gastritis, Bile (RGB) classification score, which indicates the degree of gastritis, was significantly associated with the rate of change (rate of decrease) in the psoas muscle area (PMA) during the first 6 months after surgery (p = 0.014). Propensity score matching was performed according to HP infection, and the rate of change in the PMA and the degree of remnant gastritis in 56 patients were compared. Neither was significantly associated with HP infection. CONCLUSIONS Remnant gastritis did contribute to psoas muscle mass loss during the initial 6 months after gastrectomy, and HP infection was not significantly associated with either remnant gastritis or psoas muscle mass loss. Nevertheless, the potential for HP eradication to prevent muscle loss and improve the survival prognosis for gastrectomy patients merits further research.
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Affiliation(s)
- Shiro Fujihata
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan. shiro--
- Department of Surgery, Narita Memorial Hospital, 134 Hanei-Honmchi, Toyohashi, Aichi, Japan. shiro--
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Mizuho-Cho, 1 Kawasumi, Mizuho-Ku, Nagoya, Aichi, Japan. shiro--
| | - Shinichi Sakuramoto
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Yosuke Morimoto
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Kazuaki Matsui
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Keiji Nishibeppu
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Gen Ebara
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Shohei Fujita
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Shuichiro Oya
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Hirofumi Sugita
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Seigi Lee
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Yutaka Miyawaki
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Hiroshi Sato
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Hidaka, Saitama, 350-1298, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Mizuho-Cho, 1 Kawasumi, Mizuho-Ku, Nagoya, Aichi, Japan
| | - Keishi Yamashita
- Division of Advanced Surgical Oncology, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-Ku, Sagamihara, Kanagawa, Japan
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Muhammad Nawawi KN, El‐Omar EM, Ali RA. Screening, Surveillance, and Prevention of Esophageal and Gastric Cancers. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:42-62. [DOI: 10.1002/9781119756422.ch3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Kotani S, Shibagaki K, Hirahara N, Hasegawa N, Tanabe R, Ebisutani Y, Nonomura S, Kishimoto K, Kodama Y, Takahashi Y, Kataoka M, Oka A, Fukuba N, Mishima Y, Oshima N, Kawashima K, Ishimura N, Araki A, Kadota K, Itawaki A, Nagasaki M, Miyaoka Y, Onuma H, Ishihara S. Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and -naïve patients: a multicenter retrospective analysis. J Gastroenterol 2024; 59:1-10. [PMID: 37855982 DOI: 10.1007/s00535-023-02050-2] [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: 05/31/2023] [Accepted: 10/01/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND The incidence of gastric neoplasms in Helicobacter pylori (Hp)-naïve patients has recently increased due to a remarkable decrease in the Hp-infected population in Japan. We investigated the clinicopathologic differences between Hp-infected gastric neoplasms (HpIGNs) and Hp-naïve gastric neoplasms (HpNGNs) that have not been fully elucidated so far. METHODS This retrospective multicenter study investigated 966 consecutive patients with 1131 gastric dysplasia or cancers who underwent endoscopic or surgical treatment for the recent decade. Clinicopathologic features were compared between HpIGN and HpNGN cases. RESULTS One thousand and sixty-eight HpIGNs in 916 patients included 877 differentiated types and 191 undifferentiated types. Sixty-three HpNGNs in 50 patients included 57 differentiated types (35 foveolar types, 15 intestinal types, 6 fundic-gland types, and 1 other differentiated type) and 6 undifferentiated types. HpNGNs occurred in younger (59.5 vs. 71.8 years, p < 0.05) and female patients (40.0% vs. 26.5%, p < 0.05), were found more frequently in the proximal compartment (p < 0.05), and had smaller size (median 4.0 vs. 20.0 mm, p < 0.05). Histologically, HpNGNs and HpIGNs both primarily consisted of differentiated type (90.5% vs. 82.1%, p = 0.089) and HpNGNs showed lower prevalence of invasive cancer (11.1% vs. 37.6%, p < 0.05) and lymphovascular invasion (1.6% vs. 31.6%, p < 0.05). Nearly all HpNGNs (62/63, 98.4%) were diagnosed in early pathological stage, while 16.1% (172/1068) of HpIGNs were diagnosed in advanced stage (p < 0.05). CONCLUSIONS HpNGNs is recently on the increase but shows lower malignant nature regardless of histologic type than HpIGN. Endoscopic gastric cancer screening will be reviewed via cost effectiveness for Hp-naïve individuals in future.
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Affiliation(s)
- Satoshi Kotani
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kotaro Shibagaki
- Department of Endoscopy, Shimane University Hospital, 89-1 Enya, Izumo, 693-8501, Japan.
| | - Noriyuki Hirahara
- Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Nobuaki Hasegawa
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Ryo Tanabe
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yuri Ebisutani
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Saya Nonomura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kenichi Kishimoto
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yasuhide Kodama
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yusuke Takahashi
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Masatoshi Kataoka
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Akihiko Oka
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Nobuhiko Fukuba
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yoshiyuki Mishima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Naoki Oshima
- Department of Endoscopy, Shimane University Hospital, 89-1 Enya, Izumo, 693-8501, Japan
| | - Kousaku Kawashima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Norihisa Ishimura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Asuka Araki
- Department of Pathology, Shimane University Hospital, Izumo, Japan
| | - Kyuichi Kadota
- Department of Pathology, Shimane University Hospital, Izumo, Japan
| | - Ayako Itawaki
- Department of Gastroenterology, National Hospital Organization Hamada Medical Center, Hamada, Japan
| | - Makoto Nagasaki
- Department of Pathology, National Hospital Organization Hamada Medical Center, Hamada, Japan
| | - Yoichi Miyaoka
- Department of Gastroenterology, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Hideyuki Onuma
- Department of Pathology, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Shunji Ishihara
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
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Shah D, Bentrem D. Environmental and Genetic Risk Factors for Gastric Cancer. Cancer Treat Res 2024; 192:1-17. [PMID: 39212913 DOI: 10.1007/978-3-031-61238-1_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Gastric cancer is a heterogeneous and prevalent disease. The traditional environmental exposures associated with elevated risk of gastric cancer are less prevalent in the USA today. Genetic risks and risks associated with inflammation remain. Most cases are sporadic, and familial clustering is observed in about 10% of the cases. Hereditary gastric cancer accounts for a very low percentage of cases. Here we review the genetic and environmental risk factors associated with the disease. In addition, we will review screening guidelines and current modalities that are available for screening in high-risk populations.
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Affiliation(s)
- Dhavan Shah
- Northwestern Quality Improvement, Research, and Education in Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Evanston, USA
| | - David Bentrem
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Evanston, USA.
- Jesse Brown VA Medical Center, Chicago, USA.
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Shibagaki K, Ishimura N, Kotani S, Fukuyama C, Takahashi Y, Kishimoto K, Yazaki T, Kataoka M, Omachi T, Kinoshita Y, Hasegawa N, Oka A, Mishima Y, Mishiro T, Oshima N, Kawashima K, Nagase M, Araki A, Kadota K, Ishihara S. Endoscopic differential diagnosis between foveolar-type gastric adenoma and gastric hyperplastic polyps in Helicobacter pylori-naïve patients. Gastric Cancer 2023; 26:1002-1011. [PMID: 37543537 DOI: 10.1007/s10120-023-01420-2] [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: 06/24/2023] [Accepted: 07/27/2023] [Indexed: 08/07/2023]
Abstract
BACKGROUND Foveolar-type gastric adenoma (FGA) occurs in Helicobacter pylori (Hp)-naïve individuals and morphologically mimics Hp-naïve gastric hyperplastic polyp (HpN-GHP). FGA is often difficult to distinguish from HpN-GHP even by biopsy, due to its low-grade histologic atypia. We conducted a retrospective study to create an endoscopic diagnostic index. METHODS We analyzed 51 FGAs in 41 patients and 36 HpN-GHPs in 24 patients. All lesions were photographed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). Three experts and three non-experts reviewed the WLE and WLE+NBIME images to assess six items for lesion diagnosis. We analyzed correlations between the diagnostic items and histologic features and compared the diagnostic accuracy between modalities. We created a composite diagnostic index and calculated its accuracy and consistency. RESULTS FGAs more frequently showed the following features vs. HpN-GHPs: bright-red color (94.1% vs. 44.4%), peripheral hyperplasia (58.8% vs. 8.3%), papillary/gyrus-like microstructure (96.1% vs. 33.3%), visible capillaries (70.6% vs. 38.9%), and demarcation line (98.0% vs. 41.7%) (P < 0.05). White-zone thickening was seen only in HpN-GHPs (52.8%). Diagnostic accuracy (mean, WLE vs. WLE+NBIME) was 90.8 ± 1.1% vs. 93.5 ± 2.4% (P = 0.15) for experts and 88.5 ± 3.0% vs. 86.6 ± 3.5% (P = 0.51) for non-experts. When satisfying the four criteria (bright-red color, papillary/gyrus-like microstructure, demarcation line, and absent white-zone thickening), sensitivity and specificity for FGA were 90.2% and 94.4%, respectively, with a kappa value of ≥ 0.6 for interobserver diagnostic agreement. CONCLUSIONS Composite diagnostic index contributes to the reproducible, accurate, preoperative differential diagnosis of FGA and HpN-GHP.
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Affiliation(s)
- Kotaro Shibagaki
- Department of Endoscopy, Shimane University Hospital, 89-1 Enya, Izumo, Shimane, 693-8501, Japan.
| | - Norihisa Ishimura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Satoshi Kotani
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Chika Fukuyama
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yusuke Takahashi
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kenichi Kishimoto
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Tomotaka Yazaki
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Masatoshi Kataoka
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Taisuke Omachi
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yasuhito Kinoshita
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Nobuaki Hasegawa
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Akihiko Oka
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yoshiyuki Mishima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Tsuyoshi Mishiro
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Naoki Oshima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kousaku Kawashima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Mamiko Nagase
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Asuka Araki
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kyuichi Kadota
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Shunji Ishihara
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
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Qin Y, Geng JX, Huang B. Clinical value of serum pepsinogen in the diagnosis and treatment of gastric diseases. World J Gastrointest Oncol 2023; 15:1174-1181. [PMID: 37546552 PMCID: PMC10401465 DOI: 10.4251/wjgo.v15.i7.1174] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/28/2023] [Accepted: 06/14/2023] [Indexed: 07/12/2023] Open
Abstract
Pepsinogen, secreted from the gastric mucosa, is the precursor of pepsin. It is categorized as pepsinogen 1 and pepsinogen 2 based on its immunogenicity. The pepsinogen content that can enter the blood circulation through the capillaries of the gastric mucosa is approximately 1% and remains stable all the time. The pepsinogen content in serum will change with the pathological changes of gastric mucosa. Therefore, the level of pepsinogen in serum can play a role in serologic biopsy to reflect the function and morphology of different regions of gastric mucosa and serve as an indicator of gastric disease. This study conducts relevant research on serum pepsinogen 1, pepsinogen 2, and the ratio of pepsinogen 1 to pepsinogen 2, and reviews their important value in clinical diagnosis of Helicobacter pylori infection, gastric ulcer, and even gastric carcinoma, providing ideas for other researchers.
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Affiliation(s)
- Yuan Qin
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Jia-Xin Geng
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Biao Huang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
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11
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Yamaguchi N, Sakaguchi T, Isomoto H, Inamine T, Tsukamoto R, Fukuda D, Ohnita K, Kanda T, Matsushima K, Hirayama T, Yashima K, Tsukamoto K. Polymorphism in autophagy-related genes LRP1 and CAPZA1 may promote gastric mucosal atrophy. Genes Environ 2023; 45:18. [PMID: 37198664 DOI: 10.1186/s41021-023-00274-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 04/27/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND Helicobacter pylori secretes cytotoxin-associated gene A (CagA) into the gastric epithelium, causing gastric mucosal atrophy (GMA) and gastric cancer. In contrast, host cells degrade CagA via autophagy. However, the association between polymorphisms in autophagy-related genes and GMA must be fully elucidated. RESULTS We evaluated the association between single nucleotide polymorphisms (SNPs) in autophagy-related genes (low-density lipoprotein receptor-related protein 1, LRP1; capping actin protein of muscle Z-line alpha subunit 1, CAPAZ1; and lysosomal-associated membrane protein 1, LAMP1) and GMA in 200 H. pylori-positive individuals. The frequency of the T/T genotype at rs1800137 in LRP1 was significantly lower in the GMA group than in the non-GMA group (p = 0.018, odds ratio [OR] = 0.188). The frequencies of the G/A or A/A genotype at rs4423118 and T/A or A/A genotype at rs58618380 of CAPAZ1 in the GMA group were significantly higher than those in the non-GMA group (p = 0.029 and p = 0.027, respectively). Multivariate analysis revealed that C/C or C/T genotype at rs1800137, T/A or A/A genotype at rs58618380, and age were independent risk factors for GMA (p = 0.038, p = 0.023, and p = 0.006, respectively). Furthermore, individuals with the rs1800137 C/C or C/T genotype of LRP1 had a 5.3-fold higher susceptibility to GMA. These genetic tests may provide future directions for precision medicine for individuals more likely to develop GMA. CONCLUSION LRP1 and CAPZA1 polymorphisms may be associated with the development of GMA.
