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Kotelevets SM, Chekh SA, Chukov SZ. Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention. World J Gastrointest Endosc 2024; 16:462-471. [PMID: 39155993 PMCID: PMC11325870 DOI: 10.4253/wjge.v16.i8.462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 06/30/2024] [Accepted: 07/25/2024] [Indexed: 08/01/2024] Open
Abstract
BACKGROUND New markers are needed to improve the effectiveness of serological screening for atrophic gastritis. AIM To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity. METHODS Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. All 169 patients were examined for postprandial levels of gastrin-17 (G17) and pepsinogen-1 (PG1) using GastroPanel® (Biohit Plc, Helsinki, Finland). RESULTS We used the histological standard of five biopsies of the gastric mucosa, in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy. We also compared the morpho-functional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1, as the markers of atrophic gastritis. The sensitivity of postprandial G17 was 62.2% for serological levels of G17 (range: 0-4 pmol/L) and 100% for serological G17 (range: 0-10 pmol/L) for the detection of monofocal severe atrophic gastritis. No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus. In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis, there is a pronounced positive long-term dynamics of the serological marker of atrophy - postprandial G17, after five months of rennet replacement therapy. CONCLUSION Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity. Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system. Therefore, postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.
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Affiliation(s)
- Sergey M Kotelevets
- Department of Therapy, North Caucasus State Academy, Cherkessk 369000, Karachay-Cherkess Republic, Russia
| | - Sergey A Chekh
- Department of Mathematics, North Caucasus State Academy, Cherkessk 369000, Karachay-Cherkess Republic, Russia
| | - Sergey Z Chukov
- Department of Pathological Anatomy, Stavropol State Medical University, Stavropol 355017, Russia
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Wang X, Lu CJ, Li H, Zhang JY, Zheng JW, Wu N, Yang WL, Yu J, Huang WF. Clinicopathological characteristics of autoimmune gastritis: A single-center retrospective study. Clin Res Hepatol Gastroenterol 2023; 47:102154. [PMID: 37311519 DOI: 10.1016/j.clinre.2023.102154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/28/2023] [Accepted: 06/05/2023] [Indexed: 06/15/2023]
Abstract
BACKGROUND AND AIM Autoimmune gastritis (AIG) is a prominent risk factor for pernicious anemia (PA) and gastric neoplasia. This study aimed to investigate the clinicopathological characteristics of AIG patients in China, with a focus on those who had positive anti-intrinsic factor antibodies (AIFA). METHODS A total of 103 AIG patients who were diagnosed between January 2018 and August 2022 were reviewed in a large academic tertiary teaching hospital. Patients were divided into two groups based on the presence or absence of AIFA, and their serologic and histopathological characteristics were analyzed. RESULTS The mean age of the 103 AIG patients was 54.16±11.92 years (range 23-79), with 69 (66.99%) being women. AIFA were present in 28.16% of patients. Patients with AIFA-positive had a higher risk of PA than those with AIFA-negative, as demonstrated by a larger mean corpuscular volume (MCV), lower hemoglobin level, and lower vitamin B-12 level (P<0.05). There were no statistically significant differences in gastric histopathology, gastrin level, and pepsinogen level when patients were divided into AIFA-positive and AIFA-negative group. Of the 103 cases, 34 (33.01%) were concomitant with other autoimmune diseases, with autoimmune thyroid diseases being the most common (25.24%, 26/103). Thyroid peroxidase antibody, which accounted for 45.45% (25/55), was the most prevalent thyroid antibody, followed by anti-thyroglobulin antibody (34.55%, 19/55), thyroid stimulating antibody (12.73%, 7/55), and thyrotropin receptor antibody (3.64%, 2/55). CONCLUSION This study highlights the increased risk of severe anemia in AIFA-positive AIG patients, particularly for PA. Clinicians should consider the presence of AIFA as a warning sign for PA and prioritize early diagnosis and appropriate treatment to prevent serious complications.
