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Rai RP, Syed A, Elgorban AM, Abid I, Wong LS, Khan MS, Khatoon J, Prasad KN, Ghoshal UC. Expressions of selected microRNAs in gastric cancer patients and their association with Helicobacter pylori and its cag pathogenicity island. Microb Pathog 2025; 202:107442. [PMID: 40049249 DOI: 10.1016/j.micpath.2025.107442] [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: 07/11/2024] [Revised: 02/24/2025] [Accepted: 02/28/2025] [Indexed: 03/12/2025]
Abstract
BACKGROUND Helicobacter pylori infection and the resulting inflammation of the stomach are widely recognized as the primary risk factors for the development of gastric cancer (human health). Despite numerous attempts, the correlation between various virulence factors of H. pylori and stomach cancer remains mainly unexplained. The cag pathogenicity island (cagPAI) is a widely recognized indicator of virulence in H. pylori. MicroRNAs play crucial roles in a wide range of biological and pathological processes and dysregulated expressions of miRNAs have been detected in numerous cancer types. However, research on the correlation between H. pylori infection and its cagPAI, as well as the differential expression of microRNAs in gastric cancer, is lacking. AIM The aim of this study was to examine the differential expression of miRNAs in 80 patients with gastric cancer, specifically in connection to the presence of H. pylori and its cag pathogenicity island (cagPAI). METHODS Biopsies of 80 gastric cancer patients were collected and used for H. pylori DNA isolation and tissue miRNA isolation, and further analyzed for cagPAI and miRNA expression and their association. RESULTS Elevated levels of miR-21, miR-155, and miR-223 were detected in malignant tissues. The expression of miR-21 and miR-223 was considerably elevated in biopsies that tested positive for H. pylori, whereas the expression of miR-34a was reduced. H. pylori cagPAI samples that are functionally intact exhibit greater expression of miR-21 and miR-223 compared to cagPAI samples that are partially deleted, in both normal and malignant tissues. CONCLUSION Thus, the novelty of our study lies in its focus on the differential expression of specific miRNAs in relation to the functional integrity of the cagPAI in H. pylori-infected gastric cancer patients, offering a more detailed understanding of the interplay between H. pylori virulence factors and miRNA regulation than previous studies.
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Affiliation(s)
- Ravi Prakash Rai
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Asad Syed
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.
| | - Abdallah M Elgorban
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Islem Abid
- Center of Excellence in Biotechnology Research (CEBR), King Saud University, Riyadh, Saudi Arabia.
| | - Ling Shing Wong
- Faculty of Health and Life Sciences, INTI International University, Putra Nilai, 71800, Nilai, Negeri Sembilan, Malaysia.
| | - Mohd Sajid Khan
- Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Jahanarah Khatoon
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; Department of Biosciences, Integral University, Lucknow, Uttar Pradesh, India.
| | - Kashi N Prasad
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
| | - Uday Chand Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, Lucknow, India.
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Kang HJ, Chung H, Kim SG, Kim J, Kim JL, Lee E, Jung HC. Synergistic Effect of Lymphatic Invasion and Venous Invasion on the Risk of Lymph Node Metastasis in Patients with Non-Curative Endoscopic Resection of Early Gastric Cancer. J Gastrointest Surg 2020; 24:1499-1509. [PMID: 31313145 DOI: 10.1007/s11605-019-04302-0] [Citation(s) in RCA: 8] [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: 02/07/2019] [Accepted: 06/07/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Although additive radical surgery is recommended for patients with non-curative endoscopic resection for early gastric cancer (EGC), lymph node (LN) metastasis or remnant tumor is detected in only about 10% of patients. Therefore, we aimed to identify patients who required surgery by identifying significant risk factors for LN metastasis and evaluate long-term outcomes in patients with non-curative endoscopic resection. METHODS We retrospectively analyzed the database of Seoul National University Hospital to identify patients who underwent endoscopic resection for EGC from June 2005 to December 2016. RESULTS Three hundred and twenty-nine patients did not meet the criteria for curative resection after endoscopic resection. Among them, 140 patients underwent additional surgery and 171 patients refused surgery and regularly received follow-up. In the surgery group, LN metastasis was found in 12.1% of patients. Logistic regression analysis revealed that the rate of LN metastasis was significantly higher in patients with lymphatic invasion (LI) (odds ratio [OR] 5.84, p = 0.014) and venous invasion (VI) (OR 5.66, p = 0.006). We analyzed LN metastasis based on LI and VI in the surgical group. LN metastasis was significantly increased in the positive LI and VI groups compared with the negative LI and VI groups (OR 68.32; 95% confidence interval, 4.74-984.82; p = 0.002). CONCLUSIONS Both LI and VI were significant predictors of LN metastasis. The risk of LN metastasis was augmented when both LI and VI were positive. Therefore, LI and VI should be evaluated separately in patients with non-curative endoscopic resection. Additive surgery should be recommended for patients with LI and/or VI.
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Affiliation(s)
- Hye Jin Kang
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul, South Korea
| | - Hyunsoo Chung
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul, South Korea.
- Division of Gastroenterology, Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul, South Korea
| | - Jung Kim
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul, South Korea
| | - Jue Lie Kim
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul, South Korea
| | - Eunwoo Lee
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul, South Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, College of Medicine, Seoul National University, Seoul, South Korea
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H. pylori infection and gastric cancer in Bangladesh: a case-control study. INTERNATIONAL JOURNAL OF SURGERY-ONCOLOGY 2017; 2:e44. [PMID: 29177209 PMCID: PMC5680990 DOI: 10.1097/ij9.0000000000000044] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Accepted: 08/15/2017] [Indexed: 12/13/2022]
Abstract
Background: Like that of other Asian countries gastric cancer (GC) is also a leading cancer in Bangladesh and also a cause for cancer-related mortality. Infection with Helicobacter pylori (H. pylori) is the strongest recognized risk factor for gastric adenocarcinoma. The infection is also prevalent in common people. This case-control study was carried out to find an association between GC and H. pylori infection in the community. Materials and Methods: To evaluate association of H. pylori and carcinoma of stomach this study was conducted at National Institute of Cancer Research & Hospital, Dhaka from January 2013 to December 2014. H. pylori status was determined serologically by using H. pylori kit in the department of Biochemistry laboratory of Bangabandhu Sheikh Mujib Medical University. In total, 114 patients with GC and 520 patients not having GC were studied as controls. Logistic regression method was used to calculate the odds ratio. Results: Significantly more patients in the case group (86.8%) were found to be seropositive for H. pylori antigen in contrast to the control group (67.5%). All of the cases in the present study were in advanced stage. No significant association between H. pylori seropositivity and tumor location was found. It was noted that undifferentiated gastric carcinoma had slightly more association with H. pylori infection. Younger H. pylori–infected patients had been found to be at higher relative risk for GC than older patients. Conclusion: As there is a strong association found between GC and H. pylori infection special emphasis to eradicate H. pylori infection might reduce the incidence of this dreadly disease.
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Abstract
BACKGROUND CagA+ and vacuolizing cytotoxin (VacA)-specific strains of Helicobacter pylori have been associated with different risks for developing gastric lesions. We aim to summarize a possible association between these genotypes and the risk for developing different gastric phenotypes. MATERIALS AND METHODS A MEDLINE database (PubMed) search was performed and a meta-analysis conducted. RESULTS Forty-four studies were retrieved, all with either a case-control (n=13) or cross-sectional (n=31) design, including 17 374 patients. CagA positivity was associated with an increased risk for gastric cancer [odds ratio (OR) 2.09 (95% confidence interval (CI), 1.48-2.94)] compared with that in individuals without gastric lesions [OR 2.44 (95% CI 1.27-4.70)] and in those with previously identified gastritis. In addition, there was an increased risk for peptic ulcer disease [OR 1.69 (95% CI 1.12-2.55)]. Individuals harboring the H. pylori strains VacA s1 (vs. s2), m1 (vs. m2), s1m1 (vs. s1m2), and s1m1 (vs. s2m2) had an increased risk for development of cancer [OR of 5.32 (95% CI 2.76-10.26), 2.50 (95% CI 1.67-3.750), 2.58 (95% CI 1.24-5.38), and 4.36 (95% CI 2.08-9.10), respectively]. s1m1 strains (vs. s2m2) were also associated with peptic ulcer disease [OR 2.04 (1.01-4.13)]. CONCLUSION Our results indicate that individuals infected with CagA+ H. pylori strains and those infected with VacA s1 and m1 strains have an increased risk for gastric cancer. Cohort studies are welcome to integrate this information in the management of at-risk individuals such as those with precancerous cancer conditions and/or a family history of gastric cancer.
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Shukla SK, Prasad KN, Tripathi A, Singh A, Saxena A, Ghoshal UC, Krishnani N, Husain N. Epstein-Barr virus DNA load and its association with Helicobacter pylori infection in gastroduodenal diseases. Braz J Infect Dis 2012. [PMID: 22218519 DOI: 10.1016/s1413-8670(11)70255-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
UNLABELLED Helicobacter pylori and Epstein-Barr virus (EBV) infections are common worldwide. Although H. pylori infection is a major factor in gastroduodenal diseases, its role in association with EBV infection is unknown. OBJECTIVE To study the association of H. pylori infection and EBV DNA load in patients with gastroduodenal diseases. METHODS Biopsy samples were collected from 200 adult patients [non-ulcer dyspepsia (NUD) 100, peptic ulcer disease (PUD) 50, gastric carcinoma (GC) 50] undergoing upper gastrointestinal endoscopy. H. pylori infection was diagnosed by rapid urease test, culture, histopathology, PCR and Q-PCR. EBV DNA was detected by non-polymorphic Epstein-Barr nuclear antigen-1 (EBNA-1) gene based Q-PCR. RESULTS In patients with GC and PUD, EBV DNA was detected more often than NUD (GC versus NUD = 90% versus 37%, p < 0.001; PUD versus NUD = 70% versus 37%, p < 0.001). The dual prevalence of H. pylori infection and EBV DNA was significantly higher in patients with GC and PUD than in those with NUD. Median copy number of EBV DNA was considerably higher in GC and PUD than NUD (p < 0.01). The copy number of EBV DNA was significantly higher in H. pylori infected patients (p = 0.015). The number of ureA gene copies was also found to be significantly higher in PUD and NUD with presence of EBV DNA. However, in GC no significant difference was seen between EBV positive and negative status. CONCLUSION There was a trend for higher EBV DNA load in H. pylori positive individuals suggesting a probable role of H. pylori in modulating the conversion of EBV to its lytic phase.