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Affiliation(s)
- Naoyuki Yamaguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Takuki Sakaguchi
- Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, 683-8504, Japan.
| | - Hajime Isomoto
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
- Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, 683-8504, Japan.
| | - Tatsuo Inamine
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Ryoya Tsukamoto
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Daisuke Fukuda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
- Department of Surgical Oncology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
- Fukuda Yutaka Clinic, 3-5 Hamaguchi-machi, Nagasaki, 852-8107, Japan
| | - Ken Ohnita
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
- Shunkaikai Inoue Hospital, 6-12 Takara-machi, Nagasaki, 850-0045, Japan
| | - Tsutomu Kanda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
- Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Kayoko Matsushima
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Tatsuro Hirayama
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
| | - Kazuo Yashima
- Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, 683-8504, Japan
| | - Kazuhiro Tsukamoto
- Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
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12
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Mizutani S, Takahashi Y, Shimamoto T, Nakagawa H, Hisada H, Oshio K, Kubota D, Mizutani H, Ohki D, Sakaguchi Y, Yakabi S, Niimi K, Kakushima N, Tsuji Y, Wada R, Yamamichi N, Fujishiro M. Performing the ABC Method Twice for Gastric Cancer Risk Stratification: A Retrospective Study Based on Data from a Large-Scale Screening Facility. Diagnostics (Basel) 2023; 13:1284. [PMID: 37046502 PMCID: PMC10093546 DOI: 10.3390/diagnostics13071284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/20/2023] [Accepted: 03/26/2023] [Indexed: 03/31/2023] Open
Abstract
The ABC method is a classification method used for stratifying the risk of gastric cancer. However, whether the ABC method should be performed only once or multiple times throughout an individual's lifetime remains unclear. Therefore, this study aimed to analyze whether performing ABC screening twice in a lifetime is useful. We retrospectively analyzed the data of individuals who participated in health checkups in 2010 and 2015. We collected data on patient characteristics, pepsinogen levels, anti-Helicobacter pylori antibody titers, and the presence of gastric cancer. Overall, 7129 participants without a history of H. pylori eradication were included in this study. The participants' average age in 2010 was 48.4 ± 8.3 years, and 58.1% were male. In addition, 11 and 20 cases of new H. pylori infection (0.15%) and spontaneous eradication (0.28%), respectively, were recorded. No significant difference was found in the incidence of gastric cancer between participants who underwent the ABC method once and those who underwent it twice (Group A: 0.16% vs. 0.16%; Group B: 0.47% vs. 0.39%; and Group C + D: 1.97% vs. 1.82%). Therefore, performing the ABC method twice, 5 years apart, does not significantly improve gastric cancer risk stratification.
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Affiliation(s)
- Satoru Mizutani
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yu Takahashi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Takeshi Shimamoto
- Kameda Medical Center Makuhari CD 2F, 1-3 Nakase, Mihama-ku, Chiba-City, Chiba 261-8501, Japan
| | - Hideki Nakagawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Hiroyuki Hisada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Kaori Oshio
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Dai Kubota
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Hiroya Mizutani
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
- Next-Generation Endoscopic Computer Vision, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Daisuke Ohki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
- Infection Control and Prevention Service, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yoshiki Sakaguchi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Seiichi Yakabi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
- Center for International Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Keiko Niimi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
- Center for Epidemiology and Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Naomi Kakushima
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
- Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yosuke Tsuji
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
- Next-Generation Endoscopic Computer Vision, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Ryoichi Wada
- Kameda Medical Center Makuhari CD 2F, 1-3 Nakase, Mihama-ku, Chiba-City, Chiba 261-8501, Japan
| | - Nobutake Yamamichi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
- Center for Epidemiology and Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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13
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Tanaka S, Goto A, Yamagishi K, Iwasaki M, Yamaji T, Shimazu T, Iso H, Muraki I, Yasuda N, Saito I, Kato T, Aoyagi K, Arima K, Sakata K, Tanno K, Inoue M, Sawada N, Tsugane S. Long-term Response of Helicobacter pylori Antibody Titer After Eradication Treatment in Middle-aged Japanese: JPHC-NEXT Study. J Epidemiol 2023; 33:1-7. [PMID: 33907066 PMCID: PMC9727212 DOI: 10.2188/jea.je20200618] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is an established causative factor of gastric cancer. Although the expansion of insurance coverage has led to an increase in the number of patients treated for H. pylori, the population impact of eradication treatment for H. pylori has been scarcely investigated. This study aimed to clarify the long-term responses of H. pylori antibody titer after eradication treatment using large scale cross-sectional data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). METHODS A total of 55,282 Japanese participants aged 40 to 74 years residing in 16 areas provided blood samples from 2011 through 2016. From these, treated (n = 6,276) and untreated subjects who were seropositive for H. pylori or had serological atrophy (n = 22,420) formed the study population (n = 28,696). Seropositivity was defined as an anti-H. pylori IgG titer of ≥10 U/mL. Antibody level was compared among subjects according to self-reported treatment history as untreated, and treated for less than 1 year (<1Y), 1 through 5 years (1-5Y), and 6 or more years ago (6Y+). RESULTS Median serum antibody titer was 34.0 U/mL, 7.9 U/mL, 4.0 U/mL, and 2.9 U/mL for the untreated, <1Y, 1-5Y, and 6Y+ groups, respectively. While those treated for H. pylori within the previous year had a 76.8% lower antibody titer compared to untreated subjects, approximately 41% of subjects were still seropositive. CONCLUSION A significant reduction in H. pylori antibody titer occurs within 1 year after eradication treatment, but that a long period is needed to achieve complete negative conversion.
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Affiliation(s)
- Shiori Tanaka
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Atsushi Goto
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan,Department of Health Data Science, Graduate School of Data Science, Yokohama City University, Yokohama, Japan
| | - Kazumasa Yamagishi
- Department of Public Health Medicine, Faculty of Medicine, and Health Services Research and Development Center, University of Tsukuba, Ibaraki, Japan,Ibaraki Western Medical Center, Ibaraki, Japan
| | - Motoki Iwasaki
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Taiki Yamaji
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Taichi Shimazu
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Hiroyasu Iso
- Department of Public Health Medicine, Faculty of Medicine, and Health Services Research and Development Center, University of Tsukuba, Ibaraki, Japan,Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Isao Muraki
- Public Health, Department of Social Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Nobufumi Yasuda
- Department of Public Health, Kochi University Medical School, Kochi, Japan
| | - Isao Saito
- Department of Public Health and Epidemiology, Faculty of Medicine, Oita University, Oita, Japan
| | - Tadahiro Kato
- Center for Education and Educational Research, Faculty of Education, Ehime University, Ehime, Japan
| | - Kiyoshi Aoyagi
- Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kazuhiko Arima
- Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kiyomi Sakata
- Department of Hygiene and Preventive Medicine, Iwate Medical University, Iwate, Japan
| | - Kozo Tanno
- Department of Hygiene and Preventive Medicine, Iwate Medical University, Iwate, Japan
| | - Manami Inoue
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Norie Sawada
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
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14
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Nishizawa T, Yoshida S, Toyoshima A, Matsuno T, Sakitani K, Kato J, Ebinuma H, Fujishiro M, Suzuki H, Toyoshima O. Increasing trend of Helicobacter pylori-uninfected gastric cancer without gastric atrophy. J Clin Biochem Nutr 2022; 71:245-248. [PMID: 36447484 PMCID: PMC9701589 DOI: 10.3164/jcbn.22-56] [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: 05/23/2022] [Accepted: 05/28/2022] [Indexed: 09/19/2023] Open
Abstract
The prevalence of Helicobacter pylori (H. pylori) has decreased during several decades due to improvements in the sanitary environment in Japan. Consequently, a relative increase in the incidence of H. pylori-uninfected gastric cancer is expected. We analyzed the trends in H. pylori-uninfected gastric cancer. Two hundred fifty-eight patients with gastric cancer were retrospectively analyzed. The study was divided into four periods: 2008-2011 (first period), 2012-2014 (second period), 2015-2017 (third period), and 2018-2021 (fourth period). The status of H. pylori infection was divided into four categories: uninfected, successful eradication, spontaneous eradication, and persistent infection. Gastric mucosal atrophy was divided into six grades according to the Kimura-Takemoto classification. The proportion of H. pylori infections significantly changed over the study period (p = 0.007). In particular, the rate of H. pylori-uninfected gastric cancer tended to increase over time (0%, 2.9%, 4.9%, and 13.4% in the first, second, third, and fourth periods, respectively; p = 0.0013). The rate of no atrophy (C-0) in gastric cancer tended to increase over time (0%, 2.9%, 4.9%, and 11.0% in the first, second, third, and fourth periods, respectively; p = 0.0046). In conclusion, the rate of H. pylori-uninfected gastric cancer without gastric atrophy tended to increase over time.
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Affiliation(s)
- Toshihiro Nishizawa
- Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Narita Hospital, 852 Hatakeda, Narita, Chiba 286-8520, Japan
| | - Shuntaro Yoshida
- Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan
| | - Akira Toyoshima
- Department of Colorectal Surgery, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935, Japan
| | - Tatsuya Matsuno
- Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan
| | - Kosuke Sakitani
- Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan
- Department of Gastroenterology, Sakiatani Endoscopy Clinic, LoharuTsudanuma 4, 7-7-1 Yazu, Narashino, Chiba 275-0026, Japan
| | - Jun Kato
- Internal Medicine, Kato Medical Clinic, 2-22-11 Kitazawa, Setagaya-ku, Tokyo 155-0031, Japan
| | - Hirotoshi Ebinuma
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Narita Hospital, 852 Hatakeda, Narita, Chiba 286-8520, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
| | - Osamu Toyoshima
- Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan
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15
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Mishiro T, Shibagaki K, Fukuyama C, Kataoka M, Notsu T, Yamashita N, Oka A, Nagase M, Araki A, Kawashima K, Ishimura N, Maruyama R, Kinoshita Y, Ishihara S. KLF4 Mutation Shapes Pathologic Characteristics of Foveolar-Type Gastric Adenoma in Helicobacter pylori-Naive Patients. THE AMERICAN JOURNAL OF PATHOLOGY 2022; 192:1250-1258. [PMID: 35750256 DOI: 10.1016/j.ajpath.2022.06.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 06/03/2022] [Accepted: 06/08/2022] [Indexed: 11/20/2022]
Abstract
Along with a recent remarkable decrease in Helicobacter pylori-infected individuals, reports of gastric neoplasms such as sporadic foveolar-type gastric adenoma (FGA) in H. pylori-naive patients have been increasing. This tumor, with its raspberry-like appearance, is common in H. pylori-naive gastric mucosa. The current study investigated the genomic features of sporadic FGA. Fresh-frozen sporadic FGA tissue samples from H. pylori-naive patients were subjected to whole genome analysis using a next-generation sequencer. Proliferation ability and apoptotic profiles of human gastric epithelial cells, along with plasmid transfection of candidate variants, were examined. A mean of 6.65 × 108 total reads were obtained for each sample. Common genetic abnormalities in well-known proliferation driver genes of conventional gastric dysplasia/cancer were not found. However, a common single-nucleotide variation (SNV) was noted within the DNA-binding domain of the tumor suppressor gene KLF4. This novel SNV was located in the zinc finger 2 region. Additional experiments showed that it significantly suppressed proliferation of gastric epithelial cells compared with wild-type KLF4 plasmid-transfected cells, although suppression was reduced in early apoptotic phase-related genes. A novel SNV in the KLF4 zinc finger 2 region was commonly found in sporadic FGA tissue samples, which may explain the slow-growing properties of this neoplasm.