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Affiliation(s)
- Xu Wang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Chun-Jing Lu
- Department of Blood Transfusion, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China
| | - Hua Li
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - Jin-Yan Zhang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Zheng
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Na Wu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Wei-Lin Yang
- Endoscopy Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Juan Yu
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
| | - Wei-Feng Huang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, Fuzhou, China.
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Taniguchi M, Sudo G, Sekiguchi Y, Nakase H. Autoimmune gastritis concomitant with gastric adenoma and subacute combined degeneration of the spinal cord. BMJ Case Rep 2021; 14:14/5/e242836. [PMID: 33975851 PMCID: PMC8118001 DOI: 10.1136/bcr-2021-242836] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
A 62-year-old woman was referred to our department for further investigation of anaemia. Blood test showed macrocytic anaemia. Oesophagogastroduodenoscopy (OGD) revealed proximal-predominant gastric atrophy and flat elevated lesion in the gastric body. Several days after OGD, she complained of gait disturbance and was diagnosed with subacute combined degeneration of the spinal cord. Furthermore, laboratory tests showed positive for both anti-parietal cell and anti-intrinsic factor antibodies, as well as increased serum gastrin level and decreased pepsinogen I level, which confirmed the diagnosis of autoimmune gastritis (AIG). Anaemia and neurological symptoms were improved after vitamin B12 supplementation. Subsequently, the patient underwent gastric endoscopic submucosal dissection; histopathological examination revealed gastric adenoma. AIG can cause gastric neoplasms and vitamin B12 deficiency, with the latter resulting in pernicious anaemia and neurological disorders. These diseases are treatable but potentially life-threatening. This case highlights the importance of early diagnosis of AIG and proper management of its comorbidities.
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Affiliation(s)
- Masahiro Taniguchi
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Gota Sudo
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | | | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
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Terao S, Suzuki S, Yaita H, Kurahara K, Shunto J, Furuta T, Maruyama Y, Ito M, Kamada T, Aoki R, Inoue K, Manabe N, Haruma K. Multicenter study of autoimmune gastritis in Japan: Clinical and endoscopic characteristics. Dig Endosc 2020; 32:364-372. [PMID: 31368581 DOI: 10.1111/den.13500] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 07/28/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM In Japan, the prevalence of autoimmune gastritis (AIG) is assumed to be very low. With the recent rapid decrease in Helicobacter pylori (Hp) prevalence, reports on AIG are increasing. This multicenter registry study aimed to clarify the characteristics of AIG, especially its endoscopic appearance. METHODS A total of 245 patients with AIG from 11 institutions in Japan from January 2010 to October 2016 were included, and their clinical and endoscopic findings were evaluated. RESULTS Mean age was 67.2 ± 11.4 years, and 63.7% of the participants were women. The most common approach to diagnose AIG was endoscopic examination. Repeated incorrect treatment for Hp infection, due to a false-positive result in 13 C-urea breath test, ranked third among the basis for diagnosis of AIG. Associated gastric lesions were type 1 neuroendocrine tumor (11.4%), adenocarcinoma (9.8%), and hyperplastic polyps (21.1%). Corpus pan-atrophy was the most common appearance (90.1%); however, remnant oxyntic mucosa was found in 31.5% of the patients (flat, localized type, 48.6%). Sticky adherent dense mucus and scattered minute whitish protrusions were also observed in approximately 30% of the patients. Despite the prevailing presumption of the antral mucosa remaining normal, 42.3% of the patients presented with various extents of atrophy, and patchy redness and circular wrinkle-like patterns were both observed in approximately 20% of the patients. CONCLUSIONS The present study showed some prominent clinical characteristics and endoscopic findings of AIG. We believe that our study will facilitate the diagnosis of potential AIG.