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Affiliation(s)
- Sanket Kumar Shukla
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Tanaka A, Kamada T, Inoue K, Shiotani A, Kusunoki H, Manabe N, Ito M, Hata J, Haruma K. Histological evaluation of patients with gastritis at high risk of developing gastric cancer using a conventional index. Pathol Res Pract 2011; 207:354-8. [PMID: 21664555 DOI: 10.1016/j.prp.2011.03.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2010] [Revised: 03/13/2011] [Accepted: 03/16/2011] [Indexed: 02/09/2023]
Abstract
Although gastric cancer (GCa) is strongly associated with Helicobacter pylori infection, only some H. pylori-positive subjects develop gastric cancer. The aim of this study is to identify H. pylori-positive subjects at high risk of developing GCa by assessment of the histopathological findings in the non-cancer-containing mucosa of patients with and without GCa. The subjects were 35 patients with diffuse-type gastric cancer (D-GCa), 55 with intestinal-type gastric cancer (I-GCa), and 99 H. pylori-positive controls without GCa. Two specimens were taken from the greater curvature of the antrum and the middle body. Histopathological gradings were evaluated using the updated Sydney System, and the risk of GCa was evaluated using a modified Meining's gastric cancer risk index (GCRI). Among the H. pylori-positive controls, corpus gastritis was seen in 98.0% (97/99) and corpus atrophic gastritis in 78.8% (78/99). The mean GCRI for the D-GCa (5.514±2.03) and I-GCa (6.836±2.08) groups was significantly greater than that for the H. pylori-positive controls (4.071±2.07; p=0.0005, p<0.0001). In addition, the mean GCRI for the I-GCa group was significantly greater than that for the D-GCa group (p<0.005). The GCRI-positive rate was significantly higher in subjects with GCa than in H. pylori-positive controls (D-GCa: p<0.005, I-GCa: p<0.0001). Many H. pylori-positive Japanese still carry a high risk for gastric cancer. However, H. pylori-positive patients at high risk of developing GCa (not only intestinal-type but also diffuse-type) may be detected using a simple GCRI.
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Affiliation(s)
- Aki Tanaka
- Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan
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Shukla SK, Prasad KN, Tripathi A, Ghoshal UC, Krishnani N, Nuzhat H. Quantitation of Helicobacter pylori ureC gene and its comparison with different diagnostic techniques and gastric histopathology. J Microbiol Methods 2011; 86:231-7. [PMID: 21624400 DOI: 10.1016/j.mimet.2011.05.012] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2011] [Revised: 05/16/2011] [Accepted: 05/16/2011] [Indexed: 12/19/2022]
Abstract
Numerous diagnostic assays for Helicobacter pylori detection are available. However, these techniques have their own advantages as well as limitations. Here we tried to develop a real-time quantitative (Q) PCR assay to measure ureC copy number to detect H. pylori, based on the fact that there is only one copy of the ureC gene per bacterium. We enrolled 120 adult patients [non-ulcer dyspepsia (NUD) 60, peptic ulcer disease (PUD) 20, gastric cancer (GC) 40] undergoing upper gastrointestinal endoscopies. During each endoscopic examination, antral biopsies from normal region of the antrum were obtained and subjected to the following tests: RUT, culture, histopathology, H. pylori-specific ureC PCR and ureC Q-PCR. Calculation of H. pylori copy number was based on the standard curve generated using 10-fold dilutions of DNA extracted from the H. pylori control strain varying from 10(5) to 10(1) copies. The prevalence of H. pylori infection in our study population was 54% with no significant difference among disease and control population. The sensitivity of Q-PCR was found to be 100% which was highest among all diagnostic tests. The established Q-PCR is around 10 times more sensitive than the conventional PCR method. The copy number of H. pylori DNA was significantly increased when overall gastritis, H. pylori density, chronic inflammation and intestinal metaplasia were present. In summary, we developed a rapid and sensitive Q-PCR method for detecting H. pylori. This technique offers a significant improvement over other available methods for detecting H. pylori in clinical and research samples.
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Affiliation(s)
- S K Shukla
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Bresciani C, Latif I, Coser RB, Yagi O, Deutsch CR, Mucerino D, Zilberstein B, Cecconello I. Determinação histopatológica da presença do helicobacter pylori em câncer gástrico. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2011. [DOI: 10.1590/s0102-67202011000100013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
RACIONAL: A causa do câncer gástrico (CG) é controversa e tem vários fatores envolvidos no seu processo de carcinogênese, incluindo o Helicobacter pylori (Hp) O papel da infecção pelo Hp no CG permanece incerto, com vários estudos controversos. OBJETIVO: Correlacionar a presença da infecção pelo Hp com câncer gástrico, através de exame anatomopatológico convencional do estômago ressecado. MÉTODO: Noventa e um pacientes tratados por ressecção cirúrgica foram revistos. O exame anatomopatológico foi feito em todos os pacientes para determinar a presença de infecção por Hp, metaplasia intestinal (MI) e confirmação do tipo histológico por hematoxilina-eosina. A análise estatística foi realizada através do qui-quadrado e testes de log-rank. RESULTADOS: MI foi observada em 81 tumores (89%). Em geral, a presença de infecção pelo Hp foi observada em 46 casos (50,5%). Não houve associação entre idade e Hp. Nos grupos de pacientes com CG avançado e precoce, a infecção pelo Hp estava presente em 47,7% e 54% dos tumores. A infecção pelo Hp ocorreu em 40 tumores (49%) no grupo de pacientes com MI. Nos com tumores sem MI, Hp estava presente em cinco (50%). Tumores proximais tiveram mais infecção por Hp, quando comparados aos tumores distais. CONCLUSÕES: A taxa de infecção não teve associação significativa com o tipo histológico, sexo, MI ou estágio de desenvolvimento tumoral. Esses resultados podem indicar que a participação da infecção pelo Hp durante o desenvolvimento do CG não pode ser descartada; no entanto, provavelmente não é essencial em todas as fases e o mecanismo do CG pode ser distinto da gastrite crônica e MI. Finalmente, é possível que a associação proposta é mera coincidência e que não há nenhuma influência real das bactérias no processo de carcinogênese.
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Cho SJ, Choi IJ, Kim CG, Lee JY, Kook MC, Seong MW, Park SR, Lee JS, Kim YW, Ryu KW, Lee JH, Nam BH, Park YI. Helicobacter pylori Seropositivity Is Associated with Gastric Cancer Regardless of Tumor Subtype in Korea. Gut Liver 2010; 4:466-74. [PMID: 21253294 DOI: 10.5009/gnl.2010.4.4.466] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2009] [Accepted: 04/20/2010] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS To evaluate the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC) according to tumor subtype in Korea. METHODS H. pylori status was determined serologically using the enzyme-linked immunosorbent assay. In total, 2,819 patients with GC and 562 healthy controls were studied. A logistic regression method was used after adjusting for possible confounders. RESULTS The prevalence of H. pylori infection was significantly higher in the GC patients (84.7%) than in the controls (66.7%) (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.46-3.97). The adjusted OR was significantly higher in H. pylori-infected patients aged <60 years (OR, 4.69; 95% CI, 3.44-6.38) than in those aged ≥60 years (OR, 1.48; 95% CI, 0.88-2.46; p<0.001). Subgroup analyses revealed no differences in seroprevalence between early gastric cancer (84.8%; OR, 3.01; 95% CI, 2.27-4.01) and advanced gastric cancer (84.6%; OR, 2.94; 95% CI, 2.24-3.85), cardia cancer (83.8%; OR, 2.98; 95% CI, 2.16-4.02) and noncardia cancer (84.8%; OR, 3.17; 95% CI, 2.48-4.04), and differentiated carcinoma (82.7%; OR, 2.99; 95% CI, 2.21-4.04) and undifferentiated carcinoma (86.8%; OR, 3.05; 95% CI, 2.32-4.00). CONCLUSIONS The seroprevalence of H. pylori was higher in GC patients than in healthy controls, especially in younger patients. H. pylori infection is associated with GC, regardless of the tumor location, stage, or differentiation.
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Fiske WH, Tanksley J, Nam KT, Goldenring JR, Slebos RJC, Liebler DC, Abtahi AM, La Fleur B, Ayers GD, Lind CD, Washington MK, Coffey RJ. Efficacy of cetuximab in the treatment of Menetrier's disease. Sci Transl Med 2009; 1:8ra18. [PMID: 20368185 PMCID: PMC3638759 DOI: 10.1126/scitranslmed.3000320] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Ménétrier's disease is a rare premalignant disorder of the stomach with no proven effective medical therapy. Increased epidermal growth factor receptor signaling has been implicated in the pathogenesis of Ménétrier's disease. We conducted a single-arm clinical trial with cetuximab, a monoclonal antibody that blocks epidermal growth factor receptor signaling, in nine individuals with clinically and histologically documented severe Ménétrier's disease that impaired quality of life to the extent that gastrectomy was being considered. Of the seven patients who completed the 1-month course of treatment, all showed statistically significant improvement both clinically (quality-of-life indices) and biochemically (increased parietal cell mass and gastric acidity). Furthermore, all seven patients who completed the 1-month trial elected to continue treatment, and four subsequently showed near-complete histological remission. Cetuximab should be considered as first-line therapy for Ménétrier's disease.
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Affiliation(s)
- William H Fiske
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
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Kim CG, Choi IJ, Lee JY, Cho SJ, Nam BH, Kook MC, Hong EK, Kim YW. Biopsy site for detecting Helicobacter pylori infection in patients with gastric cancer. J Gastroenterol Hepatol 2009; 24:469-74. [PMID: 19067779 DOI: 10.1111/j.1440-1746.2008.05679.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Helicobacter pylori eradication is recommended in post-gastric cancer resection, but premalignant changes may prevent the detection of H. pylori. The aim of this study was to determine appropriate biopsy site for detecting H. pylori in gastric cancer patients. MATERIALS AND METHODS Consecutive patients (194) with gastric adenocarcinoma were prospectively enrolled. Helicobacter pylori was evaluated by serology, histology and rapid urease test. Biopsy sites included antrum lesser curvature, upper body lesser curvature (UBLC) and upper body greater curvature (UBGC). Two biopsy specimens were obtained from each site for histological examination. One additional specimen was obtained from UBGC for the rapid urease test. RESULTS The overall infection rate of H. pylori was 84.0% (95% CI 78.9-89.2). The sensitivity of histology for detecting H. pylori at various sites was: antrum (54.9%; 95% CI 45.7-63.9), UBLC (80.3%; 95% CI 72.2-87.0) and UBGC (95.1%; 95% CI 89.6-98.2). Specificities of all three biopsy sites were more than 95%. Sensitivity and specificity of the rapid urease test performed at UBGC were 96% and 100%, respectively. Sensitivities of histology decreased in correlation with increasing severity of atrophy and intestinal metaplasia (both P < 0.001 using the chi-square test for trend). The proportions of moderate to marked atrophy/intestinal metaplasia at UBGC (12.8%/14.7%) were significantly lower than those at antrum (50.0%/57.8%, P < 0.001 respectively) or UBLC (40.0%/48.9%, P < 0.001 respectively). CONCLUSIONS The UBGC side is the most sensitive and specific biopsy site to detect H. pylori in gastric cancer patients due to less frequent atrophy and intestinal metaplasia than at the antrum or UBLC side.