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Affiliation(s)
- Tsuyoshi Mishiro
- Department of Gastroenterology and Hepatology, Izumo, Shimane, Japan.
| | | | - Chika Fukuyama
- Department of Gastroenterology and Hepatology, Izumo, Shimane, Japan
| | - Masatoshi Kataoka
- Department of Gastroenterology and Hepatology, Izumo, Shimane, Japan
| | - Takumi Notsu
- Department of Gastroenterology and Hepatology, Izumo, Shimane, Japan
| | | | - Akihiko Oka
- Department of Gastroenterology and Hepatology, Izumo, Shimane, Japan
| | - Mamiko Nagase
- Organ Pathology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan
| | - Asuka Araki
- Organ Pathology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan
| | - Kousaku Kawashima
- Department of Gastroenterology and Hepatology, Izumo, Shimane, Japan
| | - Norihisa Ishimura
- Department of Gastroenterology and Hepatology, Izumo, Shimane, Japan
| | - Riruke Maruyama
- Organ Pathology, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan
| | - Yoshikazu Kinoshita
- Department of Medicine, Steel Memorial Hirohata Hospital, Himeji, Hyogo, Japan
| | - Shunji Ishihara
- Department of Gastroenterology and Hepatology, Izumo, Shimane, Japan
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16
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Negative-High Titer of Helicobacter pylori Antibody and Lipid Profiles. BIOMED RESEARCH INTERNATIONAL 2022; 2022:9984255. [PMID: 36017395 PMCID: PMC9398768 DOI: 10.1155/2022/9984255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 08/03/2022] [Indexed: 11/18/2022]
Abstract
Background. Helicobacter pylori (HP) is a causative factor for several gastrointestinal diseases. A HP seropositive antibody titer (i.e., ≥10 U/mL), a threshold indicating an HP infection, is known to be associated with changes in lipid metabolism. There is evidence that HP infection can be found in some individuals with HP antibody titer of between 3 and 9.9 U/mL (termed as “negative-high titer”). However, it is unknown about the relationship between HP negative-high titer and lipid metabolism. The present study aimed to quantify the association between HP negative-high antibody titer and lipid profiles. Materials and Methods. We surveyed 2,478 people who underwent a Ningen Dock examination and had serological HP antibody data, from May 2016 to December 2020 at National Center for Global Health and Medicine, Tokyo, Japan. Multiple regression models were used to quantify the association between HP antibody titer and serum lipid levels. Results. The adjusted odds ratio (95% confidence interval [CI]) for dyslipidemia in HP negative-high and positive titer was 1.24 (0.96, 1.79) and 1.36 (1.10, 1.68), respectively, compared with HP negative-low titer;
trend =0.005. The adjusted mean (95% CI) of high-density lipoprotein cholesterol (HDL-C) in HP negative-low, negative-high, and positive titer was 58.78 (57.86–59.71), 55.30 (53.70–56.91), and 53.76 (52.90–54.63) mg/dL, respectively;
trend <0.001. Higher HP antibody titers were also associated with higher ratio of low-density lipoprotein cholesterol (LDL-C) to HDL-C, but not triglycerides, or total cholesterols. Conclusion. The present cross-sectional study suggests that a HP negative-high antibody titer may be associated with dyslipidemia, HDL-C, and LDL-C to HDL-C ratio among Japanese Ningen Dock’s participants.
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17
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Kang S, Park M, Cho JY, Ahn SJ, Yoon C, Kim SG, Cho SJ. Tumorigenic mechanisms of estrogen and Helicobacter pylori cytotoxin-associated gene A in estrogen receptor α-positive diffuse-type gastric adenocarcinoma. Gastric Cancer 2022; 25:678-696. [PMID: 35391613 DOI: 10.1007/s10120-022-01290-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 03/09/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Diffuse-type gastric cancer (DGC), for which Helicobacter pylori infection is a causal factor, is associated with poor prognosis among young women, possibly due to female hormones such as estrogen. We aimed to identify the carcinogenesis induced by estrogen and H. pylori in DGC. METHODS We screened and selected estrogen receptor alpha (ERα)-positive (MKN45) and ERα-negative (SNU5) DGC cell lines. H. pylori strain 60190 and its isogenic mutant strain lacking cytotoxin-associated gene A (60190ΔCagA) were used to infect MKN45 cells. And the cytotoxin-related gene A (CagA) cDNA which was cloned into pSP65-SR-HA (cagA-pSP65SRa) vector was used to transfect MKN45 cells. Tumor samples were used for DGC organoid culture. RESULTS In MKN45 cells, we found that estradiol promotes epithelial-mesenchymal transition (EMT) and stemness phenotypes via HOTAIR expression. These effects were further enhanced by the addition of CagA secreted by H. pylori but were reversed by co-treatment with fulvestrant (ICI 182,780), a selective ER degrader. We also validated the effect of estrogen on DGC organoids. ERα expression was associated with tumor invasion and HOTAIR expression in DGC patients with overt H. pylori infection. CONCLUSIONS These findings may explain the rapid DGC progression in young women with physiologically high levels of estrogen and suggest that fulvestrant with ovarian function suppression could serve as a tumor-suppressive agent in premenopausal patients with DGC.
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Affiliation(s)
- Seungkyung Kang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Miree Park
- Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Jung Yeon Cho
- Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Su Jin Ahn
- Seoul National University College of Medicine, 103, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Changhwan Yoon
- Department of Surgery, Columbia University Irving Medical Center, 630 W. 168th St, New York, NY, 10032, USA
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea
| | - Soo-Jeong Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
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18
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Sijmons D, Guy AJ, Walduck AK, Ramsland PA. Helicobacter pylori and the Role of Lipopolysaccharide Variation in Innate Immune Evasion. Front Immunol 2022; 13:868225. [PMID: 35634347 PMCID: PMC9136243 DOI: 10.3389/fimmu.2022.868225] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 04/04/2022] [Indexed: 11/30/2022] Open
Abstract
Helicobacter pylori is an important human pathogen that infects half the human population and can lead to significant clinical outcomes such as acute and chronic gastritis, duodenal ulcer, and gastric adenocarcinoma. To establish infection, H. pylori employs several mechanisms to overcome the innate and adaptive immune systems. H. pylori can modulate interleukin (IL) secretion and innate immune cell function by the action of several virulence factors such as VacA, CagA and the type IV secretion system. Additionally, H. pylori can modulate local dendritic cells (DC) negatively impacting the function of these cells, reducing the secretion of immune signaling molecules, and influencing the differentiation of CD4+ T helper cells causing a bias to Th1 type cells. Furthermore, the lipopolysaccharide (LPS) of H. pylori displays a high degree of phase variation and contains human blood group carbohydrate determinants such as the Lewis system antigens, which are proposed to be involved in molecular mimicry of the host. Lastly, the H. pylori group of outer membrane proteins such as BabA play an important role in attachment and interaction with host Lewis and other carbohydrate antigens. This review examines the various mechanisms that H. pylori utilises to evade the innate immune system as well as discussing how the structure of the H. pylori LPS plays a role in immune evasion.
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Affiliation(s)
- Daniel Sijmons
- School of Science, RMIT University, Melbourne, VIC, Australia
| | - Andrew J. Guy
- School of Science, RMIT University, Melbourne, VIC, Australia
- ZiP Diagnostics, Collingwood, VIC, Australia
| | - Anna K. Walduck
- School of Science, RMIT University, Melbourne, VIC, Australia
| | - Paul A. Ramsland
- School of Science, RMIT University, Melbourne, VIC, Australia
- Department of Immunology, Monash University, Melbourne, VIC, Australia
- Department of Surgery, Austin Health, University of Melbourne, Heidelberg, VIC, Australia
- *Correspondence: Paul A. Ramsland,
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19
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Kayamba V, Kelly P. Introducing the Sanguis-Filum for Detection of Gastric Mucosal Lesions Prior to Endoscopy: A Study Protocol. Diagnostics (Basel) 2022; 12:1160. [PMID: 35626320 PMCID: PMC9139864 DOI: 10.3390/diagnostics12051160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/12/2022] [Accepted: 04/20/2022] [Indexed: 11/17/2022] Open
Abstract
Early diagnosis of gastric cancer (GC) is compromised by a lack of specific signs to enable identification of affected individuals. We designed the Sanguis-filum (S-filum) as a simple bedside tool that could be used to detect the presence of gastric mucosal lesions prior to endoscopy. We previously published evidence that at a sensitivity of 91%, the presence of free blood in the stomach was associated with mucosal lesions. The S-filum is made of an inert but absorbent string coiled up in a gelatin capsule (Capsuline, FL, USA), which can be swallowed and the string retrieved to test for free blood. Preliminary testing of the S-filum was successfully conducted on healthy volunteers. We now intend to test it on actual patients, comparing the results to oesophagogastroduodenoscopy (OGD) findings. This will enable us to determine the diagnostic accuracy of the S-filum at detecting GC and other mucosal lesions. The S-filum as a bedside tool has the potential to assist healthcare providers to identify individuals likely to have early gastric mucosal lesions and requiring OGD examination. The S-filum could, in the long run, facilitate population-wide screening for early GC prior to endoscopy.
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Affiliation(s)
- Violet Kayamba
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka P.O. Box 50398, Zambia;
| | - Paul Kelly
- Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka P.O. Box 50398, Zambia;
- Blizard Institute, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK
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20
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Shibagaki K, Itawaki A, Miyaoka Y, Kishimoto K, Takahashi Y, Kotani S, Mishiro T, Oshima N, Kawashima K, Ishimura N, Onuma H, Nagasaki M, Nagase M, Araki A, Kadota K, Kushima R, Ishihara S. Intestinal-type gastric dysplasia in Helicobacter pylori-naïve patients. Virchows Arch 2022; 480:783-792. [PMID: 34787713 DOI: 10.1007/s00428-021-03237-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/27/2021] [Accepted: 11/09/2021] [Indexed: 01/05/2023]
Abstract
Gastric dysplasia and gastric cancer in Helicobacter pylori (Hp)-naïve patients usually exhibit a gastric phenotype, reflecting gastric mucosa without intestinal metaplasia (IM). We showed that intestinal-type gastric dysplasia (IGD) rarely occurs in the Hp-naïve stomach. In the last 10 years, we treated 1760 gastric dysplasia and gastric cancer patients, with 3.6% (63/1760) being Hp-naïve. Among these, ten were diagnosed with 14 IGDs and enrolled in this retrospective analysis. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We analyzed their endoscopic and microscopic features and patient demographics. Five men and five women aged 64 ± 21 years were included. WLE showed the depressed lesions mimicking a benign raised erosion in the prepyloric compartment. Multiple growths were confirmed in 30% (3/10) of patients. NBIME showed a near-regular microstructure and capillaries in 50% (7/14) of lesions with a gastritis-like appearance. Histologically, background mucosa was non-atrophic pyloric gland tissue, but 40.0% of samples (4/10) contained sporadic IM. Most of the lesions (8/14) were low-grade dysplasia, and others had a high-grade component, with one progressing to intramucosal carcinoma. The neoplastic surface was widely covered with foveolar epithelium in 57.1% (8/14). Immunohistochemically, neoplastic cells expressed CDX2 in all patients (14/14), MUC2 and CD10 in 92.9% (13/14), MUC5AC in 14% (2/14), and no expression of MUC6, showing an intestinal phenotype. Ki-67 was overexpressed with a mean labeling index of 58.3 ± 38.5%, and p-53 was overexpressed in 92.9% (13/14), regardless of the dysplastic grade. The IGD rarely occurs in Hp-naïve patients with distinctive clinicopathologic characteristics.