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Affiliation(s)
- Shuichi Terao
- Department of Gastroenterology, Kakogawa Central City Hospital, Hyogo, Japan
| | - Shiho Suzuki
- Department of Gastroenterology, Kakogawa Central City Hospital, Hyogo, Japan
| | - Hiroki Yaita
- Division of Gastroenterology, Matsuyama Red Cross Hospital, Ehime, Japan
| | - Koichi Kurahara
- Division of Gastroenterology, Matsuyama Red Cross Hospital, Ehime, Japan
| | | | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Yasuhiko Maruyama
- Department of Gastroenterology, Fujieda Municipal General Hospital, Shizuoka, Japan
| | - Masanori Ito
- Department of Gastroenterology and Metabolism, Hiroshima University Hospital, Hiroshima, Japan
| | - Tomoari Kamada
- Department of Health Care Medicine, Kawasaki Medical School, Okayama, Japan
| | - Rika Aoki
- Tokushima Health Screening Center, Tokushima, Japan
| | | | - Noriaki Manabe
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Okayama, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
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Nehme F, Rowe K, Palko W, Tofteland N, Salyers W. Autoimmune metaplastic atrophic gastritis and association with neuroendocrine tumors of the stomach. Clin J Gastroenterol 2019; 13:299-307. [PMID: 31782113 DOI: 10.1007/s12328-019-01074-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 11/19/2019] [Indexed: 02/07/2023]
Abstract
Autoimmune metaplastic atrophic gastritis (AMAG) previously called type A chronic gastritis is an immune-mediated chronic inflammatory disease characterized by the immune-mediated destruction of gastric parietal cells in the fundus and body of the stomach. AMAG is an uncommon disease that often presents with hematological manifestations and may lead to the development of gastric carcinoids. AMAG can be reliably diagnosed by antibody assays, functional serology, and histology. The understanding of the disease process is essential for the detection and management of hematological complications and gastric lesions. The prevalence of AMAG is on the rise and subsequently gastric carcinoids. However, this association is not well recognized in clinical practice, and management and diagnosis of AMAG and gastric carcinoids remain suboptimal. In the current review, we will discuss the pathophysiology, diagnosis and management of AMAG. A special focus is given to the association between AMAG and gastric carcinoids. We will also review the management options of type 1 gastric carcinoids.
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Affiliation(s)
- Fredy Nehme
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City, 4800 Oak Street, Kansas, MO, 64112, USA.
| | - Kyle Rowe
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Dallas, TX, USA
| | - William Palko
- Department of Pathology, Kansas University School of Medicine, Wichita, KS, USA
| | - Nathan Tofteland
- Department of Gastroenterology and Hepatology, Kansas University School of Medicine, Wichita, KS, USA
| | - William Salyers
- Department of Gastroenterology and Hepatology, Kansas University School of Medicine, Wichita, KS, USA
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Immune Homeostasis of Human Gastric Mucosa in Helicobacter pylori Infection. Bull Exp Biol Med 2015; 159:157-63. [PMID: 26033608 DOI: 10.1007/s10517-015-2913-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Indexed: 01/21/2023]
Abstract
We present the results of electron microscopic, microbiological, immunohistochemical, and molecular genetic studies of gastric biopsy specimens taken for diagnostic purposes according by clinical indications during examination of patients with gastrointestinal pathology. Immune homeostasis of the gastric mucosa against the background of infection with various pathogen strains of Helicobacter pylori was studied in patients of different age groups with peptic ulcer, gastritis, metaplasia, and cancer. Some peculiarities of Helicobacter pylori contamination in the gastric mucosa were demonstrated. Immune homeostasis of the gastric mucosa in different pathologies was analyzed depending on the Helicobacter pylori genotype.
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Dacha S, Razvi M, Massaad J, Cai Q, Wehbi M. Hypergastrinemia. Gastroenterol Rep (Oxf) 2015; 3:201-8. [PMID: 25698559 PMCID: PMC4527266 DOI: 10.1093/gastro/gov004] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Accepted: 01/08/2015] [Indexed: 12/26/2022] Open
Abstract
Gastrin is an important hormone of the digestive system, which assists gastric acid secretion. It may be pathologically elevated in conditions such as Zollinger-Ellison syndrome, or due to common medications such as proton pump inhibitors. In this review we provide an overview of the pathophysiology and medical causes of hypergastrinemia, diagnostic testing and clinical consequences of chronic hypergastrinemia.