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Affiliation(s)
- Chan Gyoo Kim
- Research Institute and Hospital, National Cancer Center, Ilsandong-gu, Goyang, Gyeonggi, Korea
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Saxena A, Nath Prasad K, Chand Ghoshal U, Krishnani N, Roshan Bhagat M, Husain N. Association of Helicobacter pylori and Epstein-Barr virus with gastric cancer and peptic ulcer disease. Scand J Gastroenterol 2008; 43:669-74. [PMID: 18569983 DOI: 10.1080/00365520801909660] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Helicobacter pylori and Epstein-Barr virus (EBV) infections are common world-wide. Though H. pylori infection is a major factor in gastroduodenal diseases, its role in association with EBV infection is unknown. We prospectively studied the association of H. pylori and EBV in patients with gastric cancer (GC) and peptic ulcer disease (PUD). MATERIAL AND METHODS A total of 348 adult patients (non-ulcer dyspepsia (NUD) 241, PUD 45, GC 62) undergoing upper gastrointestinal endoscopy between September 2003 and May 2007 were enrolled in the study. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and polymerase chain reaction (PCR). EBV DNA was detected by non-polymorphic Epstein-Barr nuclear antigen-1 (EBNA-1) gene-based PCR and sequence analysis. RESULTS The rate of H. pylori infection was higher in patients with PUD than in those with GC (80% versus 56.5%, p=0.01) and NUD (80% versus 55.2%, p=0.002). In patients with GC and PUD, EBV DNA was detected more often than in those with NUD (GC versus NUD - 82.3% versus 37.3%, p<0.001; PUD versus NUD - 75.5% versus 37.3%, p<0.001). H. pylori infection and EBV DNA detected in different groups of patients was as follows: 62.2% in PUD, 46.8% in GC and 29.5% in NUD. PUD and GC were significantly associated (p<0.001 and <0.05, respectively) with the presence of H. pylori infection and EBV DNA as compared with NUD. CONCLUSIONS EBV DNA either alone or in combination with H. pylori infection was significantly associated with GC and PUD, suggesting that EBV might play an important role in gastroduodenal pathology.
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Affiliation(s)
- Ashish Saxena
- Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Araújo-Filho I, Brandão-Neto J, Pinheiro LAM, Azevedo IM, Freire FHMA, Medeiros AC. Prevalence of Helicobacter pylori infection in advanced gastric carcinoma. ARQUIVOS DE GASTROENTEROLOGIA 2007; 43:288-92. [PMID: 17406757 DOI: 10.1590/s0004-28032006000400009] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Received: 08/23/2005] [Accepted: 07/04/2006] [Indexed: 12/24/2022]
Abstract
BACKGROUND [corrected] There is substantial evidence that infection with Helicobacter pylori plays a role in the development of gastric cancer and that it is rarely found in gastric biopsy of atrophic gastritis and gastric cancer. On advanced gastric tumors, the bacteria can be lost from the stomach. AIMS To analyze the hypothesis that the prevalence of H.pylori in operated advanced gastric carcinomas and adjacent non-tumor tissues is high, comparing intestinal and diffuse tumors according to Lauren's classification METHODS A prospective controlled study enrolled 56 patients from "Hospital Universitário", Federal University of Rio Grande do Norte, Natal, RN, Brazil, with advanced gastric cancer, treated from February 2000 to March 2003. Immediately after partial gastrectomy, the resected stomach was opened and several mucosal biopsy samples were taken from the gastric tumor and from the adjacent mucosa within 4 cm distance from the tumor margin. Tissue sections were stained with hematoxylin and eosin. Lauren's classification for gastric cancer was used, to analyse the prevalence of H. pylori in intestinal or diffuse carcinomas assessed by the urease rapid test, IgG by ELISA and Giemsa staining. H. pylori infected patients were treated with omeprazole, clarithromycin and amoxicillin for 7 days. Follow-up endoscopy and serology were performed 6 months after treatment to determine successful eradication of H. pylori in non-tumor tissue. Thereafter, follow-up endoscopies were scheduled annually. Chi-square and MacNemar tests with 0.05 significance were used. RESULTS Thirty-four tumors (60.7%) were intestinal-type and 22 (39.3%) diffuse type carcinomas. In adjacent non-tumor gastric mucosa, chronic gastritis were found in 53 cases (94.6%) and atrophic mucosa in 36 patients (64.3%). All the patients with atrophic mucosa were H. pylori positive. When examined by Giemsa and urease test, H. pylori positive rate in tumor tissue of intestinal type carcinomas was higher than that in diffuse carcinomas. In tumor tissues, 34 (60.7%) H. pylori-positive in gastric carcinomas were detected by Giemsa method. H. pylori was observed in 30 of 56 cases (53.5%) in tissues 4 cm adjacent to tumors. This difference was not significant. Eradication of H. pylori in non-tumor tissue of gastric remnant led to a complete negativity on the 12th postoperative month CONCLUSIONS The data confirmed the hypothesis of a high prevalence of H. pylori in tumor tissue of gastric advanced carcinomas and in adjacent non-tumor mucosa of operated stomachs. The presence of H. pylori was predominant in the intestinal-type carcinoma.
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Affiliation(s)
- Irami Araújo-Filho
- Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil
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Wang C, Yuan Y, Hunt RH. The association between Helicobacter pylori infection and early gastric cancer: a meta-analysis. Am J Gastroenterol 2007; 102:1789-98. [PMID: 17521398 DOI: 10.1111/j.1572-0241.2007.01335.x] [Citation(s) in RCA: 96] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Helicobacter pylori (H. pylori) is recognized as a definite carcinogen for gastric cancer. The prevalence of H. pylori infection in patients with gastric cancer varies widely among studies and no meta-analysis on the prevalence of H. pylori infection in early gastric cancer (EGC) has been performed. We aimed to review systematically the relationship between H. pylori infection and EGC, and different types of EGC. METHODS Observational studies reporting raw data on the prevalence of H. pylori infection in EGC and controls, or comparing different types of EGC, conducted in adult populations, and published in the English language were identified through MEDLINE and EMBASE up to June 2006. RESULTS Of 87 relevant studies, 19 case-control studies met inclusion criteria. Of these, 15 studies compared EGC (N = 2,722) and non-neoplasm controls (N = 13,976) or advanced gastric cancer (AGC) (N = 1,130), 9 studies compared the intestinal-type (I-EGC) and diffuse-type (D-EGC) of EGC, and 2 studies compared the differentiated-type (DF-EGC) and undifferentiated-type (UDF-EGC) of EGC and were included in the meta-analysis. The prevalence of H. pylori infection was significantly higher in patients with EGC (87.3%) than in non-neoplasm controls (61.4%) (OR 3.38, 95% CI 2.15-5.33, P < 0.00001). However, significant heterogeneity was seen (P < 0.00001). Four large sample (N > or = 100) studies (N = 2,060) may result in the heterogeneity, but the conclusion remained unchanged when sensitivity analysis was made with the other 11 homogeneous small sample studies alone, in which the prevalence of H. pylori infection was significantly higher in EGC (N = 662) than that in controls (N = 5,898) (87.8%vs 68.6%, P < 0.00001), and the odds ratio (OR 3.28, 95% CI 2.34-4.61) was similar to the large sample studies alone (OR 3.40, 95% CI 1.14-10.12). The prevalence of H. pylori infection in EGC was significantly higher than in AGC (6 studies) (OR 2.13, 95% CI 1.75-2.59) and 16-fold higher in patients with DF-EGC than in those with UDF-EGC (OR 16.53, 95% CI 2.64-103.43). No significant difference in the prevalence of H. pylori infection was seen between the patients with I-EGC and D-EGC types (OR 0.75, 95% CI 0.26-2.18). CONCLUSIONS This study indicates that H. pylori infection is strongly associated with early gastric cancer when compared with non-neoplasm controls or advanced gastric cancer. To determine more accurately the effect size of H. pylori in EGC, age-matched normal controls or adjusting for age in the analysis should be considered in H. pylori-related gastric cancer case-control studies.
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Affiliation(s)
- Changcheng Wang
- Division of Gastroenterology, Health Science Centre, McMaster University, Hamilton, Ontario, Canada
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Zhang C, Yamada N, Wu YL, Wen M, Matsuhisa T, Matsukura N. Helicobacter pylori infection, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer and early gastric cancer. World J Gastroenterol 2005; 11:791-6. [PMID: 15682469 PMCID: PMC4250585 DOI: 10.3748/wjg.v11.i6.791] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the histological features of gastric mucosa, including Helicobacter pylori infection in patients with early gastric cancer and endoscopically found superficial gastritis, gastric erosion, erosive gastritis, gastric ulcer.
METHODS: The biopsy specimens were taken from the antrum, corpus and upper angulus of all the patients. Giemsa staining, improved toluidine-blue staining, and H pylori-specific antibody immune staining were performed as appropriate for the histological diagnosis of H pylori infection. Hematoxylin-eosin staining was used for the histological diagnosis of gastric mucosa inflammation, gastric glandular atrophy and intestinal metaplasia and scored into four grades according to the Updated Sydney System.
RESULTS: The overall prevalence of H pylori infection in superficial gastritis was 28.7%, in erosive gastritis 57.7%, in gastric erosion 63.3%, in gastric ulcer 80.8%, in early gastric cancer 52.4%. There was significant difference (P<0.05), except for the difference between early gastric cancer and erosive gastritis. H pylori infection rate in antrum, corpus, angulus of patients with superficial gastritis was 25.9%, 26.2%, 25.2%, respectively; in patients with erosive gastritis 46.9%, 53.5%, 49.0%, respectively; in patients with gastric erosion 52.4%, 61.5%, 52.4%, respectively; in patients with gastric ulcer 52.4%, 61.5%, 52.4%, respectively; in patients with early gastric cancer 35.0%, 50.7%, 34.6%, respectively. No significant difference was found among the different site biopsies in superficial gastritis, but in the other diseases the detected rates were higher in corpus biopsy (P<0.05). The grades of mononuclear cell infiltration and polymorphonuclear cell infiltration, in early gastric cancer patients, were significantly higher than that in superficial gastritis patients, lower than that in gastric erosion and gastric ulcer patients (P<0.01); however, there was no significant difference compared with erosive gastritis. The grades of mucosa glandular atrophy and intestinal metaplasia were significantly highest in early gastric cancer, lower in gastric ulcer, the next were erosive gastritis, gastric erosion, the lowest in superficial gastritis (P<0.01). Furthermore, 53.3% and 51.4% showed glandular atrophy and intestinal metaplasia in angular biopsy specimens, respectively; but only 40.3% and 39.9% were identified in antral biopsy, and 14.1% and 13.6% in corpus biopsy; therefore, the angulus was more reliable for the diagnosis of glandular atrophy and intestinal metaplasia compared with antrum and corpus (P<0.01). The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pylori-positivity was 50.7%, 34.1%; of erosive gastritis 76.1%, 63.0%; of gastric erosion 84.8%, 87.8%; of gastric ulcer 80.6%, 90.9%; and of early gastric cancer 85.5%, 85.3%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis with H pylori-negativity was 9.9%, 6.9%; of erosive gastritis 42.5%, 42.1%; of gastric erosion 51.1%, 61.9%; of gastric ulcer 29.8%, 25.5%; and of early gastric cancer 84.0%, 86.0%, respectively. The positivity rate of glandular atrophy and intestinal metaplasia of superficial gastritis, erosive gastritis, gastric erosion, and gastric ulcer patients with H pylori positivity was significantly higher than those with H pylori negativity (P<0.01); however, there was no significant difference in patients with early gastric cancer with or without H pylori infection.
CONCLUSION: The progression of the gastric pre-cancerous lesions, glandular atrophy and intestinal metaplasia in superficial gastritis, gastric erosion, erosive gastritis and gastric ulcer was strongly related to H pylori infection. In depth studies are needed to evaluate whether eradication of H pylori infection will really diminish the risk of gastric cancer.
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Affiliation(s)
- Chuan Zhang
- Department of Gastroenterology, Baogang Hospital, Shanghai Second Medical University, Shanghai 201900, China.