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Affiliation(s)
- Kotaro Shibagaki
- Department of Endoscopy, Shimane University Hospital, Zip code 693-8501, 89-1 Enya, Izumo, Japan.
| | - Ayako Itawaki
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yoichi Miyaoka
- Department of Gastroenterology, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Kenichi Kishimoto
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yusuke Takahashi
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Satoshi Kotani
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Tsuyoshi Mishiro
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Naoki Oshima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kousaku Kawashima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Norihisa Ishimura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Hideyuki Onuma
- Department of Pathology, Shimane Prefectural Central Hospital, Izumo, Japan
| | - Makoto Nagasaki
- Department of Pathology, National Hospital Organization Hamada Medical Center, Hamada, Japan
| | - Mamiko Nagase
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Asuka Araki
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kyuichi Kadota
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Otsu, Japan
| | - Shunji Ishihara
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
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21
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Kishikawa H, Nakamura K, Ojiro K, Katayama T, Arahata K, Takarabe S, Sasaki A, Miura S, Hayashi Y, Hoshi H, Kanai T, Nishida J. Relevance of pepsinogen, gastrin, and endoscopic atrophy in the diagnosis of autoimmune gastritis. Sci Rep 2022; 12:4202. [PMID: 35273265 PMCID: PMC8913737 DOI: 10.1038/s41598-022-07947-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 02/28/2022] [Indexed: 02/07/2023] Open
Abstract
Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin, and endoscopic findings can predict AIG. The diagnostic performance of endoscopic findings and serology in distinguishing AIG was evaluated. AIG was diagnosed in patients (N = 31) with anti-parietal cell antibody and/or intrinsic factor antibody positivity and histological findings consistent with AIG. Non-AIG patients (N = 301) were seronegative for anti-parietal cell antibodies. Receiver operating characteristic curve analysis of the entire cohort (N = 332) identified an endoscopic atrophic grade cutoff point of O3 on the Kimura-Takemoto classification (area under the curve [AUC]: 0.909), while those of pepsinogen-I, I/II ratio, and gastrin were 20.1 ng/mL (AUC: 0.932), 1.8 (AUC: 0.913), and 355 pg/mL (AUC: 0.912), respectively. In severe atrophy cases (≥ O3, N = 58, AIG/control; 27/31), the cutoff values of pepsinogen-I, I/II ratio, and gastrin were 9.8 ng/mL (AUC: 0.895), 1.8 (AUC: 0.86), and 355 pg/mL (AUC: 0.897), respectively. In conclusion, endoscopic atrophy is a predictor of AIG. High serum gastrin and low pepsinogen-I and I/II ratio are predictors even in the case of severe atrophy, suggesting their usefulness when the diagnosis of AIG is difficult or as serological screening tests.
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Affiliation(s)
- Hiroshi Kishikawa
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan.
| | - Kenji Nakamura
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Keisuke Ojiro
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Tadashi Katayama
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Kyoko Arahata
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Sakiko Takarabe
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Aya Sasaki
- Department of Pathology and Laboratory Medicine, Ichikawa General Hospital, Tokyo Dental College, Ichikawa, Chiba, Japan
| | - Soichiro Miura
- Graduate School, International University of Health and Welfare, Minato-ku, Tokyo, Japan
| | - Yukie Hayashi
- Center for Diagnostic and Therapeutic Endoscopy, Keio University Hospital, Tokyo, Japan
| | - Hitomi Hoshi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University, Shinjuku-ku, Tokyo, Japan
| | - Jiro Nishida
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan
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22
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Seroreactivity against Helicobacter pylori VacA,50kDa and 30kDa along with alarm features may improve the diagnostic approach to uninvestigated dyspepsia: A pilot study. VOJNOSANIT PREGL 2022. [DOI: 10.2298/vsp200720134m] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background/Aim. Alarm features (AF) are of limited utility in predicting endoscopic findings, and the majority of patients with uninvestigated dyspepsia will have no organic pathology identified at upper gastrointestinal endoscopy. In our previous study, we highlighted seroreactivity against Helicobacter pylori (HP) antigens VacA, 50 kDa, and 30 kDa as biomarkers for gastric cancer, peptic ulcers, and functional dyspepsia. We designed and conducted this pi-lot study in order to compare the diagnostic utility of seroreactivity against HP VacA, 50 kDa, and 30 kDa with AF and investigate the possibility and adequacy of its synchronous application. Method. A careful history and physical examination with special attention to AF, esophagogastroduodenoscopy with biopsy, abdominal ultra-sound or computer tomography, complete blood count (CBC) and blood biochemistry, a Western Blot IgG against HP antigens VacA, 50 kDa, and 30 kDa, were per-formed in 123 patients with dyspepsia: 31 with gastric cancer, 31 with duodenal ulcer, 31 with gastric ulcer, and 30 with gastritis and functional dyspepsia. AF vs various combinations of seroreactivity against HP VacA, 50 kDa, and 30 kDa in patients with functional dyspepsia and others were analyzed in this study. Synchronous and alternative seroreactivity against VacA, 50 kDa, and 30 kDa, along with/without AF in patients with functional dyspepsia and other groups of patients were also analyzed. Results. VacA and 50 kDa seropositivity or AF had excellent case-findings clinical utility index for investigating dyspepsia. The absence of AF and seroreactivity against VacA either with: 50 kDa or 30 kDa seropositivity or 50 kDa and 30 kDa seropositivity had an excellent screening clinical utility index for investigating dyspepsia. Conclusion. Se-roreactivity against HP antigens VacA, 50 kDa, and 30 kDa might improve our approach to patients in investigating dyspepsia if used along with AF.
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23
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Cho JH, Jin SY, Park S. Scoring model for discriminating gastric cancer risk in patients with negative serum pepsinogen and anti-Helicobacter pylori antibody results. J Gastroenterol Hepatol 2021; 36:3345-3353. [PMID: 34328237 DOI: 10.1111/jgh.15630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/07/2021] [Accepted: 07/16/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND The ABC test measures serum pepsinogen and anti-Helicobacter pylori IgG antibody levels to predict precancerous conditions in the stomach and gastric cancer. However, a limitation of this test is that the gastric cancer risk is not negligible in patients with a negative result. METHODS Based on their ABC results, 1157 patients were classified into Groups A (n = 392), B (n = 479), C (n = 247), and D (n = 39). In Group A, 24.2% of patients had atrophic gastritis and/or intestinal metaplasia and had thus been incorrectly assigned to Group A. Patients in Group A were then assigned to derivation (n = 236) and validation (n = 156) cohorts by 3:2 random sampling. Logistic regression analyses were performed to identify the factors discriminating between a correct (true) and incorrect (false) Group A classification. RESULTS A 4-point discriminative model was constructed based on a high-negative H. pylori IgG antibody titer and the patient's age (50-64 and ≥65 years). The areas under the receiver operating characteristic curve for the derivation and validation cohorts were 0.868 and 0.894, respectively. In the validation cohort, the addition of a discriminative model score ≥2 to the ABC method showed a similar accuracy for predicting gastric cancer risk compared with the ABC method alone (93.8% vs. 92.4%). CONCLUSION The 4-point discriminative model may help identify patients with a normal serological test who are nonetheless at risk of developing gastric cancer.
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Affiliation(s)
- Jun-Hyung Cho
- Digestive Disease Center, Soonchunhyang University Hospital, Seoul, South Korea
| | - So-Young Jin
- Department of Pathology, Soonchunhyang University Hospital, Seoul, South Korea
| | - Suyeon Park
- Department of Medical Biostatistics, Soonchunhyang University Hospital, Seoul, South Korea
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24
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Shibagaki K, Mishiro T, Fukuyama C, Takahashi Y, Itawaki A, Nonomura S, Yamashita N, Kotani S, Mikami H, Izumi D, Kawashima K, Ishimura N, Nagase M, Araki A, Ishikawa N, Maruyama R, Kushima R, Ishihara S. Sporadic foveolar-type gastric adenoma with a raspberry-like appearance in Helicobacter pylori-naïve patients. Virchows Arch 2021; 479:687-695. [PMID: 34043063 DOI: 10.1007/s00428-021-03124-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 05/12/2021] [Accepted: 05/14/2021] [Indexed: 02/07/2023]
Abstract
Sporadic foveolar-type gastric adenoma (FGA) has been described as an extremely rare polyp that is whitish and flatly elevated. However, we recently found that sporadic FGA with a raspberry-like appearance (FGA-RA) is not rare in Helicobacter pylori (H. pylori)-naïve gastric mucosa. We endoscopically or surgically treated 647 patients with gastric epithelial neoplasms in the last 5 years, with 7.7% (50/647) being H. pylori-naïve. Among these, 43 FGA-RAs were diagnosed based on histologic and endoscopic features in 34 patients, who were all enrolled in this retrospective study. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We subsequently analyzed their endoscopic and microscopic features and patient characteristics. The patients were 22 males and 12 females aged 57±23 years (mean±2SD). WLE showed raspberry-like small polyps mimicking gastric hyperplastic polyps in the oxyntic gastric compartment (body/fundus). Multiple growths were confirmed in 20.6% (7/34) of the patients. NBIME revealed irregularly shaped papillary/gyrus-like microstructures with abnormal capillaries. Histologically, all lesions were intraepithelial neoplasms, and most of lesions (62.8%, 27/43) exhibited low-grade dysplasia. Immunohistochemically, neoplastic cells featured strong and diffuse MUC5AC expression, negative or very low MUC6 expression, and negative MUC2/CD10 expression. They also showed Ki-67 hyperexpression with a mean labeling index of 59.4±48.7%. The coexistence of fundic gland polyps in the background mucosa was significantly higher in multiple FGA-RA cases than in solitary cases (100% vs. 55.5%, P< 0.05). FGA-RA is a newly suggested histologic variant of sporadic FGA whose occurrence is not rare in daily endoscopic practice.
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Affiliation(s)
- Kotaro Shibagaki
- Department of Endoscopy, Faculty of Medicine, Shimane University, 693-8501, 89-1 Enya, Izumo, Japan.
| | - Tsuyoshi Mishiro
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Chika Fukuyama
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Yusuke Takahashi
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Ayako Itawaki
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Saya Nonomura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Noritsugu Yamashita
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Satoshi Kotani
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Hironobu Mikami
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Daisuke Izumi
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Kousaku Kawashima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Norihisa Ishimura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Mamiko Nagase
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Asuka Araki
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Noriyoshi Ishikawa
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Riruke Maruyama
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Otsu, Japan
| | - Shunji Ishihara
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
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25
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Tsukadaira T, Hayashi S, Ota H, Kobayashi N, Sekiguchi Y, Kodaira H, Matsumoto T, Horiuchi K, Negishi T, Kurahashi M. Prevalence, clinical features, and esophagogastroduodenoscopy (EGD) findings of non-Helicobacter pylori Helicobacter infection: A study of 50 cases at a single facility in Japan. Helicobacter 2021; 26:e12811. [PMID: 33908121 DOI: 10.1111/hel.12811] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 03/16/2021] [Accepted: 03/17/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM There are only a few reports of non-Helicobacter pylori Helicobacter (NHPH) gastritis in Japanese patients. We aimed to examine its prevalence, clinical features, and esophagogastroduodenoscopy (EGD) findings based on 50 patients encountered in one facility. MATERIALS AND METHODS Subjects were all patients who had undergone gastric mucosal biopsy endoscopically at Kenwakai Hospital for approximately 10 years. NHPH infection was diagnosed by microscopic findings of Giemsa staining performed on all specimens. PCR analysis of urease genes was performed to detect and identify NHPH, when informed consent was obtained. Helicobacter pylori-diagnostic tests were also performed. NHPH-infected patients were questioned about symptoms and animal contact. RESULTS NHPH gastritis was found in 50 of 3847 patients (1.30%). The percentage increased to 3.35% (30 of 896 patients) in the latter 2 years and 4 months with increasing recognition of its characteristic endoscopic findings by endoscopists. PCR analysis, performed in 30 patients, detected NHPH in 28 patients: 26 as Helicobacter suis and 2 as Helicobacter heilmanii/Helicobacter ailurogastricus. Helicobacter pylori-diagnostic tests were almost negative. However, anti-H. pylori antibody showed high-negative titer (3.0-9.9 U/ml) in 12. Of 50 patients (consisting of 49 men and 1 woman), almost all were asymptomatic, and 25 were keeping pets. Regarding EGD findings, in all 50 patients, "crack-like mucosa" and/or nodular gastritis was noted in gastric antrum, and regular arrangement of collecting venules (RAC) was noted in gastric corpus. None of the patients infected with NHPH were co-infected with H. pylori. CONCLUSIONS The prevalence was finally estimated to be approximately 3.35%. Helicobacter suis was the most common NHPH species. "Crack-like mucosa" and/or nodular gastritis in gastric antrum, RAC in gastric corpus, and H. pylori-negativity by H. pylori-diagnostic tests especially containing a high-negative titer of anti-H. pylori antibody may indicate NHPH infection.