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Affiliation(s)
- Sunil Dacha
- Internal Medicine, Emory University, Atlanta, GA, USA
| | | | - Julia Massaad
- Internal Medicine, Emory University, Atlanta, GA, USA
| | - Qiang Cai
- Internal Medicine, Emory University, Atlanta, GA, USA
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Atrophic gastritis: a related factor for osteoporosis in elderly women. PLoS One 2014; 9:e101852. [PMID: 25003598 PMCID: PMC4087012 DOI: 10.1371/journal.pone.0101852] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Accepted: 06/10/2014] [Indexed: 01/11/2023] Open
Abstract
Purpose Osteoporosis poses a great threat to the aging society. Hypochlorhydric or achlorhydric conditions are risk factors for osteoporosis. Atrophic gastritis also decreases gastric acid production; however, the role of atrophic gastritis as a related factor for osteoporosis is unclear. We investigated the relationship between atrophic gastritis and osteoporosis in postmenopausal women over 60 years of age. Subjects and Methods A total of 401 postmenopausal women were included in this cross-sectional study, which was conducted during their medical check-ups. Bone mineral densitometry was measured using a dual energy X-ray absorptiometry. Atrophic gastritis was defined endoscopically if gastric mucosa in the antrum and the body were found to be atrophied and thinned and submucosal vessels could be well visualized. Results The proportion of people with atrophic gastritis was higher in the osteoporotic group than in the group without osteoporosis. A linear relationship was observed in the proportion of atrophic gastritis according to the categories of normal, osteopenia, and osteoporosis at the lumbar spine (p for trend = 0.039) and femur (p for trend = 0.001). A multiple logistic regression analysis revealed that the presence of atrophic gastritis was associated with an increased odds of osteoporosis after adjusting for age, body mass index, triglyceride, high-density lipoprotein cholesterol, alcohol consumption, and smoking status (odds ratio 1.89, 95% confidence interval 1.15–3.11). Conclusions Atrophic gastritis is associated with an increased likelihood of osteoporosis in Korean elderly women.
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Agudo A, Bonet C, Sala N, Muñoz X, Aranda N, Fonseca-Nunes A, Clavel-Chapelon F, Boutron-Ruault MC, Vineis P, Panico S, Palli D, Tumino R, Grioni S, Quirós JR, Molina E, Navarro C, Barricarte A, Chamosa S, Allen NE, Khaw KT, Bueno-de-Mesquita HB, Siersema PD, Numans ME, Trichopoulou A, Lagiou P, Trichopoulos D, Kaaks R, Canzian F, Boeing H, Meidtner K, Johansson M, Sund M, Manjer J, Overvad K, Tjonneland A, Lund E, Weiderpass E, Jenab M, Fedirko V, Offerhaus GJA, Riboli E, González CA, Jakszyn P. Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Carcinogenesis 2013; 34:1244-50. [PMID: 23389292 DOI: 10.1093/carcin/bgt045] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.
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Affiliation(s)
- Antonio Agudo
- Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
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Affiliation(s)
- Jason Y Park
- Department of Pathology, Children's Medical Center, and University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA
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Bornschein J, Selgrad M, Wex T, Kuester D, Malfertheiner P. Serological assessment of gastric mucosal atrophy in gastric cancer. BMC Gastroenterol 2012; 12:10. [PMID: 22289789 PMCID: PMC3280182 DOI: 10.1186/1471-230x-12-10] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2011] [Accepted: 01/31/2012] [Indexed: 12/24/2022] Open
Abstract
Background Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1), pepsinogen 2 (PG2) and gastrin 17 (G17) offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia. Methods Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation), degree of mucosal abnormalities (intestinal metaplasia, atrophy) and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status). Association of the general factors to the different serological values have been statistically analyzed. Results Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003). The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058). The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p < 0.01). Laurén-specific analysis revealed that this is only true for intestinal type tumors. Univariate ANOVA revealed atrophy and CagA-status as the only independent factors for low PG1 and a low PG1/2-ratio. Conclusions Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer.