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Abstract
Gastric adenocarcinoma is a disease of high mortality and poor prognosis that is second only to lung cancer as a leading cause of cancer-related deaths worldwide. Although gastric cancer has a multifactorial etiology, infection with Helicobacter pylori is highly associated with its development. New information on bacterial and host genetics and results of epidemiologic studies suggest that better identification of individuals at high risk for gastric malignancy may be possible. Studies suggest that cure of H pylori infection may be associated with retardation of glandular atrophy and intestinal metaplasia but not reversal of dysplasia. Theoretically, it is attractive to believe that eradication of H pylori infection might prevent gastric cancer; however, studies supporting this hypothesis are not yet available. Public policy strategies for the identification of patients at risk for H pylori-related gastric malignancy are likely to be complex, but testing and treating for the infection earlier rather than later in life is anticipated to be the more beneficial approach.
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Affiliation(s)
- Richard H Hunt
- McMaster University Medical Center, Hamilton, Ontario, Canada
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17
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Unger Z, Molnár B, Prónai L, Szaleczky E, Zágoni T, Tulassay Z. Mutant p53 expression and apoptotic activity of Helicobacter pylori positive and negative gastritis in correlation with the presence of intestinal metaplasia. Eur J Gastroenterol Hepatol 2003; 15:389-93. [PMID: 12655259 DOI: 10.1097/00042737-200304000-00009] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Mutation of the p53 gene is detectable in most cases of gastric cancer, as it is the most common genetic alteration in human malignancies. It is also well documented that Helicobacter pylori infection plays an important role in gastric carcinogenesis. There is still no clarification, however, concerning how genetic instability influences the homeostasis of gastric epithelium. We have studied the effect of H. pylori infection on apoptosis of the antral epithelium in the presence/absence of intestinal metaplasia and the expression of the p53 oncoprotein. The relationship between these two processes is analysed. METHODS Antral biopsies were taken from 36 patients who underwent routine upper endoscopy (17 men, 19 women, mean age 61.0 years). The biopsies were fixed in formalin and embedded in paraffin. Patients were classified into two histological groups: (1) as chronic gastritis without intestinal metaplasia (n = 19), and (2) chronic gastritis with intestinal metaplasia (n = 17). An immunohistochemical method was used to detect the expression of p53 oncoprotein, and the terminal transferase mediated dUTP nick end-labelling (TUNEL) method was used to detect apoptotic cells. RESULTS In the absence of intestinal metaplasia, both the apoptotic index (0.0272 +/- 0.011 vs 0.0128 +/- 0.006) and expresssion of p53 (35.55 +/- 31.16 vs 18.33 +/- 19.65) were significantly higher in H. pylori positive cases compared to H. pylori negative cases. In the presence of intestinal metaplasia, p53 expression was further increased (P < 0.05), but apoptosis was similar to that observed in H. pylori negative gastritis without intestinal metaplasia. In the presence of intestinal metaplasia, H. pylori infection did not influence apoptosis (0.013 +/- 0.004 vs 0.011 +/- 0.004), or p53 ratio (70.16 +/- 22.54 vs 68.50 +/- 28.96). In the sequence of gastritis-intestinal metaplasia the two indices show a close negative correlation (P < 0.05). CONCLUSION In the absence of intestinal metaplasia H. pylori infection increases both apoptotic activity and expression of p53 oncoprotein in the gastric mucosa. The lack of increased apoptosis with a higher p53 expression in the presence of intestinal metaplasia suggests an increased genetic instability and also may suggest that mutation of the p53 gene is an early step in the multistep process of gastric carcinogenesis.
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Affiliation(s)
- Zsuzsa Unger
- Semmelweis University, Faculty of Medicine, 2nd Department of Internal Medicine, 1088 Budapest, Szentkirályi út 46, Hungary.
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Takeuchi K, Ohno Y, Tsuzuki Y, Ando T, Sekihara M, Hara T, Kuwano H. Helicobacter pylori infection and early gastric cancer. J Clin Gastroenterol 2003; 36:321-4. [PMID: 12642738 DOI: 10.1097/00004836-200304000-00008] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Helicobacter pylori has recently been associated with an increased risk of gastric cancer. This study aimed to examine the association between H. pylori, histologic chronic gastritis, and intestinal metaplasia in early gastric cancers of different histologic types. STUDY Seventy-four patients who were surgically diagnosed as having early gastric cancer were included in this study. All tissue specimens were obtained from patients by endoscopic biopsy and were classified histopathologically as intestinal-type early gastric cancer in 55 patients and diffuse-type early gastric cancer in 19 patients. RESULTS H. pylori infection was found in 67 patients (90.5%) but not found in seven (9.5%). And the prevalence of H. pylori infection with nongastric cancer patients was also high (68.5%). There was no significant difference between the intestinal-type and the diffuse-type early gastric cancer in chronic active gastritis and atrophic chronic gastritis. Intestinal metaplasia was observed more frequently in patients with the intestinal-type than with the diffuse-type early gastric cancer (P = 0.0102). CONCLUSIONS Infection with H. pylori has an important relationship to both histopathologic types of early gastric cancer.
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Affiliation(s)
- Kunio Takeuchi
- Department of Surgery, Tone Chuo Hospital, Gunma, Japan.
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19
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Testoni PA, Bonassi U, Bagnolo F, Colombo E, Scelsi R. In diffuse atrophic gastritis, routine histology underestimates Helicobacter pylori infection. J Clin Gastroenterol 2002; 35:234-9. [PMID: 12192199 DOI: 10.1097/00004836-200209000-00007] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND histologic detection of shows high diagnostic accuracy in chronic nonatrophic gastritis. However, when atrophy occurs, the sensitivity of bacterial detection varies. This study assessed the routine histologic sensitivity for current infection in patients with atrophic gastritis, with and without intestinal metaplasia. STUDY five hundred and ten consecutive patients with diffuse chronic atrophic gastritis, with (174 cases) and without (336 cases) intestinal metaplasia, were investigated following the Sydney System recommendations. In cases with negative tissue staining for Helicobacter-like organisms, serum immunoglobulin G (IgG) antibodies to were assayed. RESULTS the overall rate of positive staining for Helicobacter-like organisms was 51.8% (264 of 510 cases), 62.8% and 30.4% in cases without and with intestinal metaplasia, respectively. Serum IgG antibody determination was consistent with current infection in 180 (73.2%) of the 246 cases with negative histology. detection rate was significantly lower ( < 0.01) in Grade 3 than in Grade 1 atrophy. When intestinal metaplasia was present, histologic bacterial detection progressively decreased, from 46.3% to 20%, depending on severity. infection was found by histology in 42.2% and in 56.2% of cases with inactive and active disease, respectively. Overall, the diagnostic accuracy of histology was significantly lower ( <0.001) than that of histology combined with serology. CONCLUSIONS most (87.1%) diffuse chronic atrophic gastritis patients showed serum antibody IgG levels consistent with current infection, although histology was positive in only 59.5% of cases. Gastritis activity and current infection did not ever correlate in the presence of mucosal atrophy and/or intestinal metaplasia. Routine biopsy sampling, hematoxylin and eosin staining, and Giemsa staining therefore underestimated the true prevalence of infection.
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Affiliation(s)
- Pier Alberto Testoni
- Division of Gastroenterology and Gastrointestinal Endoscopy, University Vita-Salute San Raffaele, IRCCS San Raffaele Hospital, Milano, Italy.
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Fujioka N, Fahey MT, Hamada GS, Nishimoto IN, Kowalski LP, Iriya K, Rodrigues JJ, Tajiri H, Tsugane S. Serological Immunoglobulin G antibody titers to Helicobacter pylori in Japanese Brazilian and Non-Japanese Brazilian gastric cancer patients and controls in São Paulo. Jpn J Cancer Res 2001; 92:829-35. [PMID: 11509113 PMCID: PMC5926828 DOI: 10.1111/j.1349-7006.2001.tb01168.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection is considered a cause of gastric cancer (GC), though evidence for this association is scarce in high-risk areas. Possible case control and/or ethnic differences were investigated as to the presence of H. pylori and its immunogloblin G antibody titer in the multi-ethnic city of São Paulo, where the incidence of GC is relatively high. We performed a cross-sectional comparison of antibody titers to H. pylori in Japanese Brazilian, and non-Japanese Brazilian GC patients and their controls. Japanese Brazilian patients were matched by age, sex and ethnicity with two controls, while non-Japanese Brazilian patients were matched as above with one control. Among Japanese Brazilians, 59 of 93 (63.4%) patients with GC and 127 of 186 (68.3%) controls were positive for H. pylori-specific antibody (odds ratio (OR) = 0.80, 95% confidence interval (CI) = 0.47 - 1.36), while among non-Japanese Brazilians, 171 of 228 patients with GC (75.7%) and 178 of 226 controls (78.8%) were positive (OR = 0.84, 95% CI = 0.54 - 1.30). The median serum antibody titer was lower in cases than in controls in both ethnic groups. A high titer (H. pylori titer > or = 50) was associated with less likelihood of GC for both ethnic groups (for Japanese Brazilians, OR = 0.39, 95% CI = 0.16 - 0.92; for non-Japanese Brazilians, OR = 0.56, 95% CI = 0.31 - 1.02). The high titer can be regarded as a sign of the necessity of eradication, and low titer is regarded as a sign of the necessity of close screening for GC in both ethnic groups, because extended atrophy may cause spontaneous disappearance of H. pylori from the stomach.
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Affiliation(s)
- N Fujioka
- Epidemiology and Biostatistics Division, National Cancer Center Research Institute East, Kashiwa, Chiba 277-8577, Japan.
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Arista-Nasr J, Jiménez-Rosas F, Uribe-Uribe N, Herrera-Goepfert R, Lazos-Ochoa M. Pathological disorders of the gastric mucosa surrounding carcinomas and primary lymphomas. Am J Gastroenterol 2001; 96:1746-50. [PMID: 11419824 DOI: 10.1111/j.1572-0241.2001.03868.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Gastritis, intestinal metaplasia, atrophy, and dysplasia are disorders that frequently precede the full development of gastric adenocarcinoma. On the other hand, primary gastric lymphomas seem to arise from mucosa-associated lymphoid tissue. It is well accepted that these histological changes are caused by Helicobacter pylori infection. The objective of this study is to determine the frequency and characteristics of epithelial and lymphoid tissue disorders of the gastric mucosa surrounding primary carcinomas and lymphomas. METHODS We studied 111 gastrectomies from patients harboring primary adenocarcinomas (30 intestinal and 30 diffuse type) and 51 gastric lymphomas. For comparative purposes, we analized 86 stomachs from patients who died of diseases other than gastric malignancies. Histopathological disorders of the gastric mucosa adjacent to primary neoplasms such as atrophy, intestinal metaplasia, and dysplasia were recorded. Lymphoid follicles were classified in two groups, with or without expansion. Expansion was characterized by increased size, irregular borders, enlarged marginal zone, and expanded germinal centers. Differences were statistically evaluated with chi2 and Fisher exact tests, odds ratio, and relative risk, with 95% CI. p values <0.05 were considered statistically significant. RESULTS Most intestinal-type adenocarcinomas showed atrophy (76.6%) and intestinal metaplasia (86.6%) and less frequently, dysplasia (23.3%), in the surrounding gastric mucosa. Expansive lymphoid follicles were more frequent among lymphomas than in adenocarcinomas (56.8% vs 25%); however, a high percentage of lymphomas were also associated with atrophy (50.9%), intestinal metaplasia (62.7%), and rarely dysplasia (11.8%). On the contrary, diffuse-type adenocarcinoma displayed less frequently atrophy (33%), intestinal metaplasia (50%), and dysplasia (3%). Gastric mucosa from patients without any gastric neoplasia was almost normal (84%), whereas the remaining 16% showed, both or alone, atrophy and intestinal metaplasia. CONCLUSION Histopathological disorders of the gastric mucosa are not specific for any neoplasm, but intestinal-type adenocarcinomas frequently showed atrophy, intestinal metaplasia, and not uncommonly, dysplasia of the surrounding non-neoplastic gastric mucosa. Diffuse-type adenocarcinomas did not frequently show such lesions. Primary lymphomas displayed expansive lymphoid follicles and also a high percentage of atrophy and intestinal metaplasia of the surrounding gastric mucosa. The presence of intestinal metaplasia, atrophy, and lymphoid follicles with expansion in endoscopic biopsies could suggest a higher suceptibility for the development of gastric intestinal-type adenocarcinoma or gastric lymphoma. Patients harboring such histopathological changes must receive eradication therapy against H. pylori and probably closer follow-up.