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Affiliation(s)
| | | | - Hiroyoshi Ota
- Department of Biomedical Laboratory Sciences, Shinshu University School of Medicine, Matsumoto, Japan
| | | | | | | | - Takehisa Matsumoto
- Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Japan
| | - Kazuki Horiuchi
- Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan
| | - Tatsuya Negishi
- Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan
| | - Mari Kurahashi
- Department of Internal Medicine, Showainan General Hospital, Komagane, Japan
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26
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Polymorphisms in Pepsinogen C and miRNA Genes Associate with High Serum Pepsinogen II in Gastric Cancer Patients. Microorganisms 2021; 9:microorganisms9010126. [PMID: 33430456 PMCID: PMC7827830 DOI: 10.3390/microorganisms9010126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 01/03/2021] [Indexed: 12/18/2022] Open
Abstract
Background: Pepsinogen (PG) II (PGII) is a serological marker used to estimate the risk of gastric cancer but how PGII expression is regulated is largely unknown. It has been suggested that PGII expression, from the PGC (Progastricsin) gene, is regulated by microRNAs (miRNA), but how PGII levels vary with Helicobacter pylori (H. pylori) infection and miRNAs genotype remains unclear. Methods: Serum levels of PGI and PGII were determined in 80 patients with gastric cancer and persons at risk for gastric cancer (74 first-degree relatives of patients, 62 patients with autoimmune chronic atrophic gastritis, and 2 patients with dysplasia), with and without H. pylori infection. As control from the general population, 52 blood donors were added to the analyses. Associations between PGII levels and genetic variants in PGC and miRNA genes in these groups were explored based on H. pylori seropositivity and the risk for gastric cancer. The two-dimensional difference in gel electrophoresis (2D-DIGE) and the NanoString analysis of messenger RNA (mRNAs) from gastric cancer tissue were used to determine the pathways associated with increased PGII levels. Results: PGII levels were significantly higher in patients with gastric cancer, and in those with H. pylori infection, than in other patients or controls. A PGI/PGII ratio ≤ 3 was found better than PGI < 25 ng/mL to identify patients with gastric cancer (15.0% vs. 8.8%). For two genetic variants, namely rs8111742 in miR-Let-7e and rs121224 in miR-365b, there were significant differences in PGII levels between genotype groups among patients with gastric cancer (p = 0.02 and p = 0.01, respectively), but not among other study subjects. Moreover, a strict relation between rs9471643 C-allele with H. pylori infection and gastric cancer was underlined. Fold change in gene expression of mRNA isolated from gastric cancer tissue correlated well with polymorphism, H. pylori infection, increased PGII level, and pathway for bacteria cell entry into the host. Conclusions: Serum PGII levels depend in part on an interaction between H. pylori and host miRNA genotypes, which may interfere with the cut-off of PGI/PGII ratio used to identify persons at risk of gastric cancer. Results reported new findings regarding the relation among H. pylori, PGII-related host polymorphism, and genes involved in this interaction in the gastric cancer setting.
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Nishizawa T, Toyoshima O, Kondo R, Sekiba K, Tsuji Y, Ebinuma H, Suzuki H, Tanikawa C, Matsuda K, Koike K. The simplified Kyoto classification score is consistent with the ABC method of classification as a grading system for endoscopic gastritis. J Clin Biochem Nutr 2021; 68:101-104. [PMID: 33536719 PMCID: PMC7844658 DOI: 10.3164/jcbn.20-41] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 04/08/2020] [Indexed: 12/11/2022] Open
Abstract
The ABC method combined with Helicobacter pylori antibody and serum pepsinogen is a useful predictive method for stomach cancer. Kyoto classification is a new grading system for endoscopic gastritis. However, the consistency of the Kyoto score with the ABC method remains unclear. The Kyoto classification score, which ranges from 0 to 8, is based on the following findings: atrophy, intestinal metaplasia, diffuse redness, nodularity, and enlarged folds. Furthermore, we defined a simplified Kyoto classification score as the sum of scores of just atrophy and intestinal metaplasia. The association between the Kyoto classification score and the ABC method was analyzed using the Kruskal-Wallis and Steel-Dwass tests. A total of 307 subjects were enrolled. Kyoto classification scores were similar in groups B, C, and D, while scores in group A were significantly lower than those of the other groups. The simplified Kyoto classification score showed the same stepwise increase as the classification of the ABC method. In conclusion, unlike the Kyoto classification score, the simplified Kyoto score showed the same significant stepwise increase as the classification of the ABC method.
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Affiliation(s)
- Toshihiro Nishizawa
- Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Mita Hospital, Minato-ku, Tokyo 108-8329, Japan
| | - Osamu Toyoshima
- Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Ryo Kondo
- Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Kazuma Sekiba
- Gastroenterology, Toyoshima Endoscopy Clinic, 6-17-5 Seijo, Setagaya-ku, Tokyo 157-0066, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Yosuke Tsuji
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Hirotoshi Ebinuma
- Department of Gastroenterology and Hepatology, International University of Health and Welfare, Mita Hospital, Minato-ku, Tokyo 108-8329, Japan
| | - Hidekazu Suzuki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
| | - Chizu Tanikawa
- Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
| | - Koichi Matsuda
- Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
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Diagnosis of Helicobacter pylori infection: Progress and challenges. Enferm Infecc Microbiol Clin 2020; 38:407-409. [DOI: 10.1016/j.eimc.2020.09.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 09/03/2020] [Accepted: 09/17/2020] [Indexed: 02/07/2023]
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Kishino T, Oyama T, Tomori A, Takahashi A, Shinohara T. Usefulness and Limitations of a Serum Screening System to Predict the Risk of Gastric Cancer. Intern Med 2020; 59:1473-1480. [PMID: 32188803 PMCID: PMC7364258 DOI: 10.2169/internalmedicine.3521-19] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objective The aim of the present study was to evaluate the effectiveness and limitations of a serum screening system for predicting the risk of gastric cancer. Methods Serum pepsinogen I (PG I)/pepsinogen II (PG II) and Helicobacter pylori (HP) antibody levels were measured. Subjects were classified into four groupsaccording to their serological status (the ABC classification system). The grade of atrophic gastritis was assessed endoscopically. We evaluated gastric cancer detection rates according to the ABC classification system and the endoscopic grade of atrophy. Patients Individuals who underwent esophagogastroduodenoscopy (EGD) in a health check were prospectively enrolled in the present study. Results According to the ABC classification system, the gastric cancer detection rates in groups A, B, C, and D were 0.07% (4/6,105), 0.5% (8/1,739), 0.8% (16/2,010), and 1.1% (3/281), respectively. The gastric cancer detection rates in subjects with no atrophy, closed type (C-type) atrophy, and open type (O-type) atrophy were 0% (0/4,567), 0.2% (4/2,581), and 0.9% (27/2,987), respectively. In group A (HP(-)/PG(-)), the proportions of subjects with no atrophy, C-type atrophy, and O-type atrophy were 71.2%, 22.8%, and 6.0%, respectively. In group A, the gastric cancer detection rates in subjects with no atrophy, C-type atrophy, and O-type atrophy were 0%, 0.07%, and 0.8%, respectively. Conclusion The ABC classification system is useful for predicting the risk of gastric cancer. However, this system was limited in group A, which included individuals with a high risk of developing gastric cancer. An endoscopic diagnosis of atrophy may be more effective than the ABC classification system for predicting the risk of gastric cancer.
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Affiliation(s)
- Takaaki Kishino
- Department of Endoscopy, Saku Central Hospital Advanced Care Center, Japan
- Department of Gastroenterology and Hepatology, Center for Digestive and Liver Diseases, Nara City Hospital, Japan
| | - Tsuneo Oyama
- Department of Endoscopy, Saku Central Hospital Advanced Care Center, Japan
| | - Akihisa Tomori
- Department of Gastroenterology, Saku Central Hospital Advanced Care Center, Japan
| | - Akiko Takahashi
- Department of Endoscopy, Saku Central Hospital Advanced Care Center, Japan
| | - Tomoaki Shinohara
- Department of Gastroenterology, Saku Central Hospital Advanced Care Center, Japan
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Hideura E, Suehiro Y, Nishikawa J, Shuto T, Fujimura H, Ito S, Goto A, Hamabe K, Saeki I, Okamoto T, Higaki S, Fujii I, Suzuki C, Hoshida T, Matsumoto T, Takami T, Sakaida I, Yamasaki T. Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer. Cancers (Basel) 2020; 12:cancers12040789. [PMID: 32224873 PMCID: PMC7226141 DOI: 10.3390/cancers12040789] [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: 01/22/2020] [Revised: 03/21/2020] [Accepted: 03/24/2020] [Indexed: 12/24/2022] Open
Abstract
The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer.
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Affiliation(s)
- Eizaburou Hideura
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (E.H.); (H.F.); (S.I.); (A.G.); (K.H.); (I.S.); (T.O.); (T.T.); (I.S.)
| | - Yutaka Suehiro
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (T.H.); (T.M.); (T.Y.)
- Correspondence: (Y.S.); (J.N.); Tel.: +81-836-22-2337 (Y.S.); Fax: +81-836-22-2338 (Y.S.); Tel./Fax: +81-836-22-2835 (J.N.)
| | - Jun Nishikawa
- Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan;
- Correspondence: (Y.S.); (J.N.); Tel.: +81-836-22-2337 (Y.S.); Fax: +81-836-22-2338 (Y.S.); Tel./Fax: +81-836-22-2835 (J.N.)
| | - Takuya Shuto
- Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan;
| | - Hiroyuki Fujimura
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (E.H.); (H.F.); (S.I.); (A.G.); (K.H.); (I.S.); (T.O.); (T.T.); (I.S.)
| | - Shunsuke Ito
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (E.H.); (H.F.); (S.I.); (A.G.); (K.H.); (I.S.); (T.O.); (T.T.); (I.S.)
| | - Atsushi Goto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (E.H.); (H.F.); (S.I.); (A.G.); (K.H.); (I.S.); (T.O.); (T.T.); (I.S.)
| | - Kouichi Hamabe
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (E.H.); (H.F.); (S.I.); (A.G.); (K.H.); (I.S.); (T.O.); (T.T.); (I.S.)
| | - Issei Saeki
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (E.H.); (H.F.); (S.I.); (A.G.); (K.H.); (I.S.); (T.O.); (T.T.); (I.S.)
| | - Takeshi Okamoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (E.H.); (H.F.); (S.I.); (A.G.); (K.H.); (I.S.); (T.O.); (T.T.); (I.S.)
| | - Shingo Higaki
- Department of Gastroenterology, St. Hill Hospital, Ube 755-8505, Japan;
| | - Ikuei Fujii
- Ajisu Kyoritsu Hospital, Yamaguchi 754-1277, Japan; (I.F.); (C.S.)
| | - Chieko Suzuki
- Ajisu Kyoritsu Hospital, Yamaguchi 754-1277, Japan; (I.F.); (C.S.)
| | - Tomomi Hoshida
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (T.H.); (T.M.); (T.Y.)
| | - Toshihiko Matsumoto
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (T.H.); (T.M.); (T.Y.)
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (E.H.); (H.F.); (S.I.); (A.G.); (K.H.); (I.S.); (T.O.); (T.T.); (I.S.)
| | - Isao Sakaida
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (E.H.); (H.F.); (S.I.); (A.G.); (K.H.); (I.S.); (T.O.); (T.T.); (I.S.)
| | - Takahiro Yamasaki
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; (T.H.); (T.M.); (T.Y.)