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Affiliation(s)
- Jan Bornschein
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany
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Shao JS, Carmel R, Alpers DH. Production of ectopic gastric intrinsic factor in gastric mucosa of humans with chronic gastritis. Dig Dis Sci 2011; 56:3209-19. [PMID: 21567190 PMCID: PMC4443845 DOI: 10.1007/s10620-011-1738-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2010] [Accepted: 04/25/2011] [Indexed: 01/03/2023]
Abstract
BACKGROUND Ectopic expression of gastric intrinsic factor (IF) has been described in rodent models of chronic gastritis. AIMS The current study undertook to determine if ectopic IF was also present in chronic gastritis in humans and might identify the process of ectopic protein expression as part of the response to chronic injury. METHODS Archived biopsies from mid-body, angularis and prepylorus of 9 patients with and without chronic gastritis and food-cobalamin malabsorption were examined in a blinded fashion by immunocytochemistry as were biopsies from 5 normal subjects. Cells with ectopic IF were further examined with antibodies against pepsin or with Griffonia simplicifolia II (GSII) to identity cells in the mucous neck cell compartment. RESULTS Ectopic IF production in non-parietal cells was identified in cells that were H(+),K(+)-ATPase-negative but IF-positive in 7 of the 9 patients (6/9 in the angularis and/or prepylorus biopsies and 1/9 only in the mid-body). These included 5 of the 6 H. pylori-infected patients and all 5 patients with severe food-cobalamin malabsorption. No normal control subjects demonstrated ectopic IF. The cells with ectopic IF were pepsinogen-positive peptic cells and were not GSII-positive. Expression was most extensive in patients and gastric regions with inflammation. In all but one sample, ectopic IF was observed near anatomical mucosal junctions, such as antral/body and prepylorus/duodenum junctions. CONCLUSIONS These data in humans with and without gastritis are consistent with the hypothesis that local factors influence ectopic gastric IF expression, arising from either the anatomical location, the focal inflammation, or both.
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Affiliation(s)
- J. S. Shao
- Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
| | - R. Carmel
- Department of Medicine, New York Methodist Hospital, Brooklyn, NY, USA. Weill Medical College of Cornell University, New York, NY, USA
| | - D. H. Alpers
- Department of Internal Medicine, Campus Box 8031, Washington University School of Medicine, 660 S Euclid Ave., St Louis, MO 63130, USA
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Optimal approach to obtaining mucosal biopsies for assessment of inflammatory disorders of the gastrointestinal tract. Am J Gastroenterol 2009; 104:774-83. [PMID: 19209164 DOI: 10.1038/ajg.2008.108] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Endoscopic evaluation and mucosal biopsy analysis have assumed important roles in the clinical management of patients with symptoms related to the gastrointestinal tract. Several common inflammatory diseases, including eosinophilic esophagitis, Barrett's esophagus, Helicobacter pylori infection, celiac disease, lymphocytic colitis, collagenous colitis, and inflammatory bowel disease, may display a patchy or discontinuous distribution and, thus, multiple mucosal samples may be required to obtain diagnostic tissue in some cases. Not surprisingly, clinicians and pathologists are increasingly challenged to determine the optimum number of procedures and tissue samples necessary to detect, or exclude, the presence of inflammatory disorders of the gastrointestinal tract. Unfortunately, clinical practice varies widely with respect to tissue sample procurement in the evaluation of these disorders, particularly when the endoscopic appearance of the gastrointestinal mucosa is normal or shows only minimal changes. Guidelines concerning the appropriate number of tissue samples are well established for some diseases, such as Barrett's esophagus and chronic gastritis, but are not clear in other instances. The purpose of this review is to discuss the available literature pertaining to appropriate endoscopic sampling in the assessment of medical diseases of the gastrointestinal tract, and to develop recommendations regarding the clinical evaluation of common gastrointestinal disorders.