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Affiliation(s)
- J Arista-Nasr
- Department of Pathology, Instituto Nacional de la Nutrición Salvador Zubirán, México DF, Mexico
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El-Zimaity HM, Graham DY. Cytokeratin subsets for distinguishing Barrett's esophagus from intestinal metaplasia in the cardia using endoscopic biopsy specimens. Am J Gastroenterol 2001; 96:1378-82. [PMID: 11374671 DOI: 10.1111/j.1572-0241.2001.03792.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES It has been suggested that Barrett's epithelium and intestinal metaplasia in the gastric cardia have different cyotokeratin (CK) staining patterns and that Barrett's epithelium can be distinguished by CK staining pattern. The aim of this study was to test the utility of CK staining for distinguishing Barrett's esophagus from gastric intestinal metaplasia. METHODS Topographically mapped gastric biopsy specimens were obtained from patients without Barrett's esophagus, and esophageal biopsies were obtained from patients with long-segment Barrett's esophagus (>3 cm). Serial sections were stained with Genta or El-Zimaity triple stain, and biopsies with intestinal metaplasia were stained with antibodies against CK 4, 13, 7, and 20. RESULTS Sections from 33 biopsies with Barrett's esophagus, 23 with intestinal metaplasia of the gastric cardia, 27 with intestinal metaplasia of the gastric body, and 33 with intestinal metaplasia of the antrum were examined. CK 4 and CK 13 stained squamous epithelium only. The proposed "diagnostic" CK Barrett's 7/20 pattern was found in only 39% of long-segment Barrett's compared to 35%, 4%, and 24% in intestinal metaplasia from the gastric cardia, body, and antrum, respectively. The criteria proposed had a sensitivity of 45% and a specificity of 65%. CONCLUSIONS These results do not support keratin phenotyping as a tool for differentiating intestinal metaplasia originating in the cardia from intestinal metaplasia of Barrett's.
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Affiliation(s)
- H M El-Zimaity
- Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA
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Unger Z, Molnár B, Szaleczky E, Törgyekes E, Müller F, Zágoni T, Tulassay Z, Prónai L. Effect of Helicobacter pylori infection and eradication on gastric epithelial cell proliferation and apoptosis. JOURNAL OF PHYSIOLOGY, PARIS 2001; 95:355-60. [PMID: 11595460 DOI: 10.1016/s0928-4257(01)00048-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
OBJECTIVES the effect of Helicobacter pylori infection on gastric epithelial cell proliferation and apoptosis is still controversial. Our aim was to evaluate the effect of H. pylori infection on cell kinetic parameters in normal gastric epithelium, gastritis with/without intestinal metaplasia and gastric cancer. PATIENTS AND METHODS antral biopsies were taken from 121 patients (61 women, 60 men, mean age 58.5+/-14.3 years of age) who underwent routine gastroscopy for upper gastrointestinal symptoms. Sections were scored for normal epithelia (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal metaplasia (n=24), and gastric adenocarcinoma (n=8). Fifty-two patients had H. pylori positive gastritis, and success of H. pylori eradication therapy was controlled in 12 cases, all with intestinal metaplasia. To characterize cell proliferation and assess apoptosis, immunohistochemistry [Proliferating Cell Nuclear Antigen (PCNA)], histochemistry [Argyrophil Nucleolar Organizer Regions (AgNOR)], and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridinetriphosphate (dUTP) nick end-labeling (TUNEL) were used, respectively. RESULTS both cell proliferation and apoptosis is was higher in chronic gastritis when compared with normal epithelia, but neither PCNA LI (54.79+/-19.1 vs. 53.20+/-20.7) nor AgNOR counts (291.43+/-44.3 vs. 277.8+/-57.54) were different in H. pylori positive versus negative chronic gastritis. A significant positive correlation (P<0.05) was found in this group between PCNA and AgNOR techniques. Apoptosis was significantly higher (P<0.05) in H. pylori positive cases only when intestinal metaplasia was not present. Cell proliferation in intestinal metaplasia decreased to the activity of normal epithelium after successful eradication of H. pylori but remained high if eradication therapy failed. CONCLUSIONS epithelial cell proliferation does not depend on H. pylori status in chronic gastritis. H. pylori increases apoptosis only in the absence of intestinal metaplasia.
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Affiliation(s)
- Z Unger
- Second Department of Internal Medicine, Clinical Gastroenterology and Endocrinology Unit, Semmelweis University, Budapest, Hungary
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Fukuda S, Tanaka M, Soma Y, Shimoyama T, Mikami T, Crabtree JE, Saito H, Munakata A, Yoshida Y. Histological analysis of gastritis and Helicobacter pylori infection in patients with early gastric cancer: a case-control study. J Gastroenterol Hepatol 2000; 15:1370-6. [PMID: 11197045 DOI: 10.1046/j.1440-1746.2000.02355.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIMS Infection with Helicobacter pylori is associated with an increased risk of gastric adenocarcinoma. However, most patients with H. pylori infection will not develop gastric cancer. The aims of the present study were to examine which histological features, including H. pylori infection, would increase the risk of gastric cancer using a case-control study. METHODS Three gastric biopsy specimens were taken from 72 patients with early gastric cancer and 72 age- and sex-matched control subjects. The grade of gastritis was examined according to the updated Sydney System. The presence of H. pylori infection was determined by serology and histology. Odds ratio (OR) of developing gastric cancer was calculated for H. pylori positivity and histological features using conditional logistic regression. For patients with H. pylori infection, histological features in cancer patients and control subjects were compared. RESULTS The OR of the presence of mononuclear cell infiltration in the corpus and intestinal metaplasia in the angulus were significantly elevated. The grade of mononuclear cell infiltration in the corpus and antrum was significantly higher in both types of cancer patients than controls. Glandular atrophy and intestinal metaplasia were increased in patients with intestinal-type cancer in the angulus and antrum. Bacterial density in the corpus and polymorphonuclear cell infiltration in the antrum were increased in patients with diffuse-type cancer. CONCLUSIONS Severe chronic gastritis induced by H. pylori infection seems to be associated with diffuse-type gastric cancer. Glandular atrophy and intestinal metaplasia, which occur in gastric mucosa with chronic inflammation, are significantly associated with intestinal-type cancer.
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Affiliation(s)
- S Fukuda
- First Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
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26
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Tokunaga Y, Shirahase H, Hoppou T, Kitaoka A, Tokuka A, Ohsumi K. Density of Helicobacter pylori infection evaluated semiquantitatively in gastric cancer. J Clin Gastroenterol 2000; 31:217-21. [PMID: 11034000 DOI: 10.1097/00004836-200010000-00006] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Helicobacter pylori infection may play a role in the development of gastric cancer; however, a quantitative evaluation of the density of H. pylori infection has not been reported previously in relation to the histologic stage and type of cancer. This study was designed to compare the density of H. pylori infection to the histologic stage and type of gastric cancer. Between March 1996 and March 1998, surgical resection of primary lesion was performed in 50 patients with gastric cancer (39 men and 11 women with a mean age of 67 years) at our institution. Using immunohistochemical stains, the density of H. pylori infection was evaluated semiquantitatively at cancer site as well as noncancerous mucosa adjacent to cancer. This density was compared with the histologic stage and the type of gastric cancer. The severity of the mucosal atrophy was evaluated using the updated Sydney System. The prevalences and density of H. pylori infection decreased in proportion to advances in the cancer stage and the mucosal atrophy. In early cancer of the intestinal- and diffuse-type, the prevalence of H. pylori in adjacent sites was almost 90% and was significantly higher (p < 0.01) than that seen in the advanced cancer lesions. In the intestinal-type early cancer, the prevalence and density of infection was higher (p < 0.05) in the adjacent mucosa than in the cancer site, whereas in the diffuse-type early cancer, H. pylori was found in all cases at the cancer site and the adjacent site. In advanced cancer, the prevalence of H. pylori was about 40% in the adjacent site and about 10% in the cancer site in both histologic types. These figures were significantly lower (p < 0.01) than in the early cancers. The prevalence and density of infection did not differ in the intestinal- and diffuse-type gastric cancers, but did decrease with more advanced cancer stages. The changes in local environment of the advanced cancer may not be conducive to the survival of H. pylori. Thus, the prevalence of H. pylori may be affected by the histologic stage rather than the histologic type of gastric cancer, and the organism may play a similar role, but through different pathways, in the pathogenesis of both types of cancer.
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Affiliation(s)
- Y Tokunaga
- Department of Surgery, Maizuru Municipal Hospital, Kyoto, Japan
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27
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el-Zimaity HM, Verghese VJ, Ramchatesingh J, Graham DY. The gastric cardia in gastro-oesophageal disease. J Clin Pathol 2000; 53:619-25. [PMID: 11002767 PMCID: PMC1762920 DOI: 10.1136/jcp.53.8.619] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND There have been conflicting reports concerning the use of cardia biopsies in screening patients for gastro-oesophageal disease. AIM To define the histopathological changes in the gastric cardia of patients with and without gastro-oesophageal disease. METHODS Topographically mapped gastric biopsy specimens were obtained from patients with gastro-oesophageal disease and from controls. Biopsies were scored on a visual analogue scale of 0 to 5 for Helicobacter pylori, intestinal metaplasia, pancreatic metaplasia, foveolar hyperplasia, and active inflammation. The presence or absence of cardiac glands was recorded. RESULTS Sixty-five patients with gastro-oesophageal disease and 71 controls were examined. Intestinal metaplasia was present in cardia biopsies of 10 patients with gastro-oesophageal disease and 11 controls. Only two patients with gastro-oesophageal disease and intestinal metaplasia in the cardia had no evidence of exposure to H pylori. Intestinal metaplasia was not found in the cardia of those with long segment Barrett's oesophagus. Carditis was strongly associated with active H pylori infection (p = 0.000) and resolved after treatment of the infection. A negative association was present between gastro-oesophageal disease and the presence of cardiac glands in cardiac biopsies (p = 0.003). Pancreatic metaplasia was found in 15 of 65 and foveolar hyperplasia in 19 of 65 cases but neither was related to gastro-oesophageal disease. CONCLUSION Intestinal metaplasia in the cardia is uncommon in gastro-oesophageal disease in the absence of H pylori infection. With chronic H pylori infection the junction between the cardia and corpus expands in a cardia-corpal direction.
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Affiliation(s)
- H M el-Zimaity
- Gastrointestinal Mucosa Pathology Laboratory, Veterans Affairs Medical Center, Houston, Texas 77030, USA.