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Kishikawa H, Ojiro K, Nakamura K, Katayama T, Arahata K, Takarabe S, Miura S, Kanai T, Nishida J. Previous Helicobacter pylori infection-induced atrophic gastritis: A distinct disease entity in an understudied population without a history of eradication. Helicobacter 2020; 25:e12669. [PMID: 31680399 PMCID: PMC7003427 DOI: 10.1111/hel.12669] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 09/29/2019] [Accepted: 10/03/2019] [Indexed: 02/06/2023]
Abstract
Individuals with chronic atrophic gastritis who are negative for active H. pylori infection with no history of eradication therapy have been identified in clinical practice. By excluding false-negative and autoimmune gastritis cases, it can be surmised that most of these patients have experienced unintentional eradication of H. pylori after antibiotic treatment for other infectious disease, unreported successful eradication, or H. pylori that spontaneously disappeared. These patients are considered to have previous H. pylori infection-induced atrophic gastritis. In this work, we define these cases based on the following criteria: absence of previous H. pylori eradication; atrophic changes on endoscopy or histologic confirmation of glandular atrophy; negative for a current H. pylori infection diagnosed in the absence of proton-pump inhibitors or antibiotics; and absence of localized corpus atrophy, positivity for autoantibodies, or characteristic histologic findings suggestive of autoimmune gastritis. The risk of developing gastric cancer depends on the atrophic grade. The reported rate of developing gastric cancer is 0.31%-0.62% per year for successfully eradicated severely atrophic cases (pathophysiologically equal to unintentionally eradicated cases and unreported eradicated cases), and 0.53%-0.87% per year for spontaneously resolved cases due to severe atrophy. Therefore, for previous H. pylori infection-induced atrophic gastritis cases, we recommend endoscopic surveillance every 3 years for high-risk patients, including those with endoscopically severe atrophy or intestinal metaplasia. Because of the difficulty involved in the endoscopic diagnosis of gastric cancer in cases of previous infection, appropriate monitoring of the high-risk subgroup of this understudied population is especially important.
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Affiliation(s)
- Hiroshi Kishikawa
- Department of GastroenterologyIchikawa General HospitalTokyo Dental CollegeIchikawaChibaJapan
| | - Keisuke Ojiro
- Department of GastroenterologyIchikawa General HospitalTokyo Dental CollegeIchikawaChibaJapan
| | - Kenji Nakamura
- Department of GastroenterologyIchikawa General HospitalTokyo Dental CollegeIchikawaChibaJapan
| | - Tadashi Katayama
- Department of GastroenterologyIchikawa General HospitalTokyo Dental CollegeIchikawaChibaJapan
| | - Kyoko Arahata
- Department of GastroenterologyIchikawa General HospitalTokyo Dental CollegeIchikawaChibaJapan
| | - Sakiko Takarabe
- Department of GastroenterologyIchikawa General HospitalTokyo Dental CollegeIchikawaChibaJapan
| | - Soichiro Miura
- Graduate SchoolInternational University of Health and WelfareMinato‐kuTokyoJapan
| | - Takanori Kanai
- Department of Internal MedicineDivision of Gastroenterology and HepatologyKeio UniversityShinjyuku‐kuTokyoJapan
| | - Jiro Nishida
- Department of GastroenterologyIchikawa General HospitalTokyo Dental CollegeIchikawaChibaJapan
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Inoue M, Sawada N, Goto A, Shimazu T, Yamaji T, Iwasaki M, Tsugane S. High-Negative Anti–Helicobacter pylori IgG Antibody Titers and Long-Term Risk of Gastric Cancer: Results from a Large-Scale Population-Based Cohort Study in Japan. Cancer Epidemiol Biomarkers Prev 2019; 29:420-426. [DOI: 10.1158/1055-9965.epi-19-0993] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/04/2019] [Accepted: 12/03/2019] [Indexed: 01/11/2023] Open
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Shibagaki K, Fukuyama C, Mikami H, Izumi D, Yamashita N, Mishiro T, Oshima N, Ishimura N, Sato S, Ishihara S, Nagase M, Araki A, Ishikawa N, Maruyama R, Kushima R, Kinoshita Y. Gastric foveolar-type adenomas endoscopically showing a raspberry-like appearance in the Helicobacter pylori -uninfected stomach. Endosc Int Open 2019; 7:E784-E791. [PMID: 31198840 PMCID: PMC6561766 DOI: 10.1055/a-0854-3818] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 12/13/2018] [Indexed: 02/06/2023] Open
Abstract
Background and study aims Foveolar-type adenoma is described as a very rare tumor that occurs in individuals without Helicobacter pylori (HP) infection and diagnosed as adenocarcinoma in the Japanese Classification of Gastric Carcinoma (JCGC). However, we have frequently encountered patients with foveolar-type adenoma that endoscopically resembles a hyperplastic polyp, suggesting that it has just been overlooked to date. Here, we analyzed clinicopathological characteristics of a special subtype of foveolar-type adenoma showing specific endoscopic findings. Patients and methods From a total of 212 patients with gastric cancer resected during a 22-month period, we enrolled 14 (6.6 %) diagnosed with foveolar-type adenoma (adenocarcinoma in JCGC). HP infection status was determined by eradication history, HP serum IgG antibody level, urea breath test, and endoscopic and histological findings. All lesions were observed using white-light endoscopy and narrow-band imaging with magnification endoscopy (NBIME). Endoscopically resected lesions were histologically examined. Results None of 14 patients had a current or past history of HP infection. All lesions were visualized on non-atrophic gastric mucosa as small reddish protrusions with fine granular surface, showing a raspberry-like appearance. NBIME showed papillary or gyrus-like microstructures with irregular capillary. Lesions were histologically diagnosed as foveolar-type adenoma showing MUC5AC-positive gastric mucin phenotype. Ki-67 was overexpressed (median labeling index 69.9 %, range 28.4 - 92.1 %), though all lesions were an intraepithelial tumor without stromal invasion. p53 over-staining was not seen in any. Conclusions Raspberry-like lesions on non-atrophic gastric mucosa in HP-uninfected individuals should be evaluated for the possibility of a special subtype of foveolar-type adenoma.
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Affiliation(s)
- Kotaro Shibagaki
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Chika Fukuyama
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Hironobu Mikami
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Daisuke Izumi
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Noritsugu Yamashita
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Tsuyoshi Mishiro
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Naoki Oshima
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Norihisa Ishimura
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Shuichi Sato
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Shunji Ishihara
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Mamiko Nagase
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Asuka Araki
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Noriyoshi Ishikawa
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Riruke Maruyama
- Department of Pathology, Faculty of Medicine, Shimane University, Izumo, Japan
| | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Otsu, Japan
| | - Yoshikazu Kinoshita
- Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan
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Nishizawa T, Sakitani K, Suzuki H, Yamakawa T, Takahashi Y, Yamamichi N, Watanabe H, Seto Y, Koike K, Toyoshima O. A combination of serum anti- Helicobacter pylori antibody titer and Kyoto classification score could provide a more accurate diagnosis of H pylori. United European Gastroenterol J 2019; 7:343-348. [PMID: 31019702 PMCID: PMC6466756 DOI: 10.1177/2050640619825947] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 12/15/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND We previously showed that the endoscopic Kyoto classification for gastritis could predict Helicobacter pylori infection in individuals with a high negative titer of serum anti-H pylori antibodies. This study evaluated H pylori infection and the Kyoto classification score in patients with a low negative titer (<3 U/ml), high negative titer (3-9.9 U/ml), low positive titer (10-49.9 U/ml), and high positive titer (≥50 U/ml). METHODS Serum antibody levels, Kyoto classification score and histology were investigated in 870 individuals with no history of H pylori-eradication therapy. Urea breath tests (UBTs) were additionally conducted for patients with a low negative titer and a Kyoto score ≥1 or an antibody titer ≥10 U/ml and a Kyoto score of 0 or 1. UBTs and/or histological studies were conducted for participants with a high negative titer. RESULTS False diagnoses based on anti-H pylori antibody titers were observed in 0.3% of the low-negative-titer group, 11.7% of the high-negative-titer group, 18.9% of the low-positive-titer group and 2.2% of the high-positive-titer group. Surprisingly, false diagnoses based on antibody titers were noted in 63.2% of patients with a low positive titer and a Kyoto score of 0 and in 62.5% of patients with a high negative titer and a Kyoto score ≥2, respectively. CONCLUSIONS Endoscopic findings could predict false diagnoses determined using serum antibody titers.
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Affiliation(s)
- Toshihiro Nishizawa
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan
| | - Kosuke Sakitani
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidekazu Suzuki
- Medical Education Center, Keio University School of Medicine, Tokyo, Japan
| | | | | | - Nobutake Yamamichi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | | - Yasuyuki Seto
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Chen XZ, Huang CZ, Hu WX, Liu Y, Yao XQ. Gastric Cancer Screening by Combined Determination of Serum Helicobacter pylori Antibody and Pepsinogen Concentrations: ABC Method for Gastric Cancer Screening. Chin Med J (Engl) 2018; 131:1232-1239. [PMID: 29722342 PMCID: PMC5956776 DOI: 10.4103/0366-6999.231512] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objective: Gastroscopy combined with gastric mucosa biopsies is currently regarded as a gold standard for diagnosis of gastric cancer. However, its application is restricted in clinical practice due to its invasive property. A new noninvasive population screening process combining the assay of anti-Helicobacter pylori antibody and serum pepsinogen (PG) (ABC method) is adopted to recognize the high-risk patients for further endoscopy examination, avoiding the unnecessary gastroscopy for most population and saving the cost consumption for mass screening annually. Nevertheless, controversies exist for the grouping of ABC method and the intervals of gastroscopy surveillance for each group. In this review, we summarized these popular concerned topics for providing useful references to the healthcare practitioner in clinical practice. Data Sources: The PubMed databases were systematically searched from the inception dates to November 22, 2017, using the keywords “Helicobacter pylori,” “Pepsinogens,” and “Stomach Neoplasms.” Study Selection: Original articles and reviews on the topics were selected. Results: Anti-H. pylori antibody and serum PG concentration showed significant changes under the different status of H. pylori infection and the progression of atrophic gastritis, which can be used for risk stratification of gastric cancer in clinic. In addition, anti-H. pylori antibody titer can be used for further risk stratification of gastric cancer contributing to determine better endoscopy surveillance interval. Conclusions: The early detection and diagnosis of gastric cancer benefit from the risk stratification, but the cutoff values for H. pylori antibody and serum PG concentration require further modification.
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Affiliation(s)
- Xian-Zhe Chen
- Second Clinical Medical College, Southern Medical University, Guangzhou, Guangdong 510515; Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
| | - Cheng-Zhi Huang
- Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080; Medical College, Shantou University, Shantou, Guangdong 515063, China
| | - Wei-Xian Hu
- Second Clinical Medical College, Southern Medical University, Guangzhou, Guangdong 510515; Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
| | - Ying Liu
- Reproductive Department, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
| | - Xue-Qing Yao
- Second Clinical Medical College, Southern Medical University, Guangzhou, Guangdong 510515; Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China
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Toyoshima O, Nishizawa T, Sakitani K, Yamakawa T, Takahashi Y, Yamamichi N, Hata K, Seto Y, Koike K, Watanabe H, Suzuki H. Serum anti- Helicobacter pylori antibody titer and its association with gastric nodularity, atrophy, and age: A cross-sectional study. World J Gastroenterol 2018; 24:4061-4068. [PMID: 30254410 PMCID: PMC6148426 DOI: 10.3748/wjg.v24.i35.4061] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 08/02/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To clarify the role of serum anti-Helicobacter pylori (H. pylori) antibody titers in gastric cancer. METHODS In this cross-sectional study, the effect of patients' baseline characteristics and endoscopic findings on their serum antibody titers were assessed. We evaluated consecutive patients who underwent esophagogastroduodenoscopy and their first evaluation for H. pylori infection using a serum antibody test. We excluded patients with a history of eradication therapy. The participants were divided into four groups according to their E-plate serum antibody titer. Patients with serum antibody titers < 3, 3-9.9, 10-49.9, and ≥ 50 U/mL were classified into groups A, B, C, and D, respectively. RESULTS In total, 874 participants were analyzed with 70%, 16%, 8.7%, and 5.1% of them in the groups A, B, C, and D, respectively. Patients in group C were older than patients in groups A and B. Gastric open-type atrophy, intestinal metaplasia, enlarged folds, diffuse redness, and duodenal ulcers were associated with a high titer. Regular arrangements of collecting venules, fundic gland polyps, superficial gastritis, and gastroesophageal reflux disease were related to a low titer. Multivariate analysis revealed that nodularity (P = 0.0094), atrophy (P = 0.0076), and age 40-59 years (vs age ≥ 60 years, P = 0.0090) were correlated with a high serum antibody titer in H. pylori-infected patients. Intestinal metaplasia and atrophy were related to age ≥ 60 years in group C and D. CONCLUSION Serum antibody titer changes with age, reflects gastric mucosal inflammation, and is useful in predicting the risk of gastric cancer.