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Zavros Y, Waghray M, Tessier A, Bai L, Todisco A, L Gumucio D, Samuelson LC, Dlugosz A, Merchant JL. Reduced pepsin A processing of sonic hedgehog in parietal cells precedes gastric atrophy and transformation. J Biol Chem 2007; 282:33265-33274. [PMID: 17872943 DOI: 10.1074/jbc.m707090200] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Sonic hedgehog (Shh) is not only essential to the development of the gastrointestinal tract, but is also necessary to maintain the characteristic acid-secreting phenotype of the adult stomach. Gastrin is the only hormone capable of stimulating gastric acid and is thus required to maintain functional parietal cells. We have shown previously that gastrin-null mice display gastric atrophy and metaplasia prior to progression to distal, intestinal-type gastric cancer. Because reduced levels of Shh peptide correlate with gastric atrophy, we examined whether gastrin regulates Shh expression in parietal cells. We show here that gastrin stimulates Shh gene expression and acid-dependent processing of the 45-kDa Shh precursor to the 19-kDa secreted peptide in primary parietal cell cultures. This cleavage was blocked by the proton pump inhibitor omeprazole and mediated by the acid-activated protease pepsin A. Pepsin A was also the protease responsible for processing Shh in tissue extracts from human stomach. By contrast, extracts prepared from neoplastic gastric mucosa had reduced levels of pepsin A and did not process Shh. Therefore processing of Shh in the normal stomach is hormonally regulated, acid-dependent, and mediated by the aspartic protease pepsin A. Moreover parietal cell atrophy, a known pre-neoplastic lesion, correlates with loss of Shh processing.
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Affiliation(s)
- Yana Zavros
- Internal Medicine-Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109
| | - Meghna Waghray
- Internal Medicine-Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109
| | - Arthur Tessier
- Internal Medicine-Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109
| | - Longchuan Bai
- Internal Medicine-Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109
| | - Andrea Todisco
- Internal Medicine-Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109
| | - Deborah L Gumucio
- Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, 48109
| | - Linda C Samuelson
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109
| | - Andrzej Dlugosz
- Department of Dermatology, University of Michigan, Ann Arbor, Michigan, 48109
| | - Juanita L Merchant
- Internal Medicine-Gastroenterology, University of Michigan, Ann Arbor, Michigan, 48109; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109.
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15
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Czesnikiewicz-Guzik M, Loster B, Bielanski W, Guzik TJ, Konturek PC, Zapala J, Konturek SJ. Implications of oral Helicobacter pylori for the outcome of its gastric eradication therapy. J Clin Gastroenterol 2007; 41:145-51. [PMID: 17245212 DOI: 10.1097/01.mcg.0000225654.85060.3d] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND AIMS Helicobacter pylori (H. pylori) is an important pathogen in gastritis, peptic ulcer and possibly gastric cancer, but several questions remain unanswered. Particularly how the organism is transmitted and what is the relationship between oral presence of H. pylori and the gastric infection. Accordingly, we aimed to characterize the H. pylori in oral cavity and to evaluate its relationship to gastric H. pylori infection. MATERIALS AND METHODS Out of total 100 screened for H. pylori infection female subjects (40 to 85 y), 49 patients (pts), who had positive C-urea breath test (UBT) and dyspeptic symptoms, agreed for 1 week regimen of triple anti-H. pylori therapy. The presence of H. pylori in oral cavity was assessed using bacterial culture from saliva and gingival pockets. Gastric H. pylori infection was estimated using capsulated C-urea breath test and plasma anti-H. pylori IgG and saliva IgA antibodies. In addition, plasma gastrin, ghrelin, and pepsinogen I were measured by radioimmunoassay. In selected patients, gastroscopy was additionally performed and gastric biopsy samples were taken for H. pylori random amplification of polymorphic DNA genetic profiling. RESULTS The triple therapy resulted in gastric H. pylori eradication in 79% pts, along with significant decrease of plasma gastrin combined with an increase in plasma ghrelin and pepsinogen I (PgI) levels and a marked alleviation of dyspeptic symptoms. In contrast to gastric effects, the eradication therapy failed to cause any changes in the presence of H. pylori in oral cavity. Moreover no relationship was observed between the presence of H. pylori in oral cavity and the gastric H. pylori eradication. In line with these findings, no relationship between gastric and oral H. pylori was found using genetic profiling by random amplification of polymorphic DNA. CONCLUSIONS H. pylori was detected both in the oral cavity and the stomach but oral H. pylori had no relation to gastric H. pylori and remained unaffected by eradication of gastric H. pylori.