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28
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Saito K, Arai K, Mori M, Kobayashi R, Ohki I. Effect of Helicobacter pylori eradication on malignant transformation of gastric adenoma. Gastrointest Endosc 2000; 52:27-32. [PMID: 10882958 DOI: 10.1067/mge.2000.106112] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND A nonrandomized trial of Helicobacter pylori eradication was conducted in patients with endoscopically diagnosed gastric adenoma to determine the long-term effect of antimicrobial treatment on progression of the adenoma. METHODS Of 64 patients with an endoscopically diagnosed gastric adenoma and H pylori infection, 32 were treated with omeprazole and antibiotics to eradicate the infection, and 32 were not. RESULTS During 2 years of follow-up, 4 (12.5%) of the 32 patients in the untreated group developed an early stage, intestinal-type gastric cancer, whereas no gastric cancer was found in the 32 patients in the treated group. CONCLUSION H Pylori eradication may inhibit progression of gastric adenoma to carcinoma.
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Affiliation(s)
- K Saito
- First Department of Internal Medicine, Gunma University School of Medicine, Japan
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29
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Vaucher C, Janvier B, Nousbaum JB, Grignon B, Pezennec L, Robaszkiewicz M, Gouerou H, Picard B, Fauchere JL. Antibody response of patients with Helicobacter pylori-related gastric adenocarcinoma: significance of anti-cagA antibodies. CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY 2000; 7:463-7. [PMID: 10799462 PMCID: PMC95895 DOI: 10.1128/cdli.7.3.463-467.2000] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The aim of this study was to search for a specific antibody pattern in sera from patients suffering from Helicobacter pylori-related gastric adenocarcinoma (GAC). The serological response of 22 patients suffering from GAC, 31 patients with gastroduodenal ulcer, and 39 asymptomatic subjects was analyzed using immunoblotting performed with three H. pylori strains: strain ATCC 43579; strain B110, isolated from a patient with ulcers; and strain B225, isolated from a patient with GAC. In addition, the latex agglutination test Pyloriset Dry was used to analyze ambiguous sera. H. pylori seropositivity was 75% in the GAC group, 61.3% in the ulcer group, and 56.4% in the asymptomatic group. Anti-CagA antibodies were found more often in the GAC group (48.8%) and in the ulcer group (47.3%) than in the asymptomatic group (21.2%). These percentages depended on the strain used as an antigen: in the GAC group, the anti-CagA frequencies were 93.3, 40, and 13.3% with strains B225, B110, and ATCC 43579, respectively. Thus the presence of anti-CagA antibodies was increased in patients suffering from H. pylori-related GAC, in particular when the CagA antigen was from a GAC strain. These data suggest the existence of a CagA protein specifically expressed by H. pylori strains isolated from GAC patients.
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Affiliation(s)
- C Vaucher
- Laboratoire de Bactériologie, Faculté de Médecine de Brest-Université de Bretagne occidentale, 29200 Brest, France
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30
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Pakodi F, Abdel-Salam OM, Debreceni A, Mózsik G. Helicobacter pylori. One bacterium and a broad spectrum of human disease! An overview. JOURNAL OF PHYSIOLOGY, PARIS 2000; 94:139-52. [PMID: 10791696 DOI: 10.1016/s0928-4257(00)00160-1] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Since the historical rediscovery of gastric spiral Helicobacter pylori in the gastric mucosa of patients with chronic gastritis by Warren and Marshall in 1983, peptic ulcer disease has been largely viewed as being of infectious aetiology. Indeed, there is a strong association between the presence of H. pylori and chronic active gastritis in histology. The bacterium can be isolated in not less than 70% of gastric and in over 90% of duodenal ulcer patients. Eradication of the organism has been associated with histologic improvement of gastritis, lower relapse rate and less risk of bleeding from duodenal ulcer. The bacterium possesses several virulence factors enabling it to survive the strong acid milieu inside the stomach and possibly damaging host tissues. The sequence of events by which the bacterium might cause gastric or duodenal ulcer is still not fully elucidated and Koch's postulates have never been fulfilled. In the majority of individuals, H. pylori infection is largely or entirely asymptomatic and there is no convincing data to suggest an increase in the prevalence of peptic ulcer disease among these subjects. An increasingly growing body of literature suggests an association between colonization by H. pylori in the stomach and a risk for developing gastric mucosa-associated lymphoid tissue (MALT), MALT lymphoma, gastric adenocarcinoma and even pancreatic adenocarcinoma. The bacterium has been implicated also in a number of extra-gastrointestinal disorders such as ischaemic heart disease, ischaemic cerebrovascular disease, atherosclerosis, and skin diseases such as rosacea, but a causal role for the bacterium is missing. Eradication of H. pylori thus seems to be a beneficial impact on human health. Various drug regimens are in use to eradicate H. pylori involving the administration of three or four drugs including bismuth compounds, metronidazole, clarithromycin, tetracyclines, amoxycillin, ranitidine, omeprazole for 1-2 weeks. The financial burden, side effects and emergence of drug resistant strains due to an increase in the use in antibiotics for H. pylori eradication therapy need further reconsideration.
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Affiliation(s)
- F Pakodi
- First Department of Medicine, Medical University of Pécs, Hungary
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31
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Tabata H, Fuchigami T, Kobayashi H, Sakai Y, Nakanishi M, Tomioka K, Nakamura S, Fujishima M. Helicobacter pylori and mucosal atrophy in patients with gastric cancer: a special study regarding the methods for detecting Helicobacter pylori. Dig Dis Sci 1999; 44:2027-34. [PMID: 10548354 DOI: 10.1023/a:1026622418625] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
We assessed the sensitivities of several methods for detecting Helicobacter pylori (culture, histology, rapid urease test, and serology), and evaluated the H. pylori positivity considering the degree of atrophy in the background mucosa in 202 gastric cancer patients and 101 controls. The positivity of H. pylori determined by culture (81%) was significantly higher than that determined by serology (62%) in gastric cancer patients (P < 0.001). The positivities of H. pylori determined by biopsy and/or serology in intestinal (84%) and diffuse (95%) types of gastric cancer were higher than that observed in controls (54%) (P < 0.001). Intestinal-type gastric cancer tended to occur in the atrophic mucosa, in which H. pylori positivity was not different from that in controls after adjusting for the degree of atrophy, whereas diffuse-type gastric cancer was observed more often in the nonatrophic mucosa, in which H. pylori positivity was higher than that in controls even after adjusting for the degree of atrophy.
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Affiliation(s)
- H Tabata
- Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan
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32
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Dellavecchia C, Guala A, Olivieri C, Haintink O, Cadario F, Luinetti O, Fiocca R, Minelli A, Danesino C, Bona G. Early onset of gastric carcinoma and constitutional deletion of 18p. CANCER GENETICS AND CYTOGENETICS 1999; 113:96-9. [PMID: 10459356 DOI: 10.1016/s0165-4608(99)00003-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
We report on the association of a gastric carcinoma and a constitutional deletion of the short arm of chromosome 18 in a 14-year-old patient. The phenotype of the patient, including microcephaly, ptosis, micrognathia, tetralogy of Fallot, and mental retardation, fits well with previously reported cases of del(18p); she also showed a positive serology against Helicobacter pylori. The comparison of the alleles of polymorphic loci located on the short arm of chromosome 18 between the patient and her parents showed a maternal origin of the abnormal chromosome. Loss of heterozygosity (LOH) for loci located in the long arm of chromosome 18 is a frequent event in gastric carcinomas; it was observed in the tumoral mass of our patient and again, the alleles lost were of maternal origin. We postulate that the constitutional chromosomal abnormality may have favored the loss of the abnormal chromosome in some cells and that the loss of the deleted chromosome 18 (demonstrated by LOH for this chromosome in the tumoral mass) has been an early step in the pathogenesis of the gastric carcinoma of our patient with Helicobacter pylori infection acting as a cofactor.
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Affiliation(s)
- C Dellavecchia
- Dipartimento di Patologia Umana ed Ereditaria, Università di Pavia, Italy
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Abstract
BACKGROUND The published epidemiological studies of chronic Helicobacter pylori infection and gastric cancer yield conflicting results, so there is uncertainty as to whether any material association exists and, if so, how strong it is. AIM To review these studies quantitatively. METHODS A systematic review of sero-epidemiological studies published before 1998 of H. pylori and gastric cancer, as identified by computer-assisted literature searches of relevant journals, reference lists and discussions with authors. All relevant studies identified were included, subdivided by study design. The following was abstracted from published reports: adjusted odds ratio (or, in prospective studies, the risk ratio) and confidence interval, study design, type of controls, mean age, mean duration of follow-up, assay methods, location of study, and degree of adjustment for confounders. RESULTS The 34 retrospective studies included in total 3300 gastric cancers, but their controls were of uncertain validity. The 10 'nested' case-control comparisons in prospective studies included in total only 800 gastric cancers, and combined analysis of them yielded a risk ratio of 2.5 (95% CI: 1.9-3.4; 2P < 0.00001) for gastric cancer in people seropositive for H. pylori antibodies. CONCLUSIONS The prospective studies suggest that gastric cancer is 2 or 3 times as common in those chronically infected by H. pylori, but to help investigate causality, further observational studies are still needed, as are large-scale randomized trials of whether antibacterial regimens reduce the eventual incidence of gastric cancer.
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Affiliation(s)
- J Danesh
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Medicine, University of Oxford, Radcliffe Infirmary, Oxford, UK.
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34
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Safatle-Ribeiro AV, Ribeiro U, Clarke MR, Sakai P, Ishioka S, Garrido AB, Gama-Rodrigues J, Safatle NF, Reynolds JC. Relationship between persistence of Helicobacter pylori and dysplasia, intestinal metaplasia, atrophy, inflammation, and cell proliferation following partial gastrectomy. Dig Dis Sci 1999; 44:243-52. [PMID: 10063907 DOI: 10.1023/a:1026681829083] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Helicobacter pylori and partial gastric resection are risk factors for gastric cancer. Our aims were to investigate the presence of H. pylori in postgastrectomy patients and to correlate that with alterations in mucosal architecture and cell proliferation. One hundred fifty-one endoscopic biopsies from 22 patients, (15-47 years of age, mean 29.2 years) following partial gastrectomy with Billroth II reconstruction for peptic ulcer disease, were examined for the presence of H. pylori using Giemsa staining. Sections were scored for grade of hyperplasia, intestinal metaplasia, dysplasia, inflammation, and atrophy. Immunohistochemistry for proliferative cell nuclear antigen (PCNA) was used to characterize cell proliferation. H. pylori was observed in 17/22 (77.3%) of patients or in 57/151 (37.7%) of biopsies. Metaplasia was seen in 18/22, chronic atrophic gastritis in 20/22, and cystic glandular dilation in 21/22 patients. The highest type of metaplasia in each patient was: four Type I, five Type IIA and nine Type IIB. Dysplasia was present in 16 biopsies from nine patients. H. pylori was more prevalent in intestinal metaplasia type I (44.8% of biopsies), than in type IIA (32.7%) or type IIB (25%). No H. pylori was detected in regions showing dysplasia or cystic glandular dilation. H. pylori colonization was associated with degree of inflammation (P = 0.00001) and cell proliferation (P = 0.0001). In conclusion, H. pylori is commonly seen many years after gastrectomy, it is associated with an increased epithelial cell proliferation, and it is not present in areas of histologic markers of premalignancy (type IIB metaplasia and dysplasia).