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Affiliation(s)
- Osamu Toyoshima
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 157-0066, Japan
| | | | - Kosuke Sakitani
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 157-0066, Japan
| | | | | | - Nobutake Yamamichi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | | | - Hidekazu Suzuki
- Medical Education Center, Keio University School of Medicine, Tokyo 160-8582, Japan
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Sakitani K, Nishizawa T, Arita M, Yoshida S, Kataoka Y, Ohki D, Yamashita H, Isomura Y, Toyoshima A, Watanabe H, Iizuka T, Saito Y, Fujisaki J, Yahagi N, Koike K, Toyoshima O. Early detection of gastric cancer after Helicobacter pylori eradication due to endoscopic surveillance. Helicobacter 2018; 23:e12503. [PMID: 29924436 PMCID: PMC6055630 DOI: 10.1111/hel.12503] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Helicobacter pylori eradication therapy is commonly performed to reduce the incidence of gastric cancer. However, gastric cancer is occasionally discovered even after successful eradication therapy. Therefore, we examined the prognosis of gastric cancer patients, diagnosed after successful H. pylori eradication therapy. MATERIALS AND METHODS All-cause death rates and gastric cancer-specific death rates in gastric cancer patients who received successful H. pylori eradication treatment was tracked and compared to rates in patients who did not receive successful eradication therapy. RESULTS In total, 160 gastric cancer patients were followed-up for up to 11.7 years (mean 3.5 years). Among them, 53 gastric cancer patients received successful H. pylori eradication therapy prior to gastric cancer diagnosis. During the follow-up period, 11 all-cause deaths occurred. In the successful eradication group, the proportion of patients with cancer stage I was higher. The proportions of patients who received curative endoscopic therapy and endoscopic examination in the 2 years prior to gastric cancer diagnosis were also higher in the successful eradication group. Kaplan-Meier analysis of all-cause death and gastric cancer-specific death revealed a lower death rate in patients in the successful eradication group (P = .0139, and P = .0396, respectively, log-rank test). The multivariate analysis showed that endoscopy within 2 years before cancer diagnosis is associated with stage I cancer. CONCLUSIONS Possible early discovery of gastric cancer after H. pylori eradication due to regular endoscopic surveillance may contribute to better prognosis of patients with gastric cancer.
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Affiliation(s)
- Kosuke Sakitani
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- The Institute for Adult DiseasesAsahi Life FoundationTokyoJapan
| | - Toshihiro Nishizawa
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of GastroenterologyTokyo Medical CenterNational Hospital OrganizationTokyoJapan
| | - Masahide Arita
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
| | - Shuntaro Yoshida
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Yosuke Kataoka
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Daisuke Ohki
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Hiroharu Yamashita
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of Gastrointestinal SurgeryGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Yoshihiro Isomura
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of GastroenterologyKanto Central HospitalTokyoJapan
| | - Akira Toyoshima
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
- Department of Colorectal SurgeryJapanese Red Cross Medical CenterTokyoJapan
| | | | - Toshiro Iizuka
- Department of GastroenterologyToranomon HospitalTokyoJapan
| | - Yutaka Saito
- Endoscopy DivisionNational Cancer Center HospitalTokyoJapan
| | - Junko Fujisaki
- Department of GastroenterologyCancer Institute HospitalTokyoJapan
| | - Naohisa Yahagi
- Division of Research and Development for Minimally Invasive TreatmentCancer CenterKeio University School of MedicineTokyoJapan
| | - Kazuhiko Koike
- Department of GastroenterologyGraduate School of MedicineThe University of TokyoTokyoJapan
| | - Osamu Toyoshima
- Department of GastroenterologyToyoshima Endoscopy ClinicTokyoJapan
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Chinda D, Shimoyama T, Mikami T, Arai T, Chiba D, Sasaki Y, Komai K, Sawada Y, Saito Y, Chiba H, Fukuda S. Serum pepsinogen levels indicate the requirement of upper gastrointestinal endoscopy among Group A subjects of ABC classification: a multicenter study. J Gastroenterol 2018; 53:924-931. [PMID: 29353347 DOI: 10.1007/s00535-018-1431-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 01/10/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND ABC classification has been used to assess the risk for gastric cancer. The current problem of ABC classification is that Group A contains individuals with current and past H. pylori infection. The aims of this study were to assesse the proportion of current and past infection in Group A and to establish a criteria for the identification of subjects with past infection from Group A subjects with negative results of urea breath test (UBT) and/or stool antigen test. METHODS 201 subjects classified into Group A received UBT and/or stool antigen test, and also subsequent upper gastrointestinal endoscopy. The subjects were classified by the status of H. pylori infection defined by endoscopic findings. Levels of pepsinogen (PG) I, PG II and PG I/II ratio were compared between the groups, and receiver operating characteristic curves were constructed to extract the corresponding cutoff values. RESULTS 22 subjects were tested positive by UBT and/or stool antigen test. Endoscopic images of 157 out of 179 subjects were studied. 15 of the subjects were regarded to have past H. pylori infection. The optimal cut-off value of PG I and PG I/II ratio for the determination of past H. pylori infection were ≤ 31.2 ng/mL and ≤ 4.6, respectively. CONCLUSIONS Approximately 20% of Group A subjects have current or past H. pylori infection. Addition of UBT and/or stool antigen test can identify current but not past infection. Serum PG levels would be useful to identify subjects with past H. pylori infection.
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Affiliation(s)
- Daisuke Chinda
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan
| | - Tadashi Shimoyama
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
| | - Tatsuya Mikami
- Division of Endoscopy, Hirosaki University Hospital, Hirosaki, Japan
| | - Tetsu Arai
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan
| | - Daisuke Chiba
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan
| | - Yoshio Sasaki
- Sasaki Clinic of Gastroenterology and Internal Medicine, Aomori, Japan
| | - Kazuo Komai
- Komai Clinic of Gastroenterology and Internal Medicine, Aomori, Japan
| | | | - Yoshiharu Saito
- Shinjo Clinic of Gastroenterology and Internal Medicine, Aomori, Japan
| | - Hironobu Chiba
- Chiba Clinic of Gastroenterology and Internal Medicine, Hirosaki, Japan
| | - Shinsaku Fukuda
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan
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Lee JY, Gong EJ, Chung EJ, Park HW, Bae SE, Kim EH, Kim J, Do YS, Kim TH, Chang HS, Song HJ, Choe J, Jung HY. The Characteristics and Prognosis of Diffuse-Type Early Gastric Cancer Diagnosed during Health Check-Ups. Gut Liver 2018; 11:807-812. [PMID: 28798286 PMCID: PMC5669596 DOI: 10.5009/gnl17033] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Revised: 03/09/2017] [Accepted: 03/12/2017] [Indexed: 12/17/2022] Open
Abstract
Background/Aims Because of the poor prognosis of diffuse-type gastric cancer, early detection is important. We investigated the clinical characteristics and prognosis of diffuse-type early gastric cancer (EGC) diagnosed in subjects during health check-ups. Methods Among 121,111 subjects who underwent gastroscopy during a routine health check-up, we identified 282 patients with 286 EGC lesions and reviewed their clinical and tumor-specific parameters. Results Patients with diffuse-type EGC were younger, and 48.1% of them were female. Serum anti-Helicobacter pylori IgG (Hp-IgG) was positive in 90.7% of diffuse-type EGC patients (vs 75.9% of intestinal-type EGC, p=0.002), and the proportion of diffuse-type EGC cases increased significantly with increasing Hp-IgG serum titers (p<0.001). Diffuse-type EGC had pale discolorations on the tumor surface (26.4% vs 4.0% in intestinal-type EGC, p<0.001) and were often located in the middle third of the stomach. Submucosal invasion or regional nodal metastasis was observed more commonly in patients with diffuse-type EGC. However, during the median follow-up period of 50 months, 5-year disease-free survival rates did not differ between the groups. Conclusions Diffuse-type EGC shows different clinical and endoscopic characteristics. Diffuse-type EGC is more closely associated with Hp-IgG seropositivity and a higher serum titer. Early detection results in excellent prognosis.
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Affiliation(s)
- Ji Young Lee
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Ju Chung
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hye Won Park
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suh Eun Bae
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Hee Kim
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jaeil Kim
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yoon Suh Do
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae Hyup Kim
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hye-Sook Chang
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ho June Song
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jaewon Choe
- Health Screening and Promotion Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Toyoshima O, Nishizawa T, Arita M, Kataoka Y, Sakitani K, Yoshida S, Yamashita H, Hata K, Watanabe H, Suzuki H. Helicobacter pylori infection in subjects negative for high titer serum antibody. World J Gastroenterol 2018; 24:1419-1428. [PMID: 29632423 PMCID: PMC5889822 DOI: 10.3748/wjg.v24.i13.1419] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Revised: 03/13/2018] [Accepted: 03/18/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the clinicopathological features of the patients testing negative for high titer serum anti-Helicobacter pylori (H. pylori) antibody. METHODS The antibody titers were measured using antigens derived from Japanese individuals. 13C-urea breath test-positive individuals were defined as having H. pylori infection. We investigated the demographic characteristics, laboratory data, endoscopic findings including Kyoto classification of gastritis, and histology in negative-high titer patients without H. pylori eradication therapy. Kyoto classification consisted of scores for gastric atrophy, intestinal metaplasia, enlarged folds, nodularity, and redness. RESULTS Of the 136 subjects enrolled, 23 (17%) had H. pylori infection. Kyoto classification had an excellent area under the receiver operating characteristics curve (0.886, 95% confidence interval: 0.803-0.968, P = 3.7 × 10-20) for predicting H. pylori infection with a cut-off value of 2. Further, Kyoto classification, H. pylori density, and neutrophil activity had high accuracies (89.7%, 96.3%, and 94.1%, respectively). Kyoto classification was independent of the demographic and laboratory parameters in multivariate analysis. CONCLUSION Endoscopic Kyoto classification of gastritis is a useful predictor of H. pylori infection in negative-high titer antibody patients.
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Affiliation(s)
- Osamu Toyoshima
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 1570066, Japan
| | - Toshihiro Nishizawa
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 1570066, Japan
| | - Masahide Arita
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 1570066, Japan
| | - Yosuke Kataoka
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 1570066, Japan
| | - Kosuke Sakitani
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 1570066, Japan
| | - Shuntaro Yoshida
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 1570066, Japan
| | - Hiroharu Yamashita
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 1570066, Japan
| | - Keisuke Hata
- Department of Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo 1570066, Japan
| | - Hidenobu Watanabe
- Department of Pathology, Pathology and Cytology Laboratory Japan, Tokyo 1660003, Japan
| | - Hidekazu Suzuki
- Medical Education Center, Keio University School of Medicine, Tokyo 1608582, Japan
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Characteristics of non-cardia gastric cancer with a high serum anti-Helicobacter pylori IgG titer and its association with diffuse-type histology. PLoS One 2018; 13:e0195264. [PMID: 29621300 PMCID: PMC5886523 DOI: 10.1371/journal.pone.0195264] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Accepted: 03/19/2018] [Indexed: 12/13/2022] Open
Abstract
Background Data on implications of a high positive titer of serum anti-Helicobacter pylori antibody on gastric cancer (GC) is limited. This study aimed to investigate the characteristics of GC with a high serum anti-H. pylori IgG (Hp-IgG) titer, and its association with diffuse-type GC. Methods We analyzed clinical and histological characteristics of 917 non-cardia GC patients who underwent gastrectomy. H. pylori infection was determined serologically by measuring Hp-IgG titer with immunoassay. Seropositive patients were divided into three groups (low-positive, mid-positive, and high-positive) according to the Hp-IgG titer value. Tumors were classified according to the Lauren criteria as diffuse or intestinal types. Results The median age of the patients was 59.0 years, and 33.8% were female. The patents were grouped as follows: seronegative, 188 (20.5%); low-positive, 288 (31.4%); mid-positive, 290 (31.6%); and high-positive 151 (16.5%). The high-positive group was significantly younger (median age, 55.0 years), with a higher proportion of female (45.0%) and non-smokers (58.9%). The proportion of diffuse-type GC increased in the order low-, mid-, and high-positive groups (p<0.001). In univariate analysis, the factors associated with diffuse-type GC were younger age, female sex, non-smokers, and a high-positive Hp-IgG titer. Younger age, female sex, and non-smokers remained significant on multivariate analysis whereas the high-positive Hp-IgG titer showed only a tendency toward the association (p = 0.078). Conclusions Non-cardia GC patients with a high Hp-IgG titer have distinct clinicopathologic characteristics. A high-positive Hp-IgG titer should be interpreted together with patients’ age, sex, and smoking status.