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16
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Rollan A, Ferreccio C, Gederlini A, Serrano C, Torres J, Harris P. Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric cancer. World J Gastroenterol 2006; 12:7172-8. [PMID: 17131482 PMCID: PMC4087781 DOI: 10.3748/wjg.v12.i44.7172] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [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 validate a non-invasive method to detect gastric mucosal atrophy in a Chilean population with high prevalence of gastric cancer and a poor survival rate.
METHODS: We first determined the optimal cut-off level of serum pepsinogen (PG)-1, PG-1/PG-2 ratio and 17-gastrin in 31 voluntary symptomatic patients (mean age: 66.1 years), of them 61% had histologically confirmed gastric atrophy. Then, in a population-based sample of 536 healthy individuals (209 residents in counties with higher relative risk and 327 residents in counties with lower relative risk for gastric cancer), we measured serum anti-H pylori antibodies, PG and 17-gastrin and estimated their risk of gastric cancer.
RESULTS: We found that serum PG-1 < 61.5 μg/L, PG-1/PG-2 ratio < 2.2 and 17-gastrin > 13.3 pmol/L had a high specificity (91%-100%) and a fair sensitivity (56%-78%) to detect corpus-predominant atrophy. Based on low serum PG-1 and PG-1/PG-2 ratio together as diagnostic criteria, 12.5% of the asymptomatic subjects had corpus-predominant atrophy (0% of those under 25 years and 20.2% over 65 years old). The frequency of gastric atrophy was similar (12% vs 13%) but H pylori infection rate was slightly higher (77% vs 71%) in the high-risk compared to the low-risk counties. Based on their estimated gastric cancer risk, individuals were classified as: low-risk group (no H pylori infection and no atrophy; n = 115; 21.4%); moderate-risk group (H pylori infection but no atrophy; n = 354, 66.0%); and high-risk group (gastric atrophy, with or without H pylori infection; n = 67, 12.5%). The high-risk group was significantly older (mean age: 61.9 ± 13.3 years), more frequently men and less educated as compared with the low-risk group.
CONCLUSION: We propose to concentrate on an upper gastrointestinal endoscopy for detection of early gastric cancer in the high-risk group. This intervention model could improve the poor prognosis of gastric cancer in Chile.
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Affiliation(s)
- Antonio Rollan
- Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago 6510260, Chile.