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Komoto K, Haruma K, Kamada T, Tanaka S, Yoshihara M, Sumii K, Kajiyama G, Talley NJ. Helicobacter pylori infection and gastric neoplasia: correlations with histological gastritis and tumor histology. Am J Gastroenterol 1998; 93:1271-6. [PMID: 9707050 DOI: 10.1111/j.1572-0241.1998.00408.x] [Citation(s) in RCA: 82] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Several authors have reported an association between Helicobacter pylori (H. pylori) and gastric carcinoma, but the data are conflicting. Atrophic gastritis and intestinal metaplasia (IM) have also been linked to gastric carcinoma, especially the intestinal tumor type. We investigated the relationship between H. pylori infection, gastric neoplasms, and histological gastritis. METHODS A total of 105 patients with gastric carcinoma, 36 patients with gastric adenoma, and 105 age- and sex-matched control subjects were examined for H. pylori infection and histological gastritis. H. pylori status was evaluated by Giemsa staining and IgG serology. Mucosal inflammation, atrophy, and IM were evaluated in biopsy specimens from antrum and corpus. RESULTS H. pylori seroprevalence was higher in patients with gastric carcinoma (98 of 105, 93%) and adenoma (34 of 36, 94%) than in control subjects (82 of 105, 71%, p < 0.05). H. pylori was more prevalent in patients with noncardia (OR, 5.67; 95% CI, 2.25-14.44) than cardia (OR, 5.20; 95% CI, 0.65-41.68) tumors. Histologic types and tumor stage (early; OR, 6.60; 95% CI, 2.23-19.69, advanced; OR, 4.27; 95% CI, 1.21-15.03) showed no difference in H. pylori prevalence. Atrophy and IM scores were higher in patients with the intestinal- but not diffuse-type of carcinoma and adenoma than in H. pylori-positive control subjects. Smoking was associated with gastric carcinoma (OR, 3.05; 95% CI, 1.58-5.93) but not alcohol or coffee use, blood group A, or a family history of gastric cancer. CONCLUSIONS Our results confirm a strong association between H. pylori and gastric carcinoma and adenoma. The intestinal-type gastric carcinoma is associated with atrophic gastritis and IM.
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Affiliation(s)
- K Komoto
- First Department of Internal Medicine, Hiroshima University School of Medicine, Japan
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36
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Basso D, Navaglia F, Brigato L, Piva MG, Toma A, Greco E, Di Mario F, Galeotti F, Roveroni G, Corsini A, Plebani M. Analysis of Helicobacter pylori vacA and cagA genotypes and serum antibody profile in benign and malignant gastroduodenal diseases. Gut 1998; 43:182-6. [PMID: 10189841 PMCID: PMC1727228 DOI: 10.1136/gut.43.2.182] [Citation(s) in RCA: 69] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Helicobacter pylori species comprise different strains, cytotoxic and non-cytotoxic, which can be identified on the basis of their genomic pattern. AIMS (1) To evaluate the polymorphism of the vacA gene and to ascertain whether the cagA gene is present in patients with gastric adenocarcinoma. (2) To study the anti-H pylori antibody profile using western blotting. PATIENTS Twenty one patients with gastric adenocarcinoma and 71 with H pylori associated benign disease (nine gastric ulcer, 29 duodenal ulcer, 25 antral gastritis, and eight duodenitis). METHODS The polymerase chain reaction was used to verify the presence or absence of cagA and to study the polymorphism of vacA in gastric mucosal samples obtained during endoscopy for patients with benign diseases and at surgery for patients with gastric adenocarcinoma. Fasting sera were used to assess anti-H pylori antibodies against different H pylori antigens by western blotting. RESULTS CagA gene and the allele s1 of vacA were significantly less frequent in patients with antral gastritis (60% and 60%) compared with patients with gastric adenocarcinoma (94% and 100%) and with other non-malignant gastroduodenal diseases (93% and 87%) (chi 2 = 16.01, p < 0.001; and chi 2 = 13.97, p < 0.01). In patients with gastric adenocarcinoma, antibodies against a 74 kDa H pylori antigen were less frequently found than in patients with benign diseases. CONCLUSIONS H pylori infection caused by cagA positive/vacA s1 strains is a frequent finding in patients with gastric adenocarcinoma. Prospective studies are needed to confirm whether the low incidence of positive serological response to the 74 kDa H pylori antigen in patients with gastric adenocarcinoma is important.
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Affiliation(s)
- D Basso
- Department of Laboratory Medicine, University Hospital of Padua, Italy
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37
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Ishihara T, Takada T, Shoji Y, Uedono Y, Takeyama N, Tanaka T. Hyperammonemia reduces water immersion--restraint stress gastric ulcers in rats. GENERAL PHARMACOLOGY 1998; 31:87-91. [PMID: 9595285 DOI: 10.1016/s0306-3623(97)00407-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
1. The influence of hyperammonemia (produced by the continuous intraperitoneal infusion of ammonium acetate for 6 days) on stress-induced gastric ulcer formation was investigated in conscious rats. 2. Continuous ammonium acetate infusion significantly reduced stress-induced gastric ulceration concomitant with an increase in gastric blood flow, as determined using radioactive microspheres. The serum levels of L-arginine as well as nitrite and nitrate (oxidative byproducts of nitric oxide) were increased by ammonium acetate infusion. 3. Prior administration of N omega-nitro-L-arginine methyl ester, a competitive nitric oxide synthase inhibitor, substantially attenuated the increase in gastric blood flow caused by ammonium acetate infusion and diminished the protective effect on gastric ulceration. 4. These findings suggest that the synthesis of endogenous nitric oxide from L-arginine is accelerated by continuous ammonium acetate infusion when the urea cycle remains intact and has a substantial cytoprotective effect on the stomach, probably through maintaining the gastric mucosal microcirculation.
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Affiliation(s)
- T Ishihara
- Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan.
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38
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Liu WZ, Zheng X, Shi Y, Dong QJ, Xiao SD. Effect of Helicobacter pylori infection on gastric epithelial proliferation in progression from normal mucosa to gastriccarcinoma. World J Gastroenterol 1998; 4:246-248. [PMID: 11819287 PMCID: PMC4723468 DOI: 10.3748/wjg.v4.i3.246] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/1997] [Revised: 03/20/1998] [Accepted: 05/10/1998] [Indexed: 02/06/2023] Open
Abstract
AIM:To study the effect of Helicobacter pylori (H. pylori) infection on gastric epithelial proliferation in the progression from normal mucosa to gastric carcinoma.METHODS:Gastric biopsy specimens from normal controls (n = 11), superficial gastritis (n = 32), atrophic gastritis with intestinal metaplasia (n= 83), dysplasia (n= 25) and gastric carcinoma (n = 10) were studied by immunohistochemical stianing of proliferating cell nuclear antigen (PCNA).RESULTS: The gastric epithelial proliferation, expressed as PCNA labeling index (LI)%, was progressively increased in successive stages from normal mucosa to gastric carcinoma regardless of H. pylori status. There was significant difference in PCNA LI% among all groups (P <0.01). The analysis pursuing the effect of H. pylori infection on gastric epithelial proliferation in the progression from normal mucosa to gastriccarcinoma showed that in superficial gastritis and mild atrophic gastritis groups, PCNA LI% in H. pylori positive patients were 13.14 ± 1.6 and 19.68 ± 2.22 respectively, significantly higher than 6.95 ± 0.78 and 11.34 ± 1.89 in H. pylori negative patients (P <0.01); but there was no such difference in other groups (P >0.05).CONCLUSION:H. pylori infection causes increased gastric epithelial proliferation in the stages of superficial and mild atrophic gastritis and may play a part in triggering gastric carcinogenesis.
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39
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Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology 1998; 114:1169-79. [PMID: 9609753 DOI: 10.1016/s0016-5085(98)70422-6] [Citation(s) in RCA: 595] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Reports in the literature regarding the relationship of Helicobacter pylori infection to gastric cancer are conflicting. The aim of this study was to identify the source of heterogeneity between studies. METHODS Meta-analysis of cohort or case-control studies with age- and/or sex-matched controls, providing raw data on H. pylori infection detected by serology, was used. RESULTS A fully recursive literature search identified 19 qualified studies with 2491 patients and 3959 controls. Test for homogeneity found a significant difference in odds ratio between patients with early and advanced gastric cancer (6.35 vs. 2.13; P = 0.01), patients with cardiac and noncardiac gastric cancer (1.23 vs. 3.08; P = 0.003), and population- and hospital-based controls (2.11 vs. 1.49; P < 0.001). The summary odds ratio for gastric cancer in H. pylori-infected patients is 1.92 (95% confidence interval [CI], 1.32-2.78), 2.24 (95% CI, 1.15-4.4), and 1.81 (95% CI, 1.16-2.84) for all studies, cohort, and case-control studies, respectively. H. pylori-infected younger patients have a higher relative risk for gastric cancer than older patients with odds ratios decreasing from 9.29 at age < or = 29 years to 1.05 at age > or = 70 years. H. pylori infection is equally associated with the intestinal or diffuse type of gastric cancer. CONCLUSIONS H. pylori infection is a risk factor for gastric cancer. The heterogeneity of reported results is caused by differences in the selection of controls, patient age, and the site and stage of gastric cancer.
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Affiliation(s)
- J Q Huang
- Department of Medicine, McMaster University Medical Center, Hamilton, Ontario, Canada
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40
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Shimizu N, Kaminishi M, Tatematsu M, Tsuji E, Yoshikawa A, Yamaguchi H, Aoki F, Oohara T. Helicobacter pylori promotes development of pepsinogen-altered pyloric glands, a preneoplastic lesion of glandular stomach of BALB/c mice pretreated with N-methyl-N-nitrosourea. Cancer Lett 1998; 123:63-9. [PMID: 9461019 DOI: 10.1016/s0304-3835(97)00405-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
H. pylori is thought to be a stomach carcinogen. Since no experimental model has hitherto been established to clarify the relationship between H. pylori and stomach carcinogenesis, the effects of infection with the bacteria on experimental carcinogenesis in the glandular stomach of mice were investigated. BALB/c mice were given salty diet or N-methyl-N-nitrosourea (MNU) and administered broth culture of H. pylori. The incidence of pepsinogen-altered pyloric glands, considered as precancerous lesions, was increased in the H. pylori inoculated group pre-treated with MNU. The findings provide the new experimental model demonstrating the relationship between stomach cancer and H. pylori.
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Affiliation(s)
- N Shimizu
- Laboratory of Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
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Ng EK, Sung JJ, Ling TK, Ip SM, Lau JY, Chan AC, Liew CT, Chung SC. Helicobacter pylori and the null genotype of glutathione-S-transferase-mu in patients with gastric adenocarcinoma. Cancer 1998; 82:268-73. [PMID: 9445181 DOI: 10.1002/(sici)1097-0142(19980115)82:2<268::aid-cncr4>3.0.co;2-n] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Chronic Helicobacter pylori infection now is recognized as an important causative agent for gastric carcinoma. However, only a small minority of infected individuals develop the malignancy, even in areas with a high prevalence of gastric carcinoma. It has been postulated that the absence of glutathione-S-transferase-mu (GST-mu), which impairs detoxification of exogenous carcinogens, might predispose some infected individuals to the development of gastric carcinoma. METHODS Patients with histologically confirmed adenocarcinoma of the stomach were tested for H. pylori infection and the GST-mu genotype. Prevalence of GST-mu gene deletion was compared with the H. pylori status of the patients. A group of gender- and age-matched control subjects with known H. pylori-related nonulcer dyspepsia also were tested for the GST-mu genotype and compared with patients with H. pylori positive carcinoma. RESULTS Fifty-one patients with gastric adenocarcinoma were enrolled into the study. Thirty-five were found to have H. pylori in the resected specimens. The null genotype of GST-mu was significantly more common among those patients with H. pylori positive carcinoma compared with the H. pylori negative group (65.7% vs. 31.3%; P < 0.05). Homozygous deletion of GST-mu was significantly higher in the H. pylori positive carcinoma patients than in the H. pylori-infected, nonmalignant control group (65.7% vs. 37.1%; P < 0.05). CONCLUSIONS The null genotype for GST-mu is found more commonly in gastric carcinoma associated with H. pylori infection. The absence of the GST-mu enzyme may increase the risk of the development of gastric carcinoma in these patients.