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Song M, Camargo MC, Weinstein SJ, Murphy G, Freedman ND, Koshiol J, Stolzenberg-Solomon RZ, Abnet CC, Männistö S, Albanes D, Rabkin CS. Serum pepsinogen 1 and anti-Helicobacter pylori IgG antibodies as predictors of gastric cancer risk in Finnish males. Aliment Pharmacol Ther 2018; 47:494-503. [PMID: 29243850 PMCID: PMC5776724 DOI: 10.1111/apt.14471] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 10/29/2017] [Accepted: 11/23/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Serum pepsinogen 1 (SPG1) and anti-Helicobacter pylori serology have been used for gastric risk stratification in Asia. AIM To assess utility of these markers in a Western population. METHODS SPG1 measurements were available for 21 895 Finnish male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We used Cox proportional hazards models adjusted for potential confounders to estimate gastric cancer hazard ratios (HR) and 95% confidence intervals (95% CI) for low SPG1 (<25 μg/L). In a subset (n = 3555) with anti-H. pylori serology, these markers jointly defined the following: Group A (H. pylori[-], SPG1[normal]; reference group), Group B (H. pylori[+], SPG1[normal]), Group C (H. pylori[+], SPG1[low]) and Group D (H. pylori[-], SPG1[low]). Odds ratios (ORs) and 95% CI were calculated using multivariate logistic regression. RESULTS There were 329 gastric cancers diagnosed an average of 13.9 years after baseline. Pre-diagnostic low SPG1 was significantly associated with increased gastric cancer risk (HR 2.68, 95% CI 1.99-3.61). Among subjects with both SPG1 and H. pylori serology, groups B, C and D had increased gastric cancer ORs (95% CI) of 1.79 (1.21-2.64), 3.85 (2.36-6.28) and 6.35 (2.20-18.34), respectively. CagA seropositives had significantly higher ORs than CagA seronegatives within group B (Pheterogeneity = 0.01). For groups B and C, repeat SPG1 level at 3 years did not further stratify gastric cancer risk. CONCLUSIONS Low SPG1 was associated with increased gastric cancer risk in our large Finnish cohort. A single measurement of SPG1 along with H. pylori whole cell and CagA serology provides potentially useful prediction of gastric cancer risk.
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Affiliation(s)
- Minkyo Song
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - M. Constanza Camargo
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Stephanie J. Weinstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Gwen Murphy
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Neal D. Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Jill Koshiol
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Rachael Z. Stolzenberg-Solomon
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Christian C. Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Satu Männistö
- Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland
| | - Demetrius Albanes
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
| | - Charles S. Rabkin
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA
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Kishikawa H, Kimura K, Ito A, Arahata K, Takarabe S, Kaida S, Kanai T, Miura S, Nishida J. Association between Increased Gastric Juice Acidity and Sliding Hiatal Hernia Development in Humans. PLoS One 2017; 12:e0170416. [PMID: 28107506 PMCID: PMC5249152 DOI: 10.1371/journal.pone.0170416] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 01/04/2017] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES Several clinical factors; overweight, male gender and increasing age, have been implicated as the etiology of hiatal hernia. Esophageal shortening due to acid perfusion in the lower esophagus has been suggested as the etiological mechanism. However, little is known about the correlation between gastric acidity and sliding hiatus hernia formation. This study examined whether increased gastric acid secretion is associated with an endoscopic diagnosis of hiatal hernia. METHODS A total of 286 consecutive asymptomatic patients (64 were diagnosed as having a hiatal hernia) who underwent upper gastrointestinal endoscopy were studied. Clinical findings including fasting gastric juice pH as an indicator of acid secretion, age, sex, body mass index, and Helicobacter pylori infection status determined by both Helicobacter pylori serology and pepsinogen status, were evaluated to identify predictors in subjects with hiatal hernia. RESULTS Male gender, obesity with a body mass index >25, and fasting gastric juice pH were significantly different between subjects with and without hiatal hernia. The cut-off point of fasting gastric juice pH determined by receiver operating curve analysis was 2.1. Multivariate regression analyses using these variables, and age, which is known to be associated with hiatal hernia, revealed that increased gastric acid secretion with fasting gastric juice pH <2.1 (OR = 2.60, 95% CI: 1.38-4.90) was independently associated with hiatal hernia. Moreover, previously reported risk factors including male gender (OR = 2.32, 95% CI: 1.23-4.35), body mass index >25 (OR = 3.49, 95% CI: 1.77-6.91) and age >65 years (OR = 1.86, 95% CI: 1.00-3.45), were also significantly associated with hiatal hernia. CONCLUSIONS This study suggests that increased gastric acid secretion independently induces the development of hiatal hernia in humans. These results are in accordance with the previously reported hypothesis that high gastric acid itself induces hiatal hernia development.
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Affiliation(s)
- Hiroshi Kishikawa
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan
| | - Kayoko Kimura
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan
| | - Asako Ito
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan
| | - Kyoko Arahata
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan
| | - Sakiko Takarabe
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan
| | - Shogo Kaida
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan
| | - Takanori Kanai
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Keio University, Shinjyuku-ku, Tokyo, Japan
| | - Soichiro Miura
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Keio University, Shinjyuku-ku, Tokyo, Japan
| | - Jiro Nishida
- Department of Gastroenterology, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan
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Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut 2017; 66:6-30. [PMID: 27707777 DOI: 10.1136/gutjnl-2016-312288] [Citation(s) in RCA: 1950] [Impact Index Per Article: 243.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Accepted: 08/09/2016] [Indexed: 02/06/2023]
Abstract
Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.
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Affiliation(s)
- P Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - F Megraud
- Laboratoire de Bactériologie, Inserm U853, Université de Bordeaux, Bordeaux, France
| | - C A O'Morain
- Faculty of Health Sciences, Trinity College, Dublin, Ireland
| | - J P Gisbert
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - E J Kuipers
- Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - F Bazzoli
- Internal Medicine and Gastroenterology, University of Bologna Italy, Bologna, Italy
| | - A Gasbarrini
- Gastroenterology, and Liver Unit, Internal Medicine, Roma, Italy
| | | | - D Y Graham
- Department of Medicine (111D), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - R Hunt
- Department of Medicine, McMaster University, Hamilton, Canada
- Hillcroft, Beaconsfield, Buckinghamshire, UK
| | - P Moayyedi
- Department of Gastroenterology, McMaster University, Hamilton, Canada
| | - T Rokkas
- Department of Gastroenterology, Henry Dunant Hospital, Athens, Greece
| | - M Rugge
- Department of Diagnostic Sciences, University of Padova, Padova, Italy
| | | | - S Suerbaum
- Medizinische Hochschule Hannover, Institut für Medizinische Mikrobiologie, Hannover, Germany
| | - K Sugano
- Department of Medicine, Jichi Medical School, Tochigi, Japan
| | - E M El-Omar
- St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
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Impact of Helicobacter pylori Immunoglobulin G Levels and Atrophic Gastritis Status on Risk of Metabolic Syndrome. PLoS One 2016; 11:e0166588. [PMID: 27851820 PMCID: PMC5113018 DOI: 10.1371/journal.pone.0166588] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2016] [Accepted: 10/31/2016] [Indexed: 12/16/2022] Open
Abstract
Background Helicobacter pylori (HP) infection is implicated in gastric and extra-gastric diseases. While gastritis-related chronic inflammation represents a known trigger of metabolic disturbances, whether metabolic syndrome (MetS) is affected by gastritis status remains unclear. We aimed to clarify the effect of HP-related gastritis on the risk of MetS. Materials and Methods We retrospectively enrolled patients undergoing screening for MetS between 2014 and 2015. Investigations included HP-specific immunoglobulin G (IgG) antibody assays to detect HP infection, and serum pepsinogen assays to evaluate atrophic gastritis status. The risk of MetS was evaluated via multiple logistic regression analyses with two covariates: serum HP infection status (IgG levels) and atrophic gastritis status (two criteria were applied; pepsinogen I/II ratio < 3 or both pepsinogen I levels ≤ 70 μg/L and pepsinogen I/II ratio < 3). Results Of 1,044 participants, 247 (23.7%) were HP seropositive, and 62 (6.0%) had MetS. HP seronegative and seropositive patients had similar risks of MetS. On the other hand, AG (defined in terms of serum PG I/II <3) was significant risk of MetS (OR of 2.52 [95% CI 1.05–7.52]). After stratification according to HP IgG concentration, patients with low HP infection status had the lowest MetS risk (defined as an odds ratio [OR] adjusted for age, sex, smoking, drinking and physical activity status). Taking this result as a reference, patients with negative, moderate, and high HP infection status had ORs (with 95% confidence intervals [CI]) of 2.15 (1.06–4.16), 3.69 (1.12–16.7), and 4.05 (1.05–26.8). Conclusions HP-associated gastritis represents a risk factor for MetS. Research should determine why low and not negative HP infection status is associated with the lowest MetS risk.
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Eom SY, Hong SM, Yim DH, Kwon HJ, Kim DH, Yun HY, Song YJ, Youn SJ, Hyun T, Park JS, Kim BS, Kim YD, Kim H. Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans. Cancer Med 2016; 5:3236-3335. [PMID: 27726301 PMCID: PMC5119980 DOI: 10.1002/cam4.926] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 08/01/2016] [Accepted: 09/04/2016] [Indexed: 12/12/2022] Open
Abstract
Although several studies reported genetic polymorphisms in protein kinase AMP‐activated alpha 1 catalytic subunit (PRKAA1) and their associations with gastric cancer risk, few have evaluated associations between Helicobacter pylori infection and PRKAA1 gene‐environment interactions. Here, we evaluated the effects of interactions between H. pylori infection and PRKAA1 polymorphisms on gastric cancer risk in Koreans. In this hospital‐based case–control study, PRKAA1 genotypes were analyzed and H. pylori infection and CagA status were examined using a serologic method in 846 pairs of gastric cancer patients and controls matched for age and sex. H. pylori seropositivity was associated with a 1.43‐fold [95% confidence interval: 1.12–1.81] increase in the risk of gastric cancer, and CagA low‐positive titers during H. pylori infection increased the risk by 1.85‐fold (95% confidence interval, 1.38–2.48). Significant positive interaction between the PRKAA1 rs13361707 genotype and H. pylori infection was verified on an additive scale [relative excess risk due to interaction, 0.55; 95% confidence interval, 0.05–1.04; P = 0.030], and the gene‐environment interaction between PRKAA1 rs13361707 and CagA status was also statistically significant (relative excess risk due to interaction, 0.50; 95% confidence interval, 0.30–0.70; P < 0.001). Our results indicated that H. pylori infection, CagA status, and PRKAA1 polymorphisms were risk factors for gastric cancer in Koreans, and that the combination of two of these factors rather than their independent effects synergistically increased the risk.
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Affiliation(s)
- Sang-Yong Eom
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Seon-Mi Hong
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Dong-Hyuk Yim
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Hyo-Jin Kwon
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Dae-Hoon Kim
- Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Hyo-Yung Yun
- Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Young-Jin Song
- Department of Surgery, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Sei-Jin Youn
- Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Taisun Hyun
- Department of Food and Nutrition, Chungbuk National University, Cheongju, Korea
| | - Joo-Seung Park
- Department of Surgery, College of Medicine, Eulji University, Daejon, Korea
| | - Byung Sik Kim
- Department of Surgery, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea
| | - Yong-Dae Kim
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Heon Kim
- Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju, Korea
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