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17
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Juncà J, de Soria PL, Granada ML, Flores A, Márquez E. Detection of early abnormalities in gastric function in first-degree relatives of patients with pernicious anemia. Eur J Haematol 2006; 77:518-22. [PMID: 17042761 DOI: 10.1111/j.0902-4441.2006.t01-1-ejh2913.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Pernicious anemia (PA), as many other autoimmune disorders, has a trend to appear in other members of the family of the affected patients. Although this fact has been recognized since some decades ago, less is known about the frequency with which the abnormalities detected in the patients appear also in their relatives, the correlations that exist among these abnormalities and to what extent these markers of the disease relate to serum cobalamin concentration. SUBJECTS AND RESULTS For these reasons we studied the values of some markers of PA in a group of 79 first-degree relatives and we detected that the most frequent abnormalities are a decrease in serum pepsinogen I (22.7% of cases), an increase in serum gastrin (16.5% of cases) and in parietal cell antibody at a titer >or=40 (23.4% of cases). From a functional point of view, a decrease in hydrogen excretion in a magnesium breath test, indicative of achlorhydria, is also frequent (29.1%). The fall in cobalamin concentration runs in parallel with these abnormalities. The concentration of this vitamin was below normal levels in as much as 15.2% of cases. CONCLUSION These findings emphasize the need for searching for the presence of occult or latent PA in relatives of patients with this diagnosis, not only to prevent the development of anemia but also to avoid other undesirable consequences of cobalamin deficiency.
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Affiliation(s)
- Jordi Juncà
- Department of Haematology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
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18
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Yoshida S, Kozu T, Gotoda T, Saito D. Detection and treatment of early cancer in high-risk populations. Best Pract Res Clin Gastroenterol 2006; 20:745-65. [PMID: 16997158 DOI: 10.1016/j.bpg.2006.01.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
In this paper we describe how to more efficiently detect and treat early gastric cancer (EGC) in high-risk populations. For detection, we first assess the value of known risk factors from the viewpoint of availability for cancer screening. Serum pepsinogen appears to be the most useful and realistic of the factors examined, although its adequacy needs to be assessed in high-risk populations other than those in Japan. Helicobacter pylori infection is known to be a universal risk factor (or gastric carcinogen), and several interventional studies have recently shown positive results. However, H. pylori infection can be eradicated from at-risk populations, thereby decreasing its availability for cancer screening. Smokers are thought to be at risk epidemiologically, but the efficacy of screening in this population has yet to be elucidated, and further studies are warranted. Gender and aging can be risk factors in Japanese populations; male gender and old age are predominant in the intestinal type of carcinoma which is dominant in Japan, although this is not the case in the West. As for early diagnosis of cancer, only endoscopy can be commonly used for the detection of gastritis-like EGC, seen as a faint mucosal irregularity or discoloration. To make early diagnosis more accurate, it is indispensable to carry out detailed endoscopy together with careful scrutiny of the mucosa using dye-spraying techniques. The remarkable progress of early diagnosis in Japan prompted the endoscopic treatment for less invasive EGCs. The first success was with endoscopic mucosal resection (EMR). Although convenient, its therapeutic efficacy is inadequate, particularly for larger lesions. Endoscopic submucosal dissection (ESD) has no limitation on resection size and is expected to replace surgery, although it needs a high level of skill and there are several technical problems to be solved.
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Affiliation(s)
- Shigeaki Yoshida
- National Cancer Centre Hospital East, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, Japan.
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Waters MF, Kang GA, Mazziotta JC, DeGiorgio CM. Nitrous oxide inhalation as a cause of cervical myelopathy. Acta Neurol Scand 2005; 112:270-2. [PMID: 16146499 DOI: 10.1111/j.1600-0404.2005.00473.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Current evidence suggests that the incidence of recreational nitrous oxide inhalation is on the rise. Due to the possibility of clinically significant myelopathy, as well as potential response to treatment, it is important to consider this diagnosis when appropriate. We present a case of acquired ataxia and myelopathy due to nitrous oxide abuse and discuss diagnosis, pathophysiology, and response to treatment.
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Affiliation(s)
- M F Waters
- Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA.
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20
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Abstract
A large number of studies on diagnostic tests have been published this year. New tests were proposed for the detection of Helicobacter pylori antigens in stools and new molecular methods (real-time polymerase chain reaction) to look for antimicrobial susceptibility. The other standard tests have been applied in different situations to improve the diagnosis of the infection.
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Affiliation(s)
- Karen A Krogfelt
- Department of Gastrointestinal Infections, Statens Serum Institut, Copenhagen, Denmark
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