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Affiliation(s)
- E K Ng
- Department of Surgery, Prince of Wales Hospital, Shatin, N.T., Hong Kong
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Iseki K, Tatsuta M, Iishi H, Baba M, Ishiguro S. Helicobacter pylori infection in patients with early gastric cancer by the endoscopic phenol red test. Gut 1998; 42:20-3. [PMID: 9505880 PMCID: PMC1726958 DOI: 10.1136/gut.42.1.20] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND An endoscopic procedure that uses a pH indicator called phenol red to assess Helicobacter pylori infected gastric mucosa has recently been developed. This test makes it possible to take biopsy specimens from H pylori infected areas. AIM This test was applied to patients with early gastric cancers to clarify the role of H pylori in gastric carcinogenesis. SUBJECTS Sixty five patients with early gastric cancer (50 with differentiated adenocarcinoma and 15 with undifferentiated adenocarcinoma). METHODS Patients with early gastric cancer underwent the endoscopic phenol red test before their operation. In this test, areas infected with H pylori can be observed as "coloured" areas where phenol red was turned from yellow to red. RESULTS H pylori infection was significantly (p < 0.001) more frequent in patients with differentiated adenocarcinomas than in those with undifferentiated adenocarcinomas. Differentiated adenocarcinomas were usually located in areas of mucosa infected with H pylori, but undifferentiated adenocarcinomas were frequently located in non-infected areas. CONCLUSION H pylori may be a strong risk factor for differentiated early gastric cancer.
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Affiliation(s)
- K Iseki
- Department of Gastroenterology, Osaka Medical Centre for Cancer and Cardiovascular Diseases, Japan
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Tan AC, den Hartog G, Meijer JW, Thies JE, de Vries RA, Mulder CJ. No additional value of bismuth subcitrate to combination omeprazole/amoxicillin therapy in the eradication of Helicobacter pylori. Helicobacter 1997; 2:194-8. [PMID: 9421123 DOI: 10.1111/j.1523-5378.1997.tb00087.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND We investigated whether addition of bismuth subcitrate (BSC, 4 x 120 mg) to a two week therapy scheme of omeprazole (OME, 2 x 40 mg)/amoxicillin (AMO, 4 x 500 mg) increases Helicobacter pylori eradication. MATERIALS AND METHODS Patients with dyspepsia underwent upper endoscopy. H. pylori positive patients were randomized to treatment A (OME/AMO, 83 patients) or treatment B (OME/AMO/BSC, 84 patients). RESULTS In 65 patients of group A (78%) H. pylori was eradicated as determined from the histological assessment (Sydney classification) of antrum and corpus biopsies. In comparison, in 68 patients of group B (81%) H. pylori was eradicated (p = NS between groups). H. pylori eradication in both groups was associated similarly with a decrease of inflammation and activity whereas atrophy and intestinal metaplasia were not affected. A positive association was revealed between the decrease of H. pylori score and the decrease of both inflammation and activity scores for antrum as well as corpus biopsies. CONCLUSIONS Addition of BSC to OME/AMO does not increase H. pylori eradication in patients with dyspepsia. Eradication of H. pylori is associated with disappearance of epithelial damage (inflammation and activity) in antral and corpus mucosa.
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Affiliation(s)
- A C Tan
- Department of Hepato-Gastroenterology, Rijnstate Hospital, Arnhem, The Netherlands.
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Hamajima N, Inoue M, Tajima K, Tominaga S, Matsuura A, Kobayashi S, Ariyoshi Y. Lifestyle and anti-Helicobacter pylori immunoglobulin G antibody among outpatients. Jpn J Cancer Res 1997; 88:1038-43. [PMID: 9439678 PMCID: PMC5921320 DOI: 10.1111/j.1349-7006.1997.tb00327.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Since eradication of Helicobacter pylori (H. pylori) is thought to be a preventive measure against stomach cancer, several studies have examined factors associated with the infection. This paper reports the association of the infection with lifestyle factors observed in a hospital-based case-control study. Cases were 140 anti-H. pylori IgG antibody-positive outpatients (75 males and 65 females). Controls were 52 antibody-negative outpatients (22 males and 30 females). Both groups had undergone gastroscopy at Aichi Cancer Center Hospital between February 1995 and February 1997, and lifestyle data collected on the first visit were linked to calculate odds ratios. A strong association was observed with smoking among males; age-adjusted odds ratio (OR) = 7.85, 95% confidence interval (CI), 2.03-30.4. Rice breakfast (OR = 3.74; 95% CI, 1.30-10.8) and soybean paste soup (every day vs. occasionally, OR = 5.24; 95% CI, 1.80-15.2) were also associated with antibody positivity in males, but not in females. In females, pickled Chinese cabbage (> or = 1/week vs. < or = 3/month, OR = 2.82; 95% CI, 1.06-7.48) and lettuce (> or = 1/week vs. < or = 3/month, OR = 2.90; 95% CI, 1.09-7.76) were significantly associated with positivity. Multivariate analysis gave similar estimates for the above factors. Although the association between smoking and H. pylori infection has not been detected in past studies of a general population, except one recent one, this study on outpatients suggested a possible association. Smoking may work as a cofactor disturbing incidental eradication of H. pylori by antibacterial agents administered for other reasons.
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Affiliation(s)
- N Hamajima
- Division of Epidemiology, Aichi Cancer Center Research Institute
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McFarlane GA, Munro A. Helicobacter pyloriand gastric cancer. Br J Surg 1997. [DOI: 10.1046/j.1365-2168.1997.02874.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Shibata T, Imoto I, Gabazza EC. Detection of Helicobacter pylori in biopsy of patients with gastric carcinoma. Biomed Pharmacother 1997; 51:22-8. [PMID: 9084726 DOI: 10.1016/s0753-3322(97)87075-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Superficial chronic gastritis caused by Helicobacter pylori may lead potentially to the development of atrophic gastritis, a precursor of gastric carcinoma. Based on histological studies, the prevalence of Helicobacter pylori infection in gastric cancer patients, has been reported to vary widely from 38% to 100%. This positivity rate tends to be higher in patients with gastric cancer in early stage than in those with advanced malignant disease, probably, due to the relative mild atrophic and intestinal metaplastic changes of the surrounding gastric mucosa that occur in the former group. The prevalence of Helicobacter pylori infection is not related to the anatomical localization of cancer in the stomach. The inclusion of cases in advanced stages of disease and the examination of a few small-sized number of gastric specimens may explain the discrepant findings reported so far regarding the prevalence of Helicobacter pylori infection in patients with gastric cancer. We found a strong association between Helicobacter pylori infection and the occurrence of gastric carcinoma. Therefore, Helicobacter pylori may be an important carcinogenetic factor for the occurrence of malignant disease in the stomach. Cure of Helicobacter pylori infection may potentially reduce the incidence of gastric cancer.
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Affiliation(s)
- T Shibata
- Third Department of Internal Medicine, Mie University School of Medicine, Tsu-City, Japan
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Showji Y, Nozawa R, Sato K, Suzuki H. Seroprevalence of Helicobacter pylori infection in patients with connective tissue diseases. Microbiol Immunol 1996; 40:499-503. [PMID: 8865155 DOI: 10.1111/j.1348-0421.1996.tb01100.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
To assess the possibility that Helicobacter pylori might be an etiologic agent, titers of anti-H. pylori IgG in sera of patients with connective tissue diseases [rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyositis or dermatomyositis (PM/DM), progressive systemic sclerosis (PSS), mixed connective tissue disease (MCTD) and Sjögren's syndrome (SjS)] were compared with those of non-patient (healthy) volunteers and of patients with chronic pulmonary diseases (CPD) by ELISA using an extract of sonicated H. pylori as the antigen. Among patients with connective tissue diseases, those with SLE and RA had anti-H. pylori titers as low as healthy volunteers. Patients with SjS had much higher average titers than patients with CPD (P < 0.05). We previously reported that levels of myeloid calcium-binding protein (MRP8 and MRP14) were elevated in the serum of patients with connective tissue diseases. No correlation was found between serum levels of anti-H. pylori IgG and of MRP, a novel marker of inflammation. Furthermore, sera with high IgG titers were selected, and their reactivity with the H. pylori antigen were analyzed by Western blotting. H. pylori antigens with a variety of molecular masses were immunostained with sera from patients and from healthy volunteers, but a 16-kDa antigen was only immunostained by reaction with the sera of patients with MCTD and SjS, although the number of test samples was small.
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Affiliation(s)
- Y Showji
- Laboratory of Microbiology and Host Defenses, University of Shizuoka School of Food and Nutritional Sciences, Japan
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Craanen ME, Blok P, Top B, Boerrigter L, Dekker W, Offerhaus GJ, Tytgat GN, Rodenhuis S. Absence of ras gene mutations in early gastric carcinomas. Gut 1995; 37:758-62. [PMID: 8537044 PMCID: PMC1382935 DOI: 10.1136/gut.37.6.758] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The aims of this study were to assess the prevalence and type of activating point mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N-ras genes in a series of early gastric carcinomas in white patients and to correlate these ras gene mutations, if any, with the histological type (Lauren classification), the type of growth pattern, and with the Helicobacter pylori status. Haematoxylin and eosin and Giemsa stained sections from 45 formalin fixed, paraffin wax embedded early gastric carcinomas were used to assess the Lauren type, the type of growth pattern, and the antral H pylori status. DNA was extracted according to standard procedures. Mutations at codon 12 of the Ki-ras gene were examined with a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) method and dot blot hybridisation with allele-specific 32P-labelled oligodeoxynucleotide (ASO) probes. All other ras genes were analysed with specific PCR amplification and dot blot hybridisation with ASO probes. Mutations were detected by overnight autoradiography at -70 degrees C. Some 20 intestinal-type and 25 diffuse-type early gastric carcinomas were seen. According to growth pattern, there were 24 small mucosal type early gastric carcinomas, five superficial spreading type early gastric carcinomas, and 16 penetrating type early gastric carcinomas (four penetrating A type, 12 penetrating B type). H pylori was found in the antral mucosa of 28 early gastric carcinomas (62%). Activating ras gene mutations were not found. It was discovered that activating point mutations at codons 12, 13, and 61 of the Ki-, Ha-, and N-ras genes do not play a part in the development of early gastric carcinomas in white subjects, irrespective of Lauren type. Moreover, differences in biological behaviour between early carcinomas with different types of growth pattern are not related to these ras gene mutations. Finally, H pylori positive and H pylori negative gastric carcinomas cannot be discriminated on the basis of ras gene mutational analysis.
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Affiliation(s)
- M E Craanen
- Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands
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